Sydney Medical Program GDMP2013

Stage 1 Essential Readings

Block 3: Respiratory Sciences

3.01 - Not At Fault // Chest Trauma & Pneumothorax pg 1 1. The Thoracic Wall And Lower Respiratory Tract 2. Thoracic Trauma 3. Pleural Structure And Function 4. Communication With Patients, Police, Family In 3.05 - Sleeping On The Job // Sleep Aponea & Respiratory Emergencies Failure pg 36 5. Posttraumatic Stress Syndrome 1. Neurobiological Consequences Of Sleep Loss 6. Autonomic Nervous System In The Thorax 2. Human Chronobiology 7. Pneumothorax 3. Autonomic Nervous System (Ans) 3.02 - Wheezing And Breathless // Asthma pg 9 4. Movement Disorders In Sleep 1. Mechanisms Of Wheezing 5. Pulmonary Circulation & Adaptation To Chronic Hypoxia 2. Atopy 6. Sedatives And Stimulants - New In 2012 3. Respiratory Infections In Infants 3.06 - A Different Cause Of Cough // Cystic Fibrosis pg 43 4. Clinical Features Of Asthma 1. Mechanisms Of Cough 5. Asthma - A National Health Priority 2. Molecular Genetics Of Cystic Fibrosis 6. Management Of Asthma 3. Bronchiectasis 7. Atopic Eczema 4. Prognosis In Cystic Fibrosis 8. Pathology Of Asthma 5. Management Of Cystic Fibrosis 3.03 - A Nasty Cough // Acute Exacerbation Of COPD pg 19 6. Dna Mutation Analysis 1. Tobacco Addiction 7. Antibiotics In Respiratory Disease 2. Pharmacology Of Nicotine 8. Recurrent Illness And Psychosocial Development 3. Public Health Policy In Tobacco Control 3.07 - Difficult Circumstances // Pneumonia & Otitis 4. Risk Reduction Following Cessation Of Smoking Media pg 53 5. Ethical Dilemmas In Tobacco Control Policy 1. Ear Infections 6. Chronic Obstructive Pulmonary Disease 2. Function Of The Ear 7. Pulmonary Rehabilitation With Focus On Copd 3. Growth And Nutrition In Indigenous Children 3.04 - Ex-Navy // Interstitial Lung Disease pg 27 4. Acute Respiratory Infection In Indigenous Children 1. Mechanisms Of The Sense Of Breathlessness 5. Management Of Pneumonia 2. The Gas Exchange Unit: Structure 6. Epidemiology Of Respiratory Infection 3. Interstitial Lung Disease 7. Causes Of Deafness 4. Mechanisms Of Lung Inflammation 5. Occupational Disability And Impairment 6. Compliance Of The Chest Wall And Lungs 7. Transport Of Oxygen And Carbon Dioxide 8. Blood Gas Analysis

i 3.01 - Not At Fault // Chest Trauma & Pneumothorax Learning Objectives Description Disciplines Revise practical notes on upper limb, lower limb and back Identify gaps in knowledge, revise and self-test Anatomy Attempt self-test questions in class (with answers) The organisation of the neural innervations of the pleurae and lungs Anatomy To develop understanding of the structural organisation of the thoracic wall, breast and thoracic cavity; to understand structure-function Anatomy relationship of the thoracic wall and structures within the thorax and to relate the structure of the thoracic cavity to clinical context. Detailed anatomical organisation of the trachea and bronchi, lungs and pleura Anatomy Behavioural Science, The doctor-patient-relatives communication in emergency settings, and the principles of communication when breaking bad news Psychiatry Describe the role of the Emergency Department to stabilise, evaluate, treat and arrange disposition for all patients presenting. The wide range of severity of illness and patient complexity mandates the Emergency Department triage patients needs and priorities. to the most potent life threats of airway, breathing and circulation. When stability is secure then a more thorough evaluation with history Emergency Medicine andLife threateningexamination, processes which can must identify be anticipated processes requiringand dealt treatmentwith in an orimmediate, formal investigations. ordered initial Emergency assessment. Department This assessment organisation attends and first procedures are essential to deal with both the urgency and breadth of its role from management of medical and surgical emergencies to the management of trauma, assault, toxicological problems and pre-hospital care. The mechanism of injury, assessment and management of thoracic trauma, and the range of chest injuries (for example pneumothorax Emergency Medicine, and haemothorax) Surgery

By the end of this session students should be able to: The contribution of road traffic crashes to injury related death and disability in Australia and internationally, and prevention strategies. describe the trends in injury related death and disability that has occurred globally over the last three decades General Practice describeunderstand the extent the to respectivewhich road roles traffic of crasheshuman andcontribute vehicle tofactors injury-related along with death physical and disabilityand social in environmental Australia and factorsinternationally in the causal • pathways for motor vehicle crash and injury • use the Haddon Matrix to identify strategies for prevention of motor vehicle crash and injury identify and discuss the evidence for the effectiveness of these strategies • •1. Differentiate between olfactory and respiratory epithelium when viewed with the light microscope 2. Recognize and describe the wall of the trachea, bronchus, bronchiole, alveolar duct and alveoli when viewed with the light microscope Histology 3. Describe the ultrastructure of the alveolar septum when viewed with the electron microscope 4. Apply your knowledge of epithelia to the changes seen in the epithelia lining the conducting versus respiratory airways

· Interpretation of normal values · Clinical indications for peak flow Medicine · Describe other common tests of respiratory function · Perform peak flow · Be familiar with inhalational devices for the delivery of medications · Understand the limitations and pitfalls in interpretation of peak flow in children Parasympathetic and sympathetic divisions of the autonomic nervous system: physiological role in the maintenance of homeostasis Transmitters - acetylcholine and noradrenaline • synthesis and storage in nerve terminals actions at cholinergic and adrenergic postsynaptic receptors Pharmacology • inactivation of transmitters to limit duration of action • • muscarinic receptor antagonists eg. atropine Pharmacologicalsympathomimetics mechanisms eg. phenylephrine, - predicting the isoprenaline, action of drugs dobutamine, which influence salbutamol normal transmitter function: • adrenoceptor antagonists eg. propranolol, atenolol, prazosin • •A range of possible psychological effects in patients that suffer traumatic injury with special reference to post traumatic stress disorder Psychiatry A patient who suffers a traumatic injury may suffer a multitude of psychological effects by a number of avenues. This lecture illuminates Psychiatry, Behavioural a variety of possible psychological effects with special reference to post-traumatic stress disorder which is described in the Learning Science Topics. Structured clinical exercises Block 3 Respiratory Medicine Respiratory Medicine

DemonstrateStudents should ability demonstrate: to carry out a respiratory system examination and report on the findings. · The ability to elicit a history of a respiratory problem Respiratory Medicine · The ability to communicate with a breathless patient · Awareness of the possible emotional reactions of patients with recurrent or severe breathlessness The concept, mechanisms, causes and treatments of pneumothorax Respiratory Medicine Respiratory Medicine

TheDescribe significance the anatomy and function of the respiratory of the gas exchangesystem and unit its mechanical properties that allow it to function as a gas exchanging organ. The of the lungs and for exchanging oxygen and carbon dioxide. The generation of a more negative pleural pressure by the contraction of Respiratory Medicine therespiratory inspiratory system muscles is a complex (mainly elasticthe diaphragm) structure draws which airhas through been arranged the conducting to function airways efficiently to the with respiratory respect zone. to moving Relaxation air in ofand the out inspiratory muscles allows the elastic system to passively return to its pre-inspiratory state, thus achieving exhalation. The anatomy and mechanical properties of the respiratory system dictate how breathing and gas exchange occurs. Because of the Respiratory Medicine concepts of how disease affects the normal functioning of the lung provides a sound basis of clinical assessment of respiratory disease. apical to basal gradient of ventilation, blood flow must also match this gradient to allow efficient gas exchange. Understanding the basic The organisation and function of the visceral and parietal pleura. The precise mechanisms that give rise to pleural pressure gradients Respiratory Medicine, across the lung Anatomy

1 3.01 - Not At Fault // Chest Trauma & Pneumothorax 1. The thoracic wall and lower respiratory tract Thoracic Cage lobes. The two layers of pleura are held together by surface tension due to a small amount of fluid in the pleural space (cavity). The The thoracic cage is comprised of the thoracic vertebrae, twelve pleural fluid allows the visceral and parietal pleura to slide over pairs of ribs and the sternum. It functions to house and protect one another but resists separation of the pleural layers. Conse- the internal organs. The thoracic cavity is limited superiorly by quently, the pleura counteracts the tendency for the thoracic cage the first ribs (thoracic inlet) and inferiorly by the muscular dia- to expand outwards and the elastic lungs to recoil inwards. The phragm. The domes of the diaphragm lie at approximately the 5th presence of air in the thoracic cavity, pneumothorax, due to a intercostal space during expiration, and consequently, the upper direct communication of the pleural space with atmospheric air abdominal organs are also protected by the thoracic cage. results in separation of the pleural layers and contraction of the Between the ribs, the intercostal space is bridged by intercostal lungs. A slight expansion of the thoracic cage may also be evident muscles and a neurovascular bundle. The intercostal arteries over the affected side. branch off the aorta; the intercostal veins drain into the azygous The lungs and visceral pleura receive only autonomic innervation system of veins; the intercostal nerves branch off the thoracic from the vagus nerve (CN10) and the sympathetic trunk. Con- spinal cord and pass through the sympathetic trunk. versely, the parietal pleura is innervated for pain by the intercostal Trachea and Bronchi nerves and the phrenic nerve (around the hilum). The sub-pleural lymphatic plexus drains to the hilar lymph nodes. Air passes to the lungs via the trachea, which begins at the inferior border of the larynx (CV6). It is held patently open by C-shaped Respiratory Muscles rings of cartilage that are deficient posteriorly. This permits expan- The diaphragm is the principle muscle of respiration. It is in- sion of the posteriorly related oesophagus during swallowing. The nervated by the phrenic nerve (spinal cord segments C3-5; trachea bifurcates to form primary bronchi behind the manubri- ‘C3-4-5 keeps the diaphragm alive” ‘). During quiet inspiration, osternal joint. Inhaled objects are more likely to be trapped in the the diaphragm descends to increase the thoracic volume and right primary bronchus as it is shorter, wider and more vertically produce a corresponding decrease in intrathoracic pressure. This oriented than the left. The primary bronchi further divide to form promotes passage of air into the lungs. During passive expiration, secondary (lobar) bronchi, which further divide to form tertiary the diaphragm recoils and the converse occurs. Contraction of the bronchi and so on. intercostal muscles also increases intrathoracic volume by elevat- Lungs and Pleura ing and separating the ribs. The lungs are spongy, expandable organs that lie within their During periods of increased oxygen requirement, e.g. exercise, own side of the thoracic cavity. The left lung comprises an upper airway obstruction etc., the accessory muscles of inspiration (pec- and lower lobe separated by an oblique fissure; the right lung toralis minor, scalenes, sternomastoid and intercostals) become ac- comprises an upper, middle and lower lobe separated by oblique tive and elevate the ribs to further increase intrathoracic volume. and transverse fissures. The bronchi and pulmonary vessels form During forced expiration, e.g. blowing a balloon, playing a trum- the lung root and pass through the hilum of the lung. The space pet etc., contraction of abdominal muscles increases intrathoracic between the lungs is the mediastinum. It is occupied by the heart, pressure facilitating air exit from the lungs. great vessels, oesophagus, trachea, and in the infant, the thymus. ______Two layers of pleura intervene between the thoracic wall and the Author: Michelle Barbara Gerke lungs that occupy the majority of the thoracic cavity (see LT3 for information on the structure and function of the pleura). The parietal pleura lines the thoracic cavity, while the visceral (pulmonary) pleura invests the lungs and intervenes between the

2 3.01 - Not At Fault // Chest Trauma & Pneumothorax 2. Thoracic Trauma Introduction For each of the following you should briefly describe the mecha- Mortality from thoracic trauma is 10%, with chest injuries caus- nism of injury, patho-physiology, clinical features and emergency ing 1 out of 4 trauma deaths. Injuries may be closed due to blunt management where appropriate. Particular attention should be trauma, eg in motor vehicle accidents and following falls from a paid to the first group. height, or open due to penetrating injuries caused by knives and guns. In Australia the majority of chest injuries are closed, but our increasingly violent society is leading to a growing number of Life threatening injuries - identified in the primary survey open injuries, especially in the western and south western regions • Airway obstruction of the Sydney Metropolitan Area. Less than 10% of blunt injuries and only 10-30% of penetrating injuries require thoracotomy, the • Tension pneumothorax rest being managed by simple techniques that should be within • Open pneumothorax the capabilities of all doctors. • Flail chest Mechanism of injury Blunt, can produce fractures of ribs together with damage to un- • Massive haemothorax derlying structures, including damage to the lung and mediastinal • Cardiac tamponade structures (especially the heart) and in the ‘abdomi’, the spleen, liver, kidney. Potentially life threatening injuries - identified in the secondary survey Assessment and management This consists of :- • Simple pneumothorax • Primary survey - in which life threatening chest injuries are • Haemothorax identified. • Pulmonary contusion • Initial resuscitation - restoration of vital functions. • Tracheobronchial disruption • Secondary survey - detailed examination of chest and whole • Blunt cardiac injury patient. • Traumatic aortic disruption • Definitive care • Traumatic diaphragmatic injury The history of the incident usually obtained from the ambulance officers or by-standers, together with a careful study of an A-P • Mediastinal traversing wounds (preferably erect) x-ray of the chest, are part of the assessment. Other injuries Summary of emergency management • Subcutaneous emphysema Most life threatening chest injuries require :- • Crushing injury to the chest (traumatic asphyxia) • Airway control - clearing of obstruction, and usually intuba- tion. • Rib, sternum and scapula fractures • Breathing support - ventilation of patient with high flow • Blunt oesophageal rupture oxygen. Insertion of tubes and/or needles. Optional references: King, Michael (ed.) 1997. Guidelines for the management of trauma. • Circulation control - rapid infusion of intravenous fluids and 2nd.ed. Westmead. NSW. Westmead Hospital Trauma Committee. early consideration of surgical control for ongoing bleeding. Driscoll, P., Skinner, D., Earlam, Richard. (eds.) 2000. ABC of major trauma 3rd.ed. BMJ Books. London. Specific chest injuries

3 3.01 - Not At Fault // Chest Trauma & Pneumothorax 3. Pleural Structure & Function The surface of the lungs is covered by a thin layer of connective inherent stress-free shape of the lung; ( 3 ) the weight of the lung; tissue and mesothelial cells which is in close contact with a similar ( 4 ) the elastic properties of the lung; and ( 5 ) possible friction layer of tissue covering the interior surface of the chest wall. between the two pleural surfaces. A complete account of current These tissue layers are respectively named the visceral and parietal knowledge of this complex topic can be found in the handbook of pleura. Between the two is a layer of pleural fluid surrounding physiology reference below (Chapter 30). both lungs which, in health, is probably only 2 ml in total volume Fluid flow follows a relationship known as Starling’s Law which and, spread over the surface area of the lungs, the thickness of states that : this layer is only about 10-30 um. The surface mesothelial cells of the visceral pleura have a high density of microvilli to enhance F = K[(Pc-Ppl) - (pc-ppl)] absorption with a lower density of these structures on the parietal where; mesothelial cells . These microvilli also trap glycoproteins which act as a lubricant between the surfaces of the constantly moving • F = the pressure moving fluid into the pleural space from lungs and chest wall. pleural surface capillaries There is a potential space between the visceral and parietal • Pc = the hydrostatic pressure in the capillaries pleurae. Normally, the right pleural space does not communicate • Ppl = the pleural pressure with the left. Each space does not normally contain gas because the total gas pressure in the predominantly venous blood perfus- • pc = the osmotic pressure in the capillaries ing capillaries around the pleural surfaces is 60 cmH2O below • ppl = the osmotic pressure in the pleural space atmospheric so any small amount of gas introduced into the pleural space will tend to resorb. The pressure in this potential • K = constant of proportionality space is subatmospheric by about - 8.5 cm H 2 O at the top of Applied to the parietal pleura, a net pressure of about 6cmH2O the lung and -2.5 cm H 2 O at the bottom when the lung is at is calculated moving fluid from parietal capillaries into the space functional residual capacity in the erect position. The negative while a net pressure of about 13 cmH 2 O exists to absorb fluid pressure is due to the elastic recoil of the lung acting against the from the space into the capillaries in the visceral pleura. This chest wall. Creating a hole in the chest wall or lung surface to results in a circulation of about 100 ml of fluid per hour from the atmosphere (pneumothorax) will result in total collapse of the parietal to the visceral pleura and virtually no accumulation in the lung and a small outward springing of the chest wall. The gradient pleural space unless some abnormality occurs such as an increase from top to bottom is a function of the gravitational field and the in visceral hydrostatic pressure (eg left heart failure), an increase in weight of the lung. The pleural pressure is more evenly negative in the pleural osmotic pressure (eg leak of proteins into the pleural microgravity. space due to trauma, inflammatory or malignant processes), or The pleural pressure changes with lung volume during the a decrease in plasma osmotic pressure (eg hypoalbuminaemic breathing cycle because the lung becomes stiffer (less compliant) states). Diseases causing a pleural effusion (collection of fluid in with expansion. In the erect position, the lower thoracic pleural the pleural space) do so by one or a combination of these mecha- pressure changes from -0.5 to -33 cm H 2 O while the upper nisms. pressure changes from -8.5 to -40 cm H 2 O as the lung expands from functional residual capacity (FRC) to total lung capacity Optional references: (TLC). The lower parts of the lung expand more during inspira- Available in Medical Library: see Library Catalogue tion because they operate on a more compliant part of the volume A very good discussion of normal and disturbed pleural function can be found in pressure relationship. That is, the volume change for a given the two concise books by John West: West JB. Respiratory physiology : the essentials. 8th ed. Philadelphia: Wolters pressure change is greater in the lower parts because they are less Kluwer Health/Lippincott Williams & Wilkins; 2008 ‘stretched’ than the upper parts at low lung volumes. A gradient of West JB. Pulmonary pathophysiology : the essentials. 7th ed. Philadelphia: Lip- ventilation - perfusion ratios exists from high at the apex to low at pincott Williams & Wilkins; 2008 the base of the lung because the blood flow gradient is consider- A more detailed and comprehensive exposition can be found in: The American Physiological Society, 1986, The Respiratory System, In, Handbook ably steeper than the ventilation gradient. of Physiology, Bethesda Md, USA. The graded increase in ventilation from top to bottom is disturbed The American Physiological Society,1986, Mechanics of Breathing, In, Handbook of Physiology, Bethesda Md, USA. if the subject inspires from residual volume (RV) because there Diseases of the pleura and some normal structure and function are well discussed is a small positive pleural pressure at the base of the lung at this in: lowest possible volume due to airway closure at the lung bases. Symposium on pleural diseases, 1985, Richard W. Light (ed.), in, Clinics in Chest Therefore, until this basal pleural pressure becomes negative again Medicine, Pleural Diseases, (Series), WB Saunders, Philadelphia. (at about FRC), the ventilation will be directed to the upper parts of the lung. ______The precise mechanisms giving rise to the negative pleural pres- Author: Michelle Barbara Gerke sure gradient around the lung are still controversial but they are broadly - ( 1 ) the shape and mechanical properties of the chest wall (which can be altered by changes in lung volume, changes in body posture and contraction of the respiratory muscles; ( 2 ) the

4 3.01 - Not At Fault // Chest Trauma & Pneumothorax 4. Communication With Patients, Police, Family In Emergencies Doctor patient communication is often difficult in emergency Breaking bad news settings: medical staff are often busy and pressured, patients and Breaking bad news to patients or relatives should take place in their relatives may be distressed and anxious, and the nature of a setting which is private, comfortable and free of interruptions the communication is one which requires empathy, kindness and (most hospital emergency departments have a room set aside for understanding. this). Communication with patients Principles of communication include: an empathic approach, sim- Although emergencies are often frightening for doctors as well plicity and clarity, an absence of jargon, provision of space during as patients and their relatives, it is the demeanour of the doc- the consultation for venting of feelings, emphasising the posi- tor which sets the tone of the consultation. The doctor should tive (whenever possible) and provision of ongoing support. The endeavour to appear calm, competent, compassionate and unhur- presence of relatives or close friends has been shown to positively ried, even in the most hectic and urgent settings. influence long term adjustment and should be encouraged when breaking bad news. Emergency Departments are alienating, anxiety provoking settings for many patients. Care should be taken to ensure patients privacy Anger is a normal reaction to misfortune and is common in emer- and confidentiality. The curtains should be drawn around the gency settings. Communication principles involved in managing bed when interviewing or examining a patient and care should be anger include: not reacting; provision of space for ventilation of taken not to reveal details of a patient’s history to any person not anger; acknowledging anger; acknowledging concerns; facilitat- directly involved in their care. ing communication by inquiry and making arrangements for concerns to be addressed. Patients are usually anxious in emergency settings, although this may not be openly expressed. Some degree of anxiety should Communication with police always to be assumed, and addressed as an important part of Police inquiry is valid and an important part of emergency care. management. Under no circumstances should details of a patient’s medical condition be revealed to the police (or any other person) without Patients should be advised of their progress as it evolves. Basic the patient’s written informed consent (normally by written future communication principles involved in giving advice includes: communication). When considering requests from the police to exploring specific concerns and level of understanding; clarity, interview a patient careful consideration should be given to the simplicity and fluency of explanation; an absence of jargon; and overriding concern of optimal patient care. establishing understanding by inviting and encouraging questions.

Patients who appear confused, unconscious or otherwise physi- Optional references: cally compromised are often aware of their surroundings and this For a detailed account of communication skills involved in breaking bad news: should be considered when communicating with colleagues and Buckman R. Breaking bad news: why is it still so difficult? BMJ 1984; 288(6430): 1597-1599. others nearby. Unconscious or physically compromised patients Brewin TR. Three ways of giving bad news . Lancet 1991; 337(8751): 1207-1209. should be advised in advance of any painful procedure or change McIntosh J. Patients’ awareness & desire for information about diagnosed but in management. undisclosed malignant disease . Lancet 1976; 308:(7980): 300-303. Quill TE. Bad news: delivery, dialogue, and dilemmas. Arch Intern Med Communication with relatives 1991;151(3):463-468. Relatives provide important emotional and practical support and Hogbin B. Getting it taped: the “bad news” consultation with cancer patients. Br have a major positive impact on patient care. Relatives are able to J. Hosp.Med 1989; 41(4): 330-332. For a very moving account of a grieving relatives’ experience in an accident and provide details of history which the patient may be unable to pro- emergency department: vide, and are able to provide ongoing support in the emergency Awooner-Renner S. I desperately needed to see my son. BMJ 1991; 302(6772): department and following discharge. Their involvement should be 356. facilitated and encouraged wherever possible. Resource Materials Teaching videos which addressed many issues in doctor-patient communica- Relatives should be advised of the patient’s progress as it evolves. tion, although not necessarily directly related to emergency settings are available through the Department of General Practice, Central Clinical School. These Important communication skills involved in explaining are include :- outlined above. The issue of patient confidentiality should be Opening the consultation, Information gathering, Explaining, Closing the consul- considered but is usually not an overriding concern when advis- tation. ing relatives in emergency settings. Where possible prior patient consent should be obtained. Author: Dr Chris Cooper, General Practice

5 3.01 - Not At Fault // Chest Trauma & Pneumothorax 5. Posttraumatic Stress Syndrome Post-traumatic stress syndrome is characterised by the devel- Once established PTSD is extremely difficult to treat. Techniques opment of characteristic psychological symptoms that follow that have some demonstrated efficacy in the treatment of PTSD exposure to an extremely stressful event that involved actual include :- or threatened death or serious injury to the sufferer or another • re-exposure to the trauma and processing of associated feel- person. In adults the response to the event involves intense fear, ings by imaginal recall of the event. helplessness or horror and the characteristic symptoms resulting from the exposure to the extreme trauma include one or more of:- • graded in-vivo exposure to feared situations • persistent re-experiencing of the traumatic event (e.g. dis- • cognitive therapy, where the patients unhelpful beliefs (e.g. tressing dreams or intrusive thoughts or images) “the world is dangerous and unpredictable”) and estimations of danger (“I am highly likely to get attacked again if I go • persistent avoidance of stimuli associated with the trauma out”) are identified and modified with the patient. (e.g. avoiding conversations, memories or reminders) • psychotherapy aimed at exploring the meaning of the event • a general numbing of emotions (including feeling detached to the individual. from others and disengaged from one’s future) • medications, such as the selective serotonin reuptake inhibi- • persistent symptoms of anxiety or arousal (e.g. increased star- tors (benzodiazepines are unhelpful in the longer-term). tle response, difficulty relaxing, irritability, sleep disturbance, poor concentration and memory) Te first three interventions above comprise cognitive-behaviour therapy (CBT), which has the most support for effectiveness. The traumatic event may be experienced directly or witnessed. Many of these interventions can be administered in group format The most common seen in practice are from major assaults and as well as individual therapy. significant accidents (e.g. motor vehicle or industrial). Possible triggering events include military combat, violent assault, torture, Eye-movement desensitisation and reprocessing (EMDR) is a incarceration as a prisoner of war or in a concentration camp, treatment procedure that involves the patient moving his/her eyes natural or man-made disasters, or being diagnosed with a life- backward and forward whilst recalling the event. While showing threatening illness. The disorder may be especially severe or long some promise in treatment of PTSD, it’s efficacy remains contro- lasting when the stressor is of human design (eg torture, rape). versial. It is possible to have a delayed onset of symptoms (e.g. several De-briefing after exposure to traumatic event to provide prophy- months after the actual event). laxis against the later development of PTSD has become com- Individuals may also describe painful guilt feelings about surviv- mon. Empirical evidence for the efficacy of such de-briefing ing when others did not survive or about the things they had to however remains scant, with some studies showing an association do to survive. with poorer outcome in disaster workers who were debriefed. Children and adolescents may also suffer posttraumatic symp- Owing to difficulty of treatment, management aimed at the toms but they may be modulated by the child’s developmental PTSD symptoms themselves is best left to clinicians with some stage. For example a five year old may “relive” a motor vehicle experience in the disorder. accident through repetitive play. Cultural factors may also play a Treatment may also be directed at co-morbid conditions such as role in modifying presentation. This is particularly important in depression and alcohol dependence, which are common among individuals who have emigrated from countries where torture is these patients. The patient may also benefit from interventions common. aimed at the family who are often perplexed by, or put under When mild and self-limiting, these features comprise a normal re- heavy burden by the change in their loved one. Rehabilitative sponse to a stressful event. When they are intense or continue on efforts to improve psychosocial function despite the persistence of and begin to interfere with the person’s normal functioning, they some symptoms are also crucial often. become a disorder - Post-traumatic Stress Disorder (PTSD). Some of the most important factors affecting the likelihood of develop- Optional references: ing (PTSD) are the severity, duration, and proximity of exposure The psychiatric textbook in the tutorial room collection contains a good (though to the traumatic event. Subjective fear of death is predictive of extremely brief) introduction to both normal acute stress reactions and posttraumatic stress disorder. worse PTSD symptoms. There is some evidence that social sup- Treatment Protocol Project, 2004, Management of mental disorders, 4th edn., ports, family history, childhood experiences, personality variables World Health Organization Collaborating Centre for Mental Health and Sub- and pre-existing mental disorders are also important risk factors. stance Abuse, Darlinghurst, NSW. Interested students may wish to augment their understanding of this area with the A large US community-based study estimated the lifetime following chapter which integrates posttraumatic stress disorder with other stress population prevalence of PTSD was 1%. In certain groups such reactions such as bereavement. Bowman, B., 1989, Crisis and adjustment reactions. In: Textbook of psychiatry, as Vietnam veterans and refugees from countries where torture is Pierre J.V. Beumont, (ed.), Blackwell Scientific Publications, Melbourne. endemic, PTSD is more common.

6 3.01 - Not At Fault // Chest Trauma & Pneumothorax 6. Autonomic Nervous System In The Thorax The autonomic nervous system in general. autonomously it can also be influenced by the autonomic system. The autonomic nervous system innervates smooth muscle, cardiac Autonomic nervous system in the thorax. muscle and glands and participates in the control of the bodies The major structures in the thorax to receive an autonomic nerve internal environment contributing to the process of homeostasis. supply are the oesophagus, lungs, heart and the blood vessels The autonomic nervous system is usually considered to be a mo- which are located throughout the cavity and its walls. tor system only. Visceral sensation while conveyed through fibres The walls of the thorax including the skin receive only a sympa- which initially travel with autonomic fibres are organized and thetic supply via the sympathetic trunk and the intercostal nerves. behave in a similar way to the somatic sensory system. The preganglionic sympathetic supply to the heart and lungs Centrally the autonomic nervous system is controlled by vari- derives from spinal cord segments T1 to T5. The post ganglionic ous parts of the brain including structures in the diencephalon fibres distribute via nerves which leave the sympathetic trunk in and brain stem. Peripherally it acts usually through a two neuron the upper thoracic and lower cervical regions. They act to dilate system, a preganglionic neuron and a postganglionic neuron. the respiratory airways and for the heart increase rate and force of It has two divisions which differ structurally, functionally and contraction. The postganglionic nerve cell bodies are located in pharmacologically. The sympathetic and parasympathetic divi- the sympathetic trunk. sions. The preganglionic parasympathetic supply to the oesophagus, The peripheral part of the sympathetic division arises from the lungs and heart originate from the cranial nerve nuclei (dorsal thoracic and upper lumbar spinal cord forms the sympathetic motor nucleus of the vagus, nucleus ambiguous) and distribute trunk and then distributes peripherally in several ways including in the vagus nerve. The post ganglionic fibres are short and the by peripheral nerves, splanchnic nerves and along blood vessels. cell bodies form collections within or near the viscera supplied. The preganglionic cell bodies are located in the lateral horn of The parasympathetic system acts to stimulate peristalsis in the the spinal cord grey matter and the postganglionic cell bodies in oesophagus, narrow airways and increase secretion in the lungs either the sympathetic trunk or peripheral ganglia such as the and to decrease heart rate. coeliac ganglia. Along the course of both systems the nerve fibres form collec- The peripheral part of the parasympathetic system arises from tions which are termed plexuses. They are found in such places as either the brain stem or sacral spinal cord segments. The cranial around the oesophagus, the arch of the aorta and the root of the part distributes through the occulomotor, facial, glossopharangeal lungs. and vagus nerves and the sacral part in peripheral nerves, splanch- While some blood vessels within the body receive both a sympa- nic nerves or along blood vessels. The cranial preganglionic nerve thetic and parasympathetic innervation which may cause either cell bodies are located in cranial nerve nuclei while the sacral vasodilatation or constriction most muscular arteries and arte- preganglionic cell bodies are in the intermediate region of sacral rioles only receive a sympathetic supply which when activated spinal cord grey matter segments two to four. Post ganglionic causes vasoconstriction. Also some veins particularly the larger parasympathetic neurons are usually short and have their cell bod- ones have an autonomic innervation. ies in or near the structures innervated.

The peripheral neurotransmitter for the sympathetic system is Optional references: noradrenalin (except for sweat glands) and acetylcholine for the Moore K.L. and Dalley A.F. ‘10. “Clinically Oriented Anatomy” 6th edition. Pub. parasympathetic division. Lippincott Williams Wilkins. Pages 46-67 Drake R.L. et al. ‘10. “Anatomy For Students” 2nd ed Pages 197 - 199 There is an additional part of the visceral motor system which is sometimes classified separately. It controls the intrinsic action of Author: Dr Richard Ward, Anatomy and Histology the gut and is termed the enteric system. While it can function

7 3.01 - Not At Fault // Chest Trauma & Pneumothorax 7. Pneumothorax This conditions occurs when gas collects in the pleural space, aetiology) rupture, allowing the escape of air from the lungs into resulting in partial or complete collapse of the lung, depending the pleural space. There is a tendency for these types of pneumo- upon the volume of gas in the pleural space. Under normal physi- thoraces to recur. The common symptoms of pneumothorax are ological conditions, the pressure in the pleural space is slightly pleuritic chest pain and dyspnoea. Typical physical signs include negative compared with atmospheric pressure because of the ten- increased respiratory rate, hyperresonance to percussion and dency for the chest wall to recoil in an outward direction and the diminished breath sounds on the affected side and tracheal devia- lung, due to intrinsic elasticity, to recoil in an inward direction. tion, if there is a mediastinal shift. The diagnosis is confirmed with a chest x-ray, which demonstrates the visceral pleural edge When air enters the pleural space, either through a rupture of and no lung markings between the edge and the bony structures the lung or bronchial tissue, or through a leak in the chest wall, of the chest wall. If there has been any bleeding, which may occur there is no longer negative pressure in the pleural space so the particularly in association with pneumothoraces due to trauma, lung progressively collapses, depending upon the extent to which an air fluid level in the pleural space may be evident in the chest pressure builds up in the pneumothorax. In some circumstances, x-ray. the pressure can build up to the extent that in younger patients, with relatively mobile mediastinal structures, the mediastinum The treatment of pneumothoraces depends upon their size. Small can shift towards the unaffected lung. A tension pneumothorax, pneumothoraces, in which the leak has sealed spontaneously, will which may occur if there is a one way leak of air into the pleural resolve without intervention because the air in the pleural space space (a so called ?ball valve leak?), leads to a marked increase in will be absorbed progressively over a period of days or weeks. pleural pressure, complete collapse of the lung, substantial shift of Larger pneumothoraces require the aspiration of the air from the the mediastinum and compromised cardiac function. pleural space, either via a canula and syringe, or the insertion of an indwelling intercostal catheter. The intercostal catheter is Pneumothoraces may occur spontaneously (most common in connected to an underwater drain to allow the air in the pleural young people), or in association with lung disease (such as asthma cavity under positive pressure to escape but prevent the re-entry of or COPD). Chest trauma, particularly associated with fractured air into the pleural cavity. ribs, can result in pneumothorax. Mechanical ventilation, where high positive pressures are generated within the airways, can result in pneumothorax. In patients with spontaneous pneumothorax, Author: Professor John Paul Seale, Pharmacology small blebs on the surface of the visceral pleura (of uncertain

8 3.02 - Wheezing And Breathless // Asthma Learning Objectives aetiology) rupture, allowing the escape of air from the lungs into Description Disciplines the pleural space. There is a tendency for these types of pneumo- Detailed anatomical organisation of the scalp, face and neck; the bones, joints (eg temporomandibular) and muscles Anatomy thoraces to recur. The common symptoms of pneumothorax are (facial expression, neck and mastication) associated with scalp, face and neck pleuritic chest pain and dyspnoea. Typical physical signs include To develop understanding of the structural organisation of the thoracic wall, breast and thoracic cavity; to understand increased respiratory rate, hyperresonance to percussion and structure-function relationship of the thoracic wall and structures within the thorax and to relate the structure of the Anatomy diminished breath sounds on the affected side and tracheal devia- thoracic cavity to clinical context. tion, if there is a mediastinal shift. The diagnosis is confirmed Dermatology with a chest x-ray, which demonstrates the visceral pleural edge Dermatology and no lung markings between the edge and the bony structures The definition of atopic dermatitis. The many factors that exacerbate eczema and the major types of treatment available of the chest wall. If there has been any bleeding, which may occur DiseasesTo acquaint caused students by hypersensitivity with: in skin, according to Gell and Coombs classification, their diagnosis and treatment the importance of preventative measures in the management of asthma General Practice, particularly in association with pneumothoraces due to trauma, the content and limitations of current preventative strategies Paediatrics an air fluid level in the pleural space may be evident in the chest the• best means communicating these strategies to the patient and the community. x-ray. The normal structures of the thoracic cage from a chest x ray. The appearance of injuries to the thorax including injury Imaging, Radiology to the heart, mediastinum, lungs and thoracic cage The treatment of pneumothoraces depends upon their size. Small Immunobiology of IgE antibody responses, including their role in protective immunity to parasites and in pneumothoraces, in which the leak has sealed spontaneously, will Immunology hypersensitivity to environmental and other allergens resolve without intervention because the air in the pleural space will be absorbed progressively over a period of days or weeks. · Describe normal respiratory physiology. · List common O2 delivery devices and the % O2 delivered to the patient for each. Larger pneumothoraces require the aspiration of the air from the · Fit oxygen mask and nasal prongs. pleural space, either via a canula and syringe, or the insertion · Fit a pulse oximeter and interpret the % saturation for this device Medicine of an indwelling intercostal catheter. The intercostal catheter is · Identify patients at risk of chronic CO2 retention. connected to an underwater drain to allow the air in the pleural · Describe the management of oxygen delivery to these patients. · Demonstrate correct use of oropharyngeal airways and bag and mask. cavity under positive pressure to escape but prevent the re-entry of air into the pleural cavity. The principal viruses and bacteria responsible for triggering acute episodes of asthma, the basic mechanisms by which Paediatrics, Infectious viruses stimulate exacerbations of asthma Diseases Asthma is a national health priority area in Australia. Thr quality of life, mortality, risk factors and management of Paediatrics, Public Author: Professor John Paul Seale, Pharmacology asthma Health The pathology of asthma; the origins of the symptoms (breathlessness, cough, haemoptysis, pain and wheeze) and signs Pathology hyperreactivity in the clinical manifestations of asthma of respiratory ill health. The factors responsible for the development of asthma, and the role of airway inflammation and The pathology of the airways with particular reference to asthma. The different types of asthma. The macroscopic and Pathology microscopic appearance of the lungs in asthma Management of patients with asthma in accordance with the steps described in the Asthma Management Handbook. Pharmacology The medications used for asthma and the drugs for long term treatment. Different drugs used to dilate airways, their mechanism of action and the clinical conditions which they are used to treat Pharmacology

Theories on the development of asthma and the associated risk factors Pharmacology, CellularThe definition pathophysiology of asthma andincluding its prevalence mediators in andAustralia cytokines Respiratory Medicine The Actions of drugs used to treat asthma Physiology

Concept of airflow limitation or obstruction. The methods that underpin measurement of airflow limitation Physiology, the pathophysiological processes that lead to continuous adventitial lung sounds Respiratory Medicine The definition of wheezing and terms such as crackles. The basic mechanisms underlying the production of wheeze and · Learn to recognise peripheral signs of acute and chronic respiratory disease. Respiratory Medicine

The lung function tests used commonly in the assessment of patients with respiratory disease and the determinants of · Learn to accommodate the difficulty of a physical exam for a breathless patient Respiratory Medicine both normal and abnormal lung function The principles of taking a history and undertaking an examination of the respiratory system Respiratory Medicine Students should learn: To assess a patient's asthma severity To assess a patient's current degree of asthma control To explain to a patient the nature of asthma To discuss potential triggers to the patient's asthma Respiratory Medicine

To describe the types of medications used to treat asthma (preventers, symptom controllers and relievers) To describediscuss with the essentialthe patient principles how triggers of choosing may be and modified reviewing optimal use of inhaler devices To describe what an individual asthma plan for a patient involves Respiratory Medicine Respiratory Medicine, TheDefine clinical atopy, manifestations and the four main and symptomtypes of allergic patterns reactions associated (Gell with and asthma Coombs classification) Paediatrics

9 3.02 - Wheezing And Breathless // Asthma 1. Mechanisms Of Wheezing Wheezes are continuous sounds generated from the within the opposite walls are almost in contact. The acceleration of gas flow lungs during breathing. These sounds are superimposed on the through the narrowed airway induces an oscillation of the airway normal breath sounds and are often referred to as adventitial walls. The pitch of the wheeze therefore depends upon the mass sounds. Wheezes may be characterised by their pitch, intensity, and elasticity of the airway walls and on the flow velocity of the location, duration in the respiratory cycle (short or long) and gas within the airway. The pitch of the wheeze is not influenced relationship to the phase of respiration in which they are heard by the length or size of the airway. (inspiratory or expiratory). No theory explaining inspiratory wheezes has yet been proposed. Attempts at standardising the nomenclature of lung sounds have During inspiration the airways are held open by the elastic tis- been proposed, within which wheezes are defined as high pitched, sues of the lung. Presumably in some circumstances this is not continuous sounds. ‘Continuous’ in this context is in relationship sufficient to enlarge an airway and flow limitation with airway to the phase of the breathing cycle in which the sound occurs; ie wall fluttering occurs. Inspiratory wheezes are often associated the sound is continuous over 0.25 to 1.5 seconds of breathing - as with more severe airways obstruction or upper airways obstruc- opposed to ‘crackles’ which are a series of discontinuous ‘pop- tion. The continuous musical respiratory sound heard in patients ping’ sounds. Analysing wheezing sounds using signal processing with upper airway obstruction is called stridor. In contrast to and analysis techniques has shown the dominant frequency of intrapulmonary airways, the upper airways tend to collapse dur- wheezing to be approximately 400 Hz. There is, however, a large ing inspiration (due to negative intra-airway pressure) and airway variability in the prominent frequency of wheezes. narrowing or closure at these sites is more prominent. The sound frequency of stridor is similar to that of wheezes, being heard The structure of the normal bronchial tree consists of a series of during inspiration and being more prominent over the neck than branches or generations from the trachea (generation 0), through the chest. The commonest cause of stridor is laryngeal obstruction the left and right main bronchi (generation 1), then to the lobar or muscle weakness. Snoring, a sound generated mostly during bronchi. This division continues to the terminal bronchioles, the inspiration, is the result of flow limitation, usually at the oro- respiratory bronchioles, alveolar ducts and finally the alveolar sacs pharynx, in which the soft palate flutters. This is the easiest sound - with an average of 20 to 23 divisions (or generations) along the to understand and is a model of the mechanism of wheezing or way. While the calibre of each individual airway decreases with stridor at all levels. each division, the total cross sectional area of the airways increases with each generation. The linear velocity of airflow in these very Many pathophysiological processes will lead to the production of peripheral airways is thus very low - far too low to produce an au- continuous adventitial lung sounds; thus wheezes can be heard in dible sound at this level, even with considerable airway narrowing. several diseases - not only asthma. These include all mechanisms Wheezing is therefore produced by diseases or disease processes, narrowing airway calibre, such as bronchospasm, intraluminal which directly or indirectly reduce the calibre or cross sectional tumours or secretions, foreign bodies, mucosal oedema, external area of the trachea or major bronchi. compression of an airway by a tumour mass, or dynamic airway compression. Furthermore, the changes in the mechanical While localised obstruction of the large airways can occur, dy- characteristics of the pulmonary system accompanying certain namic narrowing of the trachea or major bronchi may also come pathological processes influence the development of wheezes. about during expiration as a result of widespread obstruction of Examples include the reduction in airway calibre seen in asthma, the medium and smaller airways. The physiological explanation the reduction in bronchial stiffness associated with some chronic for this is referred to as the “equal pressure point theory”. The obstructive lung diseases or the decrease in elastance accompany- key elements involved include the pleural pressure or pressure ing pulmonary oedema - in all these instances changes in airway outside the airways (Ppl) which is usually negative during relaxed and/or pulmonary mechanics mean that the critical velocity at expiration, tending to keep the lungs inflated, and the elastic which airway “flutter” will occur is lowered, thus oscillations of recoil pressure of the lung tissue (Pst[L]) which tends to empty the airway walls will start more easily. Healthy individuals can also the lungs. The tissue forces driving relaxed expiration are the sum produce wheeze during a forced expiratory manoeuvre. of these two values. However, if airflow resistance increases, these driving forces may be insufficient to produce airflow and expira- The presence of a wheeze is a clinical sign found in patients with tion must become an active process; now Ppl becomes positive obstructive airways diseases particularly during acute episodes of during expiration and the pressure within the alveoli increases. asthma. There is no relationship between the intensity or the pitch This pressure will progressively fall along the airways (referred of wheezes and the pulmonary function. to as “downstream”) to reach a pressure of zero at the mouth. Optional references: Downstream from the point where Ppl exceeds the intraluminal Mikami R, Murao M, Cugell DW et al. International symposium on Lung pressure, dynamic compression of the airways can occur, and Sounds. Synopsis of Proceedings Chest 1987; 92(2): 342-345. wheeze is produced as a result of the dynamic narrowing of these Forgacs P. The functional basis of pulmonary sounds. Chest 1978; 73(3): 399-405. Waring WW, Beckerman RC, Hopkins RL. Continuous adventitious lung sounds: larger airways. site and method of production and significance. Semin Respir Med 1985; 6(3): The mechanisms underlying the production of a wheezing sound 201-208. Meslier N, Charbonneau G, Racineux JL. Wheezes. Eur Respir J 1995; 8(11): with breathing seem to involve an interaction between the airway 1942-1948. wall and gas moving through the airway. This mechanism has Murray, JF., 2000, Diagnostic evaluation: history and physical examination, In: been compared to the production of sounds by wind instruments, Textbook of respiratory medicine, 3rd edn., Murray JF, Nadel JA, eds., Saunders, which use a vibrating reed to produce their sound (eg a clarinet). Philadelphia. Phelan, P.D., Olinsky, A., Robertson, C.F., 1994, Resiratory noises, In: Respira- It is believed that the high-pitched sounds of wheezing are pro- tory illness in children, 4th edn., Blackwell Scientific, Oxford ; Boston. duced when the airway lumen is narrowed to the point where the Author: Dr Stephen Gregory McNamara, Medicine 10 3.02 - Wheezing And Breathless // Asthma 2. Atopy opposite walls are almost in contact. The acceleration of gas flow At the beginning of this century, the Austrian paediatri- because of their ability to produce IL-5 as well as IL-4, are through the narrowed airway induces an oscillation of the airway cian, Clemens von Pirquet, coined the term “allergy” to also responsible for the eosinophils often associated with walls. The pitch of the wheeze therefore depends upon the mass describe the phenomenon he had observed in which some hyperproduction of IgE in allergic subjects. In contrast, T and elasticity of the airway walls and on the flow velocity of the patients, under certain conditions, developed an increased helper cells which do not produce IL-4 (Th1 cells), or which gas within the airway. The pitch of the wheeze is not influenced reactivity instead of immunity. In 1923, Coca and Cooke produce high concentrations of IFN-gamma, do not sup- by the length or size of the airway. proposed the term “atopy” for the clinical manifestations of port IgE synthesis and in fact, the IFN-gamma can suppress No theory explaining inspiratory wheezes has yet been proposed. allergy such as hayfever and asthma in which “the individu- IL-4-dependent IgE synthesis. Regulatory T cells, such as During inspiration the airways are held open by the elastic tis- als possess a peculiar capacity to become sensitive to certain nTreg, Th3 and Tr1 cells may also play a role in determin- sues of the lung. Presumably in some circumstances this is not proteins to which their environment and habits of life ing whether the response to ubiquitous environmental sufficient to enlarge an airway and flow limitation with airway frequently expose them”. In 1921, Prausnitz showed that allergens is that of tolerance or of sensitisation and clinical wall fluttering occurs. Inspiratory wheezes are often associated with more severe airways obstruction or upper airways obstruc- atopic allergic sensitivity can be passively transferred from allergy. Thus, dysregulation of these regulatory t cells is now tion. The continuous musical respiratory sound heard in patients one individual to another by a serum factor called “reagin”. thought to play a significant role in the development of the with upper airway obstruction is called stridor. In contrast to In 1967, it was shown that reagin was actually an immuno- atopy. globulin which was named immunoglobulin E (IgE). intrapulmonary airways, the upper airways tend to collapse dur- In addition, promotion of a prevalent Th2 type response to ing inspiration (due to negative intra-airway pressure) and airway Atopy is currently defined as the predisposition to produce environmental allergens (such as foods, HDM, animal dan- narrowing or closure at these sites is more prominent. The sound frequency of stridor is similar to that of wheezes, being heard IgE antibodies in response to the ordinary exposure to al- der, pollen etc) in atopic subjects almost certainly involves a during inspiration and being more prominent over the neck than lergens in the environment. genetic predisposition as well as environmental influences. the chest. The commonest cause of stridor is laryngeal obstruction Classically, allergic reactions are divided into four main Atopic diseases (diseases in which atopy is a common al- or muscle weakness. Snoring, a sound generated mostly during types (Gell and Coombs Types I-IV). On a more clinical though not universal finding) include atopic dermatitis, im- inspiration, is the result of flow limitation, usually at the oro- basis, reactions can be classified according to the time of on- mediate food hypersensitivity, asthma and allergic rhinitis. pharynx, in which the soft palate flutters. This is the easiest sound set of symptoms. If symptoms occur within minutes of an An interesting pattern is seen in the development of atopic to understand and is a model of the mechanism of wheezing or stridor at all levels. immune reaction, it is called an immediate or early reaction. disease in childhood with atopic dermatitis and immedi- If symptoms start after hours, it is a late reaction, and after ate food hypersensitivity being prominent in infancy and Many pathophysiological processes will lead to the production of days, it is delayed reaction. The responses to antigens do not asthma and allergic rhinitis becoming more prominent in continuous adventitial lung sounds; thus wheezes can be heard in usually involve only one type of hypersensitivity reaction the pre-school and school years. This is commonly referred several diseases - not only asthma. These include all mechanisms narrowing airway calibre, such as bronchospasm, intraluminal however, and the immune response is best considered as a to as the “atopic march”.This corresponds to the pattern of tumours or secretions, foreign bodies, mucosal oedema, external sequence of events involving interactions between many cell allergen sensitisation with early and often transient respons- compression of an airway by a tumour mass, or dynamic air- types, antibodies and complement. es to ingested allergens and a progressive increase of inhalant allergen sensitisation with increasing age. Evidence of way compression. Furthermore, the changes in the mechanical The Type I immediate reaction is caused by IgE (and pos- IgE sensitisation to allergens can be demonstrated by either characteristics of the pulmonary system accompanying certain sibly IgG). Antigens which cause Type I reactions are called pathological processes influence the development of wheezes. skin prick tests or blood tests (RAST - radioallergosorbent allergens. When the allergen reacts with IgE attached to the Examples include the reduction in airway calibre seen in asthma, test or now more correctly termed “in vitro allergen specific surface of the mast cell, the cell degranulates and releases the reduction in bronchial stiffness associated with some chronic IgE measurement”). obstructive lung diseases or the decrease in elastance accompany- chemical mediators (histamine, SRS-A, ECF, PAF) responsi- ing pulmonary oedema - in all these instances changes in airway ble for the symptoms. Type 1 reactions depend on the pres- and/or pulmonary mechanics mean that the critical velocity at ence of specific IgE on high affinity receptors on mast cells. Optional references: which airway “flutter” will occur is lowered, thus oscillations of There are also IgE receptors of both low and high affinity Gold MS. Kemp AS. Atopic disease in childhood Med J Aust 2005; 182 (6) :298- the airway walls will start more easily. Healthy individuals can also 304 on other cell types, including eosinophils and macrophages. Jo A Douglass and Robyn E O’Hehir Diagnosis, treatment and prevention of produce wheeze during a forced expiratory manoeuvre. Activated B cells (plasma cells) produce IgE and this process allergic disease: the basics [MJA Practice Essentials - Allergy] Med J Aust 2006; dependent exposure to the allergen and co-stimulatory 185 (4): 228-233 The presence of a wheeze is a clinical sign found in patients with Simon G A Brown, Raymond J Mullins and Michael S Gold Anaphylaxis: obstructive airways diseases particularly during acute episodes of signalling via activated T cells, which direct the B cell to the diagnosis and management [MJA Practice Essentials - Allergy] Med J Aust 2006; asthma. There is no relationship between the intensity or the pitch production of IgE. 185 (5): 283-289. of wheezes and the pulmonary function. Katrina J Allen, David J Hill and Ralf G Heine Food allergy in childhood [MJA The mechanisms responsible for the triggering and mainte- Practice Essentials - Allergy] Med J Aust 2006; 185 (7): 394-400. Optional references: Janet Rimmer and John W Ruhno Rhinitis and asthma: united airway disease Mikami R, Murao M, Cugell DW et al. International symposium on Lung nance of allergic disorders have been investigated over the [MJA Practice Essentials - Allergy] Med J Aust 2006; 185 (10): 565-571. Sounds. Synopsis of Proceedings Chest 1987; 92(2): 342-345. last few years, but significant questions about the mecha- Role of Treg in immune regulation of allergic diseases. Forgacs P. The functional basis of pulmonary sounds. Chest 1978; 73(3): 399-405. nism still remain. IgE synthesis results from the collabora- Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA. Waring WW, Beckerman RC, Hopkins RL. Continuous adventitious lung sounds: Eur J Immunol. 2010 May;40(5):1232-40. Review. site and method of production and significance. Semin Respir Med 1985; 6(3): tion between a subset of T helper (Th) cells which produce 201-208. IL-4, but not IFN-gamma (Th2 cells). The Th2 cells, Author: Professor Dianne Campbell, Paediatrics and Child Health Meslier N, Charbonneau G, Racineux JL. Wheezes. Eur Respir J 1995; 8(11): 1942-1948. Murray, JF., 2000, Diagnostic evaluation: history and physical examination, In: Textbook of respiratory medicine, 3rd edn., Murray JF, Nadel JA, eds., Saunders, Philadelphia. Phelan, P.D., Olinsky, A., Robertson, C.F., 1994, Resiratory noises, In: Respira- tory illness in children, 4th edn., Blackwell Scientific, Oxford ; Boston.

Author: Dr Stephen Gregory McNamara, Medicine 11 3.02 - Wheezing And Breathless // Asthma 3. Respiratory Infections In Infants Acute episodes of asthma at any age, but particularly in infancy, granulocyte-macrophage colony-stimulating factor (GM-CSF), a may be preceded by upper respiratory symptoms and a large num- cytokine induced by virus infection. ber of studies have shown that respiratory viruses are the usual Rhinoviruses use ICAM-1, an intercellular adhesion molecule, as cause of these symptoms. Although other organisms such as Myco- a cell receptor for attachment and entry into epithelial cells, and plasma pneumoniae in school aged children, Chlamydia trachomatis this may lead to the release of inflammatory cytokines. Rhinovi- in infancy, and Chlamydia pneumoniae may also cause wheezing, ruses stimulate marked production of IL-8, which may cause in- these are in fact rare causes of acute exacerbations of asthma in flammatory changes that contribute to pathogenesis of wheezing. prospective studies. Bacteria do not cause wheezing, and antibiotics should not routinely be prescribed for acute asthma. RSV is a potent precipitator of wheeze in school aged asthmatic children. However, RSV is a virus which is ubiquitous and infects The principal viruses responsible for precipitating exacerbations over 95% of children by the end of their second winter. About of asthma are rhinoviruses and respiratory syncytial virus (RSV). 40% of these children develop bronchiolitis, an acute lower Other viruses less commonly implicated are parainfluenza viruses, respiratory infection characterised by tachypnoea, hyperinflation coronaviruses, enteroviruses and adenoviruses. Our ability to and crackles. Babies who develop bronchiolitis severe enough to detect respiratory viruses during exacerbations of asthma has require hospitalisation have a high risk (around 50%) of develop- been greatly enhanced by advances in technology. Inoculation of ing asthma. Some workers have detected RSV-specific IgE at- respiratory specimens from children with exacerbations of asthma tached to nasopharyngeal cells in infants with RSV and wheezing. into tissue culture yields a virus in around 20-40% of cases. Rapid The evidence suggests that RSV infection is more severe in babies antigen detection by immunofluorescence for RSV and enzyme- who were already predisposed to asthma/atopy, rather than RSV linked immunosorbent assays (ELISAs) for specific viral antigens actually inducing asthma by causing mucosal damage to airways are more rapid, and at least as sensitive as tissue culture. Polymer- allowing entry of sensitising aero-allergens. ase chain reaction (PCR) to detect rhinovirus and coronavirus sequences improves the viral yield to 80-85% of exacerbations. In Optional references: school age children rhinoviruses are the commonest viral precipi- Johnston SL, Pattemore PK, Sanderson G et al. Community study of role of tant of asthma attacks. viral infections in exacerbations of asthma in 9- 11 year old children . BMJ 1995;310(6989):1225-1228. The mechanisms by which viruses stimulate exacerbations of Gern JE, Busse WW. The effects of rhinovirus infections on allergic airway -re asthma are just beginning to be understood. Acute viral infection sponses. Am J Respir Crit Care Med 1995; 152: S40-S45. of the airways stimulates production of cytokines. In non-atopic Johnston SL. Natural and experimental rhinovirus infections of the lower respira- individuals, the typical cytokine profile produced in response tory tract. Am J Respir Crit Care Med 1995; S46-S52. Vignola Am et al. New evidence of inflammation in asthma . Thorax 2000; 55 to viruses by helper T cells called Th1 is of interferon y (IFNy) (Supp 2): S59-60. and interleukin -2 (IL-2). In contrast, atopic individuals tend Riffo-Vasquez Y, et al. Cytokines in airway inflammation . Int J Biochem Cell Biol to mount a Th2 helper cell response with production of IL-4 2000; 32(8): 833-53. and IL 5, but not IL~2 or IFNy. Asthmatic individuals also tend Author: Clinical Professor David Isaacs, Paediatrics and Child Health to develop eosinophilic infiltration of the airways secondary to

12 3.02 - Wheezing And Breathless // Asthma 4. Clinical Features Of Asthma granulocyte-macrophage colony-stimulating factor (GM-CSF), a The principal respiratory manifestations of asthma are related to The clinical pattern of asthma symptoms will also vary with age. cytokine induced by virus infection. the acute pathological events, namely bronchoconstriction, mu- Wheezing is a common symptom in infancy and may not neces- cosal oedema and mucus hypersecretion. Wheeze, breathlessness sarily reflect underlying airway inflammation. In the preschool Rhinoviruses use ICAM-1, an intercellular adhesion molecule, as (dyspnoea), cough and respiratory distress will occur to a variable child recurrent episodes of cough and wheeze, usually triggered a cell receptor for attachment and entry into epithelial cells, and degree depending on the severity of airway obstruction. Wheezing by viral respiratory tract infections, are the commonest mani- this may lead to the release of inflammatory cytokines. Rhinovi- may be absent or only audible with a stethoscope when airway festations and many of these children are non-atopic and often ruses stimulate marked production of IL-8, which may cause in- obstruction is mild whereas it may be obvious to the unaided improve with age. Recent epidemiological evidence indicates flammatory changes that contribute to pathogenesis of wheezing. ear when obstruction is moderate-severe, becoming absent again that children who cough but do not wheeze with viral infections RSV is a potent precipitator of wheeze in school aged asthmatic with very severe obstruction. More severe obstruction will also be are less likely to have asthma. In the older child and adult other children. However, RSV is a virus which is ubiquitous and infects manifest by complaints of breathlessness and ‘chest tightness’ and triggers, particularly exercise, become increasingly important. It over 95% of children by the end of their second winter. About signs of respiratory distress (tachypnoea, tracheal tug, intercostal is also important to identify those patients with persistent asthma 40% of these children develop bronchiolitis, an acute lower and subcostal recession, use of accessory muscles of respiration from those with predominantly intermittent disease as approaches respiratory infection characterised by tachypnoea, hyperinflation and pulsus paradoxus). The cough is characteristically ‘tight’ and to management will differ in these situations. The most useful and crackles. Babies who develop bronchiolitis severe enough to non productive, but may become more productive in the recov- indicators for establishing the severity of asthma are: require hospitalisation have a high risk (around 50%) of develop- ery phase, particularly when asthma occurs in association with a • The frequency of acute episodes ing asthma. Some workers have detected RSV-specific IgE at- respiratory tract infection. tached to nasopharyngeal cells in infants with RSV and wheezing. • The presence of interval symptoms (nocturnal and/or exercise The clinical manifestations of asthma are generally intermittent The evidence suggests that RSV infection is more severe in babies induced) (episodic) but in a small percentage of patients (5-10%) may be who were already predisposed to asthma/atopy, rather than RSV persistent, occurring on an almost daily basis. The most com- • Lifestyle disruption (hospitalisation, school/work absence, actually inducing asthma by causing mucosal damage to airways mon trigger for episodes of wheezing, particularly in children, are exercise restriction, growth in children) allowing entry of sensitising aero-allergens. viral respiratory tract infections. There is increasing evidence that • Frequency of bronchodilator use rhinovirus is the most important viral trigger in both children and Optional references: Finally, it is important to recognise the other atopic manifesta- Johnston SL, Pattemore PK, Sanderson G et al. Community study of role of adults and that allergic/atopic patients have an altered immune re- viral infections in exacerbations of asthma in 9- 11 year old children . BMJ sponse to rhinovirus leading to persistence of the virus and in turn tions that may be present in the asthmatic patient - atopic derma- 1995;310(6989):1225-1228. more severe acute episodes as well as enhanced ongoing airway titis, allergic rhinitis (perennial or seasonal) and immediate food Gern JE, Busse WW. The effects of rhinovirus infections on allergic airway -re inflammation. This gene environment interaction may therefore hypersensitivity. These may also require specific management. sponses. Am J Respir Crit Care Med 1995; 152: S40-S45. Johnston SL. Natural and experimental rhinovirus infections of the lower respira- be important in both the development and clinical expression of Optional references: tory tract. Am J Respir Crit Care Med 1995; S46-S52. asthma. In older children and adults, exercise becomes a more The following chapters provide details of the clinical features of asthma and atopy Vignola Am et al. New evidence of inflammation in asthma . Thorax 2000; 55 common trigger and exercise induced symptoms may be the only and differential diagnosis of wheeze and cough in children. (Supp 2): S59-60. manifestation in many of these patients. Inhalant allergens may South M., Roberton D.M., (eds.), 2006, Practical Paediatrics, 6th Edition, Riffo-Vasquez Y, et al. Cytokines in airway inflammation . Int J Biochem Cell Biol Churchill Livingstone, Melbourne 2000; 32(8): 833-53. also trigger acute episodes of wheezing but appear to have their Part 14 Respiratory Disorders most important effect on enhancing airway inflammation and 14.3 Henry, RL., Asthma, p 487 Author: Clinical Professor David Isaacs, Paediatrics and Child Health hyperresponsiveness. Dietary triggers may be important in some 14.4 Henry, RL., Wheezing disorders other than asthma, p 492 14.6 Chang AB, Sawyer SM Cystic fibrosis and other causes of chronic cough, p patients and these tend to be related to direct chemically mediated 506 effects (metabisulphite, MSG, aspirin) rather than IgE medi- Van Asperen PP. Cough and Asthma Paediatric Respiratory Reviews 2006; ated pathways (ingested allergens). Cigarette smoke may be an 7(1):26-30. important trigger, both via passive or active inhalation, and other Chang AB, Landau LI, Van Asperen PP et al Position statement. Cough in children: definitions and clinical evaluation. Med J Aust 2006; 184(8): 398-403. environmental exposures (weather changes, indoor/outdoor air Asthma Management Handbook 2006 www.nationalasthma.org.au pollution) may affect some patients. The nocturnal exacerbation Brand PLP, Baraldi E, Bisgaard H et al. - Definition, assessment and treatment of of asthmatic symptoms is most likely related to the diurnal varia- wheezing disorders in preschool children: an evidence-based approach. tion of airway hyper-responsiveness, with symptoms characteristi- Eur Respir J 2008; 32:1096-1110 cally occurring in the early morning hours. Author: Professor Peter van Asperen, Paediatrics and Child Health

13 3.02 - Wheezing And Breathless // Asthma 5. Asthma - A National Health Priority Australia’s National Health Priority Areas management, prevention and early detection of asthma based The National Health Priority Areas come under the Common- on evidence and consumer needs wealth Department of Health & Ageing ‘Safety and Quality in • Wide dissemination and consistent application of national Healthcare’ initiative. They provide a focus for effectiveness in guidelines and tools healthcare for the Australian community. They are also intended • Integration among health-care providers in delivering care to be consistent with the World Health Organisations strategy for based on the guidelines and tools and consumer needs health reform entitled “Health for all in the 21st century’ “ 1. . This • Evaluation of the development, dissemination and imple- declaration recognized the right of every human to have ‘the high- mentation of the evidence-based guidelines and tools est attainable standard of health’ and the NHPA initiative focuses • Extension of the understanding of, and knowledge about on chronic diseases that have a significant health burden in the asthma through applied research and access to quality infor- Australian community. mation Evidence for current initiatives in Asthma Management The Commonwealth, State and Territory governments have all In 2001 the Federal Budget pledged $48.4 million over four years agreed to work together on strategies that reduce the burden due to support the Asthma 3+ Visit Plan, initially developed by the to these diseases. They act at the level of prevention, treatment National Asthma Council (NAC). The Asthma 3+ Visit Plan aims and management and aim to be evidence-based 2. . to improve health outcomes for people with moderate to severe To be eligible for consideration as priority areas, a health problem asthma. It promotes the 3+ Visit Plan as best practice through must: the GP Asthma Initiative. The Asthma 3+ Visit Plan involves at least three visits to the GP over four months for the sole purpose • Pose a significant health burden of improving the management of asthma. At least two of these • Have potential for health gains and improved outcomes for visits to the GP should be planned in advance. These visits need consumers to include: • Have the support of all jurisdictions The health ministers have endorsed seven priority areas for Aus- • diagnosis and assessment (including appropriate spirometry tralia: tests) • Asthma • development of a written asthma management plan, and • Cancer control • patient education and review of asthma management plan. • Cardiovascular health • Diabetes mellitus The Asthma 3+ Visit Plan encourages partnerships in proactive • Injury prevention and control asthma care between the patient and their health professionals. • Mental health GPs may claim a special fee from Medicare on completion of this • Arthritis and musculoskeletal conditions process. The 3+ Visit Plan is based on Level I evidence (the high- Asthma as a National Health Priority Area est level for effectiveness). In particular, it is worth noting two sys- Asthma was declared a NHPA in 1999 in recognition that it has tematic reviews of the evidence for strategies in managing asthma substantial health, financial and social costs to the Australian found in the Cochrane Database of Systematic Reviews (CDSR). community. It is estimated that over 2 million Australians (11%) suffer from asthma with more than 60,000 Australians admitted Toelle et al 5 summarised the evidence for individualized written to hospital each year as a result of asthma. It is thought that up management plan and found insufficient evidence to support this. to 60% of asthma-related deaths could be prevented. It is a major However, Gibson et al 6 considered the effect of written plans cause of school and work absenteeism. Asthma affects: with patient self-management education and practitioner review and found self-management education reduced hospitalisations • One in four primary school children (relative risk (RR) 0.64, 95% confidence interval (CI) 0.50 to • One in seven adolescents 0.82); emergency room visits (RR 0.82, 95% CI 0.73 to 0.94); • One in ten adults unscheduled visits to the doctor (RR 0.68, 95% CI 0.56 to 0.81); Aside from having a significant health, financial and social bur- days off work or school (RR 0.79, 95% CI 0.67 to 0.93); noc- den, many advances have occurred in asthma management over turnal asthma (RR 0.67, 95% CI 0.0.56 to 0.79); and quality of the past decade with the potential for substantial health gains for life (standard mean difference 0.29,CI 0.11 to 0.47). Measures of the community. These include: lung function were little changed. • Improved understanding of the condition The Asthma 3+ Visit Plan includes self management education, • Development of effective, evaluated managements strategies written plan and practitioner review. Whilst systems have there- (eg Six Step Asthma Plan) fore been put in place at a population level, to manage asthma • Improved drug therapies and reduce its burden in the Australian community, the challenges • Availability & access to treatment of putting this into practice still face us all. • Consumer and professional education The Australian Government provided $8 million dollars over NB: There are numerous other systematic reviews about the man- three years in 1999 for the development of national initiatives agement of asthma in The Cochrane Library which you may want culminating in the development of the National Asthma Action to explore for further reading Plan 1999-2002 (NAAP). The National Asthma Action Plan Monitoring the outcomes of asthma management programs- Is 1999-2001 had five key strategies3. : all of this making a difference? • Development of agreed national guidelines and tools for the The Australian centre for Asthma Monitoring (ACAM) was 14 3.02 - Wheezing And Breathless // Asthma 5. Asthma - A National Health Priority (cont.) established in 2002 as a collaborative centre with AIHW and the 18. (a) Mean number of preventer prescriptions per person with USyd’s Woolcock Centre. The aims of the centre are: asthma per year 18. (b) Proportion of people with asthma for whom relievers are • To develop a systematic approach to surveillance of asthma indicated and use relievers no less than 3 times per week across Australia; 18. (c) The ratio of prescriptions of reliever to preventer medica- • To monitor and report on disease levels, burden, and trends tion among asthma patients associated with asthma in the general population and specific population groups; Education • To examine social, geographical and environmental differen- 19. Proportion of schools (primary and secondary), child care tials that may influence the development and burden associ- centres, pre schools and hospitals using nationally accredited ated with asthma; asthma education programs • To identify potential for improved prevention and manage- Severity ment strategies; 20. (a) Proportion of people with asthma who have been woken at • To track the impact of health policy, and prevention and night due to their asthma management strategies; 20. (b) Proportion of people with asthma who experience ‘morn- • To develop and manage special projects and collaborations ing dipping’ for the integration and enhancement of asthma related information. Disability They have been working identifying data sources and working 21. Proportion of people with asthma who are restricted in their definitions for 24 asthma indicators that have been identified, performance of core activities These are: Their first report ‘Asthma in Australia 2003’ can be accessed -on Disease Prevalence line via their website along with other information about moni- 1. Prevalence rate for asthma toring. (7,8) Co-morbidity CDT Learning Outcomes addressed in this Learning Topic 2. Prevalence rate for obesity and overweight in people with 4. MANAGEMENT: asthma 4.1 Describe key models for decision making at an individual and Primary care, emergency department attendance and hospital community level in healthcare separation 4.5 Identify relevant clinical protocols and guidelines for the man- 3. Rate of asthma related GP visits agement of both individual and system level health problems 4. Re-admission rate, within one month, for asthma 5. EVIDENCE-BASE 5. Rate of asthma related emergency attendance 5.4 Critically appraise the evidence for the effectiveness of strate- 6. Hospital separation rate for asthma gies for the management of health in populations (include proto- Quality of life cols, guidelines, health systems, community interventions) 7. Average number of sick days due to asthma per year 7. SOCIETAL EFFECTS 8. Proportion of persons who perceive their asthma as a limitation 7.1 Describe and discuss health impact of a given illness or injury on their physical activity, social role and emotional well being at a societal level (burden of illness) Mortality 7.2 Describe and discuss the financial impact of a given illness or 9. Death rate for asthma among persons aged 5-34 years injury at a societal level 7.3 Describe and discuss the social impact of a given illness or Risk factors injury at a societal level 10. Prevalence rate for smoking among persons with asthma 11. Prevalence rate for smoking within the household where chil- 8. SOCIETAL RESPONSE dren with asthma reside 8.1 Identify and describe the National Health Priority Areas for 12. Prevalence rate for asthma initiated (caused by occupational Australia (NHPAs) exposure 8.2 Discuss the rationale for the NHPAs 13. Prevalence rate for pre existing occupationally aggravated 8.3 Describe policies and evaluations relating to NHPAs where asthma appropriate Optional references: Management 1. World Health Organisation. ‘Health for all in the 21st Century’ 14. Proportion of people with asthma who have a recent, written 2. Australian Government National Health Priority Areas Asthma Action Plan, developed in consultation with their GP 3. The National Asthma Action Plan 1999-2002 (NAAP) 15. Proportion of people with asthma who use a peak flow meter 4. National Asthma Council. The Asthma 3+ Visit Plan 5. Gibson PG, Powell H, Coughlan J, Wilson AJ, Abramson M, Haywood P, to monitor their asthma Bauman A, Hensley MJ, Walters EH. Self-management education and regu- Health maintenance lar practitioner review for adults with asthma (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd. 16. Proportion of people with asthma who attend a health profes- 6. Toelle BG, Ram FSF. Written individualised management plans for asthma sional or carer at least six monthly for review of their Asthma in children and adults (Cochrane Review). In: The Cochrane Library, Issue Action Plan 2, 2004. Chichester, UK: John Wiley & Sons, Ltd. 17. Proportion of people with asthma who have had spirometry 7. Australian Centre for Asthma Monitoring - Asthma in Australia 2003 8. Australian Centre for Asthma Monitoring website measurements in the last 6 months 15 3.02 - Wheezing And Breathless // Asthma 6. Management Of Asthma The management of patients with asthma should be undertaken low dose beclomethasone (Fig 2). The only side effects (which are in accordance with the Plan detailed in the Asthma Management infrequent) with cromones relate to local irritation in the upper Handbook, published by the National Asthma Campaign (NAC). airways. These drugs are available as inhalational agents. The NAC states that the management aims in asthma are achieve

the patient’s best lung function & thereby achieve symptomatic 2. Inhaled corticosteroids (ICS): beclomethasone, budesonide, relief. fluticasone and ciclesonide are the drugs in this group which are The full details of the NAC Plan are available on the Internet at available in Australia. These drugs have potent topical anti-inflam- the site: matory activity, which means that when they are taken by inhala- http://www.NationalAsthma.org.au tion they will exert a local anti-inflammatory effect within the airways. Regular treatment with ICS reduces airway hyperrespon- The main aspects of management, having established the diagno- siveness. ICS are the only currently available drugs which have a sis of asthma, are as follows: substantial and sustained effect on AHR. Since AHR is an under- • assess the severity of the patient’s asthma - by taking a good his- lying abnormality in asthma, ICS are important agents in the long tory of symptoms, hospital admissions, medication requirements term management of asthma. Beclomethasone has similar potency etc to budesonide with respect to efficacy in controlling asthma and • Achieve patient’s best lung function - by giving medications to fluticasone is about twice as potent as beclomethasone. With treat the underlying inflammation and the symptoms an inhaled drug, up to 80% is deposited in the oropharynx and • Maintain best lung function - - by optimising the medications swallowed. However, there is extensive first past metabolism in the to the correct doses of the appropriate medications to keep the liver so the swallowed corticosteroid does not gain access to the patient well systemic circulation in significant amounts. When higher doses and by taking a careful history of attacks to identify any trigger are inhaled, there will be some absorption from the lung, creating factors that could be to avoided the potential for systemic side effects, such as easy bruising. Dose- response data for the airway and systemic effects of ICS (Fig. 3a) Patients should have a written Action Plan, which includes guid- have been used to determine the benefit-risk ratio (Fig.3b ). Local ance for identifying signs of worsening control & clear instruc- side effects in the upper airway, such as sore throat, oral candidi- tions for how to respond to any given change in asthma control. asis, and dysphonia can occur with these drugs. Large volume Early intervention with increased doses of medication can abort spacer devices minimise upper airway deposition and enhance troublesome exacerbations. deposition within the lungs. Patients should be well informed about the nature of asthma and

its management. It is important for the patient to understand as 3. Anti-leukotriene drugs: The cysteinyl LT receptor antagonists much as possible about asthma and how they can detect deteriora- (montelukast and zafirlukast) block the actions of LTC4, LTD4, tion and increase their medications accordingly. Patient education LTE4) at receptor sites, particularly on airway smooth muscle. is vital in giving the confidence to take a role in managing their These agents afford a degree of protection against antigen chal- disorder. lenge and exercise-induced bronchospasm. As oral tablet prepara- Medications for asthma : tions they may be useful in patients who cannot tolerate inhaled The use of medications is an important aspect of asthma manage- corticosteroids because of local side effects or who prefer to take ment. There are 2 categories of agents which are used: tablets (such as children). 1. Those which are taken long term and directed towards the underlying inflammation 4. Long acting ß agonists (LABA): These drugs (salmeterol and 2. Those which are taken to relieve the symptoms (i.e. bronchodi- eformoterol) bind to ß receptors in the same way as the short lators) [see Learning Topic entitled “Bronchodilators”] acting ß agonists (salbutamol and terbutaline) [see Learning Topic Drugs for long term treatment : “Bronchodilator drugs”]. LABA are used as regular therapy in patients taking ICS for their asthma. The addition of LABA to exist- 1. Cromoglycate & nedocromil (so called ‘cromones’): cromo- ing treatment with ICS permitted a lower dose of ICS to control glycate has been used for many years to treat asthma. Whilst its the manifestations of asthma. Fixed dose combinations (LABA + precise cellular mechanism of action is uncertain, it effectively ICS in a single inhaler device) are used in patients whose asthma blocks antigen induced bronchoconstriction (Fig. 1) and exercise is not adequately controlled with ICS alone. induced asthma. Nedocromil is a drug which has anti-inflamma- Optional references: tory activity in several experimental models. It effectively blocks Figures 1 - 3 : see computer-based Learning Topic Resources antigen induced bronchoconstriction and bronchoconstrictor Resource Materials response to neural stimulation such as inhalation of sulphur diox- NAC Asthma Management Plan is available on the Internet at the site ide. It also blocks exercise induced asthma and osmotic-induced http://www.NationalAsthma.org.au Australian Medicines Handbook Online (http://www.amh.hcn.net.au) bronchoconstriction. It has a small effect on airway hyperreson- siveness (AHR) which is of similar magnitude to effect seen with Author: Professor John Paul Seale, Pharmacology

16 3.02 - Wheezing And Breathless // Asthma 7. Atopic Eczema low dose beclomethasone (Fig 2). The only side effects (which are Atopic eczema affects around 10% of the population, and up to such as soaps, wool and sandpits. Stress has also been shown to infrequent) with cromones relate to local irritation in the upper 20% of Australian children. It usually starts in the first year of life, worsen skin barrier function, and can exacerbate eczema. airways. These drugs are available as inhalational agents. often on the face. It often localises then to the extensor surfaces of the limbs before settling in the flexures. Involvement of the

cubital and popliteal fossae is particularly common, and this often Treatment involves the following principles: 2. Inhaled corticosteroids (ICS): beclomethasone, budesonide, continues into adulthood. At the other end of the spectrum, the fluticasone and ciclesonide are the drugs in this group which are eczema may be generalised, and continue to be so throughout available in Australia. These drugs have potent topical anti-inflam- • Avoidance of exacerbating factors including soap. Bland bath or early life and sometimes into adulthood. About 10% of cases of matory activity, which means that when they are taken by inhala- shower oils are best for washing in severe cases. atopic eczema have adult onset. tion they will exert a local anti-inflammatory effect within the • Topical corticosteroids. Weaker (eg 1% hydrocortisone) or airways. Regular treatment with ICS reduces airway hyperrespon- The key clinical feature of eczema is itch, often associated with stronger (eg, 0.05% betamethasone) topical steroids should be siveness. ICS are the only currently available drugs which have a skin dryness and thickening (lichenification) because of repeated used depending on the site and severity of the eczema. substantial and sustained effect on AHR. Since AHR is an under- rubbing and scratching. • Daily or twice daily bland emollients lying abnormality in asthma, ICS are important agents in the long • Wet dressings, using a damp layer of cotton over the topical Individuals with atopic eczema are also more prone to asthma and term management of asthma. Beclomethasone has similar potency steroids and enmollients, can often improve even severe eczema hayfever, and the high concordance for eczema in identical twins to budesonide with respect to efficacy in controlling asthma and within a few days. (>70%) highlights the importance of genetic factors such as filag- fluticasone is about twice as potent as beclomethasone. With • Antibacterial therapy may be needed to treat superinfection grin mutations, which reduce skin barrier function and predispose an inhaled drug, up to 80% is deposited in the oropharynx and • UVB phototherapy can be tried for patients with more severe or to increased risk and severity of eczema, asthma and rhinitis. swallowed. However, there is extensive first past metabolism in the resistant eczema Food allergy is a frequent contributor to eczema in children, but liver so the swallowed corticosteroid does not gain access to the • Immunosuppressives. For severe atopic eczema patients (particu- is much less common in adults. IgE mediated and delayed type systemic circulation in significant amounts. When higher doses larly adults), cyclosporin or azathioprine will usually control their hypersensitivity reactions to house dust mite can also exacerbate are inhaled, there will be some absorption from the lung, creating disease. eczema, as can infection with staphylococcus aureus. Excoriated the potential for systemic side effects, such as easy bruising. Dose- skin due to scratching will be liable to secondary infection. There response data for the airway and systemic effects of ICS (Fig. 3a) Optional references: is also evidence that people with eczema have altered innate im- have been used to determine the benefit-risk ratio (Fig.3b ). Local Mackie RM. Clinical Dermatology. Oxford University Press, 1997. munity in the skin which renders them more susceptible to infec- side effects in the upper airway, such as sore throat, oral candidi- tions. Other exacerbating factors include contact with irritants Author: Dr Patricia Lowe, Dermatology asis, and dysphonia can occur with these drugs. Large volume spacer devices minimise upper airway deposition and enhance deposition within the lungs.

3. Anti-leukotriene drugs: The cysteinyl LT receptor antagonists (montelukast and zafirlukast) block the actions of LTC4, LTD4, LTE4) at receptor sites, particularly on airway smooth muscle. These agents afford a degree of protection against antigen chal- lenge and exercise-induced bronchospasm. As oral tablet prepara- tions they may be useful in patients who cannot tolerate inhaled corticosteroids because of local side effects or who prefer to take tablets (such as children).

4. Long acting ß agonists (LABA): These drugs (salmeterol and eformoterol) bind to ß receptors in the same way as the short acting ß agonists (salbutamol and terbutaline) [see Learning Topic “Bronchodilator drugs”]. LABA are used as regular therapy in patients taking ICS for their asthma. The addition of LABA to existing treatment with ICS permitted a lower dose of ICS to control the manifestations of asthma. Fixed dose combinations (LABA + ICS in a single inhaler device) are used in patients whose asthma is not adequately controlled with ICS alone. Optional references: Figures 1 - 3 : see computer-based Learning Topic Resources Resource Materials NAC Asthma Management Plan is available on the Internet at the site http://www.NationalAsthma.org.au Australian Medicines Handbook Online (http://www.amh.hcn.net.au)

Author: Professor John Paul Seale, Pharmacology

17 3.02 - Wheezing And Breathless // Asthma 8. Pathology Of Asthma Overview • Mucus plugs with: Asthma is one of the Obstructive Airways Diseases, which include • Whorls of mucus/epithelium - Curshmann’s spirals the common diseases of: • Eosinophils ++++ Charcot Leyden crystals (crystalloid from eosinophil membrane protein) • Asthma • Epithelial sloughing/hyperplastic epithelium/increased num- • Emphysema bers of goblets cells • Chronic bronchitis • Thickening of the basement membrane epithelium • Bronchiectasis • Oedema and inflammatory cellular infiltrate in bronchiolar and bronchial mucosae Obstructive Airway Disease is the result of an increased resistance • Inflammatory infiltrate: 5-50% eosinophils (neutrophils to airflow at any anatomical level within the chest cavity. In these also possible) diseases the obstruction is Expiratory. • B cells In atopic asthma, airways previously exposed to ‘foreign’ environ- • Mast cells mental allergens become hyperresponsive to these antigens. Upon • Increased size of submucosal glands re-exposure, this leads to various cascades of defensive innate • Hypertrophy of bronchial/bronchiolar wall smooth muscle (eosinophil, mast cell) and adaptive inflammatory allergic (IL-4, • IL-5-producing Th2 lymphocyte and IgE-producing B lympho- LUNG PARENCHYMA cyte) immune responses by the bronchial mucosae, resulting in Overdistended (because of overinflation) airway obstruction acutely and chronically. Additional possible features In asthma obstruction is due to • may be areas of atelectasis Anatomical narrowing, which can be caused by: • may have emphysematous changes • mucus (acute) • may have bronchitis • epithelial sloughing (acute), epithelial hyperplasia (chronic) • may have aspergillus colonisation of the mucus plugs • inflammatory swelling - oedema (acute & chronic) Possible clinicopathological outcomes • granulation tissue (if inflammation is chronic) • Ventilation-perfusion mismatching • hypertrophy/hyperplasia of smooth muscle (chronic) • With bacterial infections the following may be may be super- • hypertrophy/hyperplasia of the submucous glands (chronic) imposed: Loss of elastic recoil due to: • chronic bronchitis • inflammatory damage and remodelling (chronic) • bronchiectasis • overdistension (chronic) • pneumonia Macroscopic appearances of the lung • Fungal infections may also supervene Likely: • aspergillosis - colonisation of the mucus plugs, not parenchyma (Allergic Broncho-pulmonary Aspergillosis) • overinflation of lung, e.g., rib impressions, petechiae • Cor pulmonale possibly leading to heart failure • mucus plugging of the bronchi and bronchioles Status asthmaticus may supervene at any time and if resistant to Possible: treatment, may result in patient death • bronchitis References • atelectasis Robbins and Cotran. Pathological Basis of Disease. 7th Edition. WB Saunders 2005. • bronchiectasis Thurlbeck, W.M. ed. Pathology of the Lung. Thieme Medical Publishers 1988. • pneumothorax/pneumomediastimum Saldana, M.H. ed. Pathology of Pulmonary Disease. Lippincot. 1994. Likely Histology (in order from the lumen outwards to the Dail, D.H. and Hammar S.P. eds. Pulmonary Pathology, 2nd Edition. Springer- parenchyma) Verlag. 1993. Hasleton, P.S. ed. Spender’s Pathology of the Lung. Fifth Edition. McGraw-Hill. LUMEN 1996. Woolcock, A.J. “Asthma” in Respir Med 2nd Edition 1994; 2:1989. Eds Murray Occlusion of bronchi and bronchioles by mucus (mucus plugs) and Nadel.

• These may be lost during preservation in pathological speci- Author: Professor Nicholas King, Pathology mens.

18 3.03 - A Nasty Cough // Acute Exacerbation Of COPD Learning Objectives • Mucus plugs with: Description Disciplines • Whorls of mucus/epithelium - Curshmann’s spirals Addiction Medicine, The key characteristics of drug tolerance and drug dependency or addiction, as applied to tobacco • Eosinophils ++++ Charcot Leyden crystals (crystalloid Pharmacology from eosinophil membrane protein) Detailed anatomical organisation of the nose, sinuses and mouth; major parts, functions, blood supply and neural Anatomy • Epithelial sloughing/hyperplastic epithelium/increased num- innervartion bers of goblets cells Detailed anatomical organisation of the scalp, face and neck; the bones, joints (eg temporomandibular) and Anatomy • Thickening of the basement membrane epithelium muscles (facial expression, neck and mastication) associated with scalp, face and neck • Oedema and inflammatory cellular infiltrate in bronchiolar • The criteria for establishing causal relationships in epidemiology and their application to smoking related disease. The Cardiology, Public and bronchial mucosae evidence for the relationship between smoking and lung cancer and the impact of tobacco smoke on human health Health • Inflammatory infiltrate: 5-50% eosinophils (neutrophils At the end of this teaching session, students should: also possible) Be able to describe the features of shared decision making Medicine • B cells Be able to describe some major issues in communicating with patients about complex evidence and how decision aids • Mast cells can assist • Increased size of submucosal glands At the end of this teaching session, students should: • Hypertrophy of bronchial/bronchiolar wall smooth muscle 1. Understand the centrality of uncertainty to all medical practice • 2. Be aware of the variation in uncertainty tolerance that exists between societies, professions and individuals 3. Understand the potential psychological consequences for practitioners of concealing or managing large amounts of Medicine LUNG PARENCHYMA uncertainty 4. Be able to describe the features of shared decision making Overdistended (because of overinflation) 5. Be able to describe some major issues in communicating with patients about complex evidence and how decision aids Additional possible features can assist · Clinical indications for spirometry • may be areas of atelectasis · Revise basic respiratory physiology · Interpretation of normal values • may have emphysematous changes Medicine • may have bronchitis · Types of curves · Perform spirometry • may have aspergillus colonisation of the mucus plugs · Understand the limitations and pitfalls in interpretation of spirometry in children Possible clinicopathological outcomes The major pathophysiological features of airways dysfunction in COPD Pathology • Ventilation-perfusion mismatching Pathology, The major pathological features associated with chronic obstructive pulmonary disease • With bacterial infections the following may be may be super- Pharmacology imposed: Aspects of nicotine function and metabolism, including absorption from the respiratory tract, relevant pharmacological Pharmacology • chronic bronchitis effects, mechanism of action in the nervous system and the therapeutic use of nicotine and other agents • bronchiectasis Pulmonary rehabilitation, with particular reference to COPD Pharmacology • pneumonia The major clinical features of chronic obstructive pulmonary disease. The main mechanisms that generate this condition Physiology • Fungal infections may also supervene The price policy, public education, pack warnings, advertising bans, harm reduction policy, passive smoking restrictions, • aspergillosis - colonisation of the mucus plugs, not paren- Public Health reducing access and smoking cessation policy chyma (Allergic Broncho-pulmonary Aspergillosis) The role and process of public health advocacy in bringing about change in law, regulations, resource allocations and • Cor pulmonale possibly leading to heart failure Public Health institutional practices relevant to public health. The key role of mass media in this process Status asthmaticus may supervene at any time and if resistant to How cigarette smoking affects various organs of the human body; appreciate clinical conditions that affected patients Public Health treatment, may result in patient death may present with References The ethical dilemmas in tobacco control policy using various scenarios for example, smoking in nursing homes, tobacco Public Health, Ethics Robbins and Cotran. Pathological Basis of Disease. 7th Edition. WB Saunders sponsorship in the Grand Prix, surgical waiting lists and smokers, and the tobacco tax 2005. Thurlbeck, W.M. ed. Pathology of the Lung. Thieme Medical Publishers 1988. Saldana, M.H. ed. Pathology of Pulmonary Disease. Lippincot. 1994. · Learn to detect normal and abnormal airway sounds Dail, D.H. and Hammar S.P. eds. Pulmonary Pathology, 2nd Edition. Springer- · Learn to recognise signsnormal of andreversible abnormal airway findings disease on examination of the chest re: percussion and auscultation Verlag. 1993. · Learn to recognise signs obstructive airway disease Hasleton, P.S. ed. Spender’s Pathology of the Lung. Fifth Edition. McGraw-Hill. You should become familiar with the following elements of the chest examination: 1996. · Inspection of the thorax for scars or deformities · Assessing chest expansion Woolcock, A.J. “Asthma” in Respir Med 2nd Edition 1994; 2:1989. Eds Murray Respiratory Medicine and Nadel. · Percussion of the chest · Assessment of either vocal resonance (or fremitus) Author: Professor Nicholas King, Pathology · Auscultation of the breath sounds An adequate examination of the chest includes attention to the anterior chest and axillary regions as well as the posterior thorax. Recall the surface anatomy of the lungs. For the auscultatory component of the physical examination, the objective is to learn the characteristics of normal breath sounds and to gain an introductory understanding of some examples of abnormal breath sounds. Students should learn: · To take an occupational history with respect to respiratory illnesses. Respiratory Medicine · To explore the patient's fears, ideas, feelings and expectations regarding an illness that may be related to occupation. · To understand the emotional and financial impact of work related diseases on their patients.

19 3.03 - A Nasty Cough // Acute Exacerbation Of COPD 1. Tobacco Addiction Criteria for establishing addiction The natural history of tobacco addiction Familiarise yourself with the key characteristics of drug toler- What is a typical pattern of tobacco uptake, use, cessation at- ance and drug dependency or addiction (see the learning topic tempts, relapse and final cessation? on Tolerance and physical dependence). In 1988 the US Surgeon What is the ‘stages of change’ model of smoking cessation? General concluded that: What are the current concerns about this model? • tobacco is addictive (ie dependence producing) What does the research literature suggest are the most important • nicotine is involved in this addiction and predictors of smoking cessation? • the pharmacological and behavioural processes that deter- What proportion of smokers quit unaided, and what propor- mine tobacco addiction are similar to those that determine tion seek assistance? What are the implications of this in clinical addiction to other drugs such as heroin and cocaine. practice? Examine the evidence required to address each of these questions: What is the role of harm-minimisation in tobacco dependence? Does tolerance develop to the effects of tobacco smoking? What are the implications of this for population-wide efforts to increase smoking cessation? What is the evidence for the addictive potential for nicotine? The politics of nicotine ‘addiction’ Is there a correlation between a smoker’s blood concentration of nicotine and his/her smoking behaviour? There are important legal and political consequences involved in a determination that nicotine is addictive. The tobacco industry has Does nicotine produce a psychological ‘reward’ (ie a positive been revealed to have a long history of both experimenting with reinforcement)? ways to optimise nicotine addiction and suppressing this informa- Does nicotine produce a withdrawal syndrome? tion from government and the public. Is there a relationship between the blood concentration of nico- Familiarise yourself with the rationale for and the history of the tine and the symptoms of withdrawal syndrome? How can one manipulation of nicotine in tobacco, and with the legal and polit- measure the degree of nicotine dependency? ical implications that might flow from the notion that nicotine is a drug of addiction. See http://www.tobacco.org/ : see Resources: Are there sex differences in addiction liability to nicotine? Tobacco Documents. Are there genetic variations in nicotine metabolism? Optional references: The symptoms of nicotine withdrawal are ‘cured’ by another The single most comprehensive reference for this topic is: Giovino GA, Henningfield JE, Tomar SL, Escobedo LG, Slade J. Epidemiology of cigarette. This ‘cure’ is therefore termed a ‘negative reinforcement’. tobacco use and dependence. Epidemiol Rev 1995; 17(1): 48-65. Why? Hukkanen, J., Jacob, P., and N. Benowitz. Metabolism and Disposition Kinetics of Nicotine . Pharmacol Rev 57(1): 79-115, 2005. Which of these (positive or negative reinforcement) do you be- Journals that contain articles regarding tobacco dependence: lieve to be the more important in maintaining tobacco addiction? Nicotine and Tobacco Research The Journal of Smoking Cessation How would you explain the phenomenon that some smokers Neuropsychopharmacology continue to smoke in the face of known physical and social detri- Addiction ment? Addictive behaviours BMJ The behaviour of smoking is frequently associated with other behaviours such as coffee or alcohol drinking or after a meal. This Author: Adjunct Associate Professor Renee Bittoun, Brain and Mind Research Institute association is termed cue conditioning. Explore the role played by cue conditioning in tobacco dependence.

20 3.03 - A Nasty Cough // Acute Exacerbation Of COPD 2. Pharmacology Of Nicotine The natural history of tobacco addiction Nicotine is a naturally occurring alkaloid which was first isolated and also by activating peripheral chemo-receptors in the carotid from the leaves of tobacco (Nicotiana tabacum) in 1828. In the body and the aortic arch. What is a typical pattern of tobacco uptake, use, cessation at- latter part of the nineteenth century it was tested experimentally tempts, relapse and final cessation? Peripheral nervous system in rabbits and found to act directly in the superior cervical gan- Small doses of nicotine stimulate all autonomic ganglia and fa- What is the ‘stages of change’ model of smoking cessation? glion rather than in pre- or post-ganglionic nerve fibres. Thus, it cilitate the transmission of impulses. With larger doses the initial What are the current concerns about this model? has a revered place in the history of discovering the pharmacology stimulation is followed by blockade of transmission. The acute ef- of the autonomic nervous system. What does the research literature suggest are the most important fects of nicotine which are most evident during cigarette smoking predictors of smoking cessation? Absorption of nicotine are probably due to stimulation of afferent receptors in peripheral Nicotine is well absorbed from the respiratory tract. Since chemoreceptors such as those in the carotid body. What proportion of smokers quit unaided, and what propor- transpulmonary absorption depends primarily upon alveolar tion seek assistance? What are the implications of this in clinical Neuromuscular junction distribution, only about 10% of an inhaled dose reaches the sys- practice? Nicotine causes discharge of Renshaw cells which are located in temic circulation. There is limited absorption from the stomach as the spinal cord. These discharging Renshaw cells inhibit motor What is the role of harm-minimisation in tobacco dependence? nicotine is a strong base. In its natural form it is not well absorbed neurones, possibly leading a relaxant effect in skeletal muscle. What are the implications of this for population-wide efforts to from the buccal mucosa but when it is formulated in chewing Cardiovascular system increase smoking cessation? gum buffered to an alkaline pH it is predominantly unionised and thus absorbed across the mucosa. In general, nicotine produces increases in heart rate and blood The politics of nicotine ‘addiction’ pressure due to stimulation of the sympathetic ganglia and the Because of its rapid absorption across the lung, peak plasma adrenal medulla, although these effects are unlikely to occur There are important legal and political consequences involved in a concentrations are achieved during the smoking of the cigarette. with the concentrations during smoking. Its stimulant effect on determination that nicotine is addictive. The tobacco industry has There is a rapid decline in plasma concentration after finishing peripheral chemo-receptors in carotid bodies may result in reflex been revealed to have a long history of both experimenting with cigarette smoking and plasma concentrations reach half the peak vasoconstriction and tachycardia, which are the more common ways to optimise nicotine addiction and suppressing this informa- concentrations within approximately 10 minutes. Thereafter, the effects seen. The nicotine can also increase plasma free fatty acid tion from government and the public. decline in plasma concentration occurs more slowly, primarily due concentrations. Familiarise yourself with the rationale for and the history of the to liver metabolism. Gastrointestinal tract manipulation of nicotine in tobacco, and with the legal and polit- Metabolism and excretion Nicotine activates the parasympathetic ganglia and cholinergic ical implications that might flow from the notion that nicotine is The major site for nicotine metabolism is liver, which produces nerve endings resulting in increased tone and motor activity of the a drug of addiction. See http://www.tobacco.org/ : see Resources: a stable metabolite, cotinine. The plasma half life of cotinine is bowel. Tobacco Documents. prolonged, so the detection of this substance is frequently used as Optional references: a measurable chemical marker of active or passive cigarette smok- Acute toxicity The single most comprehensive reference for this topic is: ing. Acute poisoning with nicotine can occur in children from inges- Giovino GA, Henningfield JE, Tomar SL, Escobedo LG, Slade J. Epidemiology of tion of tobacco products or inadvertent chewing of nicotine gum. tobacco use and dependence. Epidemiol Rev 1995; 17(1): 48-65. Nicotine and its metabolites are excreted in the urine and nicotine Adults may be poisoned from accidental ingestion of insecticides Hukkanen, J., Jacob, P., and N. Benowitz. Metabolism and Disposition Kinetics of is detectable in the breast milk of lactating women. Nicotine . Pharmacol Rev 57(1): 79-115, 2005. in which nicotine is the active agent. Symptoms include nausea, Journals that contain articles regarding tobacco dependence: Acute pharmacological effects salivation, abdominal pain, vomiting and diarrhoea, disturbed Nicotine and Tobacco Research The administration of nicotine produces many and diverse vision, mental confusion and weakness. The Journal of Smoking Cessation pharmacological actions, the net effect of which is complex and Neuropsychopharmacology Therapeutic use of nicotine unpredictable from one individual to the next. Many of the acute Addiction Nicotine replacement therapy is used as an adjunct in smok- Addictive behaviours effects observed in experimental animals occur at concentrations ing cessation programs. It is available either as a chewing gum, BMJ in excess of those achieved in humans during cigarette smoking transcutaneous patches or as an inhaler. The nicotine skin patches Author: Adjunct Associate Professor Renee Bittoun, Brain and Mind Research Mechanism of action are designed to produce a relatively constant release of nicotine so Institute Nicotine binds to cholinergic receptors in autonomic ganglia, that stable plasma concentrations are achieved, thereby minimis- adrenal medulla and the neuromuscular junction. It readily ing the symptoms of withdrawal. Some non-nicotine therapies crosses the blood-brain barrier and binds to cholinergic receptors (such as bupropion and varenicline) are also used in smoking throughout the brain. The acute effects of nicotine are due to the cessation programs. activation of these cholinergic receptors throughout the body and Optional references: this activation can be antagonised by anticholinergic drugs. Rang HP, Dale MN, Ritter JM. Pharmacology (5th ed.) Churchill Livingstone. 599-602, 142-149. Central nervous system McRobbie H, Lee M, Juniper Z (2005) Non-nicotine pharmacotherapies for Nicotine is a central nervous system stimulant, giving a sense of smoking cessation. Respiratory Medicine, 99(10): 1203 - 1212. alertness and producing changes in the electroencephalograph http://www.racgp.org.au/Content/NavigationMenu/ClinicalResources/RACGP- (EEG) consistent with arousal. The stimulant action may produce Guidelines/smoking/Smoking_Cessation_Update09.pdf tremors and convulsions can occur with very high concentrations. Author: Professor John Paul Seale, Pharmacology Nicotine stimulates respiration by a direct effect on the medulla

21 3.03 - A Nasty Cough // Acute Exacerbation Of COPD 3. Public Health Policy In Tobacco Control A population-wide approach to tobacco control seeks to reduce of products, regulation of products) the burden of tobacco-caused disease in communities by reducing 6. Reducing exposure to environmental tobacco smoke (eg smoking prevalence (the number of people who smoke); the inci- establishment of smoke-free public places as the norm, increase dence of smoking (the number of people commencing smoking); awareness of risks of environmental tobacco smoke) the frequency of smoking in continuing smokers (reducing daily smoking rates); and the number of people exposed to secondhand References smoke (environmental tobacco smoke). Tobacco in Australia is the most comprehensive resource available. It has chapters on every aspect of contemporary tobacco control, with very up-to-date data. Comprehensive tobacco control policies addressing each of these See http://www.tobaccoinaustralia.org.au/ factors have been developed by groups such as the WHO and Also: http://tobacco.health.usyd.edu.au/ the International Union Against Cancer. When many or all of Suggested references: For trends in smoking: these strategies are implemented, considerable problems arise in http://www.tobaccoinaustralia.org.au/chapter-1-prevalence evaluating the impact of individual policies and programs within http://www.tobaccoinaustralia.org.au/chapter-2-consumption these total strategies because many are introduced simultaneously For health effects of active smoking: and work synergistically. http://www.tobaccoinaustralia.org.au/chapter-3-health-effects For health effects of involuntary smoking: It is often said that a litmus test of the effectiveness of a platform http://www.tobaccoinaustralia.org.au/chapter-4-secondhand For addiction and nicotine: of tobacco control policy is the response of the tobacco industry http://www.tobaccoinaustralia.org.au/chapter-6-addiction to its introduction. Ineffective strategies are often publicly sup- For public information campaigns: ported by the tobacco industry, while effective policies are vigor- http://www.tobaccoinaustralia.org.au/chapter-14-social-marketing ously opposed. Hill, D. Why we should tackle adult smoking first . Tob Control 1999;8(3):333- 335. Familiarise yourself with: Myers, ML. Adults versus teenagers: a false dilemma and a dangerous choice . Tob • each of the major strategies of tobacco control; Control 1999;8(3):336-338. Browse articles in this special supplement on the Australian campaign to the jour- • the evidence for their effectiveness; nal Tobacco Control http://tobaccocontrol.bmj.com/content/12/suppl_2 • problems in specifying the effects of individual interventions and policies; For tobacco advertising: • tobacco industry critiques of these policies http://www.tobaccoinaustralia.org.au/chapter-11-advertising For price policy: • counter-arguments to these critiques http://www.tobaccoinaustralia.org.au/chapter-13-taxation For pack warnings: National Tobacco Strategy Strahan EJ, White K, Fong GT, Fabrigar LR, Zanna, MP and Cameron, R. En- The National Tobacco Strategy in Australia aims to “improve the hancing the effectiveness of tobacco package warning labels: a social psychological health of all Australians by eliminating or reducing their exposure perspective . Tob Control 2002;11(3):183-190. to tobacco in all its forms.” It focuses on six key strategies Chapman S. and Carter S. “Avoid health warnings on all tobacco products for just as long as we can”: a history of tobacco industry efforts to avoid, delay and dilute 1. Strengthening community action (eg increasing public aware- health warnings on cigarettes . Tob Control , 2003 12(Suppl.1): iii13-iii22. ness of the harm associated with tobacco use through anti-tobacco For generic(plain) packaging: education, increasing educational support in schools, training for Freeman B, Chapman S. Review: The case for plain packaging of tobacco products health professionals, an ATSI Tobacco Forum, etc) . Addiction 2008;103:580-590. For smoking cessation: 2. Promoting cessation of tobacco use (eg increase public aware- http://www.tobaccoinaustralia.org.au/chapter-7-cessation ness of the benefits of smoking cessation, increase health profes- Chapman S, Mackenzie R. The research neglect of unassisted smoking cessation: sional skills and resources, increase incentives to quit through causes and consequences. PLoS Medicine 2010 http://www.plosmedicine.org/ health and life insurance, increase access to affordable cessation article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000216 For secondhand smoke: interventions, decrease intra-uterine exposure) For cigarette yield policy: 3. Reducing availability and supply of tobacco (eg reduction of Parish S, Collins R, Peto R, Youngman L et al. Cigarette smoking, tar yields, and affordability of tobacco products, reduction of illegal sale and sup- non-fatal myocardial infarction: 14,000 cases and 32,000 controls in the United ply of tobacco to minors) Kingdom . BMJ 1995; 311(7003): 471-477. Thun MJ, Burns, DM. Health impact of “reduced yield” cigarettes: a critical as- 4. Reducing tobacco promotion (eg reduction in the exposure to sessment of the epidemiological evidence . Tob Control 2001;10 (Suppl 1): i4-i11. messages and images that may promote smoking such as advertising, point of sale displays, value added products, legislation and Author: Professor Simon Chapman, School of Public Health sponsorship. 5. Regulating tobacco (g tobacco industry to disclose ingredients

22 3.03 - A Nasty Cough // Acute Exacerbation Of COPD 4. Risk Reduction Following Cessation Of Smoking Two of the major causes of mortality in western societies are This reduced lung cancer risk after cessation applies to men and smoking-related illnesses; atherosclerotic arterial disease (leading women, and to all pathological types of lung cancer. to myocardial infarction, cerebrovascular and peripheral vascular Smoking cessation approximately halves the risk of oral, pharyn- disease) and lung cancer. In both cases, the individual’s risk of dis- geal, laryngeal and oesophageal cancer over 5 years compared to ease is greatest in current smokers, less in ex-smokers and least in continued smokers. never smokers. Risk reduction occurs after cessation with different time courses for different diseases, but the maximum benefit from There is also risk reduction with cessation for cancers of the blad- cessation may accrue over many years, rather than immediately. der, pancreas and cervix, but the rate of risk reduction may be slower than above. A basic knowledge of the benefits of smoking cessation is necessary to help doctors to motivate their patients to stop, which is Smoking cessation does not alter the risk of breast or colon cancer. often difficult due to longstanding physical and/or psychological Respiratory Benefits addiction. Smoking cessation is associated with rapid improvement in pre- Former smokers live longer than current smokers. For example, existing cough, wheezing and sputum production. subjects who quit smoking before age 50 years have one-half the In almost all smokers, lung function improves by 5% within a few risk of dying in the next 20 years compared to continuing smok- months of smoking cessation. ers. In patients with established chronic lung disease, mortality rates Smoking cessation decreases the risk of heart attack, stroke, lung are improved in former compared to continuing smokers. cancer, some other cancers and chronic lung disease. It appears that smoking reduction only (without cessation) does not reduce Other Important Benefits 1. the risk of cardiovascular death Smoking cessation during pregnancy partially protects the foetus The benefits of smoking cessation apply to men and women of all from the adverse effects of smoking on intrauterine growth. ages, and to subjects with and without established smoke-related disease. “There are substantial effects of environmental tobacco smoke Cardiovascular Benefit (ETS) on particularly respiratory and cardiovascular health on The relative risk of dying from a heart attack decreases by 50% in others. Some data suggest that reduction of ETS exposure has the first year after cessation, and returns almost to “never smoker” health benefits for “passive” smokers.” values by 5 - 10 years after quitting. A Cochrane Systematic re- 3 Smoking-related premature menopause may be reversible by view of 20 trials showed that quitting smoking results in a 36% smoking cessation. reduction in crude relative risk of mortality compared with those who continue to smoke (RR 0.64 95%CI 0.58-0.71). There was The risk reduction associated with smoking cessation for skin also a reduction in non-fatal myocardial infarctions. This reduc- wrinkling and osteoporosis are not well studied. tion is substantial compared with other secondary prevention Optional references: strategies such as cholesterol lowering etc. Godtfredsen NS, Holst C, Prescott E, Vestbo J, Osler M. Smoking reduction, smoking cessation, and mortality: a 16-year follow-up of 19,732 men and women Smoking cessation markedly reduces the tendency to thrombosis, from The Copenhagen Centre for Prospective Population Studies . Am J Epide- partially reverses the smoke-related abnormalities in endothelial miol. 2002 Dec 1;156(11):994-1001. function, but is probably not associated with regression of pre- Ebbert JO, Yang P, Vachon CM, Vierkant RA, Cerhan JR, Folsom AR, Sellers TA. Lung cancer risk reduction after smoking cessation: observations from a prospec- existing atherosclerotic plaques. tive cohort of women . J Clin Oncol. 2003 Mar 1;21(5):921-6. Critchley J, Capewell S. Smoking cessation for the secondary prevention of coro- In addition to survival benefits, smoking cessation improves exer- nary heart disease .Cochrane Database Syst Rev. 2004;(1):CD003041. Review. cise tolerance (and therefore quality of life) in people with arterial Gottlieb SO. Cardiovascular benefits of smoking cessation. Heart Dis Stroke disease. 1992; 1(4): 173-5. Samet JM. The health benefits of smoking cessation. Med Clin North Am 1992; Benefits in Cancer Susceptibility 76(2): 399-414. There is a slow decline in lung cancer risk after smoking cessation. Friedman GD, Petitti DB, Bawol, RD, Siegelaub AB. Mortality in cigarette smok- After 10 years, the risk falls to 30 - 50% of the risk for continuing ers and quitters. N Engl J Med 1981; 304(23): 1407-10. Higgins IT, Wynder EL. Reduction in risk of lung cancer amongst ex-smokers smokers. With further abstinence, the risk continues to decline. with particular reference to histologic type. Cancer 1988; 62(11): 2397-2401. A recent cohort study in US women showed that compared with Rosenberg L, Kaufman DW, Helmrich SP, Shapiro S. The risk of myocardial never smokers, former smokers had an elevated lung cancer risk infarction after quitting smoking in men under 55 years of age. N Engl J Med up to 3 years after cessation (RR 6.6 95%CI 5.0-8.7). The risk of 1985; 313(4): 1511-4. Buist AS, Nagy JM, Sexton GJ. The effect of smoking cessation on pulmonary lung cancer for current smokers was approximately 15 times that function; a 30 month follow-up of two smoking cessation clinics. Am Rev Resp of non-smokers and this fell to 8 times after quitting and approxi- Dis 1979; 120: 953-7. mately 3 times 5 years after quitting but remained elevated above never smokers for more than 15 years. 2 Author: Professor David Celermajer, Medicine

23 3.03 - A Nasty Cough // Acute Exacerbation Of COPD 5. Ethical Dilemmas In Tobacco Control Policy It is important that clarification is made of the ethical principles decisions about priority in surgical waiting lists. underlying often taken-for-granted policy positions and clinical Opponent position: that smoking should be irrelevant to deci- decisions in the smoking and health field. sions about places on waiting lists. Consider the following scenarios and the proponent and oppo- Reading nent positions, together with the recommended readings. In your Underwood MJ, Bailey JS. Controversies in treatment: should smokers be offered tutor groups, you might consider dividing into the two camps and coronary bypass surgery?: coronary bypass surgery should not be offered to smok- working through at least one of the debates. ers . BMJ 1993;306(6884):1047-9. See also letters in reply Scenario 1. Smoking in Nursing Homes Zolese, Gabriella Access to heart surgery for smokers: each patient a special case BMJ 1993;306(6889):1408-9. The National Health and Medical Research Council’s report Grant, S.C.D Access to heart surgery for smokers: smokers waste valuable re- on passive smoking has recommended that all nursing homes sources BMJ 1993 306(6889):1408 Vithayathil, Empee Access to heart surgery for smokers: the NHS can’t treat only introduce policies on smoking by staff and residents that reflect saints BMJ, 1993 306(6889): 1408-1409 the same principles of safeguarding the health and amenity of Mamode, Nizam Access to heart surgery for smokers: denying access more costly non-smokers that the report recommends should apply in the BMJ, 1993 306(6889):1408 general community. You work in a nursing home where smoking Khalid, M.I. Access to heart surgery for smokers: denying treatment is indefensible BMJ, 1993 306(6889):1408 by some semi-ambulant elderly patients has traditionally been Scenario 4. Medical Research Funding by the tobacco industry allowed in common indoor lounge areas. There are 20 elderly You are the head of a research-based department in a teaching residents who spend hours in this area each day. Eight of them hospital. Funding is scarce and you are looking to have to lay smoke heavily. Of those who do not, three regularly object to the off several staff through lack of funding. A member of your staff smoking. One staff member argues that the nursing home serves wants to accept a lucrative grant from the tobacco industry’s as a final home for these patients; that the state has no right to Tobacco and Health Research Foundation to study the delivery of intrude into private homes; that any health effects from passive CO and nicotine to smokers via a new “tar free” cigarette thought smoking are unlikely to significantly alter the health “outcomes” likely to be a significant step in the direction of harm reduction. for the residents anyway; and that smoking represents one of the The usual conditions of “hands off” scientific independence apply. few remaining pleasures for these people. Proponent position: that all staff and residents must not smoke inside the nursing home. Proponent position: that good research is good research, regardless Opponent position: that residents who chose to smoke should be of who funds it -- including the tobacco industry. allowed to do so inside the nursing home. Opponent position: that medical researchers should not accept re- Reading search funding under any circumstance from the tobacco industry. Goodin RE. The ethics of smoking . Ethics 1989;99(3):574-624. Scenario 2. Tobacco sponsorship and the Grand Prix Reading Walsh RA, Sanson-Fisher RW. What universities do about tobacco industry The Premier of your state has made a big political play of secur- research funding? Tobacco Control 1994;3(4):308-15. ing a grand prix motor race. It is argued that the event will attract Cohen, JE. Universities and tobacco money: Some universities are accomplices in the tobacco epidemic [editorial]. BMJ 2001; 323(7303): 1-2. many millions of dollars into the state economy, create jobs etc. Roberts J, Smith R. Publishing research supported by the tobacco indus- Tobacco sponsorship is banned, but provision exists for exemp- try - journals should reverse ban on industry sponsored research . BMJ tions for special events where the event’s existence will be com- 1996;312(7024):133-4. promised by not having tobacco sponsorship. The health minister Scenario 5. Is tobacco tax regressive? has secured this exemption, arguing that the event would have The Minister for Health seeks your advice on raising signifi- otherwise moved to a neighbouring Third World nation where cantly the price of cigarettes. Evidence suggests that through the the tobacco advertising allowed there would have been subject to population, there is an elasticity of demand for cigarettes of -0.5 no controls at all. He argues that at least in Australia, there will be (ie:for a 10% rise in price, a 5% fall in demand results) and that health warnings on the ads. this elasticity is even higher for low income groups. However, the Proponent position: that there should be a total ban on all forms Salvation Army and the St Vincent de Paul Society have criticised of tobacco advertising and sponsorship. the proposal, saying that there will be many low income families who will keep on smoking regardless of the price rise and that Opponent position:that limited forms of tobacco advertising many will reduce the amount and quality of food and educational should be allowed. expenses they outlay for their children as a result. Reading Chapman S. The ethics of tobacco advertising and advertising bans . in: Doll R, Proponent position: that cigarette tax should never rise beyond Crofton J (eds.) Tobacco and health. Br Med Bull 1996;52(1):121-31. CPI-linked increases. Scenario 3. Surgical waiting lists and smokers Opponent position: that cigarettes should rise in real terms by A vascular surgeon in your department argues that smokers 10% per year above the CPI. should go to the end of the waiting list for coronary bypass sur- Reading gery, allowing non-smokers to move up in the queue. He argues Townsend J, Roderick P, Cooper J. Cigarette smoking by socioeconomic that they have contributed to their own condition, make little group, sex, and age - effects of price, income, and health publicity . BMJ 1994; effort to quit smoking, and have a poor prognosis. 309(6959):923-7. Boren P, Sutton M. Are increases in cigarette taxation regressive ? Health Econ Proponent position: that smoking should be a relevant factor in 1992;1(4):245-53. Author: Professor Simon Chapman, School of Public Health

24 3.03 - A Nasty Cough // Acute Exacerbation Of COPD 6. Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease (COPD) is characterised are cough and exertional dyspnoea. There may also be significant by airflow limitation that is not fully reversible. This airflow limi- sputum production. tation is usually progressive and associated with features of airway Because of the permanent structural changes that occur in the inflammation due to the effects of noxious particles, such as ciga- lungs with COPD, the response to drug therapy is much less than rette smoke. COPD is the third most common cause of chronic that which occurs in subjects with asthma. Bronchodilators are burden of disease in Australia and the fourth most common cause used in the treatment of COPD with some improvement in both of death. It is the leading cause of death amongst indigenous FEV , measures of health related Quality of Life and symptoms. Australians and it has the highest cost of care for any respiratory 1 There can also be an increase in inspiratory capacity after treat- disease in Australia. The major risk factor is exposure to tobacco ment with bronchodilators and this can improve exercise toler- smoke, accounting for the majority of patients with COPD in ance. The most important intervention in COPD is smoking Australia. Approximately 15% of cigarette smokers progress to cessation and the earlier in the natural history of this disease that clinical manifestations of COPD. it can be effected the better the prognosis. Other risk factors include occupational exposure to certain dusts In severe COPD, patients have repeated exacerbations, frequently and chemicals. There are also genetic factors which account for precipitated by respiratory tract infections (either viral or bacteri- susceptibility. The most well known is α anti-trypsin deficiency, 1 al), which can result in hospital admissions. The typical symptoms but research has identified other genetically pre-disposing factors. of an exacerbation are increased cough, sputum and dyspnoea. It is probable that there will be multiple genetic pre-disposing fac- There may also be a fever and a leucocytosis in the blood. Markers tors, each of which contributes a small amount to host suscepti- of inflammation such as C-reactive protein (CRP) may also be el- bility. evated. The usual treatment for an exacerbation comprises inhaled The inflammation in the lung may be due to oxidative stress, lead- bronchodilators, systemic anti-inflammatory corticosteroids and ing to increased damage to lung tissues or to imbalances between antibiotics. Oxygen is also given if the patient is hypoxic. proteinases or anti-proteinases, resulting in deficiencies in repair mechanisms and leading to destruction of lung tissue. The main Currently available therapies have not been shown to have a major pathological features of COPD include increased smooth muscle impact on the long term prognosis so the ongoing treatment is in the airways, increased neutrophils and airway inflamma- primarily symptomatic. Inhaled corticosteroids and long acting tion, destruction of lung tissue and hypertrophy of the mucous bronchodilators reduce the rate of exacerbations and hospital secreting cells (goblet cells). Studies have revealed a relationship admissions. These improvements provide significant gains in between airway smooth muscle and diminished lung function health-related quality of life. Pulmonary rehabilitation, which

(measured by FEV 1 ). There are increased numbers of neutrophils involves both endurance and strength exercises is one of the most in the sputum of people who smoke and have COPD. There is effective strategies, together with smoking cessation, in the long also some destruction of the lung parenchyma, which reduces the term management of patients with COPD. tethering of airways and allows their diameter to become reduced. Optional references: The main physiological disturbance is airflow limitation, meas- Gold website: www.goldcopd.com COPDX: www.lungnet.org.au ured by a reduced FEV 1 and reduced FEV1/VC ratio (less than 70%). There are also features of hyperinflation with increase in -to Author: Professor John Paul Seale, Pharmacology tal lung volume and residual volume. The predominant symptoms

25 3.03 - A Nasty Cough // Acute Exacerbation Of COPD 7. Pulmonary Rehabilitation With Focus On Copd Pulmonary rehabilitation is regarded as standard care for people Improved exercise capacity and reductions in dyspnoea are due with chronic lung disease, particularly COPD (COPDX Guide- to physiological changes at the muscle level that are similar to the lines 1 ). The aims of Pulmonary Rehabilitation are to reduce changes that occur in athletic training. Changes include: symptoms and activity limitation, restore patients to the highest - increased concentration of oxidative enzymes possible level of independent functioning, and reduce health-care - increased capillary density costs through stabilising or reversing systemic manifestations of - increased skeletal muscle myoglobin the disease. - increased number and density of mitochondria

Activity limitation in COPD patients is due to the underlying impairments, mainly in the ventilatory system but also in the cardiac These changes result in better oxygen extraction in the exercising and musculoskeletal systems. This is illustrated in the figure . muscle which means lower levels of lactate and therefore reduced ventilation (and dyspnoea) at equivalent submaximal workloads Dyspnoea on exertion can result in a spiral of deconditioning ( after training. illustrated here ) that pulmonary rehabilitation aims to reverse. Education A comprehensive Pulmonary Rehabilitation Program includes: There is moderate level of evidence for the effectiveness of educa- • Patient assessment tion which should include collaborative self-management and • Exercise training prevention and treatment of exacerbations • Education Health-care costs For details on how to deliver pulmonary rehabilitation see Pulmo- A number of studies have shown that pulmonary rehabilitation nary Rehabilitation Toolkit at: www.pulmonaryrehab.com.au reduces the number of hospital days and other measures of health

2 care utilisation in patients with COPD Evidence for the effectiveness of pulmonary rehabilitation : Lower limb exercise training References McKenzie D K, Frith PA, Burdon JGW, Town GI. The COPDX Plan: Australian There is high level of evidence for the effectiveness of thelower and New Zealand Guidelines for the management of Chronic Obstructive Pulmo- limb exercise training component of Pulmonary Rehabilitation nary Disease 2003 . MJA 2003 178(6 Suppl): S1-S40 Ries AL, Bauldoff GS, Carlin BW, Casaburi R, Emery C F, Mahler DA, Make B, in improving Rochester CL, ZuWallack R, Herrerias C. Pulmonary Rehabilitation. Joint ACCP/ exercise capacity, reducing dyspnoea and improving quality of life. AACVPR Evidence-based clinical practice guidelines . Chest 2007; 131:4S-42S American Thoracic Society. ATS statement: Guidelines for the six- Exercise training should be individually prescribed (i.e intensity, minute walk test . Am J Repir Crit Care Med 2002; 166: 111-117 duration, frequency, type (continuous or interval) and mode (walking or cycle) based on an initial exercise test, usually a six- Author: Mrs Jenny Alison, Institute of Respiratory Medicine minute walk test 3 .

COPD + EXERCISE

Ventilatory Cardiac Skeletal Muscle Constraints to exercise: Constraints to exercise: Constraints to exercise: • Flow limitation • Decreased cardiac output • Deconditioning • Dynamic Hyperinflation ↑ pulmonary vascular • Malnutrition • Mechanics of breathing resistance • Systemic inflammation • ↑ work of breathing ↓ venous return • Corticosteroid use • Abnormal gas exchange • Ageing

Dyspnoea Fatigue

Exercise Tolerance

Functional Activity Physical Activity

Health-Related Quality of Life

Personality Environment Physical/Financial/Social/Emotional

Alison JA and McKeough ZJ. Exercise and Quality of Life in COPD. In Handbook of Disease Burdens and Quality of Life Measures. Eds: Victor Preedy / Ronald Ross Watson. Springer-Verlag, Germany. 2009 26 3.04 - Ex-Navy // Interstitial Lung Disease Learning Objectives Improved exercise capacity and reductions in dyspnoea are due Description Disciplines to physiological changes at the muscle level that are similar to the changes that occur in athletic training. Changes include: Anaesthesia - increased concentration of oxidative enzymes perioperative period The factors that make tobacco a major identifiable risk factor relating to surgery and the - increased capillary density Detailed anatomical organisation (cartilages, ligaments and muscle) and function (swallowing - increased skeletal muscle myoglobin and phonation) of the pharynx and larynx; their blood supply and neural innervations. The Anatomy - increased number and density of mitochondria anatomy of the thyroid gland and some clinical applications Detailed anatomical organisation of the nose, sinuses and mouth; major parts, functions, blood Anatomy These changes result in better oxygen extraction in the exercising supply and neural innervartion muscle which means lower levels of lactate and therefore reduced Histology, ventilation (and dyspnoea) at equivalent submaximal workloads The ultrastructure of the alveolar septum. Respiratory after training. Medicine Education · Positioning children for ENT examination · Performing otoscopy and pneumatic otoscopy There is moderate level of evidence for the effectiveness of educa- Medicine · Be familiar with tympanogram types (A, B or C) tion which should include collaborative self-management and · Be familiar with Rinne and Weber tests prevention and treatment of exacerbations The methods of assessing occupational disability and impairment. The function of the NSW Dust Occupational Health-care costs Diseases Board Medicine A number of studies have shown that pulmonary rehabilitation Pathology reduces the number of hospital days and other measures of health Pathology, care utilisation in patients with COPD The mechanisms of interstitial and alveolar inflammation and of interstitial lung disease with extrinsic irritation, using the lung as a prime example Anaesthesia References The pathological appearance of chronic inflammatory response in the interstitium associated McKenzie D K, Frith PA, Burdon JGW, Town GI. The COPDX Plan: Australian The methods and basic mechanisms involved in blood gas analysis Physiology and New Zealand Guidelines for the management of Chronic Obstructive Pulmo- The mechanisms of transport of oxygen and carbon dioxide in mammalian blood Physiology nary Disease 2003 . MJA 2003 178(6 Suppl): S1-S40 The principles that underlie a number of lung function tests, including lung volumes (VC, TLC, Ries AL, Bauldoff GS, Carlin BW, Casaburi R, Emery C F, Mahler DA, Make B, Physiology Rochester CL, ZuWallack R, Herrerias C. Pulmonary Rehabilitation. Joint ACCP/ FRC and RV) and diffusion capacity (DLCO) AACVPR Evidence-based clinical practice guidelines . Chest 2007; 131:4S-42S Physiology, American Thoracic Society. ATS statement: Guidelines for the six- The general properties that determine elastic behaviour in the lung and chest wall; some of the minute walk test . Am J Repir Crit Care Med 2002; 166: 111-117 Respiratory respiratory diseases associated with a decrease in this elasticity Medicine Author: Mrs Jenny Alison, Institute of Respiratory Medicine Physiology, The assessment and mechanisms (stimuli and central processing) of breathlessness Respiratory Medicine · Learn to recognise signs of COPD Respiratory · Learn to assess severity of disease with COPD (including signs of respiratory failure) Medicine The concept of obstructive and restrictive lung disorders. The diagnosis, assessment and Respiratory monitoring of lung diseases using lung function tests Medicine The lung's role as a rapid regulator of arterial blood pH, through the control of the partial Respiratory pressure of carbon dioxide in the arterial blood; how this is disturbed by disease Medicine Respiratory The broad categories, causes and clinical features of diffuse parenchymal lung disease Medicine Students should learn: · To elicit a history of symptoms of obstructive sleep apnoea Respiratory · To elicit a history of sleepiness. Medicine · To elicit a history of sleep habits.

27 3.04 - Ex-Navy // Interstitial Lung Disease 1. Mechanisms Of The Sense Of Breathlessness Humans can perceive several respiratory sensations: localised irri- respiratory muscles in giving rise to unpleasant respiratory sensa- tation, respiratory discomfort, perception of position and motion. tions. Breathlessness or dyspnoea refers to a “subjective experience of • Central respiratory drive. Awareness of motor output to the breathing difficulty that consists of qualitatively distinct sensations respiratory muscles (via collateral discharge within the CNS) that vary in intensity”. A subject’s perception of this sensation rather than afferent feedback from the muscles has been proposed is determined by a complex interaction between peripheral and to represent an important component of perceived breathlessness, central receptors and cognition. An understanding of mechanisms and likely represents the major mechanism of breathlessness in influencing this perception and its effects on behaviour (eg poor neuromuscular diseases. perceivers may delay seeking treatment) and breathing (eg restrict- • Chemical ventilatory stimuli (hypercapnia, hypoxia, and acido- ing breathing pattern to avoid generating dyspnoea) underpins sis). Experimental observations suggest the role of hypercapnic the clinical management of breathlessness. or hypoxic drive in the sensation of breathlessness may be of less The Language of Breathlessness Breathlessness : Most psy- importance than the degree of reflex activation of ventilation. chophysical studies involve sensory responses to external stimuli Thus, relieving hypoxia may not relieve breathlessness. (eg. sound, light) which are readily identified by the subject and • Pulmonary receptors (stretch, irritant, C-fibres). Afferent activity experimenter. In contrast, if a subject is asked to rate a respira- from pulmonary receptors is thought unlikely to represent an tory sensation such as “breathlessness”, subjects may differ in the important source of neural information leading to the perception qualities of the experience that are rated. In the design of any of breathlessness. psychophysical study the number and kind of descriptors must be Mechanisms of Breathlessness - Central Processing considered carefully, and one must be as precise as possible with • Recently investigators have focused on the role of psychological the use of language, both in defining the experimental task to the processes (cognitive/emotional) on the perception of breathless- subject and interpreting the results. ness. Assessment of Breathlessness • Central neural networks have been identified that are associated • Indirect methods, eg. several methods possible, including the with the processing of input stimuli, genesis of the sensation of clinical interview, questionnaires for assessing exercise limitation breathlessness and modification of its perceived intensity (eg by due to breathlessness, exercise tolerance. emotional processing). • Direct methods, eg. scaling of respiratory mechanical events, Optional references: scaling of breathlessness (ratio, linear scaling [visual analogue The following provide good general background reading particularly in relation to score, Borg scale]). respiratory diseases: Edwards CRW, et al, eds. Davidson’s Principles and Practice of Medicine. (19th Mechanisms of Breathlessness - Stimuli ed.) Churchill Livingstone, 2002. The neurophysiological mechanisms resulting in breathlessness are Flenley DC, ed. Respiratory Medicine. (2nd ed.). London Bailliere Tindall, 1990; poorly understood. For example exercise results in many simulta- 265-276. Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine. (4th ed.) Philadel- neous physiological changes that could be sensed and perceived as phia WB Saunders, 2005. breathlessness. In disease, pathological changes may cause earlier The following provide more detailed discussion of the specific issues : activation of the same mechanisms or additional “abnormal” affer- Adams L, Guz A. Dyspnea on exertion. In: Whipp BJ, Wasserman K, eds. ent neural activity. Potential stimuli include: Exercise: Pulmonary physiology and pathophysiology. New York: Marcel Dekker, 1991; 449-459. • Respiratory muscles activity (perception of force/pressure, Altose M. Assessment of respiratory sensation. In: The Thorax Part B: Applied load, volume). The idea that tension developed in the respiratory Physiology. (2nd ed.) Roussos C, ed. New York: Marcel Dekker, 1995; 1285-1290. muscles can be sensed as inappropriate relative to the demand for Mahler, Donald (ed) Dyspnea New york, Marcel Dekker 1998. ventilation has been a major hypothesis for over 40 years. The role Altose M. Assessment of respiratory sensation. In: The Thorax Part B: Applied Physiology. (2nd ed.) Roussos C, ed. New York: Marcel Dekker, 1995; 1285-1290. of mechanoreceptor afferent information from respiratory muscles and its relationship to ‘central respiratory drive’ in breathlessness has been extensively researched. Recent studies during muscular Author: Associate Professor Terry Amis, Medicine paralysis however provide less support for the essential role of

28 3.04 - Ex-Navy // Interstitial Lung Disease 2. The Gas Exchange Unit: Structure respiratory muscles in giving rise to unpleasant respiratory sensa- How does the ultrastructure of the alveolus and adjacent capillar- in type I and endothelial cells are thought to permit shuttling of tions. ies facilitate gaseous exchange? selected macromolecules across the cells. • Central respiratory drive. Awareness of motor output to the Examination of electron micrographs of preserved specimens is Interalveolar pores (of Kohn) are small pores lined by epithelium respiratory muscles (via collateral discharge within the CNS) essential for an understanding of this area, as the structures are in the interalveolar septa such that air can flow between adjacent rather than afferent feedback from the muscles has been proposed below the limit of resolution by light microscopy (see electron alveoli and may allow ventilation to by-pass a blocked alveolar to represent an important component of perceived breathlessness, micrographs in recommended texts). duct. These pores are very numerous (up to 7 per alveolus). and likely represents the major mechanism of breathlessness in neuromuscular diseases. The alveolus is exceedingly thin-walled, lined by an epithelium Alveolar phagocytes like macrophages elsewhere are part of the (type I alveolar cells) which is in places only 50 nm thick. This mononuclear phagocyte system and migrate into the lumen of the • Chemical ventilatory stimuli (hypercapnia, hypoxia, and acido- rests on a thin basal lamina which is shared with adjacent capillar- alveoli to phagocytose inhaled particles or debris. They are motile sis). Experimental observations suggest the role of hypercapnic ies; the thickness of the non-fenestrated endothelial cells is about and not joined to other cells by intercellular junctions. or hypoxic drive in the sensation of breathlessness may be of less 50 nm, and the total thickness of the barrier to diffusion between importance than the degree of reflex activation of ventilation. The interalveolar interstitium has two distinct anatomic compart- air and blood (the blood-air barrier) is as little as 0.2um, although Thus, relieving hypoxia may not relieve breathlessness. ments. One is relatively thin across which the major portion of this is variable. The small distance between the alveoli and the • Pulmonary receptors (stretch, irritant, C-fibres). Afferent activity gas transfer takes place, and the other is thicker, functioning as lumen of the capillary is essential for rapid gas diffusion. Adjacent from pulmonary receptors is thought unlikely to represent an a mechanical support for the alveolus, a compartment for water alveoli frequently abut, and the resulting tissue between the two important source of neural information leading to the perception transfer and a lodging place for the various cells that regulate airspaces is termed the interalveolar septum, which includes the of breathlessness. alveolar function. In the interalveolar interstitium are various connective tissue and capillaries sandwiched between the two lay- connective tissue components including fibroblast-like cells and Mechanisms of Breathlessness - Central Processing ers of lining epithelium. myofibroblasts (interstitial cells) which are contractile and may • Recently investigators have focused on the role of psychological Type II alveolar epithelial cells are relatively large cells; they usu- regulate blood flow. No smooth muscle cells are found here. processes (cognitive/emotional) on the perception of breathless- ally rest at areas where interalveolar septa meet. Type II cells have ness. The pulmonary acinus is defined as that portion of lung distal to an essential function in reducing surface tension which would • Central neural networks have been identified that are associated the terminal bronchiole, comprising the respiratory bronchiole, otherwise close the alveoli. The type II cells secrete surfactant with the processing of input stimuli, genesis of the sensation of alveolar ducts, alveolar sacs, and alveoli. This is the anatomic unit from large multilamellar bodies (cytosomes). Although more breathlessness and modification of its perceived intensity (eg by that takes part in the gas exchange process. numerous than Type I cells, they comprise only 3% of the alveolar emotional processing). area while Type I cells comprise 90%. That they are less special- Optional references: Optional references: Williams PL, ed.. Gray’s Anatomy. The Anatomical Basis of Medicine and Surgery. ised than Type I cells is shown by the fact that they can divide and (38th ed.) London: Churchill Livingstone, 1995; 1669-1673. The following provide good general background reading particularly in relation to differentiate to replace Type I cells. respiratory diseases: Ross MH & Pawlina W (2006). Histology. A text and atlas. 5th edn. Lippincott, Williams & Wilkins. Baltimore. Edwards CRW, et al, eds. Davidson’s Principles and Practice of Medicine. (19th All of the epithelial cells, as well as endothelial cells, are joined ed.) Churchill Livingstone, 2002. Flenley DC, ed. Respiratory Medicine. (2nd ed.). London Bailliere Tindall, 1990; by tight junctions which limit the movement of fluid from blood Author: Dr Suzanne Ollerenshaw, Anatomy and Histology 265-276. and intercellular spaces into the alveolar lumen. However, vesicles Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine. (4th ed.) Philadel- phia WB Saunders, 2005. The following provide more detailed discussion of the specific issues : Adams L, Guz A. Dyspnea on exertion. In: Whipp BJ, Wasserman K, eds. Exercise: Pulmonary physiology and pathophysiology. New York: Marcel Dekker, 1991; 449-459. Altose M. Assessment of respiratory sensation. In: The Thorax Part B: Applied Physiology. (2nd ed.) Roussos C, ed. New York: Marcel Dekker, 1995; 1285-1290. Mahler, Donald (ed) Dyspnea New york, Marcel Dekker 1998. Altose M. Assessment of respiratory sensation. In: The Thorax Part B: Applied Physiology. (2nd ed.) Roussos C, ed. New York: Marcel Dekker, 1995; 1285-1290.

Author: Associate Professor Terry Amis, Medicine

29 3.04 - Ex-Navy // Interstitial Lung Disease 3. Interstitial Lung Disease Diffuse parenchymal lung diseases (DPLD), often collectively tosus referred to as Interstitial lung diseases (ILD), include a diverse • Wegener’s granulomatosis, Churg-Strauss syndrome group of acute and chronic disorders involving the lung paren- 4. Inhalational Causes (occupational/environmental) chyma. There is controversy about the terminology and classifica- • Asbestosis tion of these diseases because they are poorly understood. The • Silicosis word ‘interstitial’ suggests that the disease process is located in the • Coal-workers pneumoconiosis tissue of the alveolar wall between the capillary endothelium and • Environmental gases and fumes alveolar epithelium. Yet in many cases intra-alveolar pathology is • Hard metal dusts also present and may be more marked than in the interstitium. In 5. Inherited Causes addition, the initial injury may arise the endothelial or alveolar epithelial cells. In general terms, this is a group of diseases of lung • Tuberous Sclerosis, Neurofibromatosis parenchyma with similar clinical, radiological, physiologic and • Gaucher’s disease pathological manifestations, which may result in the development 6. Other Specific Entities of pulmonary fibrosis. The mechanism of developing fibrosis is • Drug Induced eg chemotherapeutic agents (including bleo- not completely understood, and involves a complex interaction of mycin), nitrofurantoin, methysergide a variety of cell types and products. • Alveolar proteinosis In the absence of infection, clinicians recognise DPLD as a syn- • Lymphangitic carcinomatosis drome with the following clinical features: • Idiopathic pulmonary haemosiderosis • Eosinophilic lung diseases • progressive exertional dyspnoea • Lymphangioleiomyomatosis • persistent non-productive cough • Amyloidosis • rapid shallow breathing pattern with bilateral coarse crackles To establish a specific diagnosis requires a very thorough history on auscultation. Site depends on disease but often basal and physical examination in addition to specific investigations • clubbing and development of right heart failure (late signs) including: • bilateral interstitial infiltrates on chest X-ray and high resolution CT scan (reticulo-nodular or ground glass patterns) • Chest x-ray • physiologic abnormalities of restrictive lung defect (reduction • Lung function tests (including spirometry, lung volumes, in all lung volumes, normal or high FEV1/VC ratio), im- diffusing capacity) paired gas exchange (hypoxaemia, V/Q mismatching at rest), • High resolution CT scan reduced DLCO (diffusing capacity), and stiff lungs with • Bronchoscopy and broncho-alveolar lavage reduced compliance leading to increased work of breathing • Immunological blood tests eg. RF, ANA, precipitins • histopathologic features of inflammation and fibrosis of the • Lung biopsy (open surgical eg VATS, or transbronchial) in pulmonary parenchyma on biopsy. some cases. The heterogeneous group of diseases that cause DPLD can be It must be realised that all the above DPLD’s tend eventually to broadly categorised under six main groups: lead to a common pathological end point known as ‘end-stage’ fibrotic lung disease. It may then be impossible to determine the 1. Idiopathic interstitial pneumonias (IIP) nature of the primary underlying disease. • Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveoli- Optional references: tis) For an overview and introduction to the subject of clinical causes of fibrotic lung • Desquamative interstitial pneumonia disease: • Acute interstitial pneumonia Harrison’s Principles of Internal Medicine (15th ed.) Ch 259 Reynolds H Intersti- tial Lung Disease • Non-specific interstitial pneumonia (Good and not too high powered) • Respiratory bronchiolitis ILD For in-depth reviews of the current diagnostic approach and management of • Cryptogenic organising pneumonia patients with interstitial lung disease • Lymphocytic interstitial pneumonia Idiopathic Pulmonary Fibrosis: Diagnosis and Treatment : Amer. J Respir. Critical Care Med. 161(2):646-64, 2000 2. Granulomatous diseases Michaelson JE et al. Idiopathic Pulmonary Fibrosis: A practical approach for • Sarcoid diagnosis and management. Chest 118 (3): 788-94, 2000 Wells AU et al. Update in Diffuse Parenchymal Lung Disease 2006 . Amer J • Histiocytosis-X Respir Crit Care Med ,2007 • Hypersensitivity pneumonitis (extrinsic allergic alveolitis) 175(7): 655-60. 3. Collagen-vascular/connective tissue disease and vasculitides Gotway MB et al. Challenges in pulmonary fibrosis: Use of high resolution CT scanning of the lung for the evaluation of patients with idiopathic interstitial • Scleroderma, rheumatoid arthritis, systemic lupus erythema- pneumonias. Thorax 62(6): 546-53, 2007. Author: Dr Tamera Corte, Medicine

30 3.04 - Ex-Navy // Interstitial Lung Disease 4. Mechanisms Of Lung Inflammation Underlying Mechanisms these agents, resolution tends to fail and organisation of the alveolar exudate occurs resulting in fibrosis. Lung disease for the most part is caused by the inhalation of one or other particle type. The ability of the lungs to resist the effects Interstitial Inflammations: of inhaled particles is determined by: Cytokines produced over the chronic course of these diseases stimulate fibroblast replication and collagen formation within the • the integrity of the mucociliary raft, which is markedly im- alveolar walls of the lung tissue, thickening them and reducing paired by smoking their compliance. • the size of the particles (1-5 micrometers being most danger- • Immunological reactions (organic dusts [bagassosis, farmer’s ous) lung], systemic immune disease [rheumatoid, scleroderma], • the burden of particles inhaled. sarcoid and idiopathic pulmonary fibrosis). The adaptive immune response in these diseases seems to mediate the Additionally, the physiochemical properties of the particles in- interstitial involvement. cluding their solubility, surface area and free radical availability (eg silica), may influence their irritant capabilities. The penetration of • Specific fibrogenic irritants (inorganic dust diseases [silico- potentially hazardous inhaled particles depends on their size: >10 sis, asbestosis]). Here the non-specific immune responses, micrometers are deposited in the upper airways, 3-10 micrometers principally macrophages responding to physical and chemical lodge in the trachea and bronchi, 1-5 micrometers particles (eg tissue damage, mediate the fibrotic response associated with bacteria) can make their way to the alveoli, while smaller particles these diseases. may remain suspended in air and can be exhaled. Particles can Cellular Mechanisms of Interstitial Lung Disease be cleared from air passages by nasal clearance, tracheobronchial In most types of interstitial lung disease (ILD), the earliest com- clearance (mucociliary raft) or by alveolar clearance (phagocytosed mon manifestation is alveolitis. The initial stimuli for alveolitis by alveolar macrophages). Alveolar macrophages containing par- are many and varied (see below). Alveolitis is the accumulation ticles may either digest the particle, be moved to a bronchiole for of inflammatory and immune effector cells within the alveolar clearance by the mucociliary raft or the macrophage may enter the walls and spaces. This accumulation results in the distortion of the interstitial space, from where it may enter the lymphatics. normal alveolar structure and release of mediators that can injure Inflammatory and immune effector cells normally account for parenchymal cells and stimulate fibrosis. Alveolar macrophages <10% of the total lung population and consist of macrophages increase in numbers in all interstitial diseases and release chemo- (93%), lymphocytes (7%), neutrophils and eosinophils (<10%). tactic factors for neutrophils (eg IL-8, leukotriene B4). Conse- quently, there is an increase in the number of neutrophils in both Loosely attached to the epithelial cells or lying free within the the wall and lumen of alveoli, which secrete proteases and toxic alveolus are the alveolar macrophages, derived from blood mono- oxygen free radicals, contributing to further tissue damage and cytes. Macrophages can generate toxic oxygen products, pro- maintenance of the alveolitis. teases, arachidonic acid metabolites, platelet-activating factor and cytokines that regulate inflammation. In some forms of ILD, cell-mediated immune reactions occur (eg in sarcoidosis) resulting in the accumulation of monocytes and Neutrophil infiltration during acute inflammation is often con- T-lymphocytes and the formation of granulomas and the secre- trolled by macrophage-derived cytokines (eg interleukin-8). tion of lymphokines and monokines, often with ensuing slowly Mechanisms of Interstitial and Alveolar Inflammation progressive pulmonary fibrosis. Alveolar Inflammations: Ultimately, if fibrosis in ILD becomes severe (end-stage fibrotic • Pneumonias (bacterial or viral): These are characterised by a lung) then the alveoli are replaced by cystic spaces separated by predominance of alveolar involvement, rather than interstitial thick bands of connective tissue interspersed with inflammatory tissue involvement, (although several viruses, eg cytomegalo- cells, sometimes referred to as “honey-comb” lung. This fibrosis virus, may cause a predominantly interstitial reaction). Thus results in the classic restrictive pattern of lung disease, character- during the acute reaction the alveoli fill with exudate and the ised by reduction in oxygen-diffusing capacity, lung volumes and lung tissue becomes consolidated. Resolution of the inflam- compliance. matory response is usually accompanied by clearance of Optional references: the inflammatory exudate and complete restoration of lung Kumar, Abbas, Fausto, Aster. Robbins and Cotran Pathologic Basis of Disease. (8th ed.) Saunders, c2010. Pp 693-706. function. • Toxic fumes (cadmium, beryllium, high dose oxygen): Al- Author: Professor Nicholas King, Pathology though a characteristic pneumonia accompanies exposure to

31 3.04 - Ex-Navy // Interstitial Lung Disease 5. Occupational Disability And Impairment In 2.08 ‘I always work hard’ you considered ‘The law and work-related • Asbestos induced carcinoma injury’ as one of your learning topics. Having read this you should be • Asbestos related pleural disease (ARPD) familiar with the role of ‘Workcover’ in administering a number of • Bagassosis important state laws regarding work-related health and safety. In this • Berylliosis learning topic, we will build on that knowledge to consider the role of • Byssinosis the Dust Diseases Board in compensating workers under the Workers • Coal dust pneumoconiosis Compensation (Dust Diseases) Act 1942 and some of the issues that • Farmer’s lung might be important in assessing occupational disability and impair- • Hard metal pneumoconiosis ment. • Mesothelioma When considering the effects on ability to work of a physical or mental • Silicosis impairment, whether caused by work related disease or injury, or non • Silico-tuberculosis work factors, certain key distinctions must be made at the outset. • Talcosis The compensation laws in Australia are mainly State-based with A disability is not the same as an employment handicap. To take a separate schemes and laws for Commonwealth employees (Comcare), simple example: employees in and around coal mines and self-employed individuals. A person has lost their leg in an accident (the impairment). As a result Assessing occupational disability and impairment of this they are unable to walk (the disability). Their inability to walk Usually, the assessment of an impairment and disability is done by an will preclude them from many jobs, such as being a soldier in the expert medical assessor, particularly if financial compensation is being infantry (the handicap) even though modern discrimination law has sought. done much to reduce this restriction. Depending on educational level, there may still be many other jobs open to the applicant. The disabil- A good example of the type of standardized assessment criteria that ity can be reduced by artificial limbs, and vocational retraining can might be applied is found in the assessment guide for Commonwealth 2 equip the impaired person for other employment. This is the role of Employees via ComCare . rehabilitation. Impairment is defined by them as “the loss, loss of use, damage or mal- There are primary and secondary disabilities. A long period off work function, of any part of the body, bodily system or function or part of following loss of a limb affects the ability of a person to get up in the such system or function”. It is measured by its effect on the ‘activities morning and apply him or her self to the job. The pain and discomfort of daily living’ in comparison with a normal healthy person. The meas- of an artificial limb can cause depression and anger and resentment at ure of ‘activities of daily living’ is a measure of primary biological and the way the world has treated them. psychosocial function such as standing, moving, feeding and self care. There is thus a secondary psychiatric disability involved in most physi- Non-economic loss, is also something that should be considered as the cal impairments, whether work related or not, and dealing with this is subjective effects of the impairment on the employee’s life. It includes also a rehabilitation function. When compensation issues or common pain and suffering, loss of amenities of life, loss of expectation of life law actions are also involved, another source of anxiety is introduced, and any other real inconveniences caused by the impairment. They and psychological help is often required. may include ‘Lifestyle effects’ such as an individual’s mobility and enjoyment of, and participation in, recreation, leisure activities and A physician is concerned with the effect of health on ability to work social relationships. Assessing these can be challenging as people usu- and the effect of work-related factors on health. Crucial to this role ally have equal ratings of impairment but it would not be unusual for is an ability to take an occupational history. This requires knowledge them to receive different ratings for non-economic loss because of their of workplaces and their hazards, both current and historical, diseases different lifestyles. related to workplace exposure, use of protective equipment, and safety management practice. Many occupational diseases have a long latency The concepts of ‘employability’ and ‘incapacity’ are different again to period. This is true of many occupational cancers as well as dust related impairment and non-economic loss. Incapacity is influenced by factors fibrotic lung disease and chronic chemical toxicity. Many occupational other than the degree of impairment and is compensated by weekly diseases can also be caused totally or partially by non occupational fac- payments which are in addition to these payments. tors (eg chronic obstructive pulmonary disease, lung cancer). It is also important to realise that impairment is system or function All doctors, however, should have a basic knowledge of the importance based and that a single injury or disease may give rise to multiple loss of an occupational history, an awareness of the workers’ compensation of function. system and common law relating to work related disease and injury, Optional references: and the rehabilitation process. Occupational injury and disease has NSW Dust Diseases Board http://www.ddb.nsw.gov.au Comcare Australia. Guide to the assessment of the degree of permament impairment. been estimated to cost the nation about $40 billion per year, with 3000 http://www.comcare.gov.au/compensation/permanent_impairment deaths per year due to injury and disease and about 700 000 disabling Waldron HA. Occupational Health Practice. (4th ed) London: Butterworth-Heinemann injuries per year related to work. 1997. Harber P, Schenker M, Balmes JR. Occupational and Environmental Respiratory Dis- NSW Dust Diseases Board ease. St Louis: Mosby, 1996; 28, 292-373, 857-898, 963-972. 1. The Dust Diseases Board is a statutory authority that administers American Medical Association. Guides to the evaluation of permanent impairment (5th the Workers’ Compensation (Dust Diseases) Act of 1942. It reports to ed.) Chicago: AMA, 2001.This “very comprehensive textbook” covers all organ systems the NSW Attorney General and Industrial Relations Ministers. It aims in great detail. Thoracic Society of Australia and New Zealand: Evaluation of impairment, disability to “Ensure that workers and their dependants who are eligible under the and handicap caused by respiratory disease. Aust NZ J Med 1996; 26(5): 697-701. Act are appropriately identified, assessed and compensated according to the Hendrick DJ, Burge PS,Beckett WS, Churg A. Occupational Disorders of the Lung. spirit and meaning of the Act.” London,Saunders 2002. J Occ Health and Safety (ANZ) 2002 ;18 (5). Under the Act, workers and their dependents are eligible for compen- All good, especially Introduction p 3-25 sation if their employment as workers exposes them to dust which may J LEIGH History of occupational disease recognition and control. J OHS (ANZ) cause one of the following diseases (2007) 23:519-530 (also see entire special issue containing this paper)

• Aluminosis Author: Dr James Leigh, School of Public Health • Asbestosis 32 3.04 - Ex-Navy // Interstitial Lung Disease 6. Compliance Of The Chest Wall And Lungs • Asbestos induced carcinoma The respiratory system is an elastic structure, which when acted upon in volume per unit change in pressure or slope of the curve). These • Asbestos related pleural disease (ARPD) by the respiratory muscles, increases its volume and then returns to relationships are summarised in what is called the Rahn Diagram . • Bagassosis its resting configuration when these muscles relax. Some respiratory This diagram is presented in the texts listed below and is the basis for • Berylliosis diseases have effects on the elastic properties of the chest wall and an understanding of the elastic properties of the respiratory system. • Byssinosis lungs. Increased stiffness of the lungs occurs in pulmonary fibrosis These concepts are fundamental to a consideration of the work done • Coal dust pneumoconiosis (increased fibrous tissue in the lung), and decreased lung stiffness in by the respiratory muscles to expand the lungs and have been em- • Farmer’s lung pulmonary emphysema (where there is destruction of lung tissue). ployed in developing approaches to mechanical ventilation (pressures • Hard metal pneumoconiosis The chest wall may become stiffer with some pleural diseases and needed to overcome elastic recoil) and management of respiratory • Mesothelioma conditions such as ankylosing spondylitis. Flail chest is a condition muscle fatigue (quantification of pressures developed by the respira- • Silicosis where there is a localised ‘floppy’ segment of the rib cage.Restrictive tory muscles). • Silico-tuberculosis respiratory diseases are associated with a reduced total lung capac- The elastic properties of the respiratory system are important in • Talcosis ity that is often the result of increased lung or chest wall stiffness. determining the volume of the lungs. In normal subjects total lung The compensation laws in Australia are mainly State-based with The elastic properties of the respiratory system can be assessed by capacity is influenced by decreased compliance of the lung at high separate schemes and laws for Commonwealth employees (Comcare), measuring its compliance (ie volume change achieved per unit change lung volumes while, in young healthy subjects, residual volume is employees in and around coal mines and self-employed individuals. in distending or compressing pressure). This concept can be used to influenced by decreased compliance of the chest wall at low lung Assessing occupational disability and impairment assess, separately, the elastic properties of the lung, the chest wall and volumes. During relaxed breathing functional residual capacity is Usually, the assessment of an impairment and disability is done by an the combination of both lung and chest wall. The inverse of compli- an equilibrium position for the respiratory system where the elastic expert medical assessor, particularly if financial compensation is being ance is called elastance . Elastic properties of the respiratory system recoil of the lung and chest wall are equal but opposite. In the normal sought. can also be expressed as elastic recoil pressure . This is measured as the breathing range healthy human lungs have a compliance of ~200ml/ distending pressure that must be applied to produce any particular A good example of the type of standardized assessment criteria that cm water. Compliance of the lungs depends on size. If we change the might be applied is found in the assessment guide for Commonwealth lung and chest wall volume. See Table 1 for summary of elastic effects volume of an elephant lung by 1ml this will involve little change in Employees via ComCare 2 . of fibrosis and emphysema. elastic recoil but the same volume change applied to a mouse lung Impairment is defined by them as “the loss, loss of use, damage or mal- Stiffness Compliance Elastance Restrictive would involve a substantial change in elastic recoil. Specific compliance function, of any part of the body, bodily system or function or part of Fibrosis Increased Decreased Increased Yes (ie compliance per unit volume) values are used to allow for different such system or function”. It is measured by its effect on the ‘activities Emphysema Decreased Increased Decreased No sized lungs. of daily living’ in comparison with a normal healthy person. The measure of ‘activities of daily living’ is a measure of primary biological and Table 1: Effects of fibrosis and emphysema on the elastic properties of the What are the properties that determine this kind of elastic behaviour psychosocial function such as standing, moving, feeding and self care. lung. of the lung and chest wall? The elastin and collagen fibres present in lung tissue contribute to the compliance of the lung not only Non-economic loss, is also something that should be considered as the Compliance reflects passive elastic properties so it is measured under subjective effects of the impairment on the employee’s life. It includes because of the inherent elasticity of these fibres but also because of “static conditions” (ie during relaxation of the respiratory muscles their distribution in a mesh like network that allows them to slide pain and suffering, loss of amenities of life, loss of expectation of life and with no airflow). To measure compliance the subject inhales and any other real inconveniences caused by the impairment. They in relation to each other. Lung compliance increases with increas- to total lung capacity and then exhales slowly to residual volume, ing age, presumably because of degradation of this fibre network. may include ‘Lifestyle effects’ such as an individual’s mobility and stopping every few hundred millilitres to relax against an occluded enjoyment of, and participation in, recreation, leisure activities and Diseases that destroy these fibres (eg emphysema) or increase the mouthpiece. A spirometer is used to measure the change in volume of number of less elastic fibres (eg pulmonary fibrosis) have the potential social relationships. Assessing these can be challenging as people usu- the respiratory system (with appropriate correction for gas com- ally have equal ratings of impairment but it would not be unusual for to alter lung compliance. The surface tension of the fluid lining the pression and expansion ie Boyle’s Law). Obtaining the appropriate alveoli is also a major factor determining lung compliance. This force them to receive different ratings for non-economic loss because of their distending or compressing pressure is more difficult. For the lung it different lifestyles. contributes a large part of the elastic recoil pressure of the lung and is the trans-pulmonary pressure (ie the difference between alveolar is largely responsible for a property of the pressure-volume curve of The concepts of ‘employability’ and ‘incapacity’ are different again to and pleural pressure). Alveolar pressure is easily obtained as it is the the lung, called hysteresis , where the deflation and inflation curves are impairment and non-economic loss. Incapacity is influenced by factors pressure measured in the mouthpiece (using a pressure transducer). not the same (for any given transpulmonary pressure lung volume is other than the degree of impairment and is compensated by weekly Since there is no airflow in the tracheobronchial tree when expira- payments which are in addition to these payments. larger during deflation than during inflation). The presence lungof tion is stopped with mouth occlusion, the pressure at the mouth is surfactant lowers surface tension making it easier to expand the lung It is also important to realise that impairment is system or function equal to the pressure in the alveoli. Pleural pressure is assessed by (ie increased compliance) and helps to keep alveoli dry. Diseases that based and that a single injury or disease may give rise to multiple loss using a balloon, catheter and pressure transducer system to measure reduce the amount of lung surfactant are associated with decreased of function. the pressure in the mid-oesophagus (a reflection of pleural pressure). lung compliance (eg neonatal respiratory distress syndrome). Filling Optional references: Measuring pleural pressure also allows us to obtain the pressure acting of alveoli with fluid (eg pulmonary oedema) prevents their expansion NSW Dust Diseases Board http://www.ddb.nsw.gov.au on the chest wall (ie the difference between pleural pressure and the with inhaled gas, thus reducing the increase in lung volume that can Comcare Australia. Guide to the assessment of the degree of permament impairment. pressure acting on the external surface of the chest wall - atmospheric http://www.comcare.gov.au/compensation/permanent_impairment occur for a given change in distending pressure (ie decreased compli- Waldron HA. Occupational Health Practice. (4th ed) London: Butterworth-Heinemann pressure). Furthermore, the difference between alveolar pressure (ie ance). 1997. mouth pressure during the exhalation pauses) and atmospheric pres- Optional references: Harber P, Schenker M, Balmes JR. Occupational and Environmental Respiratory Dis- sure is the trans-respiratory system pressure. When change in pressure West JB. Elastic Properties of the Lung. In: Respiratory Physiology. The Essentials. ease. St Louis: Mosby, 1996; 28, 292-373, 857-898, 963-972. (independent variable) is plotted against change in volume we obtain 6th ed. Chapter 7, Mechanics of Breathing. Lippincott Williams & Wilkins, American Medical Association. Guides to the evaluation of permanent impairment (5th Baltimore, 2000, pp81-87. ed.) Chicago: AMA, 2001.This “very comprehensive textbook” covers all organ systems a pressure-volume curve. Such curves can be generated for the lung, Covers pressure-volume curve of the lung, compliance, surface tension and in great detail. chest wall and respiratory system by plotting the appropriate pres- hysteresis. Thoracic Society of Australia and New Zealand: Evaluation of impairment, disability sure versus the change in volume (the latter may be expressed as a and handicap caused by respiratory disease. Aust NZ J Med 1996; 26(5): 697-701. West JB. Elastic Properties of the Chest Wall. In: Respiratory Physiology. The Hendrick DJ, Burge PS,Beckett WS, Churg A. Occupational Disorders of the Lung. percent of vital capacity but can also be expressed in absolute terms if Essentials. 6th ed. Chapter 7, Mechanics of Breathing. Lippincott Williams & London,Saunders 2002. residual volume is measured separately, which it usually is). In normal Wilkins, Baltimore, 2000 pp81-91. J Occ Health and Safety (ANZ) 2002 ;18 (5). subjects these relationships are curvi-linear with the lung being more Develops pressure-volume relationships of the lung and chest wall. Contains a All good, especially Introduction p 3-25 difficult to expand near total lung capacity (decreased compliance) good description of the Rahn Diagram on page 90. J LEIGH History of occupational disease recognition and control. J OHS (ANZ) Grassino AE, Roussos C, and Macklem PT. Static Properties of the Chest Wall. In: (2007) 23:519-530 (also see entire special issue containing this paper) and the chest wall being more difficult to compress (ie chest wall THE LUNG: Scientific Foundations. Vol 1. Chapter 5.1.1.5. Ed: RG Crystal, JB tends to spring out) near residual volume. At any point on these West et al, Raven Press, New York, 1991, pp855-867. Author: Dr James Leigh, School of Public Health pressure-volume relationships we can measure both the elastic recoil Read pages 855-856 for an excellent discussion of the Rahn Diagram. pressure (distending pressure at any volume) and compliance (change Author: Associate Professor Terry Amis, Medicine 33 3.04 - Ex-Navy // Interstitial Lung Disease 7. Transport Of Oxygen And Carbon Dioxide The respiratory gases are relatively insoluble in aqueous solutions The oxygen saturation of Hb in normal arterial blood (PO2 ~100 and so specialised systems have evolved to transport oxygen and mmHg) is ~ 97.5 % and that of mixed venous blood (PO 2 ~40 carbon dioxide in mammalian blood. mmHg) is ~ 75 %. Reduced Hb is purple and so a low arterial oxygen saturation causes cyanosis. Oxygen Transport: Oxygen is carried in the blood in two forms: dissolved and Carbon monoxide (CO) combines with Hb to form carboxyHb

combined with haemoglobin (Hb). Oxygen dissolved in blood and has a far greater affinity for Hb than 2O . Small amounts of obeys Henry’s law - the amount dissolved is proportional to the CO can occupy large amounts of Hb making it unavailable for 2 partial pressure. For each mmHg of PO 2 there is 0.003ml O 2 oxygen transport. The Hb concentration and the PO of blood 2 / 100ml of blood. Therefore, normal arterial blood with a PO2 will be normal in CO toxicity but the content of O in the blood

of ~100mmHg will carry only 0.3ml O 2 / 100ml. This amount will be greatly reduced. of oxygen is clearly inadequate for normal tissue function. Carbon Dioxide Transport: Even breathing 100% oxygen (to give an alveolar PO of ~600 2 Carbon dioxide (CO ) is carried in the blood in three forms: mmHg), will only result in 2 .0ml O 2 / 100ml blood. 2 dissolved, as bicarbonate (HCO 3 ) and combined with proteins Haemoglobin is a protein that binds reversibly with oxygen. One (carbamino compounds). Carbon dioxide dissolved in blood 2 gram of pure Hb can combine with ~1.39ml O 2 . Normal blood also obeys Henry’s law, but CO is more soluble than O 2 and so t has ~15gm Hb / 100ml blood. Therefore, the oxygen carrying ~10% of CO 2 ransported to the lungs is in this form.

capacity of normal blood is ~ 2 0.8ml O 2 /100ml blood. The HCO 3 is formed in the blood through the following reactions: affinity of Hb for oxygen varies with PO2 and a number of other

factors. The relationship between the PO2 and the number of The first reaction is catalysed by carbonic anhydrase, which is in binding sites of Hb that have oxygen attached (OR the satura- high concentrations in red cells. The second reaction occurs rap-

tion of Hb with oxygen) is known as the oxygen dissociation idly without enzymes. HCO 3 diffuses out of the red cells, but H+ curve. (see below). Familiarity with this curve is essential to the cannot so Cl moves in to maintain electrical neutrality. Some of understanding of respiratory physiology. Note that the amount the H+ binds to reduced Hb (which is less acid than oxygenated

of oxygen carried by Hb increases rapidly up to a PO 2 of around Hb). Therefore, reduced Hb assists the loading of CO2 whereas 50 mmHg but above this the curve flattens off. The shape of this oxygenated Hb assists in the unloading of CO 2 (facilitating trans- curve has a number of physiological advantages. The flat upper fer to the lungs). This is called the Haldane effect. part means that loading of Hb with O is preserved even when 2 Carbamino compounds are formed by the combination of CO alveolar PO falls somewhat. The steep lower part means that 2 2 with the terminal amine groups of blood proteins, including the large amounts of O are unloaded in the peripheral tissues for 2 globin chain of Hb. Again reduced Hb can bind more CO than only a small drop in PO 2 . Thus, Hb is beautifully designed to 2 oxygenated Hb. deliver oxygen from areas of high PO 2 (lungs) to areas of low PO 2 (tissues). The transport of CO2 by the blood has a profound effect on acid- base status of the blood and the body. The lungs excrete 100 times The oxygen dissociation curve is shifted to the right (ie Hb affinity more acid than the kidneys each day. The human body is able to for oxygen is reduced) by increases in temperature, H+ concentra- exert great control over its acid-base status simply through altering tion, PCO and 2 ,3-diphosphoglycerate (DPG) (a by-product of 2 alveolar ventilation and so elimination of CO . red cell metabolism) concentration in red blood cells. This means 2 that more O 2 is unloaded for a given PO , effectively increasing Optional references: 2 West JB. Respiratory Physiology - the essentials (6th ed.) Lippincott, Williams and oxygen delivery to tissues that are acidic, hot and hypercarbic (eg Wilkins 2000. Chapter 6, pp 63-77. exercising muscle). This effect of PCO2 on Hb affinity for 2O Related areas of interest include comparative respiratory physiology, fetal haemo- 2 globin and exercise physiology. (where an increase in PCO 2 reduced Hb affinity for O ) is called the Bohr effect.

34 3.04 - Ex-Navy // Interstitial Lung Disease 8. Blood Gas Analysis

The sampling of arterial blood for blood gas analysis is an that while SaO 2 may be measured using a pulse oximeter, the important investigation used in the diagnosis and management result obtained is not the same as the PaO 2 measured from blood of patients with a wide range of respiratory disorders (including gas analysis; the relationship between SaO 2 and PaO 2 is sigmoidal respiratory failure), in situations where a patient’s ventilation is and is plotted as the oxyhaemoglobin dissociation curve. being supported or maintained mechanically (eg during a general An important calculation made from ABGs is the difference be- anaesthetic or while ventilated in an Intensive Care or High tween the oxygen tension in alveolar gas (PAO 2 ) and the oxygen Dependency environment) or as part of the investigation of a tension in arterial blood (PaO - obtained from the ABG sample) number of metabolic disorders where acid-base status is affected. 2 This calculated value is abbreviated as the ‘A-a DO ‘ or ‘A-a gra- From the respiratory viewpoint, arterial blood gas (ABG) analysis 2 dient for oxygen’. Even in normal healthy individuals this differ- measures the partial pressures of O and CO in arterial blood 2 2 ence is 5 to 15 mmHg, and increases with age. PAO is not easily (ie PaO and PaCO respectively). These partial pressures do not 2 2 2 measured, and so must be calculated using the simplified alveolar directly measure the quantity of O and CO in the blood, but 2 2 gas equation which takes into account the partial pressure of oxy- instead measure the driving pressure of each gas being carried in gen in inspired air (PiO ), the patient’s metabolic state reflected the blood. 2 by the respiratory quotient (R - the ratio of CO 2 production to 2 - Arterial blood collected for ABG analysis is usually taken from O consumption) and the PACO 2 the other major gas being a peripheral artery (eg radial, brachial, femoral), although other ‘exchanged’ in the alveolus. Because of the nature of CO 2 , its access points may be used, depending upon the clinical circum- diffusion across the alveolar membrane and its carriage in blood stances. The collection of arterial blood should be taken when the in a dissolved form (rather than being bound to a carrier molecule patient is in a steady state (usually at rest) and has been inspiring like haemoglobin), the PACO 2 is usually taken to be equal to the - a constant, known level of oxygen for at least fifteen to twenty PaCO 2 obtained from the ABG analysis. The PiO2 should take minutes. The concentration or fraction of oxygen in the inspired into account the saturated water vapour pressure (PH 2 O) of gas o air (FiO 2 ) should be noted when the ABG sample is collected at body temperature. At 37 C this is approximately 47 mmHg.

(eg room air = 0. 2 1), remembering that the FiO 2 delivered by If the FiO 2 and the barometric pressure (PB) are known, PiO 2 nasal prongs or a mask apparatus is unreliable and non-constant. may be calculated using the formula: Similarly, the patient should be relaxed at the time of the proce- PiO 2 = FiO x (PB - PH 0) dure - if the patient is conscious, local anaesthetic is usually used 2 2 at the puncture site to reduce the effects of hyperventilation dur- The simplified alveolar gas equation is given by: ing sampling. The blood is collected into a pre-heparinised syringe PAO = PiO - (PaCO / R) that is sealed air-tight after sampling. The sample is transported 2 2 2

(on ice) immediately for laboratory analysis. Although blood gas To be precise, R should be measured by calculating O 2 consump- analysis can be performed on small samples of blood, optimally a tion and CO 2 production for a period of time. The normal range sample volume of 2 .5 to 3mls is required in the adult. is between 0.7 and 1.0; for quick clinical calculations of the A-a DO 2 , a value for R of 0.8 is usually used. Similarly, a PB of 760 Analysis is undertaken using automated equipment, calibrated mmHg is usually used for quick clinical calculations at or near to against well controlled standards. Essentially, these analysers are sea level. composed of specially designed electrodes encased in a thermo- statically controlled chamber. Measurements of arterial partial The A-a DO2 is then given by: pressure of oxygen (PaO 2 ; normal range 90 to 100 mmHg), 2 2 A-a DO = PAO 2 - PaO arterial partial pressure of carbon dioxide (PaCO 2 ; normal range 35 to 45 mmHg), and arterial pH (normal range 7.34 to 7.44) Elevations in the A-a DO 2 reflect abnormalities in gas exchange are made by the equipment, while Base Excess (BE; normal range of O 2 between the alveolus and the arterial blood. These may +1 to -1 mmol/l), Bicarbonate (HCO 3- ; normal range 2 5 to 35 come about via a number of pathophysiological mechanisms, including shunting of cardiac output, impairment of diffusion mmol/l) and arterial oxygen saturation (SaO 2 ; normal range 94 to 99%) are calculated from these results and (if provided) other across the alveolar membrane and - by far the most important patient data (including body temperature and haemoglobin). The clinically - mismatching of ventilation and perfusion (also termed results give valuable information about the patient’s respiratory V/Q mismatch or V/Q inequality). and acid base status, applicable to a wide range of diagnostic and Optional references: management settings. By taking into account the pH of the sam- West JB. Respiratory physiology : the essentials. 8th ed. Philadelphia: Wolters ple and the other factors reflecting acid base status in the patient, Kluwer Health/Lippincott Williams & Wilkins; 2008. West JB. Pulmonary pathophysiology : the essentials. 7th ed. Philadelphia: Lip- some conclusions may be drawn about the chronicity of any de- pincott Williams & Wilkins; 2008. rangements in PaO 2 or PaCO 2 and the relative contributions of Fauci AS. Harrison’s principles of internal medicine. 17th ed. New York: McGraw- metabolic and respiratory components to the measured ABG pro- Hill Medical; 2008. Chapter 246 Disturbances of Respiratory Function file. Nomograms are sometimes used to aid interpretation. Note Author: Dr Stephen Gregory McNamara, Medicine

35 3.05 - Sleeping On The Job // Sleep Apnoea & Respiratory Failure Learning Objectives Description Disciplines Detailed anatomical organisation (cartilages, ligaments and muscle) and function (swallowing and phonation) of the pharynx and larynx; their blood supply and neural innervations. The anatomy of the Anatomy thyroid gland and some clinical applications Detailed anatomical organisation and function of the eye; the different tunics of the globe, blood supply and neural innervations of the globe and associated structures. The different extraocular eye muscles, their Anatomy innervations, functions and clinical testing. The bones that make up the cave of the orbit. Detailed anatomical organisation and function of the greater ear complex; the internal, middle and external Anatomy ears. The bony and cartilagenous frameworks, neural innervations and some clinical applications. By the end of this session students will be better able to: 1) Explain the relationships between spirituality, religion and health and their role in the experience of suffering 2) Recognize some of the spiritual issues patients may want to explore in relation to acute or chronic Interdisciplinary illness and the place of a spiritual history

4) Understand the role of chaplains/pastoral care workers in the health system and when referral is appropriate3) Appreciate the influence of spirituality on patient decision making in treatment and therapy

Pathology The disease process associated with chronic airflow limitation; the pathological features associated with The major pathological features related to smoking Pathology chronic airflow limitation; the microscopic and macroscopic features of chronic bronchitis and emphysema

the parasympathetic and sympathetic parts of the autonomic nervous system; the parasympathetic and Pharmacology sympatheticThe basic organisation effects on differentand structure structures of the ofautonomic the body nervous system; the function and significance of The pulmonary physiology and anatomy in relation to pulmonary circulation; the effects of gravity on Physiology, Anatomy pulmonary function and circulation the lungs; the distribution of blood flow in the lungs; definition of hypoxia and hypoxaemia in relation to · To perform a comprehensive examination of the respiratory system in a patient with a respiratory disorder Respiratory Medicine · Learn to look for and interpret normal and abnormal features of chest x-rays · To report the findings of a respiratory examination accurately The range of movement disorders that occur exclusively or predominantly in sleep, including restless legs Respiratory syndrome (with periodic leg movements in sleep), the parasomnias and sleep epilepsy Medicine

Respiratory the endocrine variables that show circadian rhythmicity; what happens when circadian rhythms are Medicine disrupted?The significance of circadian rhythms; how the sleep-wake state is regulated by the circadian system; Respiratory disrupted sleep on the individual Medicine The concepts of normal and abnormal sleep and circadian physiology. The effects of insufficient or The prevalence, neurobehavioural effects (and countermeasures) of sleep loss, as well as the real world Respiratory effects of sleep loss Medicine The common sleep disorders, their epidemiology and modes of presentation, basic differential diagnosis, Respiratory consequences Medicine How abnormalities of breathing during sleep lead to the clinical syndrome of obstructive sleep apnoea Respiratory and its physiological consequences. The pathophysiological mechanisms contributing to upper airway Medicine obstruction and central apnoea during sleep The normal physiological regulation of breathing; the disease states that alter normal control of Respiratory respiration; the acute & chronic consequences of respiratory failure Medicine Students should learn: · to take a structured history from a patient with COPD (previously used synonyms CAL = chronic Respiratory Medicine · to summarise the main features of the history and present the case concisely and clearly. ·airflow possible limitation, causes COAD of chronic = chronic dyspnoea obstructive and cough, airway and disease). try to distinguish between them. Respiratory The effects of shiftwork and extended work hours on neurobehavioural and physiological variables; the Medicine, occupational impact of sleep disorders Occupational Medicine

36 3.05 - Sleeping On The Job // Sleep Apnoea & Respiratory Failure 1. Neurobiological Consequences Of Sleep Loss What is the prevalence of sleep loss? drive for sleep. Typically following total sleep deprivation subjects ex- Recent studies have demonstrated that when sleep is restricted to be- perience an increase in the amount of slow wave sleep relative to their low 8 hours per night a sleep debt accumulates, leading to significant baseline levels. During chronic sleep restriction the amount of slow deficits in alertness and neurobehavioral functioning. Epidemiological wave sleep remains stable across different sleep restriction conditions, studies in USA have demonstrated that many people sleep between such that subjects get equal amounts of slow wave sleep whether they 6 to 6.5 hours per night. The increasing prevalence of chronic sleep are allowed 4, 6 or 8 hours time in bed for sleep. Therefore, the per- restriction is due to several factors including increased work hours, centage of the sleep period spent in slow wave sleep is increased when shiftwork, sleep and other medical disorders, caring for others, and allowed sleep duration is reduced. To compensate for this increase in family or social demands. slow wave sleep there is typically a decrease in the other sleep stages, particularly stages 1 and 2 and the amount of wake after sleep onset. What are the neurobehavioural effects of sleep loss? The effects of sleep loss may be quantified with a wide range of physi- What are the real world effects of sleep loss? ological, neurocognitive, behavioural and subjective tasks. During Similar to the effects of sleep loss on driving simulators, decreased laboratory studies of sleep deprivation neurobehavioural performance driving ability and increased risk of motor vehicle accidents in the measures are affected by sleep loss, such as reaction time, vigilance, real world have been attributed to sleep loss. A recent epidemiological sustained attention, mental arithmetic, short-term recognition study reported increased incidence of sleep related crashes in drivers memory, logical reasoning, tracking ability, word generation, vocal who averaged less than 7 hours sleep per night. Additional factors intonation and mood. contributing to these drowsy driving crashes included poor sleep quality, dissatisfaction with sleep duration (i.e. under sleeping), daytime In one study of truck drivers, subjects were randomised to 7 nights sleepiness, previous instances of driving drowsy, time driving and time of 3, 5, 7 or 9 hours time in bed for sleep per night. In the other of day (driving late a night). In Australia approximately 20% of road study subjects were randomised to 4, 6 or 8 hours sleep per night fatalities are attributed to drowsy driving. for 14 nights. Taken together, these studies demonstrated that when sleep duration was chronically restricted to below 7 hours per night Further real world effects of sleep loss are evident in a number of ca- significant deficits in a variety of laboratory based performance meas- tastrophes where sleep loss and fatigue have been implicated as causal ures were evident. These performance deficits accumulated across the factors. Examples include the Chernobyl nuclear disaster (1986); experimental protocol, with no evidence of adaptation to the reduced Exxon Valdez grounding (1989); and train crash at Selby (2001). sleep schedule. In the second study, performance deficits were still Recently published papers examined performance in 1st year medical increasing at day 14 of the restricted sleep schedule. The findings from interns working on their normal shift work schedules, compared to a the subjects allowed 4, 6 and 8 hours time in bed were compared with week when the number of scheduled works hours was limited to 16 or the performance effects of subjects who underwent 88 hours (3.7 less. There were more than 1.5 times the number of attentional fail- days) total sleep deprivation. This comparison demonstrated that 4 ures during the normal work schedule compared to during the limited and 6 hours time in bed for sleep per night for 14 nights produced work schedule during the daytime hours (7am to 10pm) and more performance deficits equivalent to what occurred with 24 to 48 hours than double the number of attentional failures during the normal of total sleep deprivation. In a subsequent study with sleep placed work schedule compared to during the limited work schedule during during the daytime, performance deficits with a similar cumulative the nighttime hours (11pm to 7am). In addition, compared to the pattern were observed, but with a greater magnitude of performance limited work schedule, during the normal work schedule week interns impairment, reflecting a combined influence of the homeostatic and made 35.9 percent more serious medical errors, 56.6 percent more circadian systems. non-intercepted serious errors, 20.8 percent more serious medication The effects of sleep restriction have also been examined using driving errors and 5.6 times more serious diagnostic errors. simulators. Following one night of 5 hours sleep there was a decrease What are the countermeasures to the neurobehavioural effects of in performance on a driving simulator, and a concurrent increase in sleep loss? subjective sleepiness. In addition, during a chronic sleep restriction A number of different pharmacological and behavioural countermeas- study, with sleep durations restricted to 4 - 6 hours per 24 hours for ures have been assessed to increase performance during periods of 10 days/nights, there was a significant increase in the rate of accidents sleep loss. Naps taken prior to a period of sleep have a beneficial effect on a driving simulator, independent of the timing of the sleep period. on alertness and performance during limited periods of extended A similar finding was reported following 2 nights of restricted sleep. wakefulness. In addition, naps taken during a period of sleep loss or to In addition to these effects, an increase in sleepiness and fatigue and supplement restricted sleep have also been shown to have beneficial ef- decrease in alertness is associated with periods of sleep loss. Interest- fects on performance. Short duration naps do not return performance ingly, however, during chronic sleep restriction protocols subjects re- levels to those observed following a full night’s sleep however, and port that although they initially feel increased levels of sleepiness, they only have an effect for a limited time. It is also important to limit the do not continue to increase across days of restriction, even though duration of the nap to avoid the performance decrements associated their performance levels continue to decline. Studies have also demon- with sleep inertia - the period of time immediately following waking strated increased sleep propensity. Using the multiple sleep latency test when sleepiness levels are significantly elevated. (MSLT) where subjects are instructed to try and fall asleep as quickly Another potential countermeasure to improve alertness and perfor- as they can repeatedly across the day, and then awoken when they do, mance is caffeine administration. When used as a stimulant or wake a significant reduction in the time taken to fall asleep is evident with promoting compound it is important to use caffeine pharmacologi- increasing time awake during sleep deprivation. Therefore, despite the cally rather than socially. Caffeine has been shown to increase alertness continued increase in performance deficits and objective measures of and neurobehavioural functioning during periods of sleep deprivation, sleepiness, subjects tend to underestimate their level of sleepiness, and and reduce sleepiness and fatigue. Caffeine can have negative effects also the degree to which their performance is affected by sleep loss. on sleep, and increase sleep latency, so the timing of caffeine adminis- During periods of chronic sleep restriction and following total sleep tration relative to the timing of the sleep period is important. deprivation, the stages of sleep most affected are stages 3 and 4, or Author: Honorary Associate Professor Naomi Rogers, Psychiatry slow wave sleep, which is thought to reflect the increased homeostatic 37 3.05 - Sleeping On The Job // Sleep Apnoea & Respiratory Failure 2. Human Chronobiology What are circadian rhythms? absence of light, melatonin synthesis is stimulated via neurons origi- Circadian rhythms are endogenously produced biologic rhythms nating in the SCN In the absence of a light-dark cycle, however, with characterised by repetitive oscillations with a frequency of 1 cycle per constant light conditions (usually low light levels) circadian rhyth- 24 hour period. The circadian system is a homeostatic system that micity of the melatonin profile is maintained. Melatonin secretion co-ordinates the physiological and behavioural activities of the brain occurs independent of sleep-wake status, and is not acutely affected by and body, ensuring synchronisation within the body with regard to nocturnal sleep deprivation. the timing of various activities, as well as synchronisation between As a circadian-mediated humoral factor circulating in the blood- the internal and external environments. Activities influenced by the stream, melatonin may be responsible for relaying information from circadian system include sleep-wake timing, thermoregulation, respira- the circadian pacemaker to the physiologic systems that are regulated tory function, cardiovascular function, alertness, neurocognitive by the biologic clock. Therefore, melatonin may play a role in coordi- performance, immune function, endocrine function, gastrointestinal nating various circadian rhythms within the body. function and renal function. In many cases the circadian system can be thought of as a wake promoting system, and works both in opposi- What happens with circadian disruption? tion to and with the homeostatic sleep system (aka a sleep promot- Circadian disruption occurs when there is misalignment of the circa- ing system) to influence these various physiological and behavioural dian system relative to the environmental light-dark cycle. Circadian activities. disruption is evident in night shiftworkers and transmeridian travelers, and contributes significantly to jet lag. With jet lag zeitgebers can help How is the circadian system entrained to the 24 hour day? re-entrain the circadian system to a new rest activity cycle, however, In humans, the central circadian pacemaker, or biological clock, is with shift work most workers remain in a constant state of circadian located in the suprachiasmatic nuclei (SCN) of the anterior hypothal- misalignment. This is largely due to the fact that exposure to a new amus. The SCN is synchronised to the 24 hour day via environmental light-dark cycle does not immediately shift the timing of the circa- time cues or zeitgebers, the strongest of these being exposure to the dian system to the new phase. The process of circadian readjustment light-dark cycle. Phototransduction from the retina to the SCN occurs is gradual, and consequently may take a number of days to weeks to primarily via the retinohypothalamic tract (RHT), and is thought fully occur. to be mediated via a novel set of photoreceptor cells, independent of the rod and cone visual perception systems in the eyes. In addition to There are also a number of circadian based sleep disorders that result entraining the biological clock, zeitgebers are able to shift the timing in significant sleep disturbance. These include: delayed sleep phase of the clock, and consequently the circadian rhythms of the functions syndrome; advanced sleep phase syndrome; shift work sleep disor- under its control. Additional non-photic zeitgebers that can influence der; and non-24 hour sleep cycles, commonly seen in blind patients. the biological clock include melatonin, exercise and social cues. Delayed sleep phase syndrome (DSPS) is common in adolescents and thought to have a familial basis in adults. In this disorder the timing How is sleep-wake state regulated by the circadian system? of the circadian system is delayed relatively to normal. Most notice- The circadian system influences the timing of sleep-wake behaviour, ably the timing of sleep is significantly delayed, with patients sleeping including the optimal time for sleep to occur, sleep duration and from about 0300-0400 until 1200-1300. Advanced sleep phase sleep architecture (in particular REM sleep). A temporal relationship syndrome (ASPS) is common in elderly adults, and is characterized exists between the onset of the secretion of melatonin, which has been by the timing of the circadian system occurring earlier than normal. implicated to promote sleep onset, the nightly decrease in core body Shift work sleep disorder (SWSD) is characterised by an inability to temperature and increased sleep propensity, all of which are regulated remain alert and awake across night shifts, and insomnia when trying by the circadian system. Sleep propensity is highest during the falling to sleep during the day. In SWSD these difficulties are only associated phase of the core body temperature rhythm, and the time of sleep with the night shift, and sleep-wake behaviour is normal when on day onset relative to the phase of this rhythm can determine sleep length. shifts (i.e. sleeping at night and working during the day). Since blind It is difficult to fall and remain asleep when core body temperature is subjects receive reduced or no light input from the environment their high, which may explain why shiftworkers report difficulty sleeping circadian system lacks the necessary photic input to entrain to the 24 during the day, when body temperature is high, despite having worked hour day. Consequently their circadian system tends to ‘free run’ and all night. the timing of their circadian rhythms drifts across days, with sleep oc- The circadian and homeostatic sleep systems also influence neurobe- curring progressively later each day. havioral capabilities and alertness levels across the 24 hour day. Dur- Appropriately timed exposure to bright light can act as an artificial ing sleep deprivation or extended wakefulness the homeostatic drive zeitgeber, and hence has been suggested as a treatment for circadian for sleep increases, increasing the likelihood of sleep onset and reduc- disruption. The most effective timing of light administration to ing alertness and neurocognitive performance levels. Coincident with achieve the greatest chronobiotic effect can determined using a phase the increasing sleep need is the 24 hour variation in these variables response curve. This curve describes the effects of light exposure due to the circadian system. Consequently, alertness or performance depending on the time of administration. Essentially, light administra- levels at any given time are the sum of effects of these two systems. It tion prior to the nadir in core body temperature will produce a phase is possible therefore to be more alert late in a period of sleep depriva- delay (put the timing of the temperature nadir or melatonin onset tion, compared to an earlier time with a shorter duration of sustained later) while light administration after the core body temperature nadir wakefulness, depending on the time of day (e.g., during the night will produce a phase advance (put the timing of the temperature nadir compared to the day). or melatonin onset earlier). In addition, appropriately timed admin- Which endocrine variables demonstrate circadian rhythmicity? istration of melatonin may also be used to reentrain the circadian Melatonin is an indoleamine produced in and secreted by the pineal system, although this is a weaker zeitgeber compared to light. Some gland. The SCN receive light information from the retina, and send therapies suggest using a combination of light exposure and melatonin this information via the spinal cord to paraventricular nuclei (PVN) administration to achieve the best results. and superior cervical ganglia (SCG), which terminate near the pineal Author: Honorary Associate Professor Naomi Rogers, Psychiatry gland. During the day melatonin synthesis is inhibited via suppression of the sympathetic neurons originating in the SCN. At night, in the 38 3.05 - Sleeping On The Job // Sleep Apnoea & Respiratory Failure 3. Autonomic Nervous System (ANS) The sympathetic nervous system is very large. It innervates visceral organs together with all sweat glands and blood vessels in the The nervous system has two basic compenents: body. It has origins in the spinal cord. Somata of the preganglion- 1. Central nervous system (CNS): neurones that house all ic cells are located in the thoracic and lumbar spinal cord. Axons their parts (axons, dendrites, somata) within the brain and from these cells project to ganglia within the sympathetic chain. spinal cord Here, most preganglionic cell axons synapse with postganglionic cells. A small number of preganglionic axons project to ganglia 2. Peripheral nervous system (PNS): neurones that have some outside of the sympathetic chain. These axons are referred to as of their parts (axons, somata) in the periphery (muscle, skin, the splanchnics. The postganglionic cells then sends axons to the viscera) target (eg gland; splanchincs target abdominal organs mainly). Within these two basic compenents, there are two functional The neurotransmitter used by the preganglionic cells is acetylcho- systems at work line, while the neurotransmitter used by the postganglionic cells is SOMATIC NERVOUS SYSTEM noradrenaline (the only exception is the postganglionic innervation of the sweat galnds when acetylcholine is used) • the system that we have voluntary control over. We have appreciation of its function and are aware of it. We may Parasympathetic Nervous System generate movements (eg, picking up things) and appreciate This system is used under normal circumstances. It keeps things sensations (eg, touch, sight). running smoothly. • it general deals with skin and skeletal (voluntary) muscles. The parasympathetic system is less extensive than the sympathetic one - it does not innervate the sweat glands and blood vessels. • sensory neurones have their cell bodies outside the CNS, within sensory ganglia (for spinal nerves, this is called the The somata of the parasympathetic nervous system are located in dorsal root ganglia [DRG]). One process attaches to the the spinal cord (sacral) and in the brainstem. In the brainstem, target (eg, skin), the other to the CNS (eg, spinal cord) (see cranial nerves (III, VII, IX, X) contain the preganglionic axons. Fig). Motoneurones have their cell bodies within the CNS The preganglionic axons from the brainstem or spinal cord project (eg. spinal cord), and their axons extend toward their periph- to ganglia very close to the target organ. The neurotransmitter eral targets (eg, muscle) (see Fig). used at all parasympathetic synapses is acetylcholine. AUTONOMIC NERVOUS SYSTEM (ANS) Some specific examples of differential action of the two systems of the ANS are outlined below. • the system that we have little control over - involuntary. For the most part, we are not aware of its workings. Structure Sympathetic Parasympathetic • it generally deals with smooth muscles of abdominal and Iris pupil dilation pupil constriction thoracic organs, cardiac muscle and gland cells. It controls Salivary Glands saliva reduced saliva increased reflexes that govern the function of our visceral organs, namely the heart, lungs, gastrointestinal system and urogeni- Mouth/Nose mucus reduced mucus increased cavity tal system. Heart heart rate increased heart rate decreased • Sensory neurones of the ANS have a similar organisation and connectivity to the somatic sensory neurones (although we Lung bronchial muscle bronchial muscle know much less about the ANS sensory cells). The motor ef- relaxed contracted ferents are organised very differently, however. Their cell bod- GIT activity reduced secretions and activity ies (preganglionic) are located in the CNS (eg, spinal cord) increased and they project to other cells (postganglionic) in autonomic Kidney decreased urine increased urine ganglion located in the periphery. Here a synapse occurs, a transfer of information. The postganglionic cell in the auto- Bladder bladder muscle bladder muscle nomic ganglion then projects to the target (eg, visceral organ) relaxedexternal contractedexternal sphincter closed sphincter relaxed (see Fig) Optional references: This learning topic will focus on the ANS. For a very good overview of the ANS see - Barrs’s Human Nervous System. JA Keirnan. 7th Edition. c1998. Lippincott and There are two major parts of the ANS; sympathetic, parasympa- Raven. page 423. thetic. Author: Professor John Mitrofanis, Anatomy and Histology Sympathetic Nervous System This system is used in emergency situations. Prepares us to take “flight” or “fright”.

39 3.05 - Sleeping On The Job // Sleep Apnoea & Respiratory Failure 4. Movement Disorders In Sleep Some movement disorders occur exclusively or predominantly occur early in the sleep period when deep (slow wave sleep) sleep in sleep and thereby may potentially impact sleep in pathophysi- is more prominent, are relatively common and usually (but not ological ways that lead to excessive arousals, unwanted motor exclusively) occur in childhood, and abate with time. Mostly, after behaviours, fear/anxiety, and their consequences. These disorders adequate diagnosis, reassurance is all that’s required, but occasion- include diverse clinical entities such as restless legs syndrome al complex, atypical or self- or other-harming cases may require with periodic leg movements in sleep, the parasomnias and sleep further investigation and management through specialist sleep epilepsy. clinic services; the benzodiazepines and tricyclic antidepressants have been effective pharmaceutical agents. There is no evidential Restless legs syndrome (RLS) is a chronic neurological disorder. linkage to underlying psychiatric disorder. It is characterised by paraesthesia or dysesthesia of the legs, an intense urge to move the legs (sometimes trunk and arms), and Rapid eye movement sleep will normally concentrate in the motor restlessness that is usually relieved with movement such as second half of the sleep period and in some instances there can be walking. It tends to occur leading up to bedtime and in periods of dissociation between REM sleep stage and the normally accompa- immobility. Most patients with RLS have periodic limb move- nying profound skeletal muscle atonia. Dreaming occurs largely ments during sleep (PLMS) . PLMS are repetitive rhythmic in REM sleep, and dream content involving action may be acted dorsiflexions of the ankle with extensions of the big toe (with out by the sleeper in REM stage behaviour disorder (RBD) with occasionally flexion of the knee and hip). These movements last consequent potential harm to self or other, usually bed-partner. 0.5-5 seconds and are repeated every 20-40 seconds during sleep. RBD occurs mainly in older males, may be associated with other They typically occur during the first part of the night predomi- sleep disorders such as sleep apnoea, and there is a significant pro- nantly in non-REM sleep. portion of RBD cases that go on to eventually develop a neurode- generative disorder such as Parkinson’s disease. Clinical assessment The diagnosis of RLS relies on a detailed clinical history; a sleep will usually include overnight sleep study (polysomnography) study or neurological tests such as nerve conduction studies are in which RBD may be readily diagnosed. Holistic management not usually required. RLS can be associated with disorders such includes attention to associated sleep disorders and where neces- as end-stage renal failure, iron deficiency and even pregnancy but sary recourse to pharmacotherapy (such as the benzodiazepine most subjects have a primary disorder. Therapy of RLS consists of clonazepam ). correcting secondary causes if apparent. The mainstay of therapy in symptomatic patients is dopaminergic medication which is The parasomias can manifest with a wide range of motor, verbal divided into either dopaminergic precursors (such as levodopa + and other experiential sleep behavioural phenomena, and certain carbidopa) or dopamine agonists (such as ropinirole). Second-line types of sleep epilepsy (particularly partial complex seizure dis- therapy includes benzodiazepines, opioids and selected anticon- order) can perfectly mimic these events. Thus in occasional cases vulsants may be needed in severe or resistant cases. special attention needs to be given to suspecting, diagnosing and treating sleep epilepsy presenting as abnormal sleep movements. Parasomnias are broadly defined as abnormal behaviours in sleep; Anticonvulsant medications such as carbamazepine are effective. the primary parasomnias are disorders of arousal, partial arousal and sleep state transition in which sleep state and wakefulness are References not mutually exclusive and dissociated elements of REM (rapid Kryger, Roth and Dement’s Principles and Practice of SLEEP MEDICINE, 4th ed 2005 eye movement) sleep, non-REM sleep and wakefulness can be - see chapters 70, 72, 74, 75 for detailed descriptions of RLS/PLMS, sleep epilepsy admixed or oscillate rapidly to produce twilight states involving and the parasomnias behavioural dyscontrol. The primary parasomnias include con- - a web-based version of the 4th edition is available via the CIAP site (see under fusional arousal, sleepwalking and sleep terrors, all of which arise the Books section of MDConsult) Berry’s Sleep Medicine Pearls, 2nd ed 2003 from non-REM sleep. The clinical features of confusional arousal - a practical case-oriented approach to sleep medicine and sleepwalking are self-evident from their respective nomencla- Author: Clinical Associate Professor Brendon Yee, Woolcock Institute of Medical tures; sleep terrors are notable for a sudden arousal marked by a Research piercing scream, marked autonomic and motor arousal and incon- Author: Dr Peter Buchanan, Institute of Respiratory Medicine solable perception of terror. These non-REM parasomnias tend to

40 3.05 - Sleeping On The Job // Sleep Apnoea & Respiratory Failure 5. Pulmonary Circulation & Adaptation To Chronic Hypoxia Pulmonary circulation in the face of chronic hypoxia. The pulmonary circulation is a high flow, low resistance and low pres- The immediate response to the stress of hypoxia (and hypercapnia) sure circulation. The entire venous return to the right atrium enters is increased ventilation and cardiac output in an attempt to main- the lungs via the pulmonary artery and constitutes the pulmonary tain adequate tissue oxygen delivery via highly integrated responses flow. In addition, the bronchial arteries provide a small flow (1-2 % that involve both local and reflex mechanisms. The local effects in of cardiac output) of fully oxygenated blood which provides the meta- vascular beds increase perfusion to vital (and more hypoxia sensitive) bolic needs of the tissues of the lung. The pulmonary artery pressure organs such as the brain. Reflex responses are mediated via central and is about 25/10 mm Hg (systolic/diastolic), the capillary pressure aver- peripheral chemoreflexes, increasing ventilation while maintaining ages about 6-8 mm Hg and the pressure in the pulmonary veins is 1-3 or increasing blood pressure through increases in cardiac output and mm Hg. The entire cardiac output flows through the lungs with lower vasoconstriction in less vital and less oxygen-sensitive tissues (such pressure gradients, so the pulmonary resistance is only about 17-20% as skeletal muscle and gastro-intestinal tract). In addition, a range of of the systemic system. The pulmonary arterioles and capillaries are biochemical, neurochemical and cellular adaptations occur. shorter and have less smooth muscle and less muscular tone than their The effects of hypoxia and the adaptive mechanisms which respond systemic counterparts. depend upon the degree, duration and the speed at which the hypoxia Effects of gravity on the lungs has developed. Additionally, the clinical scenario is often clouded by The lungs are roughly 30 cm in height and therefore pressures in the concurrent hypercapnia and many other factors related to any under- arteries, capillaries and veins are all lower at the apex of the lungs by lying or coexistent disease process - eg the effects of vascular disease about 10 mm Hg and greater at the base of the lungs by about 10 mm on tissue perfusion. In summary the major adaptative responses to Hg (in the upright human). Because the pressures inside the vessels chronic hypoxia include: compared with alveolar pressure are much lower at the apex of the • An increase in ventilation mediated by peripheral chemoreceptors lungs, the capillaries and small vessels tend to collapse while at the • Compensation via metabolic (including renal) and / or respira- base of the lungs the capillaries are maximally dilated. Consequently tory mechanisms to maintain acid base balance in response to blood flow is higher at the base of the lungs and lower at the apex changes in the arterial partial pressure of CO (PaCO ) and (though this distribution of flow is eliminated when lying down). 2 2 blood pH These regional variations in blood flow may contribute to the distribu- • Increased cerebral and myocardial blood flow at the expense of tion of pathological lesions in the lungs e.g. tuberculous lesions are blood flow to less vital organs commoner at the apex. • Increased cardiac output via increased peripheral vascular resist- Because the capillary pressure is lower in the lungs, the lungs are ance, aiming to maintain blood flow to more vital tissues and less susceptible to oedema (plasma oncotic pressure is 25 mm Hg organs while the capillary pressure is only 6-8 mm Hg). This is fortunate • Increased pulmonary arterial pressures as a result of reflex pul- because oedema of the lungs, if it progresses to fluid in the alveoli monary vasoconstriction; pulmonary blood flow also increases and consequent impairment gas transport, it can result in potentially as a result of increased cardiac output. Continued or worsening lethal hypoxaemia. However the benefits of reduced capillary pressure hypoxaemia may lead to cor pulmonale and right heart failure. in the lungs are partly offset by a larger interstitial oncotic pressure • Increases in haemoglobin concentration, with secondary and a more negative interstitial hydrostatic pressure. The gradient of polycythaemia. Additionally, a shift occurs in the oxyhaemoglo- capillary pressure from apex to base of the lungs noted above means bin dissociation curve, which moves to the right as a result of that oedema production is greater at the base of the lungs. Likewise mechanisms including increases in red cell 2,3-DPG (diphospho- in the pleural space, gravity ensures that in the upright human fluid glycerate) concentration as well as any effects of respiratory or accumulation is first noticeable around the base of the lungs. metabolic acidosis which may accompany the underlying cause of The commonest causes of pulmonary oedema are left sided heart the hypoxaemia. failure which results in an increase in left atrial pressure and there- • Changes in the sympathetic nervous system, primarily leading to fore pulmonary venous pressure and pulmonary capillary pressure. increased levels of circulating catecholamines, with further effects Alternatively infection of the lungs tissue (pneumonia) cause increased on vascular haemodynamics. pulmonary capillary and alveolar wall permeability so that interstitial • At a cellular level effect include increased levels of anaerobic oedema and alveolar flooding occur. metabolism, in an attempt to maintain levels of ATP needed for Distribution of blood flow in the lungs cellular function. Blood flow in the systemic tissues is regulated by metabolic autoregu- • The release of a number of endocrine substances such as renin lation, which ensures increased flow to metabolically active tissues, and vasopressin, which are also vasoactive. and by sympathetic vasoconstriction, to maintain peripheral resistance Much of our understanding of these mechanisms has come from the and blood pressure. If a region of the lungs is underventilated (low study of people living at high altitude. Depending upon the severity PO 2 ), then efficient gas exchange requires a reduction of blood flow of the hypoxia, the duration of the insult and the presence of other to this poorly ventilated region. The smooth muscle of pulmonary factors (eg hypercapnia), these mechanisms begin to fail and may even vessels vasoconstricts in response to low PO 2 , in contrast to systemic contribute to the derangements in organ and cellular function seen in vessels. This hypoxic pulmonary vasoconstriction is a key reflex which chronic hypoxia as a result of the pathophysiology of disease processes contributes to matching of perfusion to ventilation. Sympathetic or environmental hypoxia. nerve supply to pulmonary vessel smooth muscle is minimal. References Guyton AC. Textbook of Medical Physiology. (9th ed.) Philadelphia: WB Saun- Hypoxia and hypoxaemia ders. c1996. Hypoxaemia may occur as a result of lung disease, cardiovascular Murray JF, Nadel JA. Textbook of Respiratory Medicine. (2nd ed.) Philadelphia: disease (as a result of inadequate cardiac output or significant shunting WB Saunders. c1994. of cardiac output), or because of a low environmental oxygen (most Pulmonary circulation, in Principles of Physiology, Berne and Levy Gas exchange commonly seen at altitude and referred to as hypobaric hypoxia). in Human Physiology: from cells to systems, L Sherwood Author: Dr Stephen Gregory McNamara, Medicine Whatever the mechanism, there are several common features to the adaptive steps the body takes to maintain cellular and organ function 41 3.05 - Sleeping On The Job // Sleep Apnoea & Respiratory Failure 6. Sedatives And Stimulants New for 2012 - Learning Objectives TBA - Please Check Online Author: Professor John Paul Seale, Pharmacology

42 3.06 - A Different Case Of Cough // Cystic Fibrosis Learning Objectives Description Disciplines Detailed anatomical organisation of the cranial nerve system; their peripheral distributions including Anatomy structures and the clinical signs and symptoms after lesion major branches and patterns of innervations. The functional fibres that each nerve may carry to target Detailed anatomical organisation and function of the greater ear complex; the internal, middle and external Anatomy ears. The bony and cartilagenous frameworks, neural innervations and some clinical applications. Detailed anatomical organisation and function of the eye; the different tunics of the globe, blood supply and neural innervations of the globe and associated structures. The different extraocular eye muscles, their Anatomy innervations, functions and clinical testing. The bones that make up the cave of the orbit. The major clinical features of the head and neck; the key anatomical structures and their clinical relevance. Anatomy, Surgery The psychosocial issues related to the chronically ill child; the concept that families experience illness as a Behavioural Science a coping mechanism unit; gender differences and quality of life among patients with cystic fibrosis; the significance of "hope" as Evidence based medicine - Causality II Epidemiology General Practice, Medicine The issues involved in living with cystic fibrosis from the time of diagnosis, managing during childhood, Genetic Medicine, adolescence and adulthood, and finally in the terminal stages family counselling and DNA mutation scanning Biomedical Science The value of DNA genetic diagnosis; describe the significance of the CFTR gene and appreciate the role of At the end of this teaching session, students should be able to understand contemporary models of stress exposure and stress response Medicine the effects of acute and chronic stressors on biopsychosocial health parameters the difference between appropriate and inappropriate coping behaviours Revisiting the learning objectives of the week (Meet the Expert). Medicine

Medicine, Genetic Medicine impactThe aetiology of chronic and diseasepathogenesis on child of andmulti-organ family damage in cystic fibrosis; the pathogenesis of the clinical features of cystic fibrosis; the multidisciplinary team approach to management of cystic fibrosis; the Molecular Medicine have broadened the potential for future therapeutic approaches The molecular (DNA) changes found in cystic fibrosis; how improvements in the diagnosis of cystic fibrosis Molecular Medicine The history and positional cloning of cystic fibrosis; the significance of the CFTR gene and the delta F508 The 2-stage hypothesis for function of exocrine glands and its implications for exocrine gland function in deletion; the phenotypic variants of cystic fibrosis Paediatrics variouscystic fibrosis. mechanisms The mechanisms by which mutations by which insweat the CFducts, gene pancreatic lead to abnormal ducts, colonic function. crypts The and physiological respiratory basis epithelium transport ions and how the function of these affected organs is affected by cystic fibrosis. The Paediatrics of pharmacological therapies for cystic fibrosis Paediatrics, The survival rates of patients with cystic fibrosis. The main features of the cystic fibrosis genotype Rehabilitation There is clinical variation in cystic fibrosis and that deterioration in individual patients is quite uncertain. Medicine The bacterialprinciples causes of management of lower respiratory of cystic fibrosis tract infections acquired by immunocompetent hosts in the Pharmacology, community; the approach to prescribing antibiotics in patients with chronic lung disease and bronchial Infectious Diseases infection The functions, mechanisms and different types of cough; the range of defence mechanisms in the lungs; the Physiology triggers for cough and the distribution of cough receptors in the respiratory tract The different types of exocrine glands in the body (eg lacrimal glands, sweat glands salivary glands and Physiology transport pancreas); the functions of the different types of exocrine glands; cystic fibrosis as a defect in epithelial Students should learn: · to take a structured history in a patient with a respiratory complaint - in particular an infective illness · To differentiate between infective and non-infective acute respiratory presentations, and between Respiratory acute/sudden and subacute/chronic presentations of respiratory infection (e.g. TB, some bacterial and Medicine fungal infections) · to summarise the main features and present the case concisely and clearly The physiological effects of excess secretions and the impact on these on various mucous clearance Respiratory techniques. The range of techniques for mucous clearance. The physical effects of some of these Medicine techniques. Respiratory Medicine, Infectious mechanisms behind the development of bronchiectasis Diseases The meaning and significance of bronchiectasis; the clinical course of bronchiectasis; the cellular 43 3.06 - A Different Case Of Cough // Cystic Fibrosis 1. Mechanisms Of Cough Cough is an airway defence mechanism, the primary function of mechanical, or inflammatory stimuli, with the sensitivity to these which is to prevent the inhalation of foreign particles and to assist stimuli varying according to the site of stimulation. Inflammation the removal of foreign particles and secretions from the airways. is a potent tussive stimulus for cough (tussive stimulus) in the Coughing may be initiated either voluntarily or by multiple larynx, trachea, and larger airways. stimuli that can elicit the cough reflex. It is a very common symp- Cough receptors are most numerous at the carina and points tom seen in many cardiorespiratory disorders. of bifurcation of the bronchial tree. Rapidly adapting receptors The lung has numerous defence mechanisms to deal with the (RAR’s, also known as irritant receptors) are probably the main potential of inhaling foreign particles, including aeroallergens and mediators of cough. They respond to a wide variety of mechanical bacteria. In addition to the nose filtering inhaled air, the passage and chemical stimuli, with passage of the signal via myelinated of foreign particles to the lower respiratory tract is prevented by fibres along the vagus to the “cough centre” in the medulla oblon- laryngeal receptors which induce reflex glottic closure and the gata. Unmyelinated C fibre receptors respond to the same stimuli ‘expiration reflex’. The mucociliary escalator (comprised of cili- as RAR’s, but cause direct inhibition of cough, possibly through a ated cells, airway surface liquid, and mucous producing cells and gating mechanism. Bronchial C fibres are also capable of neuro- glands) and the cough reflex provide a secondary line of defence genic inflammation, in which stimulation of C fibres causes the in removing mucous secretions and foreign particulate matter, in- local release of inflammatory mediators including bradykinin and cluding bacteria-containing alveolar macrophages, from the lower tachykinins from nearby nerve terminal endings. These media- airway. Stimulation of lower respiratory tract cough receptors pro- tors may then stimulate RAR’s, such that C fibre stimulation may duces a typical cough of three phases; an initial inspiratory phase, indirectly induce cough. Thus, C fibres modulate cough. Pulmo- followed by glottic closure and simultaneous compression of the nary C fibres, in the alveolar wall, and slowly adapting receptors thorax by diaphragmatic relaxation and intercostal and abdominal are also involved in regulation of cough, accounting for the great muscle contraction, and finally the expulsive phase of cough when diversity of cough response seen to various stimuli. Central regula- airflow rates in the trachea approach the speed of sound. Associ- tion of cough remains poorly understood. ated high frequency oscillation of the airways and the develop- Cough is usually described as dry (unproductive) or productive, ment of shearing forces along the mucosal surface result in the and as acute (present for less than three weeks) or chronic (present central movement and expulsion of mucous and foreign particles for 3 weeks or longer). Chronic cough is usually due to disorders from the airways. Reflex bronchoconstriction occurs with cough such as chronic bronchitis, asthma, post-nasal drip, gastro-oe- and improves cough clearance, but coughing may also precipitate sophageal reflux, or bronchiectasis. an attack of wheezing in subject with asthma. Optional references: The origin of cough is unique to vagally innervated structures. Widdicombe JG. Neurophysiology of the cough reflex. Eur Respir J 1995; 8(7): The character of a cough is determined by both the site and na- 1193-1202. ture of the stimulus. An immediate expiratory effort only is seen The committee for The Japanese Respiratory Society guidelines for management of cough. Mechanism of cough , Respirology 2006, 11 (s4), S137–S139. when mechanical stimulation of the larynx occurs; initial inhala- The committee for The Japanese Respiratory Society guidelines for management of tion would result in movement of a foreign body into the lower cough. Prolonged and chronic cough, Respirology 2006, 11 (s4), S160–S174. respiratory tract. Conversely, in the lower airway, an initial slow Irwin RS, Widdicombe J. Cough. In: Murray JF, Nadel JA, eds. Textbook of Res- inspiration drawing air distal to the stimulus produces a far more piratory Medicine. (3rd ed.) Philadelphia: WB Saunders Co, 2000. effective clearance of that material with the subsequent expulsive Author: Professor John Paul Seale, Pharmacology cough. Cough does not result from stimulation to airways distal to the segmental bronchi. Cough may be stimulated by chemical,

44 3.06 - A Different Case Of Cough // Cystic Fibrosis 2. Molecular Genetics Of Cystic Fibrosis mechanical, or inflammatory stimuli, with the sensitivity to these History Delta F508 stimuli varying according to the site of stimulation. Inflammation Cystic fibrosis (CF) is one of the most common autosomal A further observation confirming CFTR to be the correct gene for is a potent tussive stimulus for cough (tussive stimulus) in the recessive disorders in caucasians with a carrier rate in northern CF was the finding of a 3 base pair deletion known as delta F508 larynx, trachea, and larger airways. Europeans of approximately 1 in 22. Although the first compre- which occurred only in those with CF. In 2001, there were over hensive clinical description was given in 1938, the underlying many hundreds of mutations which interfere with the function Cough receptors are most numerous at the carina and points aetiology remained unknown until the CF gene known as CFTR of CFTR although delta F508 is the commonest occurring in ap- of bifurcation of the bronchial tree. Rapidly adapting receptors (cystic fibrosis transmembrane conductance regulator) was cloned proximately 75% of northern European CF chromosomes. Delta (RAR’s, also known as irritant receptors) are probably the main in 1989. Following this, it became possible to develop a DNA test F508 and a number of other CF mutations are easily detected by mediators of cough. They respond to a wide variety of mechanical to detect CF carriers and affected individuals. The gene structure studying DNA. and chemical stimuli, with passage of the signal via myelinated also enabled the pathogenesis of CF to be clarified. fibres along the vagus to the “cough centre” in the medulla oblon- Phenotypic variants gata. Unmyelinated C fibre receptors respond to the same stimuli Positional cloning Molecular analysis has enabled a number of other conditions to as RAR’s, but cause direct inhibition of cough, possibly through a Traditionally the understanding of a genetic disorder has required be identified as variants of CF through the sharing of mutations gating mechanism. Bronchial C fibres are also capable of neuro- the isolation and then characterisation of an abnormal protein. In in CFTR. These include: (i) congenital bilateral absence of the genic inflammation, in which stimulation of C fibres causes the the case of CF this was not possible since it was not known what vas deferens, a cause of infertility in males and (ii) some forms local release of inflammatory mediators including bradykinin and protein was defective. This impasse was overcome by positional of bronchiectasis or pancreatitis. Thus, clinical heterogeneity tachykinins from nearby nerve terminal endings. These media- cloning, a molecular genetics technique which enables a gene to observed in the form of multiple CF-related phenotypes can be tors may then stimulate RAR’s, such that C fibre stimulation may be isolated. From the gene it becomes possible to prepare a pro- explained by the different types of mutations which are present. indirectly induce cough. Thus, C fibres modulate cough. Pulmo- tein or determine what protein is involved. Identifying mutations nary C fibres, in the alveolar wall, and slowly adapting receptors which are found in the gene enables a DNA test to be developed. are also involved in regulation of cough, accounting for the great The CF story illustrates the usefulness of positional cloning. DNA Optional references: diversity of cough response seen to various stimuli. Central regula- markers first identified that CF was located on chromosome 7. Chillon M et al. Mutations in the cystic fibrosis gene in patients with congenital tion of cough remains poorly understood. The likely region was then cloned and characterised until a candi- absence of the vas deferens . New Engl J Med 1995; 332(22): 1475-1480. date gene was found. Collins FS. Positional cloning moves from perditional to traditional. Nature Genet Cough is usually described as dry (unproductive) or productive, 1995; 9(4): 347-350. and as acute (present for less than three weeks) or chronic (present CFTR gene McKusick V. OMIM - On Line Mendelian Inheritance in Man - a catalogue of for 3 weeks or longer). Chronic cough is usually due to disorders A gene in the appropriate chromosome 7 location was considered human genetic disorders accessible through the Internet such as chronic bronchitis, asthma, post-nasal drip, gastro-oe- a likely candidate for CF because it was expressed in the correct Sferra TJ, Collins FS. The molecular biology of cystic fibrosis . Annu Rev Med February 1993; 44: 133-144. sophageal reflux, or bronchiectasis. tissues (eg lung, pancreas, intestine, liver and sweat glands). The Trent RJ Molecular Medicine - an introductory text. (2nd ed.) Churchill Living- Optional references: protein coded by the gene had features to suggest that it was an stone, 1997 Widdicombe JG. Neurophysiology of the cough reflex. Eur Respir J 1995; 8(7): ATP-dependent protein transporter. Today, the CFTR gene has 1193-1202. been very well characterised and shown to be involved in the Author: Professor Ron Trent, Medicine The committee for The Japanese Respiratory Society guidelines for management of movement of chloride ions across membranes, failure of which cough. Mechanism of cough , Respirology 2006, 11 (s4), S137–S139. The committee for The Japanese Respiratory Society guidelines for management of becomes the critical component in the pathogenesis of CF. cough. Prolonged and chronic cough, Respirology 2006, 11 (s4), S160–S174. Irwin RS, Widdicombe J. Cough. In: Murray JF, Nadel JA, eds. Textbook of Res- piratory Medicine. (3rd ed.) Philadelphia: WB Saunders Co, 2000.

Author: Professor John Paul Seale, Pharmacology

45 3.06 - A Different Case Of Cough // Cystic Fibrosis 3. Bronchiectasis A different cause of cough Generalised bronchiectasis generally reflects a systemic disorder, rather than a localised foreign body etc. Bronchiectasis is the lung condition defined by the irreversible dilatation of one or more bronchi, generally caused by the de- Causes of generalised bronchiectasis struction of the elastic and muscular components of the bronchial Cystic fibrosis (CF) is the most common cause of clinically signifi- walls. The condition is the end result of a variety of underlying cant bronchiectasis in Australia. CF is an autosomal recessive dis- disease processes, such as childhood lower respiratory infection order in which there is abnormal regulation of the airway surface (whooping cough or measles), previous tuberculosis and congeni- fluid, leading to retained secretions and chronic suppurative lung tal disorders such a hypogammaglobulinaemia. It is uncommon disease. (see other sections on CF) now in Australia because of the increased use of antibiotics and vaccinations in childhood, but may still be seen in communities Structural abnormalities of the cilia of the respiratory epithelial with less health care services during childhood, such as migrants, cells gives the disease Primary Ciliary Dyskinesia (PCD), which aboriginals. Bronchiectasis is recognised clinically by the presence was previously called immotile cilia syndrome. This includes of suppurative bronchopulmonary disease, with a history of a those genetic abnormalities which do not have the appropriate frequent cough productive of copious purulent secretions. dynein arms in the cilia together with those syndromes where the cilia are not correctly aligned, so they beat in different directions, Diagnosis relies on the demonstration of the typical radiologi- termed ciliary disorientation. Most widely known is “Kartagener’s cal features (thickened airway walls and dilated airways) seen syndrome”, a triad of situs inversus bronchiectasis and sinusitis. in chest radiographs or computerised tomography (CT) scans. Whilst a similar number of PCD patients have normal situs, these Gross changes of bronchiectasis are easily seen on plain chest patients will still have the bronchiectasis and sinusitis. radiographs, but subtle evidence of the condition is easily missed. Bronchiectasis may be localised or diffuse. The severity of diffuse Primary immunodeficiency states, particularly those affecting -hu bronchiectasis may vary between adjacent lobes and even seg- moral immunity, also cause chronic sinopulmonary infection. X- ments of the lung. The typical changes are, from mild to severe linked agammaglobulinaemia is the prototype of these syndromes, respectively, cylindrical bronchiectasis, varicose bronchiectasis, where the cilia and the airway surface liquid are normal, but the and saccular (or cystic) bronchiectasis. lack of immunoglobins on the airway surface allow growth of bacteria which then can progressively damage the airways. The clinical course of bronchiectasis is characterised by chronic low-grade infection punctuated by more severe exacerbations with A variety of other disorders including recurrent gastric aspiration, deterioration of lung function. Ongoing suppurative infections Yellow nail syndrome, and congenital anatomic abnormalities are lead to progressive lung destruction, with the ultimate develop- also associated with the development of bronchiectasis. Finally, ment of chronic respiratory failure. Complications of bronchiec- other causes included Rheumatoid arthritis, severe COPD and tasis includes haemoptysis and massive pulmonary haemorrhage. asthma / allergic bronchopulmonary aspergillosis. Cor pulmonale may be seen in late stage disease. Digital clubbing is a common extrathoracic manifestation of suppurative lung disease, but the absence of clubbing does not exclude bronchi- Therapy ectasis. Other features vary with the underlying disease process. Specific treatment is indicated where possible (eg removal of bron- Auscultation of the affected lobes usually reveals the presence of chial obstruction, replacement of gammaglobulin deficiencies). coarse inspiratory and/or expiratory crackles. A variety of changes General treatment in the form of control of infection (with anti- in lung function are seen over the course of the disease. biotics), and the removal or purulent secretions (by physiotherapy Any condition causing chronic bronchial infection may result and with drug therapy) and the use of exercise to maintain airway in the development of bronchiectasis. The actions of proteolytic clearance remain the cornerstones of management. enzymes (eg collagenase and elastase) and oxygen radicals are central to the local tissue destruction. Bronchopulmonary infections, particularly in childhood (e.g. pertussis, measles, adenovirus) or Optional references: Available in Medical Library: see Library Catalogue occasionally later life (necrotising bacterial pneumonias) may lead Good basic chapters on bronchiectasis are to be found in the following: to localised bronchiectasis. 1. Harrisons Principles of Internal Medicine, (15th ed.) Ch.256 Weinberger SE Bronchiectasis Classification of bronchiectasis. 2. Luce JM Bronchiectasis , Ch.41; pp1325-1341 in Murray, Nadel (eds) Text- book of Respiratory Medicine. (3rd ed.) Philadelphia: WB Saunders, 2000 In the past, the different bronchial abnormalities were specifically The diagnosis of bronchiectasis via imaging is reviewed in: listed - varicose, saccular or cylindrical. However, more recently it 1. Kumar NA, Nguyen B, Maki D Bronchiectasis: current clinical and imaging has been realised that these distinctions are not helpful clinically, concepts Seminars in Roentgenology, 2001 36(1): 41-50. pdf so in general bronchiectasis is now only divided into local-affect- The immunodeficiency syndromes have been reviewed in: 1. Rosen FS, Cooper MD, Wedgwood RJP. Medical progress: the primary Im- ing one specific bronchus or generalised- affecting many differnt munodeficiencies . N Engl J Med; 1995; 333(7): 431-440. bronchi (in different lobes). Author: Clinical Associate Professor Peter Middleton, Respiratory Medicine Localised bronchiectasis may follow bronchial obstruction due to Author: Professor Peter Bye, Institute of Respiratory Medicine foreign bodies, mucoid impaction, hilar lymphadenopathy and neoplasm.

46 3.06 - A Different Case Of Cough // Cystic Fibrosis 4. Prognosis In Cystic Fibrosis The prognosis of patients with cystic fibrosis (CF) has improved cal defect in production of the CFTR protein. dramatically over the last 75 years. The US Cystic Fibrosis Foundation Class I mutations – STOP or non-sense mutations (eg G542X) has documented median survival of < 2 years in 1950 to 16 years in These mutations stop the translation of the mRNA into protein, there- 1970, 29 years in 1990 and 39 years in 2010. Recent data from the CF by resulting in a shortened protein which is recognised as abnormal by registry in Australia 1 shows similar improvements in Australia. the cell’s regulatory processes and is broken down. Treatment for these This improved survival most likely reflects a number of different mutations requires either the “read-through’ of the stop mutation, such factors, including improved anti-Pseudomonal antibiotics, improved as the new agent PTC-124-Ataluren, in general called “cftr correctors”. aerosol therapies, and provision of care through specialized CF clinics Class II mutations – altered processing mutations (eg DF ) with attention to detail concerning all aspects of treatment of this 508 multi-system disorder. These mutations result in a protein which is not processed normally. The protein is full length, but does not have the normal conforma- In addition, in Australia, the provision of newborn screening has tion, so is generally being recognised by the cell as being abnormal and lead to earlier diagnosis of the majority of cases of CF. In New South then broken down. Treatment for these mutations requires blocking of Wales newborn screening commenced in 1981, so the vast majority of the breakdown pathway, using different “cftr correctors”, such as the current cases were found through the newborn screening process. Im- agent Lumifactor (VX 809). proved screening has also increased diagnosis of those patients with milder forms of disease. However, some children, adolescents adults are Class III mutations –altered regulation of the channel mutations still diagnosed with CF when recurrent chest infections, pancreatitis or (eg G551D) male infertility are recognised. These mutations result in a protein which is processed normally, and A number of disease markers have been associated with better or worse sent to the cell membrane. But here the protein reveals its inabil- prognosis. Whilst CF genotype (the exact genetic mutation in CFTR) ity to open channels with normal stimuli, so the CFTR does not is predictive of exocrine pancreatic status, there is considerable variabil- work. Treatment for these mutations requires potentiating the channel ity in the severity of lung disease within a particular genotype. Howev- to respond better, such as the agent Ivacaftor (VX 770), one of a group er, between groups of patients with classical severe mutations and those of agents called “cftr potentiators”. with mild mutations, there is an overall difference in lung function and Class IV mutations –altered conductance of the channel (eg nutritional status. R117H) Prognosis These mutations result in a protein which is processed normally, sent Overall, the prognosis of CF patients depends on lung function, as to the cell membrane, and responds to normal stimuli. However the 90% of mortality is due to progressive respiratory failure. Non-genetic channel pore itself is small, so ion movement is reduced. (environmental) factors known to be involved in survival include: Class V mutations – normal channels, reduced production (eg • Sputum pathogen – early colonisation with P. Aeruginosa, B. ce- A455E) pacia These mutations result in a normal protein sent to the cell membrane, • Nutritional status responds to normal stimuli, with relatively normal conductance. How- ever the production of protein molecules is reduced, so less channels • Presence of diabetes are present for work. • Care within a specialized CF clinic Class VI mutations –decreased stability of protein or abnormal • Overall compliance, family support, regulation of other channels • Smoking – both active and passive These mutations result in a normal protein sent to the cell membrane, • Pancreatic status (the 10-15% of patients who are pancreatic suf- responds to normal stimuli, with relatively normal conductance. How- ficient tend to have better lung function overall). ever the protein molecules exhibit reduced lifespan, with increased Generally, men with CF survive slightly better than women, which degradation, so less channels are present for work. may relate to regular exercise and physiotherapy interventions or Class IV, V and VI mutations are currently undergoing testing with perhaps with the presence of hormonal factors. The development of various agents, including the cftr potentiator Ivacaftor (VX 770). pulmonary complications such as pneumothorax, massive haemoptysis Conclusion requiring intervention and cor pulmonale are all adverse predictors of In summary, the prognosis of patients with CF is a success story of outcome. modern medicine. However, the survival of the vast majority of CF pa- Many of the current therapies for cystic fibrosis have been shown to tients into adulthood is now leading to difficulties in service provision improve lung function, which is generally one of the strongest predic- on those adult hospitals with ever increasing numbers of CF patients. tors of mortality, though the link between therapies and ultimate References survival has not yet been proven. Bell SC, Bye PT, Cooper PJ, et al. Cystic fibrosis in Australia, 2009: results from a data registry. Medical Journal of Australia 2011;195:396-400. A landmark paper in the New England Journal suggested that an FEV1 of < 30%, a PaO of < 55 or a PaCO of > 50 had a two year survival Kerem E, Reisman J, Corey M, Canny GJ, Levison H. Prediction of mortality in 2 2 patients with cystic fibrosis. New England Journal of Medicine 1992;326:1187-91. of only 50% 2. However, more recently studies have shown that many Kerem B-S, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis patients with an FEV1 of ~ 30% can survive much longer than two gene: genetic analysis. Science 1989;245:1073-80. years if managed appropriately. Riordan JR, Rommens JM, Kerem B-S, et al. Identification of the cystic CF Genotype fibrosis gene: cloning and characterization of complementary DNA. Science 1989;245:1066-73. The gene causing CF was isolated in 1989 by a consortium of 3 dif- Rommens JM, Iannuzzi MC, Kerem B-S, et al. Identification of the cystic fibrosis ferent laboratories using a variety of techniques 3-5, and was termed gene: chromosome walking and jumping. Science 1989;245:1059-65. the Cystic Fibrosis Transmembrane Conductance Regulator or Further reading CFTR. Since then, more than 1800 mutations and polymorphisms Newer agents for CF - See Cystic Fibrosis Foundation website www.cff.org have been found in CFTR. The different mutations are broadly Author: Clinical Associate Professor Peter Middleton, Respiratory Medicine grouped into 6 main types of mutations, dependent on the biochemi- 47 3.06 - A Different Case Of Cough // Cystic Fibrosis 5. Management Of Cystic Fibrosis Cystic fibrosis is a chronic, progressive and at present incurable nocturnal oxygen therapy is frequently used. It improves school genetic disease usually diagnosed within a few weeks of life by and work attendance but has not so far been shown to influence neonatal screening. It has a wide variation in clinical severity mortality favourably. Non-invasive nasal assisted ventilation is and the rate of deterioration in the individual patients is quite increasingly utilised when there is worsening respiratory failure. uncertain. Despite major advances in genetic and biochemical Both of these treatments need further evaluation in large prospec- aspects of the disease the underlying pathologic process leading tive randomised studies. to lung destruction is still not fully understood and control of the Recent advances in our understanding of the basic defect in cystic disease process is based on the empiric management of symp- fibrosis have led to the development of newer respiratory therapies toms rather than treatment of the underlying cause. It is only including agents that reduce the viscosity of sputum as well as the relatively recently that there has been a more scientific evaluation potential availability of gene therapy in the future. Lung trans- (by controlled trials) of the various therapeutic approaches used. plantation remains the only potentially curative treatment option As a consequence, although in general there is a broad agreement at present. in approach, marked variations remain between different medical centres in the use of therapies available. Nutritional management consists of the regular review of growth and weight by skilled dietitian along with the provision of pan- Management of the disease combines medical treatment directed creatic enzyme supplements and high energy diets. For those with at control and prevention of deterioration with psycho-social sup- liver or GI tract involvement review by a gastroenterologist is port and education of the child and the family suffering the guilt, necessary. denial and stress often associated with a chronic disease. This approach is best provided by a hospital based multi-disciplinary Within these guidelines, treatment often has to be individualised team of medical specialists and allied health staff with community on the basis of likely compliance and coping abilities of the family nursing and social work support. Patients are reviewed regularly as well as the severity of the disease. The impact of treatment on by the team in clinic with clinical evaluation of nutritional and the quality of life of patients and families must be kept in mind. pulmonary status as well as assessment of family dynamics and Adolescence brings special problems particularly in separation of coping skills. the patient from their parents at the time of deteriorating disease. The CF team must foster the development of independence and Respiratory treatment begins at diagnosis, often when the infant self-care whilst attempting to maintain compliance and prevent is asymptomatic and continues throughout life. The basic prin- deterioration at this difficult time, prior to transition to adult ciples for the management of chest disease are (1) the aggressive care. treatment of bronchopulmonary infection and antibiotics and (2) the daily removal of viscid secretions by physiotherapy. Patients Optional references: Phelan, Peter D., Olinsky, Anthony & Roberts, Colin F. Respiratory illness in chil- with CF are characteristically colonised in their respiratory tract dren. 4th ed. Oxford ; Boston : Blackwell Scientific Publications, 1994. Chapter by certain micro organisms mainly Staph aureus (early) and 10: Cystic Fibrosis pp 207-251 in 90% at some stage with Pseudomonas aeruginosa which is Chernick V (ed.) Kendig’s disorders of the respiratory tract in children. (7th ed.) usually associated with a decline in pulmonary status. Antibiot- Philadelphia : Saunders, c2006. Section VIII: 848-901 Davis et al. Cystic Fibrosis (State of the Art). Am.J.Respiratory and Critical Care ics are chosen on the basis of sputum sensitivities and given for Medicine 1996; 154(5): 1229-1256. prolonged courses until improvement. As the lungs deteriorate, Taussig LM. Cystic Fibrosis. New York: Thieme-Stratton Inc, 1984. exacerbations become more frequent and hospitalisations for Hodson EM, Geddes DM, Bush, A. Cystic Fibrosis. Chapman & Hall Medical intravenous anti-Pseudomonas therapy (‘tune-ups’) will be neces- 2007 For Interest sary. Bronchodilators are often necessary in addition to antibiot- Detailed reviews of pathogenesis and treatment, including recent new therapies. ics for the increased airway activity that often develops with CF Aitken M, ed. Cystic Fibrosis Current opinion in pulmonary medicine, lung disease. Physiotherapy is initially provided by the mother 1995 1(6):425-471. but the growing child is encouraged to develop independent Author: Peter Cooper self-physiotherapy techniques. Regular exercise and good general Author: Professor Peter Bye, Institute of Respiratory Medicine fitness are encouraged at all ages. As respiratory failure supervenes

48 3.06 - A Different Case Of Cough // Cystic Fibrosis 6. DNA Mutation Analysis nocturnal oxygen therapy is frequently used. It improves school CFTR gene against DNA genetic testing are many including the appropriate- and work attendance but has not so far been shown to influence The CFTR (cystic fibrosis transmembrance conductance regula- ness of the clinical indication, the correct utilisation of resources, mortality favourably. Non-invasive nasal assisted ventilation is tor) gene is the one associated with cystic fibrosis (CF). It is a the potential invasion of privacy or discrimination which may increasingly utilised when there is worsening respiratory failure. large gene (27 exons over ~250 kb of DNA) and is a good model result from showing that an individual carries a DNA mutation. Both of these treatments need further evaluation in large prospec- to illustrate the uses of DNA mutation analysis in clinical prac- DNA mutation scanning tive randomised studies. tice. The finding of multiple mutations (ie. heterogeneity) in CF is a Recent advances in our understanding of the basic defect in cystic DNA genetic diagnosis common feature of most genetic disorders. Because present tech- fibrosis have led to the development of newer respiratory therapies The value of DNA genetic diagnosis includes: (1) a genetic diag- nology does not enable all mutations to be detected, there is the including agents that reduce the viscosity of sputum as well as the nosis can be made at any age or stage of development including possibility to use techniques, such as DNA scanning (an example potential availability of gene therapy in the future. Lung trans- before signs and symptoms of that disorder appear. This would of which would be the technique known as SSCP - an abbrevia- plantation remains the only potentially curative treatment option include prenatal testing, carrier testing and predictive/presymp- tion for single stranded conformation polymorphism), which at present. tomatic testing. (2) Any tissue provides a satisfactory source allow regions of the gene likely to carry a mutation to be identi- of DNA ie. unlike protein-based assays, diseased tissue is not fied. Another lesson from DNA mutation analysis in CF is that Nutritional management consists of the regular review of growth required. There is an increasing trend towards the use of DNA for not all mutations can be found, and it is a very time consuming and weight by skilled dietitian along with the provision of pan- genetic analysis. In terms of CF, DNA genetic diagnosis is used to process to attempt a more comprehensive DNA genetic diagnosis. creatic enzyme supplements and high energy diets. For those with detect carriers of this disorder as well as in prenatal detection of Thus, it is important to take a good family history to determine, liver or GI tract involvement review by a gastroenterologist is at-risk pregnancies. early on, who is at risk, and so allow maximal time for mutation necessary. analysis. DNA mutation analysis CF Within these guidelines, treatment often has to be individualised There are many hundreds of mutations which are associated with Counselling on the basis of likely compliance and coping abilities of the family the CFTR gene. Fortunately, the most common is deltaF508. The The CF model also illustrates the increasing importance placed as well as the severity of the disease. The impact of treatment on abbreviations mean that the phenylalanine (F) at position 508 on counselling when DNA genetic diagnosis is undertaken. As the quality of life of patients and families must be kept in mind. in the protein is deleted (delta). This mutation is found in about well as knowing when to test and what the DNA result means eg. Adolescence brings special problems particularly in separation of 70% of CF chromosomes. Probably another 4-6 other mutations not finding the deltaF508 mutation does not necessarily exclude the patient from their parents at the time of deteriorating disease. are commonly found in the Australian population allowing the CF, the medical practitioner must then take the time to explain The CF team must foster the development of independence and overall detection rate by DNA testing to be about 80%. These to the patient the results. This is not necessarily a straightforward self-care whilst attempting to maintain compliance and prevent figures will vary depending on the population being tested (since process because: (1) the technology is complex, and (2) the result deterioration at this difficult time, prior to transition to adult there are some ethnic groups which are less likely to have the delta obtained may have wider implications eg. other family members care. F508 mutation and/or more likely to have other defects). The may be affected. Optional references: finding of ethnic-specific mutations is a feature of many genetic Phelan, Peter D., Olinsky, Anthony & Roberts, Colin F. Respiratory illness in chil- Optional Resources: dren. 4th ed. Oxford ; Boston : Blackwell Scientific Publications, 1994. Chapter disorders, especially thalassaemia. Because being a carrier for CF http://www.genet.sickkids.on.ca/cftr/ 10: Cystic Fibrosis pp 207-251 causes no clinical problems, it is generally not considered appro- This is the Canadian database for CF mutations. It also has useful links to other Chernick V (ed.) Kendig’s disorders of the respiratory tract in children. (7th ed.) priate to test for carrier status unless there is an indication. One CF and genetic resources. R J Trent, Molecular Medicine - an introductory test. 2nd ed 1997. Churchill Philadelphia : Saunders, c2006. Section VIII: 848-901 such reason might be a reproductive decision taken in the context Davis et al. Cystic Fibrosis (State of the Art). Am.J.Respiratory and Critical Care Livingstone. Medicine 1996; 154(5): 1229-1256. of a family history of CF. The consideration of when to use DNA Discusses the topics of DNA mutation analysis and also cystic fibrosis. Taussig LM. Cystic Fibrosis. New York: Thieme-Stratton Inc, 1984. testing for genetic disorders is thus an important issue that will Hodson EM, Geddes DM, Bush, A. Cystic Fibrosis. Chapman & Hall Medical frequently face the medical practitioner. The reasons for and 2007 For Interest Detailed reviews of pathogenesis and treatment, including recent new therapies. Aitken M, ed. Cystic Fibrosis Current opinion in pulmonary medicine, 1995 1(6):425-471.

Author: Peter Cooper Author: Professor Peter Bye, Institute of Respiratory Medicine

49 3.06 - A Different Case Of Cough // Cystic Fibrosis 7. Antibiotics In Respiratory Disease Most community-acquired lower respiratory tract infections are a certain amount of overprescribing is inevitable especially when viral rather than bacterial and, with the possible exception of there is high or persistent fever or extending radiological consoli- influenza, they do not require treatment with antimicrobials. dation. Empirical prescribing always includes an antibiotic with activity against the pneumococcus (Streptococcus pneumoniae) The common bacterial infections include the following: but the high mortality from less common conditions such as le- Clinical entity Pathogens Treatment gionnaires’ disease and staphylococcal pneumonia encourages the Bronchitis 2 , includ- Streptococcus pneumoniae Amoxycillin use of antibiotic combinations which cover all the possibilities. ing exacerbations Haemophilus influenzae OR of chronic obstructive Moraxella catarrhalis Doxycline pulmonary disease

(COPD) 3 Australia’s national guidelines for antibiotic use are revised every Bronchiolitis Bordetella pertussis Azithromycin few years 1 . They are based on current bacteriological and clinical OR trial data and they emphasise the use of relatively few less expen- Clarithromycin sive agents which have had extensive clinical trials. It is worth OR noting that they differ somewhat from UK/European, and quite Erythromycin 8 significantly from American, guidelines . Bronchiectasis 4 , in- As for bronchitis, plus: Therapy is often There is almost no clinical role for antibiotics in acute bacterial cluding cystic fibrosis guided by findings Staphylococcus aureus on sputum examina- bronchitis provided the patient does not have chronic lung disease Pseudomonas aeruginosa tion – but too often medical practitioners continue to prescribe them. In an effort to reduce this wasteful use of resources, Australia’s Pneumonia 5,6,8 Streptococcus pneumoniae β-lactam (eg, ampi- National Prescribing Service offers helpful advice on management Mycoplasma pneumoniae* cillin) of acute respiratory tract infections to both patients and doctors. 7 Chlamydia pneumoniae* PLUS Macrolide (eg, rox- References ithromycin) 1 Respiratory tract infections: pneumonia . In Therapeutic Guidelines: Antibiotic, Legionella pneumophila version 13, 2006, published by Therapeutic Guidelines Ltd., Melbourne. Pages Chlamydia psittaci 199 to 230 Staphylococcus aureus These are less com- 2 Wenzel RP, Fowler AA. Acute bronchitis . New Engl J Med 2006;355:2125 Mycobacterium tuberculosis mon causes of pneu- 3 Stoller JK. Acute exacerbations of chronic obstructive pulmonary disease . New Anaerobes monia. See Antibi- Engl J Med 2002;346:988 Burkholderia pseudomallei otic Guidelines1 for 4 Barker AF. Bronchiectasis . New engl J Med 2002;346:1383 specific treatment. 5 Halm EA, Teirstein AS. Management of community-acquired pneumonia . New Engl J Med. 2002;347:2039 * these agents of ‘atypical’ pneumonia may cause bronchitis, as 6 McIntosh K. Community-acquired pneumonia in children . New Engl J Med well. 2002;346:429 7 National Prescribing Service website: www.nps.org.au Because establishing a microbiological diagnosis is slow, expensive 8 Charles PGP, Johnson PDR, Grayson ML. Conundrums in community-ac- and even misleading, most antibiotic prescribing for lower respira- quired pneumonia . Med J Aust. 2006;185:131 tory tract infections is empirical, ie, it is not guided by laboratory investigation. Good clinical skills (history taking, physical exami- Author: Sharon Paull nation, clinical judgement) are critical to good management but

50 3.06 - A Different Case Of Cough // Cystic Fibrosis 8. Recurrent Illness And Psychosocial Development a certain amount of overprescribing is inevitable especially when Introduction ening. Furthermore, the actual illness itself is difficult for the child to there is high or persistent fever or extending radiological consoli- The survival of patients with cystic fibrosis has changed over the last understand and can cause intense anxiety. The infant is egocentric, dation. Empirical prescribing always includes an antibiotic with 60 years. The median survival expectancy in some countries in now and aware of only his or her own needs. Therefore, separations from activity against the pneumococcus (Streptococcus pneumoniae) more than 30 years, and an increasing proportion of CF patients are the parent figure, as happens with hospitalisation, prior to the age of but the high mortality from less common conditions such as le- surviving to adulthood. Their longer survival raises psychological two can result in extreme depression and anxiety. issues, including their development through their lifespan with the gionnaires’ disease and staphylococcal pneumonia encourages the The diagnosis of depression is very difficult to make in infants and significant impact of CF. Their childhood development will of course use of antibiotic combinations which cover all the possibilities. pre-schoolers because their lack of self awareness and verbal abilities. affect their adult development. In a large study of depressed pre-schoolers, it was concluded that The Chronically or Recurrently ill Child - Intra Personal Issues younger children are more likely to present their depression through Australia’s national guidelines for antibiotic use are revised every somatic complaints such as crying, enuresis, encopresis, sleep distur- Regressive behaviour few years 1 . They are based on current bacteriological and clinical bance, and anorexia. Regression is a frequent behavioural reaction observed in all patients, trial data and they emphasise the use of relatively few less expen- both adults and children, during the stress of physical illness, and it Three to five year olds can normally separate from the parent and sive agents which have had extensive clinical trials. It is worth refers to the turning back from a more mature pattern of behaviour to accept a parent substitute for part of the day at least, but the ability noting that they differ somewhat from UK/European, and quite a more immature or childlike state of feeling or thinking. The process to do so can be compromised when they are ill or in hospital. This is 8 significantly from American, guidelines . of regression often serves a self protective or defensive purpose. when regression can occur. In children, this regressive behaviour can be shown as clinging or There is almost no clinical role for antibiotics in acute bacterial Denial or rebellion dependence, or the kind of demanding behaviour that is typical of a bronchitis provided the patient does not have chronic lung disease When children are restricted by hospital rules, by the medical condi- younger child. – but too often medical practitioners continue to prescribe them. tion itself, or by parents who have extreme concern for the child’s In an effort to reduce this wasteful use of resources, Australia’s Low self-esteem, social withdrawal, oversensitivity health, their normal exploratory behaviour can be affected. As a National Prescribing Service offers helpful advice on management Throughout development, an individual constructs a self-concept reaction to these limitations and to the fear and anxiety, the child of acute respiratory tract infections to both patients and doctors. 7 which is a personal perspective on their own thoughts, feelings and may act out with anger and oppositional behaviour or maybe become behaviours. The person’s self concept is continually reformulated as withdrawn, apathetic and passive. If they are acting out, they can be

References that person is exposed to new information in the environment. A perceived by hospital personnel as a bad child or a brat. If they are 1 Respiratory tract infections: pneumonia . In Therapeutic Guidelines: Antibiotic, relevant component of self-concept is self-esteem, a construct that withdrawn or passive they can be perceived as the model child and the version 13, 2006, published by Therapeutic Guidelines Ltd., Melbourne. Pages refers to judgements that people make about their self-worth. Usually, perfect patient. It is therefore important to go beyond the superficial 199 to 230 the child’s overall self-concept as well as their estimation of their social presentation so that depressive symptoms will not go unnoticed and 2 Wenzel RP, Fowler AA. Acute bronchitis . New Engl J Med 2006;355:2125 and physical self-worth, increases with age, except early in primary possibly cause adverse developmental consequences. 3 Stoller JK. Acute exacerbations of chronic obstructive pulmonary disease . New school, and in the transition to high school. A strong relationship Engl J Med 2002;346:988 Some researchers indicated that 3-5 year olds are especially at risk exists between a child’s self-evaluation, and their performance in all 4 Barker AF. Bronchiectasis . New engl J Med 2002;346:1383 during hospitalisations for three major reasons: 5 Halm EA, Teirstein AS. Management of community-acquired pneumonia . New aspects of their life. Negative self-evaluation is seen as a causal factor Engl J Med. 2002;347:2039 in the development and maintenance of depression. Theorists assert 1. The parent is the primary attachment object, and yet is unable to 6 McIntosh K. Community-acquired pneumonia in children . New Engl J Med that depressed individuals experience feelings of inadequacy, inferiori- control much of what happens to the child in hospital, even the 2002;346:429 ty, worthlessness and incompetence. Therefore, the early development amount of time they spend with the child, 7 National Prescribing Service website: www.nps.org.au of poor self-esteem in a child as a result of their chronic illness can be 8 Charles PGP, Johnson PDR, Grayson ML. Conundrums in community-ac- 2. The child is at a stage (see Erikson) where they wish to establish damaging to their ongoing development. quired pneumonia . Med J Aust. 2006;185:131 independence and autonomy, but they cannot do this as a more

Even pre schoolers are making self-evaluations, although in very con- passive role is usually required in the hospital, crete terms. Primary school children can use internal descriptors of Author: Sharon Paull 3. Pre-operational cognitive abilities exist (see Piaget) making the themselves and can evaluate themselves on the basis of their identity entire ordeal difficult if not impossible for the child to compre- as well as their actions. They also begin to evaluate themselves in com- hend. parison to others. Therefore, if a child feels less competent in their life they are likely to evaluate themselves in negative terms, and perhaps Secondary Gain to withdraw from their peer group. Secondary gain refers to the gains that a child (or an adult) gets out of the illness. Whilst at first it might be thought that a child does not get Moodiness and Depression very much out of having a severe illness and going to hospital, they Various studies have provided an estimated prevalence of children nevertheless are likely to receive increased attention, special treatment, with moderate to severe chronic handicapping illness or disability to and possibly some privileges that other children in the family or the be 5-10%. At any given time, about one in six children will have a peer group might not receive. Ironically, the secondary gain may serve chronic or recurrent illness or impairment that may range from rela- to reinforce the illness, and in extreme situations can be a major factor tively minor to life threatening. Studies of the prevalence of depres- contributing to therapeutic non-compliance. sion in various types of illness or impairment have revealed differing results, suggesting that some illnesses are more likely to be linked Families experience illness as a unit with depression. Diagnosis of depression in children can be difficult Surprising low levels of compliance with prescribed medication to make, and the clinical manifestations in various age groups are have been noted when parents are administering the medication to important to consider. their children. One study found that there was a range between 11 and 89% of parents who complied with medication for their child’s As most medically ill children will have at least one hospital admis- chronic condition. Whilst there are a number of factors that can sion, and sometimes frequent hospitalisations it is important to look hinder or promote parental compliance, one of the important aspects at the hospital environment itself, as a contributor to both anxiety is the parents’ perceptions of the child’s vulnerability, parents’ own and depression. health beliefs, their perceptions of the severity of the illness, their Separation from the parent is the first stressful event a child undergoes child’s actual vulnerability, and the potential effectiveness of medical when hospitalised, and this may be especially difficult for the younger treatment. In other words, the parents are imposing their health belief child. The sights, sounds and smells of the hospital can be very fright- model on their children. Compliance by parents with medication can 51 3.06 - A Different Case Of Cough // Cystic Fibrosis 8. Recurrent Illness And Psychosocial Development (cont.) be low when the severity of the child’s illness is seen to be low, but adolescent women, have been found to use more of both positive and also when it is seen to be high, implying that a severe illness on the negative coping strategies to withstand pain, in other words, they have part of the child can sometimes result in a family which is disrupted a wider spectrum of coping strategies, including more emotion-ori- and disorganised. Levels of anxiety on the part of the parent also ented and problem oriented coping strategies than adolescent males probably contribute to low compliance with therapy and medication Some data suggest that gender differences play a more significant role for their child. than socio-economic differences with regard to differences in health. When the child has a chronic or recurrent illness, parents can experi- Similar to studies done in non-CF populations [31], we found gender ence a range of emotions such as guilt, helplessness, anxiety, shame, differences among adolescents with CF in the areas of mental health anger or misery, all of which can influence child-care practices. Over- and general health perceptions. protection, rejection, leniency or excessive strictness can be the result. Coping with CF Some researchers found that children who coped most successfully The impact of optimistic ways of coping on treatment adherence has with an ongoing illness have parents who have mastered feelings of been researched. Higher levels of optimism and self efficacy corre- guilt or fear and who treat them as much like a healthy child as pos- late with greater treatment adherence in CF adolescents and adults. sible. Nevertheless over-indulgence and lack of discipline are nowhere Similarly, greater optimism is associated with increased adherence to near as serious in terms of the child’s physical and mental wellbeing as physiotherapy and medication taking in children and young adults. the opposite, that is, parental rejection, criticism or neglect. There is some suggestion that utilisation of better coping strategies Having non-supportive family members correlates negatively with ad- may favourably influence disease progression (Abbott, 2003). olescent psychological adjustment for this group. The most common Hope or hopelessness problems are internalising behaviours such as depression and anxiety, The significance of the concept of hope as a coping strategy is empha- and behavioural problems related to peer relationship difficulties. A sised in many groups of chronically ill patients, including cardiac and limited number of family functioning studies shows that better family HIV patients. Hope is a “multi-dimensional dynamic life force that functioning is associated with better child functioning. is characterised by a confident yet uncertain expectation of achiev- Siblings of children with CF are at increased risk of psychological and ing good, which is realistically possible and personally significant” behavioural problems, possibly because of less attention and care from (Dufault and Martochhio, 1985). their parents. In a study of hope amongst patients with CF, they were found to be Parents may also be suffering. Parents (especially mothers) of children slightly lower when compared with the general population (Rustoen with CF have increased psychological problems, role strain, and et al, 2004). There were interesting psychosocial differences in the decreased marital satisfaction. Decreased marital satisfaction is related lives of the two groups - to having less time to spend together, decreased communication skills, • CF patients scored higher on “deep inner strength” decreased sexual intimacy, and role strain between parenting and care giving (Berge and Patterson, 2004). • CF patients were more likely to be scared about the future Quality of life (QOL) amongst patients with CF • CF patients achieved similar levels of education compared with QOL is a concept that assesses a number of life domains, including the general population physical, psychological and social functioning; it examines outcomes • CF patients were less likely to be in paid employment that are relevant to the patient rather than to their medical carers, and includes the patient’s assessment of dysfunction associated with the • CF patients were more likely to live alone illness, treatment and health care policy. • CF patients do not have poorer psychosocial functioning com- Patients with CF tend to be aware of their physical health limitations, pared with the general population and recent research indicates that they do not deny their symptoms, • Those with the lowest pulmonary function scored lowest on and male patients especially tend to rely less on denial as a protective hope mechanism. Parents’ and patients’ reports of QOL may often differ, and it is important to obtain the view of both. QOL measures assist • Married CF patients scored highest on hope within the CF in determining how the patient is faring in terms of their emotional, group, whereas those who were divorced/separated scored lowest psychological and social adjustment (Powers, Gerstle and Lapey, These results indicate that CF or any chronic illness need not have a 2001). negative effect on psychosocial outcomes and quality of life. Gender differences References in the text: Female patients with CF tend to have a shorter life expectancy than Abbott, J (2003) Coping with cystic fibrosis. Journal of the Royal Society of Medi- males. Significant differences have also been found in QOL (Ar- cine, Supplement, 96 (43): 42-50. rington-Sanders et al, 2006), with female adolescents with CF scoring Arrington-Sanders, R, Yi, MS, Tsevat, J, Wilmott, RW, Mrus, JM and Britto, lower on all health domains with the exception of the role behaviour MT (2006) Gender differences in health-related quality of life of adolescents with domain. Even when controlling for age and lung disease severity, cystic fibrosis. Health and Quality of Life Outcomes, 4:5. Berge, JM and Patterson, JM (2004) Cystic Fibrosis and the family: a review and female adolescents had significantly lower scores in mental health, critique of the literature. Families, Systems, and Health, 22(1): 74-100. global health, and perceptions of general health. However, physical Dufault, K and Martochhio, BC (1985) Symposium on compassionate care and functioning was not related to gender when controlling for age and the dying experience. Hope. Its spheres and dimensions. Nursing Clinics of North lung disease severity, which may indicate that age and disease severity America, 20(2): 379-91. Powers, P, Gerstle, R and Lapey, A (2001) Adolescents is more important than gender in predicting physical aspects of QOL. with cystic fibrosis: family reports of adolescent health-related Quality of Life and forced expiratory volume in one second. Pediatrics, 107(5): 70- Female adolescents with CF have a more accurate perception of objec- Rustoen, T, Wahl, AK, Hanestad, BR, Gjengedal, E, Moum, T (2004) Expressions tive clinical health status than male adolescents, but rely more on of hope in cystic fibrosis patients: a comparison with the general population. Heart denial to cope, as mentioned above. Compared with adolescent males, and Lung, 33(2): 111-118. Professor Susan Hayes, Medicine 52 3.07 - Difficult Circumstances // Pneumonia & Otisis Media Learning Objectives Description Disciplines Detailed anatomical organisation and function of the greater ear complex; the internal, middle and external Anatomy ears. The bony and cartilagenous frameworks, neural innervations and some clinical applications.

Ear, Nose & Throat adults The different classifications of hearing loss, together with main cause of hearing loss in children and in The pathogenesis of ear infection, and the different types of bacteria involved and appreciate the Ear, Nose & Throat, environmental factors that contribute to ear infection Infectious Diseases Ear, Nose & Throat, The patterns and causes of conductive and sensorineural loss in children and adults Physiology The main features of the development of the head and neck: cranium, pharyngeal apparatus, thyroid gland Embryology, and palate. Consider some major abnormalities associated with head and neck embryology, for example Anatomy cleft palate/lip, holoprosencephaly and acrania The major radiological features of the head and neck Imaging, Anatomy The importance of age and underlying disease in predicting the most likely causative organisms in Infectious Diseases viruses, interpretation of sputum gram stains, use of antigen detection methods, use of blood cultures and serologicalpneumonia. methods. The methods available for examining specimens, including immunofluorescence, and for To understand clinical and public health importance of the most common causes of pneumonia and mechanisms of their transmission Infectious Diseases

To understand differences in aetiology, clinical significance and methods of laboratory diagnosis of The mechanisms of anti-microbial action in respiratory disease Infectious Diseases community- and hospital-acquired pneumonia" The nature and mechanisms of action of vaccines; the range of vaccines that are used, their effectiveness Paediatrics and impact on the health of populations The major reasons for, and issues associated with, the hospitalisation of children Paediatrics The factors that contribute to malnutrition among Aboriginal children; wasting and stunting are indices of Paediatrics, undernutrition Nutrition How the molecular events of bacterial pathogenesis in pneumonia are affected by virulence and other factors; to understand the pathological appearance of bronchopneumonia and lobar pneumonia To illustrate how the molecular events of bacterial pathogenesis in pneumonia are due to virulence and other factors. Pathology, To emphasise that patient management should include both antibiotic therapy and strategies for Infectious Diseases prevention and treatment of septic shock. To understand the pathological development of bronchopneumonia and lobar pneumonia To understand the pathological appearance of bronchopneumonia and lobar pneumonia The major functions of the different parts of the ear, particularly the internal ear Physiology Physiology, The methods of testing ear function Anatomy Taking the pulse of indigenous health Public Health The epidemiology of acute respiratory infection in children and adults, and in the Indigenous population. Public Health, The different pathogens causing acute respiratory infection Infectious Diseases Revision/Clinical Exercises Respiratory This tutorial should be Revision of any topic in the current block, The tutorial can also incorporate Medicine completing Clinical Exercises. Respiratory The state of aboriginal health in rural and remote communities Medicine Respiratory The epidemiology, pathogenesis, management and prevention of acute respiratory infections in indigenous Medicine, Infectious children Diseases Respiratory The principles of management of pneumonia. The importance of immunisation, different types of therapy Medicine, Pharmacology and identification of the pathogen

53 3.07 - Difficult Circumstances // Pneumonia & Otisis Media 1. Ear Infections Acute otitis media is second only to the common cold as a cause Antibiotics effective against beta-lactamase-producing organisms of infectious illness in pre-school children in industrialised coun- such as cotrimoxazole or amoxycillin-clavulanic acid reserved for tries. It is primarily a disease of infancy and early childhood. second-line treatment. Analgesics are indicated to relieve pain. Because most episodes of acute otitis media resolve spontaneously, Host factors in the pathogenesis of ear infection include Eus- many doctors now use a delayed prescription for children aged >6 tachian tube dysfunction, age and immunity. Children with cleft months. The parents are given a prescription fopr antibiotics but palate have abnormal Eustachian tube dysfunction and a greatly told to fill it only if the child is still unwell after 48 hours. increased risk of otitis media. The incidence of acute otitis media is highest in the first two years of life. In a Boston study, the mean Optional references: incidence was 1.2 episodes per child in the first year and 1.1 Books Bluestone CD, Klein JO. Otitis media in infants and children. (3rd ed.) Philadel- episodes in the second year of life. Children with impaired IgG phia: WB Saunders, 2001 antibody production or IgG subclass deficiency are at high risk Cochrane Reviews on therapeutic interventions for recurrent otitis media, often with purulent ear discharge. In Glasziou PP, Del Mar CB, Sanders SL, Hayem M. Antibiotics for acute otitis addition, normal ciliary function is important to clear middle ear media in children . Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD000219. secretions: ciliary activity is impaired in immotile cilia syndrome, Leach AJ, Morris PS. Antibiotics for the prevention of acute and chronic suppura- but may also be impaired by tobacco smoke and respiratory vi- tive otitis media in children . Cochrane Database of Systematic Reviews 2006, ruses. There is a group of “otitis prone” children without demon- Issue 4. Art. No.: CD004401. strable epidemiological or immunological risk factors. Lous J, Burton MJ, Felding JU, Ovesen T, Rovers MM, Williamson I. Grom- mets (ventilation tubes) for hearing loss associated with otitis media with effusion Environmental factors are also important in otitis media. The in children . Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD001801. incidence of acute otitis media and otitis media with effusion Spurling GKP, Del Mar CB, Dooley L, Foxlee R. Delayed antibiotics for respira- increases with increased exposure to infection, e.g. child care, and tory infections . Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: with exposure to environmental factors such as tobacco and wood CD004417. smoke. Breast-feeding protects against otitis media. Aboriginal Papers on epidemiology and pathogenesis Chonmaitree T, Owen MJ, Patel JA et al. Effect of viral respiratory tract infection children have a very high incidence of middle ear disease, prob- on outcome of acute otitis media . J. Pediatr 1992; 120: 856-62. [Role of respira- ably due to early, heavy colonisation with bacterial pathogens as a tory viruses] result of living conditions. Bluestone CD. Pathogenesis of otitis media: role of Eustachian tube . Pediatr Infect Dis J 1996; 15: 281-91. Organisms: bacteria can be isolated from middle ear fluid Leach AJ, Boswell JB, Asche V, Nienhuys TG, Mathews JD. Bacterial colonisa- obtained by tympanocentesis in 70 90% of episodes of acute tion of the nasopharynx predicts very early onset and persistence of otitis media otitis media. Bacteria attach to respiratory mucosa by expressing in Australian Aboriginal infants . Pediatr Infect Dis J 1994; 13: 983-9. [Important paper on origins of Aboriginal middle ear disease] adhesins which bind the organism to epithelial cell receptors. Bac- McCormick D, Lim-Melia E, Saeed K, Baldwin CD, Chonmaitree T. Otitis terial adhesins may be part of fimbriae or pili, fibrillae, cell walls media: can clinical findings predict bacterial or viral etiology? Pediatr Infect Dis J or other peripheral bacterial structures. Haemophilus influenzae 2000; 19: 256-8. (untypeable) and Streptococcus pneumoniae (pneumococcus), the Casey JR, Pichichero ME. Changes in frequency and pathogens causing acute otitis media in 1995-2003 . Pediatr Infect Dis J 2004; 23: 824-8. predominant bacterial pathogens causing acute otitis media, are Papers on treatment particularly likely to attach to nasopharyngeal epithelial cells of Rosenfeld RM. What to expect from medical treatment of otitis media . Pediatr “otitis-prone” children. Respiratory viruses can cause acute otitis Infect Dis J 1995; 14(9): 731-8. [Antibiotic therapy] media, and when viruses and bacteria co-infect the middle ear, Damoiseaux RA et al. Primary care based randomised, double blind trial of amoxi- cillin versus placebo for acute otitis media in children aged under 2 years . BMJ children are more likely to develop persistent infection. 2000; 320(7231): 350-4. Cohen R et al. Five vs. ten days of antibiotic therapy for acute otitis media in Complications of acute otitis media include persistent mid- young children . Ped Infect Dis J 2000; 19(5): 458-63. dle ear effusion (‘glue ear’), which can cause significant hearing Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J. Pragmatic loss, perforation of the tympanic membrane, purulent otorrhoea randomised controlled trial of two prescribing strategies for childhood acute otitis (acute or chronic suppurative otitis media), facial nerve palsy and media. British Medical Journal 2001;322(7282):336-42. Guidelines rarely cholesteatoma. In pre-antibiotic days, meningitis and brain NSW Health Department Working Party. Guidelines on the management of abscess were recognised complications, but are virtually never seen paediatric middle ear disease . Med J Aust 1993; 159 (suppl. 4): S1 -S8. [Particular nowadays. emphasis on the management of glue ear]. NSW Health Department Working Party on Ear Disease in Aboriginal Children: There is some controversy as to whether or not immediate an- Guidelines on the prevention and control of otitis media and its sequelae in Abo- tibiotic treatment of acute otitis media is indicated. Overall, 15 riginal children . Med J Aust 1996; 164 (supp): S1-S17. [Overview of Aboriginal children have to be treated with antibiotics to prevent one child ear disease]. American Academy of Pediatrics Subcommittee on Management of Acute Otitis having ear pain after 2 days. Most doctors would give antibiotics Media. Diagnosis and management of acute otitis media . Pediatrics 2004; 113(5): immediately to infants <6 months old and to Aboriginal children. 451-65. Amoxycillin is a suitable first-line choice, with activity against pneumococcus and most untypeable Haemophilus influenzae. Author: Clinical Professor David Isaacs, Paediatrics and Child Health

54 3.07 - Difficult Circumstances // Pneumonia & Otisis Media 2. Function Of The Ear Antibiotics effective against beta-lactamase-producing organisms Familiarise yourself with the structures of the outer, middle and will decrease sound transmission from the outer to the inner ear. such as cotrimoxazole or amoxycillin-clavulanic acid reserved for inner ear. Particular points to note are: This is the basis of many types of conductive hearing loss. An second-line treatment. Analgesics are indicated to relieve pain. increase in stiffness increases the resonance frequency and causes • The outer and middle ears are air filled spaces and the inner Because most episodes of acute otitis media resolve spontaneously, a decrease in the transmission of low frequencies. An increase in ear is fluid filled. many doctors now use a delayed prescription for children aged >6 the mass decreases the resonant frequency and the transmission of months. The parents are given a prescription fopr antibiotics but • The inner ear is the site of neural transduction of sound. high frequencies. A combination of the two or an increase in the told to fill it only if the child is still unwell after 48 hours. damping of the system causes an overall reduction in transmis- • The eardrum (tympanic membrane) defines the boundary sion. Optional references: between the outer and middle ear. Books The middle ear is a sealed system with the exception of the Eus- Bluestone CD, Klein JO. Otitis media in infants and children. (3rd ed.) Philadel- • The eustachian tube provides the only means by which the tachian tube which connects the middle ear cavity to the naso- phia: WB Saunders, 2001 air pressure in the middle ear can be equalised to atmospheric Cochrane Reviews on therapeutic interventions pharynx. Although this tube is normally closed it opens periodi- pressure. Glasziou PP, Del Mar CB, Sanders SL, Hayem M. Antibiotics for acute otitis cally to allow the static pressure in the middle ear to be equalised media in children . Cochrane Database of Systematic Reviews 2004, Issue 1. Art. The general function of the ear is to transduce acoustic (mechani- to atmospheric pressure. If the Eustachian tube fails to open or No.: CD000219. Leach AJ, Morris PS. Antibiotics for the prevention of acute and chronic suppura- cal) energy into neural signals. Note that the frequency range of becomes blocked then a negative pressure builds up in the middle tive otitis media in children . Cochrane Database of Systematic Reviews 2006, human hearing is matched to the frequency content of sounds of ear as the mucosa lining the cavity absorbs the trapped oxygen. Issue 4. Art. No.: CD004401. biological interest to humans (eg communication sounds) The negative pressure results in a painful inward distension of the Lous J, Burton MJ, Felding JU, Ovesen T, Rovers MM, Williamson I. Grom- tympanic membrane and an increase in stiffness of the middle ear mets (ventilation tubes) for hearing loss associated with otitis media with effusion A physical problem solved by the middle ear is the impedance in children . Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: mismatch between sounds transmitted from air into the fluid mechanics. Prolonged periods of negative pressure can also be ac- CD001801. filled inner ear. As fluid is much more incompressible than air, companied by a build up of fluid in the middle ear and can result Spurling GKP, Del Mar CB, Dooley L, Foxlee R. Delayed antibiotics for respira- in conductive hearing loss of up to 40-50dB. tory infections . Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: most of the sound energy would be reflected at the air-water CD004417. interface rather than passing into the inner ear. The middle ear Optional references: Papers on epidemiology and pathogenesis compensates for this impedance mismatch using three different Kandel, E. R., Schwartz, J. H., & Jessell, T. M. (2000). Principles of neural science (4th ed.). New York: McGraw-Hill. [Available as an E-Book] Chonmaitree T, Owen MJ, Patel JA et al. Effect of viral respiratory tract infection mechanisms: Lever action of the middle ear bones, areal differ- on outcome of acute otitis media . J. Pediatr 1992; 120: 856-62. [Role of respira- This is a general introduction to the auditory system. tory viruses] ences between the tympanic membrane and the stapes foot plate Schmidt RF, ed. Fundamentals of sensory physiology. (3rd ed.) Berlin ; New York : Bluestone CD. Pathogenesis of otitis media: role of Eustachian tube . Pediatr and buckling motion of the tympanic membrane. Springer-Verlag, 1986. Infect Dis J 1996; 15: 281-91. This has an introductory section on the human auditory performance Chap.6. Leach AJ, Boswell JB, Asche V, Nienhuys TG, Mathews JD. Bacterial colonisa- As the middle ear is a mechanical system it has a resonant Pickles, James O. An introduction to the physiology of hearing. 3rd ed. London ; tion of the nasopharynx predicts very early onset and persistence of otitis media frequency which is around 1000Hz. As a result it transmits the San Diego : Academic Press, 1988. in Australian Aboriginal infants . Pediatr Infect Dis J 1994; 13: 983-9. [Important middle range of frequencies to which humans are sensitive more A fairly advanced text (despite the title). Chapter 2 is the most relevant. paper on origins of Aboriginal middle ear disease] McCormick D, Lim-Melia E, Saeed K, Baldwin CD, Chonmaitree T. Otitis effectively than low and high frequencies. The resonance of a -me Author: Associate Professor Simon Carlile, Physiology media: can clinical findings predict bacterial or viral etiology? Pediatr Infect Dis J chanical system is determined by its mass and stiffness. Changes 2000; 19: 256-8. in the mass and/or stiffness of the components in the middle ear Casey JR, Pichichero ME. Changes in frequency and pathogens causing acute otitis media in 1995-2003 . Pediatr Infect Dis J 2004; 23: 824-8. Papers on treatment Rosenfeld RM. What to expect from medical treatment of otitis media . Pediatr Infect Dis J 1995; 14(9): 731-8. [Antibiotic therapy] Damoiseaux RA et al. Primary care based randomised, double blind trial of amoxi- cillin versus placebo for acute otitis media in children aged under 2 years . BMJ 2000; 320(7231): 350-4. Cohen R et al. Five vs. ten days of antibiotic therapy for acute otitis media in young children . Ped Infect Dis J 2000; 19(5): 458-63. Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. British Medical Journal 2001;322(7282):336-42. Guidelines NSW Health Department Working Party. Guidelines on the management of paediatric middle ear disease . Med J Aust 1993; 159 (suppl. 4): S1 -S8. [Particular emphasis on the management of glue ear]. NSW Health Department Working Party on Ear Disease in Aboriginal Children: Guidelines on the prevention and control of otitis media and its sequelae in Abo- riginal children . Med J Aust 1996; 164 (supp): S1-S17. [Overview of Aboriginal ear disease]. American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media . Pediatrics 2004; 113(5): 451-65.

Author: Clinical Professor David Isaacs, Paediatrics and Child Health

55 3.07 - Difficult Circumstances // Pneumonia & Otisis Media 3. Growth And Nutrition In Indigenous Children Growth and nutrition in Indigenous children Low birth weight in Indigenous children has been linked to: Childhood malnutrition is prevalent in many developing coun- 1. increased perinatal mortality, tries. It also occurs within certain socially and economically 2. impaired growth in childhood, at least until the age of five deprived groups in developed countries such as Australia, Indig- years, enous children being a very concerning and ongoing example. 3. increased risk of sudden infant death syndrome (SIDS). Wasting and stunting - indices of undernutrition In childhood, malnutrition is most clearly seen as an aberration in 4. increased risk of cardiovascular disease and type 2 diabetes in the expected pattern of growth. The World Health Organisation adulthood (the “fetal origins of adult disease” hypothesis). (WHO) has recommended that wasting and stunting be used as 5. increased risk of subsequent abdominal obesity, and associated indices of poor nutritional status in populations of children. These complications. concepts can also be useful when assessing the nutritional status of individual children. The program, “Strong Women - Strong Babies - Strong Culture”, has been implemented since 1994 in the Northern Territory and Wasting is low weight for age or height (length) and is defined Western Australia. The program uses a family cultural model most readily as a weight < 3rd centile for age for the reference which was developed by Indigenous women and health work- population. This is approximately equivalent to < 80% of standers. Initial results suggest that the program has been successful in ard weight for height (ie the weight on the 50th centile for a child the modification of antenatal services (ie sensitive to the needs of of that height). It usually indicates a deficit in lean tissue or mass Indigenous women, together with high quality health care) and in and results from failure to gain weight at the expected rate, or improving the health status of pregnant women and their babies. even actual weight loss. It is generally a sign of acute undernutrition and is often precipitated by infection or inadequate food Faltering of growth and malnutrition intake. While the birth weight of Indigenous children is low, growth during the first few months appears to be adequate. However, Stunting, or low height for age (ie < 3rd centile for the refer- in many populations, weight for age falters between six and 12 ence population; approximately equivalent to < 90% of standard months in particular and generally does not start to recover until height for age), indicates slowing of skeletal growth and can be 18 months to two years of age. In some regions, adequate “catch- seen as a sign of chronic undernutrition. Stunting may be associ- up” growth may not occur, with deficits in height and weight ated with poor socioeconomic circumstances, repeated or chronic often persisting until at least 15 years of age. These problems are infections and chronically poor nutritional intake. Wasting and more common in remote Indigenous communities. stunting often co-exist in malnourished children. Causes of malnutrition A word of caution in interpreting growth charts: by definition Infectious diseases are now recognised to play a pivotal role in 3% of a population of children will fall below the third centile. the aetiology and continuation of childhood malnutrition. As a Children below the third centile may be quite healthy or may result of the negative effect of malnutrition on childhood immune be growing slowly due to undernutrition or infection. Sequen- defence mechanisms, a vicious cycle of malnutrition - infection - tial measurements of length and weight (ie growth monitoring) malnutrition can develop in at-risk children. Nutritional status is will tell if the child’s length or weight is diverging away from the thus both a risk factor for infection, as well as being affected by it. percentile track. [Note: There will be further discussion of this topic in Block 7] Note that growth and growth charts will be covered in more detail The causes of malnutrition in Indigenous children are complex in Block 7. and relate to the extreme social disadvantage experienced by many Malnutrition amongst Indigenous children Indigenous children and communities. Many remote Indigenous Low birth weight, growth faltering and frank malnutrition have communities lack basic resources (eg a clean and dependable been regularly documented in Aboriginal children since the water supply, sanitation, adequate housing and a reasonable food 1960s. While there have been improvements in Aboriginal infant supply), have poor access to primary health care and have no and child health, significant problems still remain, and Australia organised child health programs. Clearly, profound social and remains the only developed country with high rates of under- economic change remains fundamental to any long-term solution nutrition in its Indigenous children. Wasting rates of more than to these problems. 10% have been reported in some rural and remote areas. Remote and urban differences Low birth weight In 2003, McKerras et al published a study of 482 Indigenous Low birth weight is more common among Indigenous babies than children from the Northern Territory and showed that remote non-Indigenous babies. In 2005, approximately 13% of babies Indigenous children were likely to be shorter, lighter and have a born to Indigenous women were of low birth weight (ie < 2,500g) lower BMI than their urban counterparts. They were also more compared with ~ 6% of babies born to non-Indigenous women. likely to have potential markers of adult chronic diseases such as Intrauterine growth retardation (“born small”) and prematurity higher systolic blood pressure, higher total cholesterol levels, high (“born early”) both contribute to this problem. Low birth weight density lipoprotein and insulin levels. They were also more likely in Indigenous children is associated with a number of maternal to have visible signs of infection. factors including maternal undernutrition, urinary tract infec- Obesity in Indigenous children tions, anaemia, diabetes, hypertension, smoking, alcohol con- Adult Indigenous people have higher prevalence rates of over- sumption and lack of regular antenatal supervision. weight and obesity than non-Indigenous Australians, but until 56 3.07 - Difficult Circumstances // Pneumonia & Otisis Media 3. Growth And Nutrition In Indigenous Children (cont.) recently there have been no data on obesity rates in Indigenous synopses/n26syn.htm. (Note: This publication is currently under assessment for children. Data from the Longitudinal Study of Australian currency but has not yet been updated) This document (available on-line) provides a detailed collection of information on Children (2004 collection), of 4 and 5 year old children, has broad nutrition issues in Aboriginal and Torres Strait Islander peoples. The above- shown that Indigenous children have a 1.6 higher odds of being mentioned sections also describe some interventions used to improve nutritional overweight or obese than their non-Indigenous peers, even after status of mothers and children, including the “Strong Women - Strong Babies - adjustment for a range of socioeconomic variables. The prevalence Strong Culture” program. The following review looks at undernutrition and obesity in Indigenous children of overweight and obesity was 20.5% in the general population of in Australia, New Zealand, the USA and Canada: young children, but 28.1% in Indigenous children. Thus, Indig- Ruben AR. Undernutrition and obesity in Indigenous children: Epidemiology, enous children are at risk for both over- and under-nutrition (the prevention and treatment. Pediatr Clin North Am 2009; 56:1285-1302[LB1] . “double burden of malnutrition”). The following document provides an overview of nutrition for Indigenous Austral- ians – adults and children alike:Burns J, Thomson N (2008) Review of nutrition Optional references: and growth among Indigenous peoples. Retrieved [access date] from http://www. Mackerras DE, Reid A, Sayers SM, Singh GR, Bucens IK, Flynn KA. Growth and healthinfonet.ecu.edu.au/health-risks/nutrition/reviews/our-review[LB2] morbidity in children in the Aboriginal Birth Cohort Study: the urban-remote Stokes GD, Jeffries-Stokes C. Indigenous culture and health. Part 1: Australian in- differential. Med J Aust. 2003 Jan 20;178(2):56-60. digenous culture and health. In: D.M. Robertson, M. South. Practical Paediatrics. Mackerras D. Birthweight changes in the pilot phase of the Strong Women Strong 6th ed. Edinburgh, London : Churchill Livingstone, 2006. Babies Strong Culture Program in the Northern Territory. ANZ J Publ Health For those who wish to pursue the issue of wasting and stunting in childhood in 2001; 25(1):34-40. more depth, the following is a very useful reference: Wake M, Hardy P, Canterford L, Sawyer M, Carlin JB. Overweight, obesity and Measuring change in nutritional status: guidelines for assessing the nutritional girth of Australian preschoolers: prevalence and socio-economic correlates. Int J impact of supplementary feeding programmes for vulnerable groups. Geneva : Obesity 2007; 31:1044-1051. World Health Organization ; [Albany, N.Y. : obtainable from WHO Publications AIHW. Indigenous health section: Mothers and babies http://www.aihw.gov.au/ Centre USA], 1983. indigenous/health/mothers_babies.cfm Web-site: AIHW. The Health & Welfare of Australia’s Indigenous People 2003. http://www. Australian Indigenous HealthInfoNet. Available at: http://www.healthinfonet.ecu. aihw.gov.au/publications/index.cfm/title/9226 edu.au/health-risks/nutrition National Health & Medical Research Council. Nutrition in Aboriginal and Torres This website has a range of resources on indigenous nutrition, including a section Strait Islander Peoples. An Information Paper. 2000 (ISBN 186496068X). See on maternal and child nutrition. particularly Section II on Maternal and Child Health, including the chapters on “Pregnancy and Fetal Growth” (pp 83-96) and “Childhood Growth” (pp109 - Author: Professor Louise Baur, Paediatrics and Child Health 132). This publication is available on-line http://www.nhmrc.gov.au/publications/

57 3.07 - Difficult Circumstances // Pneumonia & Otisis Media 4. Acute Respiratory Infection In Indigenous Children Background and Epidemiology more common it is also true that indigenous children generally Indigenous children in developed countries have generally high have higher rates of chronic infection such as bronchiectasis and rates of acute respiratory infection. The pattern of illness is similar this may require different therapeutic strategies. to that of developing country children, although mortality rates Ear Disease are generally lower than the developing countries. In particular Whilst ear disease and hearing impairment is very common in the children of Inuits in Alaska, Indians in the United States Aboriginal children in all regions, the pattern of illness varies and Aborigines in Australia have been well documented to have substantially. In urban settings most children are effected by sirus high rates of pneumonia. It is likely that both viral and bacterial otitis media with an intact tympanic membrane. In remote areas, infections are common in these groups although the attack rates particularly in desert regions, children often have a perforated for bacterial pneumonia are many times higher than they are for tympanic membrane and subsequent chronic suppurative chronic non-indigenous children in these countries. In Australia the data otitis media. These conditions generally commence in the first few for urban Aboriginal children are scarce but it is likely that these months of life and there is some evidence that they are related to children have lower attack rates than their remote area counter- early naso-pharyngeal colonisation with bacteria. The treatment parts. In central Australia Aboriginal children have the highest at- algorithms for these conditions vary significantly. tack rate for invasive pneumococcal disease that has been reported anywhere in the world. Prevention Some key issues in prevention are improvements in the living Pathogenesis environment, maternal practice particularly for young and unedu- In general indigenous groups share risk factors of poverty, crowd- cated mothers and the potential of new vaccines for respiratory ing and poor living conditions. In addition, they suffer from syncytial virus and the conjugated pneumococcal vaccines. the cycle of recurrent infection and growth failure producing a relatively large number of children with some degree of malnu- Key Issues for Assessment trition in early childhood. Evidence from developing countries • Increased rates of acute respiratory infection in indigenous suggests that children in these regions have early colonisation of children. the nasopharynx with bacterial pathogens such as Streptococcus pneumoniae and Haemophilus influenzae. This has also been • Importance of early upper airway colonisation of the naso- shown in remote area Aboriginal children where acquisition pharynx with bacteria. occurs in the first 1-2 months of life. It is likely that at least one • Factors in the pathogenesis of pneumonia. important mechanism in the pathogenesis of pneumonia is micro- aspiration of upper airway secretions with dense colonisation of • Role of vaccines in prevention. these bacterial pathogens. Pneumonia may also be facilitated by Optional references: impaired muco-ciliary clearance mechanisms due to preceding or Leach AJ, Boswell JB, Asche V et al. Bacterial colonisation of the nasopharynx concurrent viral infection. predicts very early onset and persistence of otitis media in Australian Aboriginal infants. Pediat Infect Dis J 1994; 13(11): 983-989. Pathogens Torzillo PJ, Morey F, Gratten M, Murphy D, Matters R, Dixon J. Changing epi- Common viral pathogens such as respiratory syncytial virus are demiology of invasive pneumococcal Disease in central Australia prior to conjugate vaccine :a 16 year study. Vaccine.25(13):2007 likely to be important in indigenous populations. Streptococcus Morris PS. Leach AJ. Halpin S. Mellon G. Gadil G. Wigger C. Mackenzie G. Wil- pneumoniae is probably the most common bacterial pathogen. son C. Gadil E. Torzillo P. An overview of acute otitis media in Australian Aborigi- There is less data about the role of Haemophilus influenzae. Hae- nal children living in remote communities. Vaccine. 25(13):2389-93, 2007. mophilus influenzae type B has been shown to be important in Chang AB, Chang CC, O’Grady KA, Torzillo PJ. Lower respiratory tract infections.in Health Issues in Indigenous children: an evidenced based approach for the developing countries where immunization is not available. Non- General Pediatrician. Pediatr Clin N Am 56; 1303-1321:2009. serotypable Haemophilus influenzae may be a significant cause of O’Grady KA, Taylor-Thomson D, Chang AB, Torzillo PJ, Morris P, Macken- pneumonia. zie G, Wheaton G, Bauert P, De Campo M, De Campo J, Ruben A. High rates of World Health Organization-defined radiologically confirmed pneumonia in Management Northern Territory Indigenous children. Med J Aust, 192(10):592-5, 2010 In urban areas the treatment of pneumonia would probably fol- Chang AB, Torzillo PJ. Respiratory Infections (including Bronchiectasis) in Abo- riginal Primary Health Care.An evidence based approach. 2nd Ed Eds. Couzos S low conventional guidelines. In more remote areas intra-muscular and Murray R. Oxford University Press, Melbourne. 2007. antibiotics are usually the first line of treatment and Procaine Penicillin or Benzylpenicillin are generally satisfactory except for Author: Clinical Professor Paul John Torzillo, Medicine treatment in young infants. Whilst acute respiratory infection is

58 3.07 - Difficult Circumstances // Pneumonia & Otisis Media 5. Management Of Pneumonia more common it is also true that indigenous children generally Once the diagnosis of pneumonia has been made on the basis of The penicillins, cephalosporins and macrolides have short plasma have higher rates of chronic infection such as bronchiectasis and the symptoms, clinical signs and typical radiological appearances, half-lives (usually < 2 hours) and they are cleared via the kidneys this may require different therapeutic strategies. the management principles are as follows: or liver (macrolides). Dose reduction is not usually necessary in patients with renal or liver impairment as the therapeutic index Ear Disease • Prescribe antimicrobial therapy, initially on an empirical basis for these drugs is quite high. The only group of antimicrobial Whilst ear disease and hearing impairment is very common in • Maintain arterial oxygen saturation greater than or equal to agents which need careful dose modification are the aminoglyco- Aboriginal children in all regions, the pattern of illness varies 90% with supplemental oxygen sides which are excreted unchanged in the urine and cause toxicity substantially. In urban settings most children are effected by sirus if given in the usual doses to patients with renal impairment. otitis media with an intact tympanic membrane. In remote areas, • Provide resuscitation for complications such as bacteraemic particularly in desert regions, children often have a perforated shock and respiratory failure Immunisation tympanic membrane and subsequent chronic suppurative chronic The NH&MRC guidelines recommend annual influenza vaccina- • Investigate and treat complications such as empyema in otitis media. These conditions generally commence in the first few tion for individuals in the following categories: patients who fail to respond to initial treatment months of life and there is some evidence that they are related to Individuals at particular risk of complications early naso-pharyngeal colonisation with bacteria. The treatment • Investigate and treat any underlying predisposing conditions algorithms for these conditions vary significantly. such as lung cancer, chronic lung disease (eg bronchiectasis) • adults and children with chronic debilitating disease, or immunological disorders especially those with chronic cardiac, pulmonary,renal and Prevention metabolic disorders; Some key issues in prevention are improvements in the living Antimicrobial therapy environment, maternal practice particularly for young and unedu- The treatment with antimicrobial drugs is normally begun before • persons over the age of 65 years; cated mothers and the potential of new vaccines for respiratory a specific aetiological agent has been identified. The choice of • residents of nursing homes and other chronic care facilities syncytial virus and the conjugated pneumococcal vaccines. antibiotic is determined by • persons receiving immunosuppressive therapy Key Issues for Assessment • the likely pathogen in the particular patient Persons engaged in medical and health services, and essential • Increased rates of acute respiratory infection in indigenous • the clinical severity of the illness. public utilities, if they are at increased risk owing to medical children. Empirical therapy for community acquired pneumonia should disorders such as those above. In the event of a pandemic or other • Importance of early upper airway colonisation of the naso- provide good cover against Streptococcus pneumoniae (eg penicil- major outbreak, advice should be given about vaccination of staff pharynx with bacteria. lin, ampicillin or a cephalosporin). If a patient is ill with severe particularly liable to exposure. pneumonia, or there is no response after a day or two of penicillin • Factors in the pathogenesis of pneumonia. The available data do not support a public health strategy to therapy, it is usual to add a macrolide antibiotic to the penicillin vaccinate all individuals in particular clinical categories which are • Role of vaccines in prevention. (or to the cephalosporin), The culture of a specific pathogen may deemed to be at risk of pneumococcal infections. However, clini- guide change in antibiotic therapy . Optional references: cians may regard certain individuals in these ‘at risk’ categories to Leach AJ, Boswell JB, Asche V et al. Bacterial colonisation of the nasopharynx Oral administration of the anti-infective agents is acceptable warrant vaccination. The categories are: predicts very early onset and persistence of otitis media in Australian Aboriginal in patients without clinical features of systemic toxicity but the infants. Pediat Infect Dis J 1994; 13(11): 983-989. • All individuals with functional or anatomic asplenia Torzillo PJ, Morey F, Gratten M, Murphy D, Matters R, Dixon J. Changing epi- intravenous route should be used initially in patients who have demiology of invasive pneumococcal Disease in central Australia prior to conjugate hypoxia and other signs of severe pneumonia. • Adults with chronic disease including chronic lung disease, vaccine :a 16 year study. Vaccine.25(13):2007 cardiac failure, chronic alcoholism, chronic liver disease or Morris PS. Leach AJ. Halpin S. Mellon G. Gadil G. Wigger C. Mackenzie G. Wil- Identifying the pathogen nephrotic syndrome son C. Gadil E. Torzillo P. An overview of acute otitis media in Australian Aborigi- If the patient has sputum, a gram stain may be helpful. In general, nal children living in remote communities. Vaccine. 25(13):2389-93, 2007. Chang AB, Chang CC, O’Grady KA, Torzillo PJ. Lower respiratory tract infec- sputum cultures have relatively low sensitivity and low specificity • Patients with HIV infection which is asymptomatic or associ- tions.in Health Issues in Indigenous children: an evidenced based approach for the and the culture of the sputum identifies the pathogen in less than ated only with lymphadenopathy General Pediatrician. Pediatr Clin N Am 56; 1303-1321:2009. 50% of cases of pneumonia. Blood cultures, if positive, are quite • Patients with chronic and surgically incorrectable cerebrospi- O’Grady KA, Taylor-Thomson D, Chang AB, Torzillo PJ, Morris P, Macken- specific but the sensitivity is low. It is good clinical practice to zie G, Wheaton G, Bauert P, De Campo M, De Campo J, Ruben A. High rates nal fluid leak of World Health Organization-defined radiologically confirmed pneumonia in take blood cultures (in addition to sputum cultures) on patients Northern Territory Indigenous children. Med J Aust, 192(10):592-5, 2010 admitted to hospital with pneumonia. In summary, the majority • Selected groups of Aboriginal adults in regions with high Chang AB, Torzillo PJ. Respiratory Infections (including Bronchiectasis) in Abo- of patients with pneumonia receive empirical antibiotic therapy attack rates riginal Primary Health Care.An evidence based approach. 2nd Ed Eds. Couzos S because the pathogen is not often identified. and Murray R. Oxford University Press, Melbourne. 2007. • Patients over 2 years of age with nephrotic syndrome Specific therapy Optional references: Author: Clinical Professor Paul John Torzillo, Medicine If a bacterial pathogen has been identified in the laboratory, its Rang HP, Dale MN, Ritter JM. Pharmacology. (5th ed.) Churchill Livingstone, sensitivity to antibiotics will also be determined. This profile will 639 - 649. assist in the selection of additional antibiotic therapy if the initial Therapeutic guidelines : antibiotic. Publisher North Melbourne, Vic. : Therapeutic Guidelines Limited 2006. Edition 13 ed. therapy is ineffective. Author: Professor John Paul Seale, Pharmacology Pharmacokinetics of antimicrobial agents

59 3.07 - Difficult Circumstances // Pneumonia & Otisis Media 6. Epidemiology Of Respiratory Infection The epidemiology of acute respiratory infection (ARI) depends on: highest recorded incidence of pneumococcal bacteraemia in the world, which was associated with pneumonia in about one third of cases. • exposure to infectious agents (primarily environmental factors) ARIs are over three times more common in Indigenous people living and in NSW compared with non-indigenous. Take a look at the NSW • host susceptibility (primarily age and underlying disease) Chief Health Officer’s Report athttp://www.health.nsw.gov.au/public- health/chorep/atsi/atsi_reshos.htm to see figures for hospitalization Case definition due to ARI from 1993-2005. Aboriginal and Torres Strait Islander Studies of the epidemiology of ARI often rely on clinical case defini- children are recommended to have pneumococcal vaccination at 2, 4 tions, which in turn are based on anatomic categories such as pharyn- and 6 months of age as part of the Australian Standard Vaccination gitis and otitis media (upper respiratory tract infection - URTI) and Schedule. tracheitis, bronchitis, bronchiolitis and pneumonia (lower respiratory tract infection - LRTI). Pathogens causing ARI by age The probability of various pathogens is strongly influenced by age. -Vi Case ascertainment ral infection is most common in young children. Respiratory syncytial Case ascertainment of ARI depends on the case definition used and virus (RSV) is the most important viral cause of ARI throughout the the population studied. Groups such as hospitalised patients are easier world. RSV causes about 80% of bronchiolitis and is responsible for to identify, but may not be representative of the community. All cases an estimated 2 - 3 % of hospitalisations in the first two years of life. are identified over a period of time in a cohort (such as all members of RSV can cause recurrent infections in older children and adults, but a particular medical practice or a well-defined community), popula- these are not associated with such high morbidity. Other viral causes tion-based incidence estimates can be made, allowing assessment of of ARI include influenza and parainfluenza viruses and adenoviruses. the need for community-wide programmes, such as immunisation against a particular pathogen. Mycoplasma pneumoniae infection can occur in the very young and the very old, but its incidence is maximal from school age to young Respiratory infections in the general community adults. Legionella infection is most common over the age of 50 years, Leder et al reported on health diaries for 600 families in Melbourne unless pre-existing lung disease is present, and is rarely recognised in from 1997-1999. More than 80% of participants reported at least one children. Chlamydia trachomatis, acquired from the birth canal, can respiratory episode over 15 months with an average of 2.2 respiratory cause pneumonia in infants under six months of age, while Chlamydia episodes per person per year. The mean duration of an episode was pneumoniae has been primarily recognised in young adults. 6.3 days. Children under 2 years of age were the most likely to have a respiratory infection. One in three (27.7%) of infections were associ- Viral infection frequently precedes and predisposes to bacterial infec- ated with a doctors visit and one in four (23%) necessitated time off tion. Streptococcus pneumoniae is the most important bacterial cause work or school. of both otitis media and pneumonia. Haemophilus influenzae, of cap- sular type b and, more commonly, unencapsulated strains, is the next ARI in children most important cause of ARI including bronchitis. Other important, Overall burden of ARI but less common, bacterial causes of community-acquired pneumonia ARI is the most common cause of illness in childhood, accounting for in normal hosts include Staphylococcus aureus and Streptococcus 50% of illness under 5 years and 30% 5 to 12 years. Of these, 95% pyogenes. are URTIs, which includes colds, pharyngitis and otitis media. The ARI in adults peak incidence is between two and four years of age, when 8 to 10 ARI occurs at a low but constant rate throughout adult life. The inci- episodes occur annually, falling to average adult levels of 4 to 6 per dence and severity of pneumonia in those under 65 years is increased year by 8 to 10 years of age. by underlying conditions such as HIV infection, chronic airway Lower respiratory tract infection disease and exposure to tobacco smoke. From the age of 55 - 60 years, there is a significant increase in the proportion of deaths due to res- Industrialised communities piratory disease in general and respiratory infection in particular. After The peak rate of LRTI is in the first year of life, with estimates of 75 years, there is a further steep increase in the incidence and severity about 25 episodes per 100 children per year from a number of of pneumonia, particularly bacteraemic pneumococcal pneumonia. community-based studies in the USA. No comparable Australian data Immunisation against influenza and pneumococcal infection are are available. The rate falls to 10 to 12 episodes per 100 children per important for prevention of premature death from ARI in the elderly. year by age 5 and to about 5 episodes in adolescence. Bronchiolitis In rural Aboriginal communities, immunisation of younger adults accounts for most of the LRTI (10 to 15 per 100 per year) in the first against pneumococcal disease is indicated, as disease occurs at a much year, with about 1% of children admitted to hospital with bronchioli- earlier age. tis. Pneumonia is less commonly diagnosed, with an incidence of two to four per 100 in the first three years of life, falling to one per 100 Optional references: by adolescence. It is estimated that about 10% of cases of recognised Leder K, Sinclair MI, Mitakakis TZ, Hellard ME, Forbes A. A community-based pneumonia are hospitalised. Studies in the UK and the USA estimated study of respiratory episodes in Melbourne, Australia . Aust N Z J Public Health. 2003;27(4):399-404. that about 5% of children have been admitted to hospital with a Phelan PD, Landau LI, Olinsky A. Epidemiology of acute respiratory infections. respiratory illness by the age of four years. In: Respiratory illness in children. (3rd ed.) Oxford: Blackwell, 1991; 24 - 46. Denny FW, Clyde WA. Acute lower respiratory tract infections in non-hospitalised Indigenous populations and non industrialised countries children . J Pediatr 1986; 108(5): 635-646 Both the incidence and severity of ARI are greatly increased in less Crofton J. Respiratory disorders - an introductory review. In: Weatherall DJ et al, advantaged groups. Worldwide, it is estimated 96% of the deaths in eds. Textbook of Medicine. Oxford 1994. children under 5 years are in the third world and one third are due to Lim I, Shaw DR, Stanley DP, Lumb R, McLennan G. A prospective hospital study pneumonia. In Australia, rates of ARI and chronic respiratory morbid- of the aetiology of community-acquired pneumonia. Med J Aust 1989; 151(2): ity are much higher in rural Aboriginal children than in non-Aborig- 87-91. Author: Professor Peter McIntyre, Paediatrics and Child Health inal populations. Aboriginal children in Central Australia have the

60 3.07 - Difficult Circumstances // Pneumonia & Otisis Media 7. Causes Of Deafness Deafness infers a near total loss of hearing - hearing loss is the tion using a hearing aid. A profound hearing loss often prevents a term for partial loss (similar to blindness and visually impaired). child from acquiring speech even using the best hearing aids available. In the past children were taught mostly by ‘sign’ but today Classification The normal range of hearing is from 15 Hz to 15 there is a parental choice as the early fitting of a cochlear implant kHz. Hearing loss is measured in decibels hearing loss at frequen- will provide the means to acquire useable speech. cies from 125 Hz , 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz, 8 kHz. A whisper reaches 30 dBHL; normal conversational voice, Hearing loss is is one of the commonest congenital problems and 70 dBHL, and shouting, 90 dBHL. early diagnosis is essential for effective therapy. Hearing loss may be low frequency (125 Hz-1 kHz), mid-fre- SWISH testing (Statewide Infant Screening of Hearing) is now quency (1 kHz-4 kHz), or high frequency (4-8 kHz). carried out on all newborn babies in NSW. Automated auditory brainstem potentials are recorded within the first 48 hours of life. Conductive hearing loss is due to loss of conduction of sound to the cochlea due to a problem in the outer or middle ear ( eg. OME (‘glue’) ear, tympanic membrane perforation or otosclerosis. Hearing loss in adults Presbyacusis or ‘old age hearing loss’ causes a progressive high frequency sensory hearing loss. By the Sensory hearing loss is due to loss of the sensory structures (hair- age of 65 years, one third of the population have lost hearing cells) in the cochlea (eg. Presbyacusis, noise induced hearing loss, affecting the speech range. Hearing loss causes social isolation but Meniere’s disease). modern hearing aids are very effective in countering the problem. Neural hearing loss is due to auditory nerve dysfunction (eg Noise induce hearing loss (NIHL) causes a high frequency sensory acoustic neuroma). loss often peaking at 4 kHz. Noise levels in excess of 90 dBA over 8 hours, 93 dBA over 4 hours, 96 dBA over 2 hours, etc can cause Mild hearing loss 25-50 dBHL hearing losses. Compensation is available if the employer is found Moderate hearing loss 50-70 dBHL to be responsible for the hearing loss of an employee. Severe hearing loss 70-90 dBHL Profound hearing loss (deafness) 90 dBHL or worse Other forms of hearing loss commonly affecting adults are middle Hearing loss in children A mild loss causes minimal problems ear disease, otosclerosis, Meniere’s disease, autoimmune hearing in an adult but may lead to inattention and poor performance in loss and Cogan’s syndrome, ototoxic medications, and acoustic school age children. The commonest cause is OME (‘glue’) ear. neuroma. A moderate hearing loss is a social inconvenience and requires Optional references: treatment surgically or using a hearing aid. Lecture notes on ‘Diseases of the Ear, Nose and Throat’ PD Bull Blackwell Science Pty Ltd, Carlton, Victoria ( Tel 03 9347 0300) A severe hearing loss prevents the acquisition of normal speech Author: Professor William Gibson, Surgery communication skills in children and urgently requires amplifica-