4.1 THE CLINICAL PRESENTATION OF CHEST DISEASES 347

Table 1 Modified Borg Scale∗ Chapter 4.1 Number Verbal description 10 Severe The clinical presentation of chest 9 diseases 8 Moderately severe 7 D. J. Lane 6 5 Moderate 4 The predominant symptoms of chest diseases are cough, breath- 3 lessness, chest pain and haemoptysis. 2 Slight 1 0 None

∗Modified from Borg, G.A.V. (1982). Psychological basis of perceived exertion. Cough Medical Science of Sports and Exercise, 14, 377–81. The cough reflex is initiated by stimulation of receptors in the larynx and major airways, by mechanical or chemical irritants. The afferent fibres run in branches of the superior laryngeal nerve and vagus. Haemoptysis A dry cough, short and repeated, is heard in tracheobronchitis A definite cause is only found in some 50 per cent of cases and it is and early pneumonia. In laryngitis the sound is hoarse and harsh. important to be sure that the blood does truly come from the lungs In abductor paralysis of the vocal cords it is prolonged and and not from the nose or gastrointestinal tract. Haemoptysis is a blowing. Weakness of thoracic muscles lessens the expulsive force classical presenting feature of tuberculosis, carcinoma, and bronchi- and cough may be suppressed when there is severe thoracic or ectasis, but there are many other causes, for instance Goodpasture’s upper abdominal pain. Cough with expectoration in the morning syndrome, mitral valve disease, coagulation defects, or even endo- is characteristic of chronic bronchitis and large volumes of yellow metriosis. It is rare in pulmonary embolism, when it reflects infarction sputum throughout the day suggests bronchiectasis. Bouts of of the lung. coughing when eating point to oesophageal or neuromuscular disease causing aspiration. A dry cough over many weeks can Treatment of cough signify a neoplasm. A cough may be dry because there is nothing Cough suppressants act centrally; most are opiate derivatives. They to produce, because secretions are swallowed, because of muscular are invaluable in terminal bronchial carcinoma. Atropine can be weakness, or because secretions are too viscid. useful to reduce the production of bronchial mucus and corti- costeroids reduce secretion in alveolar cell carcinoma and in asthma. Phlegm and sputum Aerosolized water is an effective expectorant. Volatile oils probably Phlegm from the lower respiratory tract is often combined with act as irritants. Mucociliary clearance increases under the influence secretions from the nose and pharynx and saliva to form sputum. of guiaphenesin, inhaled
-adrenergic agonists, or hypertonic saline. In health, only about 100 ml of phlegm is produced each day Mucolytic agents are ineffective. A source of life threatening haemo- and most of this is swallowed. Intrabronchial mucus exists in two ptysis is only rarely found at bronchoscopy, but topical adrenaline, layers, one of low viscosity and high elasticity touching the cilia balloon tamponade, or cold saline lavage may help, as may em- and above this, a more viscous layer. Elasticity of phlegm depends bolization of the appropriate bronchial artery. on the rate of beating of the bronchial epithelial cilia. Airway mucus is 95 per cent water, the remainder being serous fluid and Breathlessness glycoprotein. There is a shift towards glycoprotein production in chronic bronchitis and greater transudate formation in asthma. A complaint of breathlessness may reflect true dyspnoea, hyperpnoea, Breakdown of leucocytes in infection increases the DNA content or hyperventilation. The history is critical in detecting the true nature of the complaint and the clinician must evaluate the quality of of sputum, making it less viscid and debris of cells and micro- breathlessness, its timing, severity, and the circumstances which pre- organisms give it a yellow colour. Non-infected sputum is clear cipitate or relieve it. and often jelly-like (mucoid). Viscid mucoid sputum often with pellets or branching plugs is seen in asthma. City dwellers produce Quality Asthmatics tend to recognize wheeze and usually find it more grey sputum. In lower respiratory tract infection, pus mixed with difficult to breathe in than out. A sense of suffocation is a feature of mucus produces mucopurulent sputum, but pure pus suggests a pulmonary oedema or massive pleural effusion. Phrases like I can’t lung abscess or stagnant bronchiectatic cavity. Anaerobic organisms fill my lungs properly’ suggest psychogenic breathlessness, but muscle ff give sputum a particularly o ensive odour. Large quantities of weakness must be excluded. watery mucus may come from alveolar cell carcinoma. Laboratory examination of sputum may be unrewarding in de- Severity A simple visual analogue scale relating breathlessness to tecting infecting organisms, but cytology may reveal an underlying activity (Table 1) can be useful, but no scale deals with breathlessness carcinoma and eosinophilia suggests airway allergy. which is significantly variable. 348 RESPIRATORY DISEASE 4

Table 2 Conditions causing breathlessness classified by rate of onset depress respiration; there has been a sad failure to find opiate derivatives with a more selective action on breathlessness. 1. Dramatically sudden: over 4. Chronic: over months or years minutes Chronic airflow obstruction Pneumothorax Diffuse fibrosing conditions Pulmonary embolism Chronic non-pulmonary causes, Chest pain Pulmonary oedema e.g. anaemia, hyperthyroidism The greater part of the lower respiratory tract is insensitive to pain. 2. Acute: over hours 5. Intermittent: episodic Acute pulmonary infiltrations, breathlessness Most parenchymal lung disorders proceed to an advanced state e.g. allergic alveolitis Asthma without pain. However, the parietal pleura is exquisitely sensitive Asthma Left ventricular failure to painful stimuli and unpleasant sensations can arise from the Left ventricular failure tracheobronchial tree. Pneumonia 3. Subacute: over days Pleurisy Pleural effusion Bronchogenic carcinoma Typical pleural pain is sharp and accentuated by respiratory move- Subacute pulmonary ment. Afferent pain fibres from the central diaphragm run in the infiltrations, e.g. sarcoidosis phrenic nerve to the cervical cord (C3/4), giving referred pain in the shoulder tip. The outer diaphragm is served by intercostal nerves (T7–12), causing referred pain to the upper abdomen. Most conditions giving rise to pleuritic pain are acute and in- flammatory in origin: either infection or infarction. Recurrent pleurisy should suggest bronchiectasis or embolism. In pleural effusion, the Timing and occurrence The rate of onset can give a clue to diagnosis typical pleuritic pain largely disappears and is replaced by a dull (Table 2), as can the circumstances precipitating breathlessness. ache. Pleural fibrotic disease is rarely painful, but pleural neoplasia Psychogenic breathlessness bears no relation to exertion. Breath- frequently is. A superior sulcus tumour of bronchial origin (Pancoast’s lessness made worse by lying flat (orthopnoea) is characteristic of left tumour) infiltrating the brachial plexus gives very severe pain in the ventricular failure or diaphragmatic paralysis. Nocturnal wakening shoulder and arm. with severe breathlessness (paroxysmal nocturnal dyspnoea) suggests left ventricular failure. The asthmatic wakes in the night with breath- Pain from the chest wall lessness, coughing, and wheezing. Postexertional breathlessness and Chest-wall pain can mimic pleurisy. Epidemic myalgia or Bornholm the triggering of wheezing breathlessness by irritants and allergic disease (see Chapter 16.22) is a bothersome manifestation of Coxsackie stimuli also suggest asthma. B infection which can involve the intercostal muscles (pleurodynia). The pre-eruptive stage of thoracic herpes zoster gives a stabbing pain. Investigation of the breathless patient Costal cartilage pain is generally not inflammatory, but can be If the clinical history points to chest disease simple lung function troublesome. Rib fractures can present diagnostic problems. Metastatic tests and radiology are the most useful investigations. Spirometry will disease of bone may be symptomatic before radiological change is define three groups; normal, an obstructive pattern, or a restrictive evident. pattern (see Chapter 4.3). The chest radiograph is of most value in Fleeting transient chest pains are often part of chronic, somatized furthering the diagnosis of conditions giving a restrictive pattern. The anxiety states. farther investigation of a patient with airflow obstruction is dealt with in Chapters 4.14 and 4.17. Breathlessness in a patient with Central chest pain normal spirometry and a clear chest radiograph presents special Sensations arising from the major airways are unpleasant and referred problems. Asthmatics, when well may have normal lung function and to the anterior chest wall. Tracheal inflammation causes a raw, painful cardiac conditions may be occult or intermittent. Neurological or sensation retrosternally. Persistent coughing can itself lead to soreness muscular disorders affecting the muscles of respiration must always in the upper airways and trachea. be considered and pulmonary hypertension is all too easily missed. The mediastinal structures of the thorax are responsible for a Hyperthyroidism and anaemia should not be forgotten as causes of multitude of pains. Of central pulmonary lesions likely to give breathlessness. Clues to psychogenic breathlessness include the sensation of in- mediastinal pain, neoplasia is the most likely culprit. ability to take a full breath, irregular breathing, paraesthesiae, and dizziness. Some patients with anxiety about their heart may also suffer palpitation and a stabbing left submammary pain. Other pulmonary symptoms A harsh inspiratory wheezing sound arising from obstruction in the Treatment larynx or major airways is termed stridor. Wheeze is the externally If management of the underlying condition does not relieve audible counterpart of the sounds heard with the stethoscope in breathlessness, symptomatic treatment is unsatisfactory, but chronic asthma and obstructive bronchitis. bronchitics of the pink puffer’ type can be helped by diazepam In response to changes in atmospheric conditions or to the or promethazine. Opiates reduce breathlessness but can dangerously inhalation of dusts or fumes, the patient with irritable airways 4.1 THE CLINICAL PRESENTATION OF CHEST DISEASES 349 will respond with cough, tightness in the chest, wheeze, or breath- Percussion of the chest lessness. In percussion the sides of the chest must be compared from identical sites. A dull note lacks resonance and is higher in pitch and softer than normal. It signifies the presence of solid tissue or General history in the patient with fluid. It is important to delineate the surface markings of the pulmonary disease dullness. Consolidation will follow the outline of the affected lobe, ff Emphasis in the history should be given to the cardiovascular system, whereas the upper limit of a pleural e usion will be determined fluid retention, deep venous thrombosis, the upper respiratory tract, by gravity. the skin, and the locomotor and nervous systems. These may be A hyper-resonant note occurs over hyperinflated lung as in em- pointers to metastatic spread or the non-metastatic manifestations physema or an air-filled space (bulla or pneumothorax). of malignant disease. The past history may reveal atopy or tuberculosis. Previous chest radiographs may be obtainable for Auscultation of the chest comparison. Breath sounds A smoking history is essential. Alcohol, and steroid and immuno- In the normal upright lung, breath sounds are loudest at the apex in suppressive therapy will depress antibacterial defences, and a detailed early inspiration and at the bases in midinspiration. During expiration, ff drug history is essential because of toxic e ects on the lungs (see normal breath sounds rapidly fade. Bronchial breathing, higher in Chapter 4.34). pitch and more blowing in quality, is heard over airless lung as in A complete occupational and environmental history is of the consolidation, atelectasis, or dense fibrosis. Very quiet breath sounds utmost importance. Both inorganic and organic materials are hazards are heard over hyperinflated lungs as in emphysema or when breath to the chest (see Chapter 4.33). Certain working environments may sounds are prevented from reaching the chest wall by a layer of air lead to exposure to organisms likely to cause pulmonary infection. or fluid (pneumothorax, pleural effusion, malignancy). Finally, certain disorders have a familial predisposition. These include asthma and other atopic diseases (see Chapter 4.14) and Adventitious sounds cystic fibrosis (see Chapter 4.15). Crackles and interrupted non-musical sounds may be coarse or moist when they are due to the movement of sputum in large airways. Fine midinspiratory crackles are characteristic of pulmonary Physical signs in pulmonary disease oedema and fibrosing alveolitis. Occasionally, a single mid to late Inspection of the chest inspiratory ‘squawk’ is heard in patients with a variety of pulmonary The normal respiratory rate is around 10 to 14 per min. A rate above fibroses. 20 per min is seen in pneumonia, interstitial lung disorders, hypoxia, Wheezes signify obstruction in airways. A sound of single pitch and anxiety. Painful conditions of the chest or upper abdomen cause (monophonic) which cannot be altered by coughing to shift mucus, an abrupt stop to inspiration. Deep sighs and an irregular breathing signifies localized obstruction in a major airway. Several sounds pattern are seen in psychogenic breathlessness. A regular alternation of varying pitch (polyphonic) heard randomly in inspiration and of apnoeic periods with increasing ventilation characterizes Cheyne– expiration are typical of the widespread airways obstruction of asthma Stokes respiration, usually associated with cerebral lesions or severe and chronic obstructive bronchitis. heart failure. A pleural rub, the diagnostic sound of pleurisy, is a superficial Poor movement of the chest on one side only always indicates grating synchronous with late inspiration. Inflammation of the pleura pathology on that side. Generally poor expansion is seen in severe close to the heart can give a friction rub that synchronises with the airflow obstruction, with indrawing of intercostal spaces during heart beat but will cease if the breath is held. inspiration. Voice sounds An increased anteroposterior diameter to give a ‘barrel chest’ is as often a sign of osteoporotic kyphosis as it is of the hyperinflation of A long sound such as ‘ninety-nine’ is transmitted by normal lung, chronic airflow obstruction. Pectus carinatum (pigeon chest), an but not by air space or fluid, and will pass through solid lung with outward protuberance of the sternum, may reflect severe attacks of undue clarity, even allowing whispered sounds to be heard (whispering asthma in childhood. The opposite, pectus excavatum (depressed pectoriloquy). Certain physical characteristics of solid lung allow low sternum), is a congenital anomaly. Scoliosis of skeletal origin is of frequency sounds to be filtered out, leaving a sound of bleating or importance because of the severe impairment of respiratory movement nasal quality (aegophony); this is particularly noticeable over collapsed ff that it causes (see Chapter 4.37). Localized collapse and fibrosis may lung adjacent to a pleural e usion. draw in the adjacent rib cage. The relevance of the general examination in Palpation of the chest respiratory disease The trachea should be localized in the suprasternal notch with the Overall appearance index finger. Deviation of the trachea to one side is either due to Obesity places an added burden on the respiratory system, and can apical fibrosis pulling it to the affected side or a mass pushing the be an unfortunate complication of corticosteroid therapy. Weight loss trachea across to the opposite side. The position of the apex beat can is a feature of emphysematous obstructive lung disease, malignancy, reflect pressure against or traction on mediastinal structures, or be and cystic fibrosis. Severe kyphoscoliosis can lead to hypoventilation, due to intrinsic cardiac disease. and Marfan’s syndrome is associated with pneumothorax. 350 RESPIRATORY DISEASE 4

Table 1 Methods of investigation Before submitting the patient to further investigation it is important that the CXR is technically adequate and correctly interpreted. CXR ...... Computed tomography (CT), including high resolution CT (HRCT) ...... Techniques in thoracic imaging Ultrasound ...... Chest radiography Magnetic Resonance Imaging (MRI) ...... The standard view is a posteroanterior (PA) projection, taken with Radionuclide imaging ...... the patient erect and the anterior chest wall against the film cassette. Pulmonary and bronchial angiography This view may be supplemented by a lateral chest radiograph and, ...... less often, oblique views of the ribs or a lordotic view to demonstrate Superior vena cavography ...... more clearly the apices, although the advent of computed tomography Percutaneous lung biopsy (CT) has decreased their importance. The lateral view aids assessment of the retrocardiac and peridiaphragmatic areas and, with experience, the hila and major airways. The normal CXR and anatomy are shown Cyanosis in Fig. 1. Peripheral cyanosis in cold weather will leave the tongue still pink, whereas in central cyanosis the tongue will be blue. Most patients with a saturation of 90 per cent or less will appear cyanosed. Cyanosis is less marked in severe anaemia and more obvious in polycythaemia.

The skin and eyes Eczema and urticaria point to an atopy. Erythema nodosum is a classical presentation of sarcoidosis. It may also be found in primary tuberculosis. Patients with diffuse neurofibromatosis and tuberous sclerosis can both develop a severe pulmonary fibrosis.

Clubbing of the fingers Loss of the natural angle between the nail and the nail bed and a boggy fluctuation of the nail bed are cardinal signs of clubbing. Among chest disorders the causes include: (a) suppurative disease (bronchiectasis and empyema); (b) fibrosing alveolitis and asbestosis; (c) malignant disease of the bronchus and pleura. If finger clubbing is associated with hypertrophic pulmonary osteoarthropathy, malig- (a) nancy is present in 95 per cent of cases.

Head and neck Neurological disease of the pharynx or structural abnormalities of the larynx encourage aspiration and respiratory tract infection. A short thick neck, retrognathia, and a large uvula predispose to sleep apnoea. A goitre may be large enough to compress the trachea and cause stridor. Signs in the neck of intrathoracic malignancy are cervical lymphadenopathy and superior vena caval obstruction.

Investigation of respiratory disease Chapter 4.2 (b)

Thoracic imaging Fig. 1(a), (b) Normal radiographic anatomy. (a) posteroanterior chest F. V. Gleeson radiograph: (1) trachea; (2) aortic arch; (3) left main pulmonary artery; (4) right main pulmonary artery; (5) right artial border; (6) left atrial appendage; (7) left ventricular border; (8) right ventricle; (9) right dome of diaphragm; (10) costophrenic angle; (11) breast shadow. (b) Lateral chest radiograph; (1) The mainstay of radiographic investigation of respiratory disease trachea; (2) scapulae; (3) anterior aortic arch; (4) right pulmonary artery; (5) remains the chest radiograph (CXR) although there are now a left pulmonary artery; (6) right ventricle; (7) breast shadows; (8) gastric multitude of additional imaging techniques to aid diagnosis (Table 1). bubble under the left hemidiaphragm; (9) left main bronchus. 4.2 THORACIC IMAGING 351

Table 2 Indications for CT of the thorax a number of advantages and disadvantages when compared to CT (Table 3). Suspected or proven lung cancer. Confirms the presence of a mass, and is part of staging procedure (in conjunction with other investigations) Radionuclide imaging ...... Ventilation–perfusion imaging is, at present, the most frequently Elucidation of an abnormal mediastinal or hilar contour on CXR...... used method for diagnosing pulmonary emboli. Minute particles of To aid diagnosis in patients with suspected diffuse lung disease. technetium-99m labelled macroaggregates of albumin are injected ...... Investigation of haemoptysis. intravenously and the patients thorax scanned in multiple projections...... The gamma rays detected produce an image dependent on the degree Investigation of pleural disease...... of pulmonary perfusion, a significant defect representing an area of Investigation of suspected pulmonary emboli (spiral CT). diminished or absent perfusion. These images are compared to the ...... Investigation of patients with large airways disease (spiral CT). ventilation images produced when the patient inhales either of the ...... inert gases xenon-133 or krypton-81m, or aerosolized technetium- To aid percutaneous needle biopsy or chest drain insertion...... 99m. Perfusion defects not matched by ventilation defects are used As part of the staging procedures in patients with malignancies that to diagnose pulmonary embolic disease (Fig. 5). The scans must be metastasize to the lung or mediastinal lymph nodes. interpreted in conjunction with a current CXR and clinical in- formation. Due to the failure to directly visualize clot using isotope scanning, the diagnosis is given as a likelihood of embolic disease; Although most CXRs are performed using conventional radio- unfortunately most patients’ scans produce an indeterminate like- graphic equipment, more recently new techniques such as digital lihood of emboli (see Chapter 2.30). Because of this, additional tests radiography have been introduced. Digital radiography enables the such as pulmonary angiography, spiral CT, and ultrasound of the CXR to be viewed on a monitor as well as film, may be stored and peripheral veins are often performed. retrieved in a similar fashion to other digital data, and has additional advantages such as data manipulation to aid diagnosis and improve Pulmonary and bronchial angiography: superior image quality even from technically inadequate radiographic ex- vena cavography posures. Pulmonary angiography is performed by injecting contrast into the Ultrasound pulmonary arteries catheterized via peripheral venous puncture (ante- The main use of ultrasound is for the localization and characterization cubital, jugular, or femoral vein). Thrombus if present is visualized of pleural fluid collections prior to aspiration or drain insertion. as a filling defect within the pulmonary arteries. Bronchial angiography Ultrasound may be used to differentiate pleural thickening from fluid is performed with selective catheterization of the bronchial arteries in cases of uncertainty post CXR. It is also of value in assessing arising from the aorta by a catheter introduced via puncture of the pleural invasion by cancers abutting the pleura and may be used to femoral artery. It is usually performed to enable embolization of guide percutaneous needle biopsy in these cases. hypertrophied bronchial arteries in patients with bronchiectasis and life-threatening haemoptysis. Superior vena cavography is performed Computed tomography by catheterization of the superior vena cava via peripheral venous The ability of CT to delineate structures that are either not clearly puncture, most commonly in patients with suspected vena cava defined or in some cases not visualized at all on CXR is responsible stenosis or obstruction. It is also now possible to insert a self- for its increased use in medicine (Table 2). The advent of Spiral expanding metal stent at the site of narrowing at the same time and CT has further expanded its role. Conventional CT produces cross- relieve the obstructive symptoms. sectional images of varying thickness of the thorax. Section thickness ranges from 1 mm to 10 mm. Normal CT anatomy of the Percutaneous needle biopsy mediastinum is shown in Fig. 2. The use of thinner sections, high Biopsy of pulmonary and mediastinal masses are most commonly resolution CT (HRCT), has enabled more accurate diagnosis in performed to diagnose malignancy in patients with a mass seen on patients with diffuse lung disease (Fig. 3). Conventional, 10 mm CXR. Lung needle biopsy is most commonly performed after sputum sections are of value in assessing the mediastinum, major airways, cytology and bronchoscopy have failed to produce a tissue diagnosis. the pulmonary parenchyma for nodules, and the pleura. Spiral CT The most common complications are pneumothorax and haemo- differs from conventional CT in acquiring a volume data set rather ptysis. The frequency of complications relates to needle size, number than cross-sectional data and also achieving this in a greatly of biopsy attempts, depth of lesion from the chest wall, and lung reduced time. It is of value in assessing the vessels and major function. Despite the relative safety of needle biopsy, it should only airways within the thorax. The ability to acquire a volume of data be performed after consideration of the risk to the patient and the enables analysis and display of the images in multiplanar formats, benefit of obtaining a diagnosis. further enhancing CT’s diagnostic capabilities.

Magnetic resonance imaging (MRI) Common radiological signs of disease Protons within the body become excited when placed in a strong Pulmonary consolidation magnetic field irradiated with a radiofrequency signal. Selective This occurs when the normal air-filled spaces distal to the bronchi absorption of frequencies produces a magnetic resonance image. are filled with either fluid or solid material rather than air. This MRI is able to produce an image in any plane (Fig. 4) and has produces the characteristic radiological sign of an air bronchogram, 352 RESPIRATORY DISEASE 4

(a) (b)

(c) (d)

Fig. 2(a)–(d) CT with contrast enhancement to show the normal anatomy at four levels through the mediastinum: (1) trachea; (2) superior vena cava; (3) brachiocephalic artery; (4) left common carotic artery; (5) left subclavian artery; (6) oesophagus; (7) aortic arch; (8) azygos vein; (9) ascending aorta; (10) descending aorta; (11) main pulmonary artery; (12) right pulmonary artery; (13) left pulmonary artery; (14) right main bronchus; (15) left main bronchus; (16) left atrium; (17) left inferior pulmonary vein; (18) segmental bronchi of the left lower lobe; (19) right atrium; (20) right ventricular outflow; (21) left ventricle.

whereby the branching bronchi are clearly visualized against a back- associated with pulmonary oedema and lymphangitis carcino- ground of increased radio-opacification. Consolidation may be focal matosis, but may also occur in association with infection and or diffuse, and the most common causes are given in Table 4. other causes.

Pulmonary collapse Reticular and reticular–nodular shadowing This may either involve a subsegment or segment of a lobe, a complete This term is used to describe innumerable small linear opacities or lobe, or an entire lung, dependent on the cause and the site of linear and nodular opacities that produce the appearance of a net or obstruction. Characteristic PA CXRs demonstrating lobar collapse are a net that has small nodules superimposed upon it. These terms are shown in Figs 6 to 10. usually used to describe pulmonary interstitial abnormalities such as pulmonary fibrosis. Septal lines These represent thickening of the normal interlobular septa within Pulmonary masses and nodules the lung. Commonly called Kerley B lines, when seen on the CXR, Masses represent lesions greater than 30 mm and nodules lesions 2 these are 1 to 2 mm in thickness and 5 to 10 mm in length, lying to 30 mm in size. Miliary nodules are 2 mm or smaller. The commonest perpendicular to the pleural surface. They are most frequently cause of a pulmonary mass is carcinoma. The differential diagnosis 4.2 THORACIC IMAGING 353

(a)

Fig. 3 High resolution CT of a patient with cryptogenic fibrosing alveolitis. The peripheral distribution of the disease and the fine detail of the small cystic air spaces in the destroyed fibrotic lung are clearly shown.

(b)

Fig. 5a, b A ventilation–perfusion radionuclide study (oblique views). The perfusion scan (a) shows a defect in the left mid-zone which is not matched on the corresponding view of the ventilation scan (b). The so-called mismatched defect is characteristic of a pulmonary embolus.

Fig. 4 Magnetic resonance image (coronal section) showing the relationship Radiological investigation of common of an apical bronchial carcinoma to the chest wall and adjacent mediastinum. There are enlarged subcarinal lymph nodes and a metastatic clinicoradiological problems deposit in the right adrenal gland (by courtesy of Dr P. Goddard). Haemoptysis Investigation is dependent on whether the CXR is normal or abnormal Table 3 Advantages and disadvantages of MRI compared to CT and whether there are other diagnostic markers of disease. Assuming that most patients are bronchoscoped, CT may be of value in staging Advantages Disadvantages tumour if detected by bronchoscopy or to provide a diagnosis such ♦♦No ionizing radiation exposure Poor spatial resolution as bronchiectasis if the bronchoscopy is negative, and it is now required ♦ Prolonged examination times thought that CT and bronchoscopy are complementary tests in ♦♦Multiplanar capability Expensive patients with haemoptysis. Contrast enhanced CT may enable a ♦♦Good contrast resolution Frequently not readily available diagnosis of pulmonary embolic disease to be made as the cause of ♦♦ Different image weighting Poor visualisation of pulmonary haemoptysis when not expected clinically. allowing good soft tissue parenchyma assessment Suspected pulmonary embolic disease Ventilation–perfusion scanning or contrast enhanced spiral CT are in patients with pulmonary nodules and miliary nodules is given in the accepted current methods of investigation. Isotope scans are Table 5. readily available and their clinical utility has been confirmed by 354 RESPIRATORY DISEASE 4

Table 4 Causes of pulmonary consolidation

Pulmonary oedema Neoplasm ♦ Cardiogenic/fluid overload♦ Bronchoalveolar cell carcinoma ♦ Adult respiratory distress sydrome♦ Lymphoproliferative disorders ♦ Inhalation injury (noxious gases) Blood ♦ Drug abuse ♦ Contusion ♦ Neurogenic (raised intracranial pressure or head injury) ♦ Infarction ♦ Renal disease ♦ Idiopathic pulmonary haemorrhage (Goodpasture’s syndrome) ♦ Traumatic (fat embolism) Other Exudative ♦ Sarcoidosis ♦ Infective consolidation ♦ Alveolar proteinosis ♦ Eosinophilic lung disease ♦ Collagen vascular disease ♦ Cryptogenic oranizing pneumonia ♦ Radiation pneumonitis

Fig. 6 Right upper lobe collapse. The CXR demonstrates increased opacity in the right upper zone, with a sharp lower border due to elevation of the minor fissure, elevation of the right hilum, and tracheal deviation to the right. Fig. 8 Right lower lobe collapse. The CXR demonstrates increased density at the right base, elevation of the right hemidiaphragm with obscuration of its medial portion, and inferior displacement of the right hilum. (Although not seen in this case, the right heart border often remains clear, and there is tracheal deviation to the right).

pulmonary artery thrombus and the studies available suggest that this technique is as useful as isotope studies, and may also be used to confirm or refute a diagnosis of emboli in patients with an in- determinate scan. Segmental/lobar/lung collapse CT may be used to stage tumour diagnosed on bronchoscopy, but is also of value if extrinsic compression is suspected by demonstrating tumour or lymphadenopathy as the cause. If tumour or lymph- adenopathy is confirmed on CT to be the cause of collapse and a tissue diagnosis has not been produced by bronchoscopy, percutaneous Fig. 7 Right middle lobe collapse. The CXR demonstrates increased right needle biopsy may be performed. mid-zone opacification, and obliteration of the right heart border. Opaque hemithorax Ultrasound may be used to confirm a large pleural effusion or mass multiple studies. Spiral CT is less readily available and a much less as the cause of an opaque hemithorax, particularly if a space-occupying well researched technique; despite this, the direct visualization of cause rather than complete lung collapse is suspected from the CXR. 4.2 THORACIC IMAGING 355

Table 5 Causes of pulmonary nodules

Solitary nodule Multiple nodules > 2mm in size ♦♦Granulomas Metastases ♦♦Bronchial carcinoma Sarcoidosis ♦♦Pulmonary metastasis Lymphoma ♦♦Pulmonary adenoma Bronchoalveolar cell carcinoma ♦♦Pulmonary hamartoma Multifocal pneumonia/abscesses ♦♦Arteriovenous malformation Fungal disease ♦♦Immunological disease Immunological disease (Wegener’s granulomatosis, ♦ Multiple arteriovenous rheumatoid disease) malformations ♦♦Hydatid disease Hydatid disease ♦ Fat emboli Multiple nodules < 2mm in size ♦ Miliary tuberculosis ♦ Fungal disease ♦ Pneumoconiosis ♦ Sarcoidosis ♦ Acute extrinsic allergic alveolitis Fig. 9 Left upper lobe collapse. The CXR demonstrates a veil-like increase in ♦ Metastases density in the left upper zone, elevation of the left hilum, and tracheal deviation to the left.

Fig. 10 Left lower lobe collapse. The CXR demonstrates a triangular density behind the heart, depression of the left hilum and loss of the medial border of the left hemidiaphragm.

Ultrasound may also be used to assist aspiration, drainage, or biopsy. Fig. 11 High resolution CT showing thickened and dilated subsegmental CT may be helpful in assessing mediastinal involvement if a tumour airways characteristic of severe bronchiectasis. is detected on bronchoscopy or ultrasound. Pleural effusion Ultrasound may confirm an effusion suspected on CXR, and dem- Mediastinal mass onstrate its nature. CT is of greater value than ultrasound in diagnosing Computed tomography should be used in most instances to confirm a malignant cause for the effusion, and in targeting a site for biopsy the presence of and the position of the abnormality, and in a large if required. number of cases will provide a specific diagnosis. MRI may be used Pulmonary mass as an alternative means of investigation, particularly in patients with suspected vascular abnormalities. Retrieving previous CXRs is often the single most valuable act when a mass is revealed on CXR. A significant increase in size, greater than 25 per cent increase in diameter, is suggestive of malignancy. Other Bronchiectasis features such as calcification or spiculation are less reliable indicators Moderate or severe bronchiectasis may be apparent on CXR. of benign or malignant disease. If malignancy is suspected, CT may However, significant numbers of patients with clinically-suspected be used to confirm the size and site of the mass, whether it is solitary bronchiectasis have a normal CXR, and these patients should now and whether associated with lymphadenopathy, and the presence or be investigated with HRCT (Fig. 11). The severity and extent of absence of metastatic disease. Percutaneous needle biopsy may be disease, that is the number of lobes involved, is readily assessed performed if a tissue diagnosis is required. by HRCT. 356 RESPIRATORY DISEASE 4

Diffuse lung disease myasthenia gravis, Guillain–Barre´ syndrome), the vital capacity gives In many instances the diagnosis may be apparent from the CXR, but a better indication of respiratory reserve than PEF. Portable meters HRCT has been shown to be more sensitive and specific in the are now available for bedside measurement of mouth pressures ff diagnosis of diffuse lung disease. The success of this technique has developed during maximum inspiratory e orts and maximum ex- ff been responsible for the decline in open lung biopsies performed in piratory e orts against a closed airway, and these provide a direct patients with diffuse lung disease. HRCT may also be used to target measurement of respiratory muscle strength. a site for open lung biopsy if a specific diagnosis may not be made, In patients requiring assisted ventilation in the intensive care unit, and in some cases to assess treatment response. a more detailed assessment of respiratory mechanics can be obtained with modern ventilators. Carbon monoxide transfer coefficient can Pulmonary nodules be measured in intubated patients with a rebreathing technique. Lung Combining clinical information, with the size, number, and dis- water and endothelial and epithelial integrity can be assessed using tribution of nodules on CXR and other abnormalities such as hilar radionuclide techniques and external counting. lymphadenopathy may enable a specific diagnosis to be made, al- though in the majority of patients without a leading clinical history Use of lung function tests in evaluating or examination this is not possible. Further radiological investigation is usually with CT, when specific features such as calcification may stable disease be helpful. If there are no specific clinical or radiological pointers, During the last 20 years, arterial blood gas analysis, oximetry, percutaneous needle biopsy may be valuable in diagnosing a malignant regional ventilation and perfusion scans, and PEF monitoring have or infectious cause. moved from the lung function laboratory to general hospital use. The standard tests widely available in lung function laboratories Further reading (Table 1) are most useful for assessing patients with airways ob- struction and restrictive lung disease. More elaborate methods are Armstrong, P., Wilson, A.W., Dee, P., and Hansell, D.M. (1994). Imaging of needed to evaluate breathing problems during sleep (Chapter 4.43), diseases of the chest, (2nd edn). Mosby Year Book, St Louis, MO. function of the diaphragm, the central control of breathing, regional Remy, J. and Remy-Jardin, M. (1996). Spiral CT of the chest. Springer- Verlag. lung function, and the pulmonary circulation (Table 2), and these Webb, W.R., Muller, N.L., and Naidich, D.P. (1996). High-resolution CT of are not so widely available. the lung, (2nd edn). Raven Press, New York. Tests of ventilatory mechanics Static lung volumes (Fig. 1) Chapter 4.3 Vital capacity (VC) is the volume expired from full inflation (total lung capacity (TLC)) to full expiration (residual volume (RV)) and Lung function testing can be measured by a spirometer or by integrating expired flow at N. B. Pride the mouth. A reduction in VC can occur with a reduction in TLC (as in lung fibrosis or inspiratory muscle weakness) or an increase in RV (as in emphysema, asthma, and other forms of intrapulmonary Bedside monitoring of respiratory function airway disease). In normal lungs resting end-tidal volume (functional in acute illness residual capacity (FRC)) is about 50 per cent of the fully expanded volume of the lung (TLC). Many tests of respiratory function depend on patient co-operation, FRC can be measured by: limiting application in acute disease where they could be particularly useful. Current monitoring is usually confined to continuous measure- 1. Gas dilution: a known volume and concentration of a relatively ment of oxygen saturation with oximetry, with frequent but in- insoluble foreign gas (usually helium) is allowed to mix with termittent measurements of arterial oxygen and carbon dioxide resident intrapulmonary gas, the volume of which is measured from the difference between the initial and final concentrations of pressures (PaO2, PaCO2), pH, and of peak expiratory flow (PEF) to follow airway function. Transcutaneous electrodes can indicate trends marker gas. In normal lungs a single breath test provides a reasonable estimate of lung volume, but multibreath methods in PCO2 with a rather slow time constant; values are considerably lasting more than 5 min may be required to achieve mixing higher than PaCO2. Often it would be useful to follow minute ventilation, for instance in acute respiratory failure or severe asthma, and avoid underestimates in patients with intrapulmonary airway but although chest wall movements (rib cage and abdomen) can be obstruction. detected by pneumographs or magnetometers, these devices are very 2. Whole-body plethysmograph method: the subject makes panting sensitive to changes in the position of the subject and therefore only efforts against a closed shutter while seated in a large air-tight provide qualitative information. The best solution at present is to chamber. As mass movement of gas is prevented, changes in place a portable pneumotachograph at the mouth for about 30 s. alveolar volume during this manoeuvre are due to compression Fortunately, PEF remains a valid measurement in distressed patients and rarefaction of alveolar gas which are reflected by reciprocal with severe asthma as the expiratory effort to achieve true PEF is changes in plethysmograph pressure, allowing absolute alveolar less in acute asthma than in the absence of airway obstruction; volume to be calculated using Boyle’s law. The volume inspired underestimates occur if PEF measurement is not preceded by a full during a maximum inspiration or expiration from FRC can then inflation. In gross weakness of the respiratory muscles (crises of be measured with a spirometer to derive TLC or RV. 4.3 LUNG FUNCTION TESTING 357

Table 1 Standard aspects of lung function assessed in lung function laboratories

Function Available techniques Applications Airway function, including response to Spirometry, peak expiratory flow Airflow obstruction due to asthma, emphysema, chronic dilator and constrictor agents Maximum flow–volume curves obstructive pulmonary disease, and extrathoracic airways Body plethysmograph (airway resistance and obstruction flow–volume curves) Tests can all be repeated after bronchodilators or bronchoconstrictor challenges (such as histamine, methacholine, exercise, cold air, specific allergens, etc.) Constrictor tests are useful for diagnosis of asthma, when initial airway function is normal ...... Lung volumes and distensibility Multibreath gas equilibration using helium Hyperinflation in airflow obstruction Diagnosis of restrictive lung disease Body plethysmography (thoracic gas volume) Lung compliance using oesophageal intubation Distinguish cause of restrictive lung disease Respiratory muscle function Mouth pressures during maximum inspiratory Systemic muscle disease and expiratory efforts Unexplained ventilatory failure or restrictive lung disease Severe hyperinflation ...... Pulmonary gas exchange Single-breath CO transfer coefficient Reduced with emphysema or interstitial lung disease Increased with intrapulmonary haemorrhage, asthma Pulse oximetry Detection of inefficiency in pulmonary gas exchange for

O2 or CO2

PaO2 and PaCO2 with simultaneous collection of expired gas: response to increasing inspired oxygen, etc...... Exercise capacity Treadmill, cycle, step ergometry or progressive Integrated performance of cardiorespiratory–muscular

walk with measurement of work, O2 system

consumption, heart rate, ventilation (O2 Assessment of response to treatment or training

saturation, PaO2, PaCO2) programmes Simple tests of walking distance against time Assess disability in severe disease

Table 2 Additional aspects of respiratory function assessed in some lung function laboratories

Function Available techniques Applications Disturbance of breathing, oxygenation, Monitoring oxygenation (oximeter) and chest Investigation of daytime somnolence, narcolepsy, and upper airway occlusion during sleep wall movements during sleep unexplained respiratory failure or polycythaemia Additional measurements to detect snoring, Adequacy of oxygen or other therapy in patients with movement, blood pressure, EMG, EEG, heart COPD or respiratory muscle weakness

rate, and transcutaneous PCO2 may be used ...... Diaphragm function Transdiaphragmatic pressure, EMG of Suspected diaphragm disease diaphragm and other muscles, electrical Further investigation of low mouth pressures with stimulation of phrenic nerves or magnetic maximum voluntary efforts stimulation of cervical nerve roots ...... Control of breathing Ventilatory response to induced hypoxia or Investigation of unexplained hypoxia or hypercapnia hypercapnia Non-invasive monitoring of chest-wall Disorder of breathing rhythm movements (pneumographs or magnetometers) ...... Pulmonary circulation Right-heart catheterization, Evaluation of pulmonary hypertension, resistance, and

Haemodynamics echocardiogram–Doppler studies response to O2 or vasodilator drugs ...... Epithelial/endothelial function Clearance of injected or inhaled∗ (e.g. radio- Progress of adult respiratory distress syndrome aerosol of DTPA) markers Lung damage after inhalation injury Interstitial lung disease ...... Regional lung function Distribution of ventilation with radiolabelled Pulmonary embolism gas or aerosols Distribution of blood flow with radiolabelled Assessment of suitability for pulmonary resection or microspheres bullectomy (plus tests of overall lung function)

∗May also reflect airway epithelial function. 358 RESPIRATORY DISEASE 4

5 TLC is often used to assess compliance in patients on assisted ventilation in the intensive care unit; this indicates the total compliance of lungs 4 and chest wall which is normally about half that of the lungs alone. IC FEV1 3 Vt VC Dynamic lung compliance measured during ordinary or accelerated FRC tidal breathing reflects the effects of airway disease as well as the Volume 2 static elastic properties of the lung and is reduced below static compliance when there is peripheral airway narrowing. ERV 1 RV 10 s 1 s Tests of forced expiration and inspiration Fig. 1 Static and dynamic lung volumes indicated as a record of tidal The physiological basis of tests of forced expiration depends on the breathing against time, followed by expiratory and inspiratory forced vital development of plateaux of expiratory flow at any particular lung capacity manoeuvres for which the time scale has been expanded. TLC, total volume once a certain minimum expiratory pressure is achieved. lung capacity; FRC, functional residual capacity; RV, residual volume; FEV1, Provided that flow plateau conditions are achieved, the values obtained forced expiratory volume in 1 s; IC, inspiratory capacity; Vt, tidal volume; ERV, expiratory reserve volume; VC, vital capacity. do not depend on the pressure applied but only on the mechanical characteristics of the lungs and airways. In contrast, tests of forced inspiration are much more dependent on the applied inspiratory pressures. Both forced expiration and inspiration can be analysed as The plethysmographic method often gives higher values than the gas change in volume versus time (by spirometry) (Fig. 1) or as change dilution method for FRC in severe intrapulmonary airway disease. in instantaneous flow rate at the mouth (usually measured by a Some of this difference occurs because plethysmography measures pneumotachograph) versus change in lung volume (maximum flow- intrathoracic gas which barely communicates with the airway (bullae volume curve) (Fig. 2). Standard spirometric measurements are the and other very poorly ventilated areas). An accurate estimate of forced expiratory volume in 1 s (FEV ) and the VC; the latter can be thoracic volume can also be obtained from spinal CT or from 1 obtained from forced expiration (forced vital capacity (FVC)) or from planimetry of standard posteroanterior and lateral chest radiographs a separate slower full expiration. In airway disease, FVC may be taken at full inflation. Corrections have to be made for tissue and considerably less than the slow VC. Normally, FEV is more than vascular volumes of the lungs so as to estimate gas volume. 1 70 per cent of VC. Two patterns of spirometric abnormality can be In normal subjects, FRC is passively determined by the balance distinguished: ‘obstructive’ in which, although there is usually some between the inward recoil of the lungs and outward recoil of the reduction in FVC, FEV1 is reduced even more so that the ratio FEV1/ chest wall. Reductions in VC in lung fibrosis, respiratory muscle FVC is low; and ‘restrictive’, in which a small FVC is associated with weakness, heart failure, and chest wall deformity are accompanied by normal or even accelerated emptying on forced expiration and a decreases in TLC and FRC. In obesity there is a reduced FRC. normal or increased FEV1/FVC ratio. The maximum flow-volume Intrapulmonary airway disease consistently leads to a rise in RV and curve (Fig. 2) shows that, on expiration, flow normally rapidly rises FRC, while TLC is either normal or, in some subjects with emphysema, to a peak value and then declines in an approximately linear fashion. increased. When TLC is increased, the accompanying increase in RV Peak expiratory flow (PEF) can also be measured with a peak flow is almost always greater so that there is still a decreased VC. When gauge. The most effort-dependent part of expiration is close to full airway obstruction is severe, slowing of tidal expiratory flow results inflation, and therefore in measuring PEF the subject must take a in FRC being considerably greater than the volume determined by full inspiration and make a rapid and forceful start to the subsequent lung and chest wall recoil. Alveolar pressure at the end of expiration, full expiration. Reduced PEF is most often due to airway disease, but which is normally equal to atmospheric pressure, is then positive is also found with expiratory muscle weakness and restrictive lung (‘intrinsic’ positive end-expired pressure (PEEP)) and provides a disease. For clinical assessment of ventilatory function, FEV1 and VC threshold load which has to be overcome by the inspiratory muscles (or FVC) are usually adequate, although these tests will not pick up before inspiratory flow can begin. mild airway disease. In asthma, the value of PEF is closely related to

the value of FEV1, and because PEF can be measured by simple Lung recoil pressure and compliance meters which can be used by patients in the home or at work, this Lung recoil pressure (Pl) is the difference between alveolar and measurement is particularly useful for identifying asthmatic episodes pleural pressure. Pleural pressure is estimated from the pressure and their response to treatment. The maximum flow-volume curve measured by a balloon-tipped catheter placed in midoesophagus. The cannot be used to distinguish the site or mechanism of intrapulmonary relation between lung recoil pressure and volume is obtained by airway narrowing, but distinctive curves are found when obstruction interrupting inspiration and expiration during vital capacity man- is extrathoracic (Fig. 2) (see also Chapter 4.12). oeuvres when mouth pressure will equal alveolar pressure. The change in volume (−V)for unit change in recoil pressure (−Pl) is the static Airways resistance lung compliance (−V/−Pl). Analysis of lung recoil and compliance Airways resistance is the ratio of driving pressure (difference between helps in determining whether a reduction in TLC associated with low alveolar and mouth pressures) to instantaneous gas flow. Alveolar compliance is due to extrapulmonary (when there is a low lPl at pressure can be obtained non-invasively with a body plethysmograph TLC) or intrapulmonary (when there is an increased Pl at TLC) or derived from oesophageal pressure obtained via a balloon-catheter disease. A low recoil pressure and a high static compliance are found system. During quiet tidal breathing via the mouth in normal subjects in emphysema; the low Pl reduces the driving pressure for expiratory about one-third of the total resistance is in the extrathoracic airway, flow and the distending forces on the airways, contributing to the about one-third is in the central intrathoracic conducting airways, airflow obstruction. Airway pressure during the end-inspiratory pause and the remaining one-third is in the peripheral airways of less than 4.3 LUNG FUNCTION TESTING 359

(a) Normal aperture, and the flow rate. In contrast, spirometry is more robust and less demanding technically. Consequently, at least in the UK, the 10 MEFV MEFV PEF measurement is used more for research into airway pharmacology FEV 3.35 1 = than for routine clinical assessment. FVC 3.96 4 5 5 FEV 3 Airway responsiveness 1 FEV1 2 In subjects with asthma there is an increased tendency for airways Time (s) Time

Expired flow (l/s) 1 TLC RV narrowing to occur in response to a whole range of stimuli (e.g. 0 0 0 1234 2 4 exercise, hyperventilation, breathing cold air, hypo- or hyperosmolar Expired volume (l) Volume (l) aerosols, constrictor drugs such as histamine or cholinergic agonists, or mediators such as bradykinin or leukotrienes). This responsiveness 5 MIFV can be quantified using an incremental dose–response technique. (b) Intrathoracic obstruction Histamine or methacholine is generally used as the stimulus and the 10 dose is increased until a 20 per cent fall in FEV1 is produced (Chapter Mild 4.14). Airway responsiveness is often increased in smokers with FEV 2.41 Advanced chronic airflow obstruction, when it may reflect altered airway geo- 1 = FVC 3.73 5 metry and increased thickness of the airway wall. 5 FEV 0.78 1 = FVC 2.16 Additional tests of airway function (see 0 0 4 4 Table 3) Respiratory muscle function 5 5 The simplest test of respiratory muscle function is to measure mouth pressure when maximum inspiratory or expiratory efforts are made

Inspired flow (l/s) Expired flow (l/s) against a closed valve. Inspiratory efforts are made at FRC or RV; expiratory efforts at full inflation (TLC). Portable meters for bedside (c) Extrathoracic obstruction use are now available. Properly performed, this test indicates the Fixed Variable overall strength of inspiratory or expiratory muscles, but low values FEV1 3.22 = FEV1 2.71 may be due to poor technique. Bilateral paralysis of the diaphragm 5 FVC 3.79 5 = FVC 3.43 can be suspected if there is orthopnoea and paradoxical inspiratory indrawing of the abdominal wall (particularly in the supine position). A reduction in VC in the sitting position is often found in respiratory 0 0 4 4 muscle weakness; a further fall of >25 per cent in VC on adopting the supine position is characteristic of diaphragmatic weakness. Serial measurements of maximum effort mouth pressures (or, failing this, Fig. 2 Characteristic patterns of maximum flow-volume curves for normal PEF or VC) may be useful in monitoring conditions where muscle subjects, and patients with intrathoracic and extrathoracic airway strength varies rapidly (e.g. myasthenia gravis). obstruction. (a) Normal subjects. Left: simultaneous record of maximum Respiratory muscle function is often impaired in generalized muscle expiratory flow versus volume (MEFV, upper curve) and expired volume disease and motor neurone disease and can then be the most important versus time (spirogram, lower curve) during a forced expiration in a healthy normal subject. The volume expired in first second (forced expiratory volume factor determining prognosis. Weakness is also common in poly- in 1 s, FEV1) is indicated. Right: maximum expiratory and inspiratory flow- myositis, some connective tissue disorders, notably systemic lupus volume (MEFV, MIFV) curves in another normal subject. Note the different erythematosus, and cachexia from whatever cause. Respiratory muscle shape of the MEFV curve in the two normal subjects. PEF, peak expiratory function should be checked when there is unexplained restrictive lung flow; TLC, total lung capacity; RV, residual volume; FVC, forced vital capacity. (b) Intrathoracic airways obstruction. Left: mild obstruction. Despite disease or hypercapnia. Weakness of the respiratory muscles can be preservation of a normal peak expiratory flow the MEFV curve shows a limiting factor preventing weaning from assisted ventilation in the marked convexity to the volume axis in contrast to the linearity or concavity intensive care unit and is related to such factors as cachexia, muscle to the volume axis in normal subjects. Right: severe obstruction with gross catabolism, electrolyte disturbance, and corticosteroid treatment, as reduction on both the flow and volume axis and convexity to the volume well as the underlying lung disease. axis. Reduction in flow on MEFV curve considerably greater than on MIFV curve. (c) Extrathoracic airways obstruction. Left: fixed obstruction pattern as An important factor compromising inspiratory muscle function is seen in tracheal stenosis with reduction in flow on MEFV and MIFV curves hyperinflation associated with severe airways obstruction. The raised and a distinctive plateau of flow on MEFV curve. Right: variable obstruction FRC shortens the initial length of the inspiratory muscles so that they with inspiratory narrowing of the upper airway but preservation of a normal operate on a suboptimal part of their force-length curve and expend MEFV curve in a patient with severe obstructive sleep apnoea. more energy to generate a given inspiratory pleural pressure, increasing their oxygen consumption, which may become a significant pro- portion of the total oxygen consumption. 2 to 3 mm internal diameter. The precise value of resistance varies Diaphragm function can be measured more directly by placing according to the lung volume at which it is measured, the phase of balloon-catheters in the oesophagus and stomach and obtaining respiration (inspiration or expiration), the size of the laryngeal transdiaphragmatic pressure from the difference between pressures 360 RESPIRATORY DISEASE 4 in these two sites. Such measurements may be made during tidal accurate prediction of postoperative spirometry after pulmonary breathing, maximum inspiratory efforts or in response to phrenic resection can be made. Because there is usually close concordance nerve stimulation. The phrenic nerves may be stimulated electrically between ventilation and perfusion defects in bronchial carcinoma, directly in the neck or by magnetic stimulation, usually applied the preoperative regional distribution of blood flow can also be used posteriorly over the cervical spine, which activates the relevant cervical to make this prediction. nerve roots. Electromyography of the diaphragm may be used to assess phrenic nerve conduction and to detect changes suggestive of Transfer factor (diffusing capacity) for carbon fatigue. monoxide The transfer of carbon monoxide across the alveolar–capillary mem- Tests of pulmonary gas exchange brane and into combination with haemoglobin within the red blood Distribution and mixing of inspired gas corpuscle mimics the diffusive conductance of oxygen. By measuring Inequalities of ventilation and inefficient gas mixing may be either carbon monoxide transfer at two or more levels of alveolar PO2 it is between regions or within regions. The topographical distribution of possible to obtain separate values for transfer across the alveolar- ventilation can be examined by detecting the distribution of inhaled capillary membrane and transfer into the haemoglobin within the radionuclides such as xenon-133 or krypton-81m with external coun- red blood corpuscle and so derive pulmonary capillary blood volume. ters. Values of carbon monoxide transfer are reduced if there is anaemia, In normal subjects, much of the inequality in ventilation is on a but correction can be made for haemoglobin level. regional basis; in the upright posture ventilation is greater in the In normal lungs, carbon monoxide transfer can be used to define ff ff dependent basal zones. In most diseases of the lung, however, in- a true di using capacity of the lungs, which depends on the di usivity equalities within a region are of greater importance than inter- of the gas and the available area and thickness of the alveolar–capillary regional differences. This applies even in diseases such as asthma membrane. The standard technique is extremely simple: the subject and emphysema, where obvious inequalities of ventilation are easily inhales a full breath of a gas mixture containing a very low carbon demonstrated by radioactive gas methods. Intraregional inequalities monoxide concentration and the gas transferred during breath-hold- may be detected by a single breath test which measures the expired ing for 10 s at TLC is measured. A rebreathing technique can be ff nitrogen concentration at the mouth after a preceding vital capacity used also. In lung disease, carbon monoxide transfer is a ected by inhomogeneities within the lungs as well as by a true loss of area or breath of 100 per cent O2. The rate of rise of expired nitrogen over the middle part of the expiration indicates the unevenness of increase in thickness of the membrane, and for this reason the less ventilation: towards the end of the breath there may be a sharp rise precise term carbon monoxide transfer factor has been adopted in in nitrogen concentration which indicates the beginning of closure Europe. of basal airways (‘closing volume’). This test is a sensitive indicator Despite these theoretical limitations, values of carbon monoxide of early lung damage as with smoking or occupational lung disease. transfer (particularly when expressed per litre alveolar volume (trans- Other techniques are based on the rate of equilibration when helium fer coefficient)) are useful in differential diagnosis (Table 4). Apart is washed in or nitrogen washed out of the lung to measure FRC. from the major reductions found in severe emphysema (which con- Regional ventilation scans are most widely used in conjunction trasts with a slight increase in asthma) and fibrosing alveolitis, smaller with regional perfusion scans to diagnose pulmonary embolism by reductions are found in systemic sclerosis, chronic renal disease, the presence of ‘unmatched’ perfusion defects. They are also useful graft-versus-host disease, pulmonary oedema, P. carinii pneumonia, in assessment for lung volume reduction surgery or bullectomy, pulmonary toxicity due to amiodarone, lymphangitis carcinomatosa, unilateral transradiancy, and suspected inhalation of foreign bodies. and a host of other conditions where the alveoli are involved with In bronchial carcinoma, defects in regional ventilation (and perfusion) disease. However, the carbon monoxide transfer coefficient is also are very often more severe than suspected from the chest radiograph. greatly influenced by pulmonary blood volume. An increase in blood Using a combination of preoperative spirometry and regional vent- volume per unit alveolar volume probably accounts for slightly ilation scans quantifying the contribution of each lung, a reasonably increased values for the carbon monoxide transfer coefficient found

Table 3 Additional tests of airway function

Function Available techniques Applications Cough responsiveness Response to increasing doses of inhaled Unexplained non-productive cough capsaicin or citric acid ...... Mucociliary transport Clearance of radiolabelled inhaled particles Investigation of recurrent bronchopulmonary infections, from the lungs Kartagener’s syndrome, etc. Ciliary beat frequency from bronchial or nasal brushings ...... Detection of mild lung damage Single-breath nitrogen test and ‘closing Occupational and environmental lung disease volume’ ...... Exposure to cigarette smoke Concentration of CO in expired air Confirmation of smoking habit ...... Airway inflammation Concentration of NO in expired air. Assessing adequacy of anti-inflammatory treatment in asthma 4.3 LUNG FUNCTION TESTING 361

Table 4 Examples of the value of carbon monoxide transfer coefficient in differential diagnosis

Reduced Normal or increased Airway obstruction Emphysema Asthma ...... Chronic restrictive lung disease Fibrosing alveolitis Often remains normal in sarcoidosis; may be slightly increased when restriction is due to respiratory muscle weakness ...... Acute pulmonary infiltration Pulmonary oedema Intrapulmonary haemorrhage

Table 5 Determinants of arterial PO2 and PCO2 modest rises in inspired oxygen concentration, thus minimizing the risk of worsening hypercapnia. In contrast, hypoxaemia due to shunt is Intrapulmonary abnormalities∗ difficult to correct with modest rises in inspired oxygen concentration. Impaired diffusion Ventilation-perfusion mismatch Shunt is found with permanent anatomical defects in the heart or ff Alveolar shunt† with pulmonary arteriovenous malformations. However, e ective ...... alveolar shunts develop with acute lung diseases which lead to Extrapulmonary modifying factors extensive fluid filling of alveoli, such as pulmonary oedema, severe Inspired O concentration/pressure 2 pneumonia, and adult respiratory distress syndrome. Increases in Total ventilation/breathing pattern (influence alveolar PO2 and CO2 excretion) inspired oxygen to levels which carry a risk of causing pulmonary toxicity are often required, but oxygenation can be assisted by applying Cardiac output/whole body metabolism (influence mixed venous PO2

and PCO2) positive end-expired pressure to expand the resting lung volume and ∗ recruiting additional alveolar surface area for gas exchange. All characterized by an increased alveolar–arterial PO2 difference. A reduced minute ventilation is an unusual cause of a low alveolar †Extrapulmonary shunts (e.g. right-to-left intracardiac shunts) also lower arterial

PO2 and increase alveolar–arterial PO2 difference. and arterial PO2 and is accompanied by a rise in alveolar and arterial PCO2. Apart from acute crises such as asphyxia due to obstruction of the upper airway or cardiorespiratory arrest, reduced total vent- ilation is only found with sedation induced by anaesthesia or drugs, with lung volume restriction in respiratory muscle weakness or with paralysis or gross weakness of the respiratory muscles, or with after pneumonectomy. Values tend to be below normal in primary rare breathing disorders such as Ondine’s curse where the central pulmonary hypertension, but increased when there is a right-to-left control of breathing is abnormal. In most patients with lung disease, shunt in atrial septal defect. The avidity of carbon monoxide uptake including chronic obstructive pulmonary disease with hypercapnia, by haemoglobin is utilized to make serial measurements of carbon there is some increase in total ventilation above normal, which plays monoxide transfer to monitor the number of haemoglobin binding an important part in minimizing the effects of impaired pulmonary sites (intra- and extravascular) accessible in the lungs in in- gas exchange. trapulmonary haemorrhage. The efficiency of carbon dioxide excretion can be assessed by ff measuring the di erence between PaCO2 and mixed expired PCO2 Assessment of arterial hypoxaemia and to estimate the physiological dead space (Vd) for carbon dioxide as hypercapnia (see Chapter 4.42) a proportion of tidal volume (Vt). Arterial PO2 (PaO2) and PCO2 (PaCO2) are determined by the ffi interaction between the e ciency of the lungs as gas exchangers and Vd = (PaCO2–mixed expired PCO2 ) extrapulmonary factors (oxygen in the inspired air, total ventilation, Vt PaCO2 cardiac output, and oxygen consumption and carbon dioxide pro- duction). Small increases in tidal ventilation, especially if associated with a ff The three types of abnormality in the lungs which impair pulmonary larger tidal volume, are considerably more e ective in reducing PaCO2 ff gas exchange (Table 5) are all characterized by an increased difference than in raising PaO2. Alterations in PaCO2 have a profound e ect on between mean alveolar and arterial PO (Chapter 4.43).Most evidence acid–base balance and arterial pH (see Chapter 4.43). Measurement 2 ff suggests that, at least at rest, diffusion limitation is not important in of the di erence between alveolar and arterial PO2 and of physiological ffi dead space for CO2 provides simple, lumped estimates of the e ciency the hypoxaemia of lung disease, and so resting alveolar–arterial PO2 difference can be assumed to be due to either shunt (blood flow of pulmonary gas exchange in lung disease, which in fact is determined ff evading contact with alveolar gas) or to ventilation–perfusion im- by large variations in ventilation–perfusion balance in di erent parts balance chiefly due to units with very low ventilation-to-perfusion of the lungs. (V/Q) ratios. The distinction between ventilation–perfusion mismatch and shunt is of considerable practical importance, because the former Other constituents of expired air can readily be corrected by modest increases in inspired oxygen Apart from oxygen and carbon dioxide, measurements of breath concentration, while this is not the case with shunt. Increase in alcohol, carbon monoxide (usually to establish smoking status), and alveolar shunt is rare in chronic obstructive pulmonary disease hydrogen (to detect bacterial overgrowth in the gut) have been used (COPD) or asthma and even in patients with severe exacerbations of for many years. Recently, expired nitric oxide has been proposed as airway disease PaO2 can almost always be raised to safe levels with a simple marker of active airway inflammation in asthma and other 362 RESPIRATORY DISEASE 4 potential makers of inflammation of oxidant stress are being in- Exercise capacity vestigated. Exercise tests play an important part in quantifying effort intolerance, investigating its cause, and monitoring progress and response to Control of ventilation treatment and rehabilitation programmes. They are also used for Measuring ventilation at rest has played a surprisingly small part in confirming a diagnosis of exercise-induced asthma and ischaemic heart clinical assessment, except in the intensive care unit. Methods that disease. An increased ventilation in relation to oxygen consumption is require breathing via a mouth-piece with the nose clipped are not found at high work loads in normal subjects when blood lactate begins well tolerated by breathless patients—always add some dead space to rise (anaerobic threshold). In lung disease, increased ventilation is and generally increase minute ventilation. Less intrusive methods, in particularly found with fibrosing alveolitis and primary pulmonary which surface pneumographs or magnetometers are used to measure hypertension; some of this increase may be due to stimulation of expansion of rib cage and abdomen, have shown that minute vent- peripheral chemoreceptors by a fall in arterial PO2 during exercise, ilation in healthy subjects at rest is less than previously believed— but mechanoreceptor stimulation has also been implicated since commonly about 5 to 6 l/min. Unfortunately, absolute values with increasing inspired oxygen does not restore exercise ventilation to these methods are greatly influenced by postural changes but they normal values. are valuable for detecting irregularities in pattern of breathing, as In chronic airflow obstruction and fibrosing alveolitis, exercise during sleep. tolerance appears to be limited by the impaired ventilatory capacity Increased resting ventilation occurs in normal subjects during and there is often a considerable fall in oxygen saturation, which in pregnancy, probably in response to increases in progesterone, and at fibrosing alveolitis is due to impaired diffusion. altitude, when the effect is due to hypoxaemic stimulation of the Quantitative exercise tests usually involve either a treadmill or a carotid chemoreceptors. It also occurs with of aspirin poisoning and bicycle ergometer although progressive walk or step tests can be used metabolic acidaemia, such as renal failure, diabetic ketosis, and lactic in the absence of such equipment. Many clinical problems can be acidosis; acidaemia probably stimulates both peripheral and central investigated by a simple progressive work load test on a bicycle chemoreceptors. Hyperventilation is a feature of many car- ergometer measuring ventilation, heart rate, electrocardiogram, and diorespiratory diseases, notably asthma, severe pneumonia, pul- oxygen consumption. This will often indicate whether exercise is monary embolism, and pulmonary oedema, and is associated with a limited by the cardiac response or by ventilation, and will give an respiratory alkalaemia; some of the increase in ventilation may be objective measurement of maximum oxygen consumption. More explained by hypoxaemic stimulation of the carotid chemoreceptors, elaborate measurements, including arterial blood gases and cardiac but stimulation of vagal afferent receptors within the lungs also plays output, may occasionally be required. These tests indicate cardio- a part. Most of the conditions associated with hyperventilation are pulmonary fitness and exercise capacity. Exercise tolerance (the easily recognized; when there is no obvious cause the differential amount of work a patient is prepared to achieve) can be assessed by diagnosis often lies between pulmonary vascular disease and psy- the distance walked on the flat in 6 or 12 min in patients with more chogenic hyperventilation. Psychogenic hyperventilation may be as- severe disability. In such patients, walking distance tests correlate well sociated with dizziness, tetany, chest pain, paraesthesiae, and an erratic with disability in daily life; they evaluate motivation as well as breathing pattern which settles during sleep (Chapter 4.1). Reduced cardiopulmonary status. total ventilation (hypoventilation) is much less common and is usually due to sedative drugs or neuromuscular disease, although occasionally Further reading it occurs with brainstem disease or severe metabolic alkalosis. In Cotes, J.E. (1993). Lung function, (5th edn). Blackwell Scientific most patients with chronic obstructive pulmonary disease, minute Publications, Oxford. ventilation is slightly above normal values; even in episodes of Gibson, G.J. (1995). Clinical tests of respiratory function, (2nd edn). acute respiratory failure. Relatively small variations in the pattern of Chapman and Hall, London. breathing can influence the development of hypercapnia in such West, J.B. (1995). Respiratory physiology—the essentials, (5th edn). Williams patients. and Wilkins, Baltimore. Examining the ventilatory response to imposed hypoxia or hy- West, J.B. (1997). Pulmonary pathophysiology, (5th edn). Williams and Wilkins, Baltimore. percapnia is most useful when lung and respiratory muscle mechanics are normal, as in studies of the effects of drugs, anaesthesia, or sleep in normal subjects, Pickwickian patients with obesity, or unusual patients with abnormal central control of breathing due to brainstem pathology. Impaired responses to hypoxia and hypercapnia are also Chapter 4.4 found in many patients with chronic airflow obstruction, but when there are abnormalities of ventilatory mechanics or respiratory muscle Microbiological methods in the weakness, a given neurological output inevitably results in less vent- diagnosis of respiratory ilation than in a normal subject. A better idea of neurological output may be obtained by measuring oesophageal pressure throughout the infections breath or mouth pressure during a transitory 0.1 s occlusion at the start of a breath; these techniques have reduced the role of decreased D. W. M. Crook and T. E. A. Peto central drive and emphasized the role of impairment of respiratory muscle and lung mechanics in limiting the ventilatory response in A wide range of bacteria, viruses, fungi, and parasites colonize or such patients. infect the airways, lung, and pleura (Table 1). The diagnosis of a 4.4 MICROBIOLOGICAL METHODS IN THE DIAGNOSIS OF RESPIRATORY INFECTIONS 363

Table 1 Bacterial, viral, and fungal respiratory pathogens

Colonizing organisms Lung abscess Hospital-acquired pneumonia Mixed oropharyngeal flora, e.g. Prevotella spp. (anaerobes) Pseudomonas aeruginosa Streptococcus spp. Escherichia coli Eikenella corrodens Klebsiella pneumoniae Non-colonizing organisms Staphylococcus aureus Legionella spp. Enterobacter spp. Nocardia spp. (many other Enterobacteriacae spp.) Chlamydia spp. Candida spp. Mycoplasma pneumoniae Aspergillus spp. Mycobacteria tuberculosis Cytomegalovirus (latent virus) Blastomyces braziliensis Community-acquired pneumonia Coccidioides immitis Streptococcus pneumoniae Histoplasma capsulatum Haemophilus influenzae Cryptococcus neoformans Moraxella catarrhalis Respiratory syncytial virus Staphylococcus aureus Influenzae A and B Parainfluenza virus respiratory tract infection can only be made clinically. The micro- 8. Blood cultures should be carried out in ill patients suspected of biology laboratory can only provide some clues as to the likely infection. Approximately 10 to 28 per cent of pneumococcal causative organism. pneumonias are associated with bacteraemia. H. influenzae, Sta- Some of the organisms that usually colonize the nasopharynx (e.g. phylococcus aureus, Klebsiella pneumoniae, and other organisms Streptococcus pneumonia, Haemophilus influenzae) may spread to the causing pneumonia can be cultured from the blood. lung and cause exacerbations of chronic bronchitis or pneumonia. Pathogens such as Mycobacterium tuberculosis, Legionella pneumophila, Histoplasma capsulatum, and the respiratory viruses do not colonize Microbiological examination of samples the nasopharynx but may infect the lung, after airborne or haema- Microscopy of unstained sputum togenous spread, where they form an infected focus. The distinction between nasopharyngeal colonizers and non-colonizers is critical Hyphae of filamentous moulds (e.g. Aspergillus spp. in a patient with for the interpretation of microbiological tests of respiratory tract fever, neutropenia, and pulmonary infiltrates), yeasts (e.g. Blastomyces secretions, fluids, or tissues. spp.), or ova of paragonomiasis may be seen in unstained sputum.

Samples for microbiological testing Direct examination of stained samples Gram staining of expectorated sputum is useful only in diagnosing 1. Expectorated or induced sputum is liable to be contaminated with pneumococcal pneumonia. However, Gram staining of organisms in upper respiratory tract colonizers. bronchoalveolar lavage fluid is highly predictive of pyogenic bacterial 2. Respiratory secretions obtained by transtracheal aspiration are infection in patients with pneumonia. In community-acquired pneu- largely free from nasopharyngeal contamination. This procedure monia, Gram-positive diplococci, pleomorphic Gram-negative co- is useful when bronchoscopy is not available, but is unpleasant ccobacilli, and Gram-positive cocci in clusters are likely to be for the patient. pneumococci, H. influenzae, and Staph. aureus respectively. In noso- 3. Bronchoscopy specimens (bronchoalveolar lavage, protected speci- comial and ventilator-associated pneumonia, Gram staining of ex- men brush, or lung biopsy) are relatively free of contaminating pectorated sputum or endotracheal aspirates is poorly predictive of upper respiratory tract flora but there is a risk from bleeding and the aetiology. However, when more than 7 per cent of cells in hypoxia which can sometimes require mechanical ventilation of a bronchoalveolar lavage fluid from a ventilated patient contain stain- patient. able intracellular organisms, the probability of pneumonia caused by 4. Fluid can be aspirated from the lung parenchyma through a fine these organisms is high (70–80 per cent). Gram staining of pleural needle introduced percutaneously in the case of peripherally located fluid is useful; the presence of many neutrophils suggests an empyema, intrapulmonary cavities (abscesses) and in childhood and adult and organisms can be seen in up to 80 per cent of these cases. pneumonias. There are risks of pneumothorax, haemorrhage, and In an appropriate clinical setting, detection of acid-fast organisms occasional sudden death. by Ziehl–Neelsen or rhodamine auramine staining of respiratory 5. Open-lung biopsy provides the most useful specimens, but this secretions or tissue is highly predictive of mycobacterial disease. technique is too invasive for routine use. Unfortunately, the sensitivity of the test is relatively low (20–78 per 6. Pleural fluid or pleural biopsy specimens obtained by percutaneous cent for sputum and less than 10 per cent for pleural fluid). Therefore needle provide reliable samples free from contamination with a negative test result does not reliably exclude mycobacterial pul- nasopharyngeal-colonizing organisms. monary or pleural disease. 7. Pleural fluid samples obtained from a chronically draining chest Direct fluorescent antibody testing is a specific and sensitive test tube are not reliable, since chest drains rapidly become colonized for detecting respiratory syncytial virus and Legionella spp. In children with potential pathogens after insertion. with suspected respiratory syncytial virus infection, the most accessible 364 RESPIRATORY DISEASE 4 specimen is a nasopharyngeal aspirate. Legionella spp. can occasionally defining the cause of a respiratory infection. There are empirical be detected in sputum or bronchoalveolar lavage fluid. antibiotic regimens (e.g. cefuroxime and erythromcyin) that have Pneumocystis carinii in respiratory secretions is highly predictive of negligible side-effects and adequately cover the majority of likely pneumocystis pneumonia. In 80 per cent of AIDS patients with pathogens in community-acquired pneumonia (e.g. Strep. pneu- pneumocystis pneumonia, induced expectorated sputum samples are moniae, H. influenzae, Mycoplasma, etc.). However, such an approach positive. Examination of bronchoalveolar lavage fluid or lung tissue is inadequate if the patient is too ill to risk a poor response to a stained with methenamine silver is highly sensitive (90 per cent) and therapeutic trial. In such patients, bronchoscopic examination may is specific (more than 95 per cent) for P. carinii. be justified even if the patient subsequently requires mechanical Histological examination of stained lung or pleural biopsy material ventilation. In less severely ill patients, bronchoscopy is justified if may reveal tuberculous granulomas, schistosome ora, fungi (e.g. tuberculosis or rarer pathogens resistant to empiric treatment, such Aspergillus spp., Rhizopus spp., Coccidioides immitis, H. capsulatum, as fungi, parasite, or multiresistant bacterial infection, are suspected. and Blastomycosis braziliensis), characteristic features of cyto- megalovirus, or measles pneumonias. Further reading Detection of antigens Bartlett, J.G., Ryan, K.J., Smith, T.F., and Wilson, W.R. (1987). In Cumitech 7A. Laboratory diagnosis of lower respiratory tract infections (ed. J.A. Pneumococcal antigen detection by latex agglutination or counter- Washington II). American Society for Microbiology, Washington, DC. current immunoelectrophoresis is highly specific with samples such Pugin, J., Acukenthaler, R., Mili, N., Janssens, J.P., Lew, P.D., and Suter, as blood, pleural fluid, bronchoalveolar lavage fluid, or urine. The P.M. (1991). Diagnosis of ventilator-associated pneumonia by sensitivity is high (80 per cent) with pleural fluid but low with blood bacteriological analysis of bronchoscopic and nonbronchoscopic ‘blind’ or urine. bronchoalveolar lavage fluid. American Review of Respiratory Disease, Legionella antigen testing of urine is both sensitive and specific for 143, 1121–9. serogroup 1 legionellosis. Cryptococcal antigen testing of serum is Research Committee of the British Thoracic Society and the Public Health useful for diagnosing pulmonary cryptococcosis. Laboratory Service (1987). Community-acquired pneumonia in adults in British hospitals in 1982–1983: a survey of aetiology, morality, Culture prognostic factors and outcome. Quarterly Journal of Medicine, 62, 195–220. The isolation from sputum of respiratory pathogens that frequently Wilson, S.M., McNerney, R., Nye, P.M., Godfrey-Faussett, P.D., Stoker, colonize the upper respiratory tract does not reliably predict the N.G., and Voller, A. (1993). Progress toward a simplified polymerase aetiology of pneumonia or lung abscess. However, isolation of non- chain reaction and its application to diagnosis of tuberculosis. Journal of colonizing organisms is strongly associated with infection caused by Clinical Microbiology, 31, 1007–8. these pathogens. The isolation of organisms from a bronchoscopic protected speci- men brush or bronchoalveolar lavage samples is useful in patients with suspected ventilation-associated pneumonia. Isolation of mixed Chapter 4.5 aerobic/anaerobic oral flora from bronchoalveolar lavage specimens or lung aspirates suggests an aspiration or suppurative pneumonia. Diagnostic bronchoscopy and The culture of Aspergillus spp. in bronchoalveolar lavage fluid in neutropenic patients indicates invasive disease. Cytomegalovirus can tissue biopsy be grown from respiratory secretions, but the sensitivity, specificity, M. F. Muers and predictive value are uncertain. The growth of organisms from pleural fluid suggests a pleural infection and, if the organisms are Diagnostic bronchoscopy and tissue biopsy are an integral part of pyognic, empyema. the investigation of respiratory disease, but should be regarded as complementary to, rather than substitutes for, simpler tests. Serological tests Serodiagnosis is useful for viral, mycoplasma, chlamydial TWAR (which refers to the first two laboratory isolates of Chlamydia pneu- Bronchoscopy moniae, TW-183 and AR-39), Q fever, and Legionella spp. infections. Indications (Table 1) In histoplasmosis, coccidioidomycosis, filariasis, and echinococcus Bronchoscopy is mainly used to investigate or confirm the possibility the presence of antibody suggests active infection. of carcinoma. The diagnosis does not depend just on tissue sampling, since many abnormal appearances are characteristic. Nor is it confined Detection of specific DNA sequences to visible lesions; the simultaneous use of flexible sampling instruments PCR is being assessed for the diagnosis of tuberculosis and pneumonia and fluoroscopy allows sampling from distal bronchi or lung par- caused by P. carinii, Mycoplasma pneumoniae, and L. pneumophila. enchyma. Techniques The microbiological investigation of Fibreoptic bronchoscopy patients with pneumonia—one approach This is usually a day case procedure with local anaesthesia and The rational approach to making a microbiological diagnosis of a light sedation. A posteroanterior and a lateral chest radiograph, and pulmonary infection rests on balancing the risk of the procedure to spirometry, are required beforehand. Any cardiac abnormalities need obtain reliable samples against the risk of treating empirically without to be assessed, and arterial blood gases measured if spirometry is