STANDARD TREATMENT GUIDELINES

Respiratory diseases

DEPARTMENT OF HEALTH AND FAMILY WELFARE GOVERNMENT OF KERALA

STANDARD TREATMENT GUIDELINES IN RESPIRATORY DISEASES

Fourteen sections Section I Section II Allergic Section III Diagnosis & Managementof Chronic Obstructive Pulmonary Disease Section IV Community acquired Section V Section VI Pleural Diseases Section VII Sleep disordered Section VIII Section IX Pumonary embolism Section X Interstitial Lung Disease Section XI Long term oxygen therapy Section XII Tuberculosis Section XIII Lung cancer Section XIV Upper Committee for Development of Standard Treatment Guidelines Respiratory diseases

Convener Dr. Sanjeev Nair, Department of Pulmonary Medicine, Medical College, Trivandrum Members 1. Prof. Dr. C Ravindran, Department of Pulmonary Medicine, WIMS, Wayanad 2. Prof. Dr. K Anitha Kumari, Department of Pulmonary Medicine, Medical College, Trivandrum 3. Prof. Dr. Rajagopal TP, Department of Pulmonary Medicine, Medical College, Kozhikode 4. Prof. Dr. Fathahudeen A, Department of Pulmonary Medicine, Medical College, Ernakulam 5. Prof. Dr. Suraj KP, Department of Pulmonary Medicine, Medical College, Kozhikode 6. Prof. Dr. Thomas George, Department of Pulmonary Medicine, Medical College, Thrissur 7. Prof. Dr. Santhosh PV, Department of Pulmonary Medicine, Medical College, Manjeri 8. Prof. Dr. Venugopal P, Department of Pulmonary Medicine, Medical College, Alappuzha 9. Dr. Ameer KA, Department of Pulmonary Medicine, KIMS, Trivandrum 10. Dr. Jayaprakash B, Department of Pulmonary Medicine, Medical College, Trivandrum 11. Dr. Ronaldwin B, Department of Pulmonary Medicine, Medical College, Trivandrum 12 Dr. Sreekala C, Department of Pulmonary Medicine, Medical College, Trivandrum 13. Dr. Reshmi S Nair, Department of Pulmonary Medicine, Medical College, Trivandrum 14. Dr. Kamala R, Department of Pulmonary Medicine, Medical College, Trivandrum 15. Dr. Praveen GS, Department of Pulmonary Medicine, Medical College, Trivandrum 16. Dr. KGR Mallan, Department of Pulmonary Medicine, Medical College, Ernakulam 17. Dr. Jyothi E, Department of Pulmonary Medicine, Medical College, Kollam

“Driven by the inspiration drawn from Shri. Rajeev Sadanandan IAS, Additional Chief Secretary, Department of Health and Family Welfare, Government of Kerala, the process of preparation of Standard Treatment Guidelines (STG) was initiated by the Director of Medical Education Dr. Remla Beevi A. The process of developing and finalizing the STG’s were coordinated by Dr. Sreekumari K. Joint Director Medical education and Dr. Suma T K, Professor of Medicine and ably supported by a dedicated team of experts, including external faculty”. TABLE OF CONTENTS Message by Chief Minister 11 Message by Health Minister 13 Foreword by Additional Chief Secretary 15 Abbreviations 17 Section - I 1.Asthma 21 1.1. When to suspect asthma 23 1.2. Making the diagnosis of asthma in special populations 24 1.3. General principles of asthma management 25 1.4. Categories of asthma medications 26 1.5. Control-based asthma management 27 1.6. Assessment of risk factors 28 1.7. Treatment 28 1.8. Reviewing response and adjusting treatment 30 1.9. Other therapies 32 1.10. exacerbation of Asthma 34 1.11. Management of Asthma in special situations 35 1.12. Acute exacerbation of Asthma 36 1.14. Discharge following IP treatment of patient with acute Asthma 42 Section - II 2. 43 2.1. Classification of allergic rhinitis 45 2.2. References 49 Section - III 3. Diagnosis & managementof chronic obstructive pulmonary disease (COPD) 51 3.1. When to suspect COPD 53 3.2. Risk factors for COPD 53 3.3. Diagnosis of COPD 54 3.4. Additional investigations in COPD 55 3.5. Treatment options 56 3.5.1. Management of stable COPD 56 3.5.2. Non pharmacological therapies 60 3.5.3.. Other treatments 61 3.6. Follow-up pharmacological management 62 Section - IV 4. Community acquired pneumonia 65 4.1. Introduction 67 4.2. Definition 67 4.3. Diagnosis of pneumonia 67 4.4. Investigations 68 4.5. Risk stratification 69 4.6. Diagnosis and management of hospital-acquired pneumonia (HAP) / ventilator-associated pneumonia (VAP) 76 4.7. References 87 Section - V 5. Bronchiectasis 89 6.4. Specific conditions and tests 5.1. Clinical features 91 5.2 Investigations 91 5.3.Investigations to determine the underlying Cause of bronchiectasis 92 5.4. Management 93 5.5. Patient education 94 5.6. Role of surgery 98 Section - VI 6. Pleural diseases 101 6.1. 103 6.2. Management of unilateral pleural effusion 103 6.3. Invasive investigations 106 6.4. Specific conditions and tests 106 6.5. Indications for pleural fluid drainage in pleural infection 109 6.6. 110 6.7. Treatment Options For Pneumothorax 111 Section - VII 7. Sleep disordered breathing 115 7.1. Overlap syndrome, obesity- and Pickwickian syndromes 117 7.2. Diagnosis of OSA 117 7.3. Various levels of sleep studies 118 7.4. Diagnostic criteria for OSA 119 7.5. Medical management of OSA 120 7.6. Surgical treatment of OSA 122 Section - VIII 8. Haemoptysis 125 8.1. Management 127 8.2. Airway protection and resuscitation 127 8.3. used 128 Section - IX 9. Pumonary embolism 129 9.1 Treatment 132 Section - X 10. Interstitial lung disease 141 10.1. Diagnosis and management of interstitial lung diseases 143 10.2. Classification of interstitial lung diseases 143 10.3. Diagnosis of interstitial lung diseases 144 10.4. Physiological evaluation 144 10.5. General management strategies in ILD 150 10.6. Treatment recommendations 152 10.7. Connective tissue disease related ILD 154 10.8. Polymyositis-dermatomyositis 155 10.9. Pulmonary langerhan's cell histiocytosis 157 Section - XI 11. Long term oxygen therapy 161 11.1. Use of long-term oxygen therapy in patients with chronic Obstructive pulmonary disease 163 11.2. LTOT in patients with ild 163 11.3. Assessment of patients for ltot 164 Section - XII 12. Tuberculosis 167 12.1. Treatment of sensitive TB 171 Section - XIII 13. Lung Cancer 175 13.1. Introduction 177 13.2. Diagnosis and staging 178 13.3. Treatment 180 13.4. Managing brain metastases 184 13.5. References 185 Section - XIV 14. Upper Airway Obstruction 187 14.1 Major Airway Obstruction 189 14.1. Causes of benign and malignant airway obstruction 189 14.2. Malignant 189 14.3. Management 191 Message

Pinarayi Vijayan Secretariat Chief Minister Thiruvananthapuram

The Government is taking many initiatives to ensure providing quality health care to all. Out of the five missions launched by the Government, the Aardram mission is primarily focussed to improve Primary Health Care to provide standard health care facilities to people at grassroots. This initiative is complemented by strategic investment for the improvement of infrastructure in secondary and tertiary health care institutions to provide quality health care services. I am happy to note that the Department of Health is also taking initiatives to bring standardization in treatment for various disciplines like Cardiology, Critical care, Diabetes Mellitus, Cancer Care, etc. It is a noteworthy initiative to improve the qualitative aspects of the health service delivery. I appreciate the efforts taken by the experts from Government sector and private sector from Kerala and also the subject experts from outside the state. I am hopeful that the introduction of standard guidelines for diagnosis and treatment will ensure better quality and consistency in health care. I wish all the success to this endeavour.

Pinarayi Vijayan Chief Minister

11

Message

13

Foreword

Patient care has moved away from management by an individual based on personal knowledge and skill to an evidence based, team managed operation. Decisions are reviewed more rigorously post facto and their alignment verified with standard practice. With the mode of payment for care moving from out of pocket payments to third party payers there will be a demand for rigorous documentation and evidence of having conformed to standard practice. When analysis of big data and machine learning becomes the norm it will require a standard set of procedures to act as the baseline from which to measure deviations and differences in impact. To meet the requirement of these developments in the field of medicine, it is necessary to have explicit, objectively verifiable set of standard operating procedures. They have to be prepared based on international guidelines with the highest acceptance, but have to be modified to suit local knowledge and practice, so that there is local ownership. Government of Kerala has been trying to get the guidelines prepared for some time now. I would like to thank and congratulate Dr. Sreekumari, Joint Director of Medical Education and Dr. T.K.Suma, Professor of Medicine, T.D. Medical College, Alappuzha who took on the task of preparing standard treatment guidelines and completed it through a long, consultative process. I also thank the conveners of the different thematic groups who coordinated the work in their field as well as the innumerable number of participants, in government and private sector, who contributed their effort and knowledge to improve the guidelines. Professional associations have also contributed in their fields. Their efforts have resulted in a product they and Kerala can be proud of. Treatment guidelines cannot be static if they are to remain relevant. They must be updated based on new knowledge and the

15 experience of treatment based on these guidelines. To do this the group which prepared the guidelines has to remain active and have a system for collecting data on the results of practice based on these guidelines. I hope such an activity is institutionalised and periodic revisions of the guidelines are prepared and published.

I wish that these guidelines contribute to raising the quality of patient care in Kerala.

Rajeev Sadanandan IAS Addl Chief Secretary Health & Family Welfare Department

16 Abbreviations 6MWT 6 Minute Walk Test ABG Arterial Blood Gas ACOS Asthma COPD overlap syndrome ADA Adenosine deaminase AEC Absolute Count AFB Acid Fast Bacilli AHI Apnoea Hypopnoea Index ANA Anti Nuclear Antibody BMI Body Mass Index BPAP Bilevel Positive Airway Pressure CAT COPD Assessment Tool CBNAAT Cartridge based nucleic acid amplification test CF CHF Congestive COP Cryptogenic Organising Pneumonia COPD Chronic obstructive pulmonary disease COX2 Cyclo oxygenase - 2 CPAP Continuous Positive Airway Pressure CT Computed Tomography DIP Desquamative Interstitial Pneumonia DLCO Diffusion capacity of the lung for carbon monoxide DR TB Drug resistant TB DST Drug susceptibility testing EBUS Endo bronchial Ultrasound EDS Excessive Daytime Sleepiness EP TB Extra pulmonary TB ESS Epworth Sleepiness Scale FEV1 Forced expiratory volume 1st second FEV1 Forced Expiratory Volume in 1 second FiO2 Fraction of O2 in inspired air FNMM Fibre-optic nasopharyngoscopy with Mueller's manoeuvre FL-LPA First line Line Probe Assay FVC Forced Vital Capacity

17 FQ Fluoroquinolone GERD Gastro esophageal reflux disease GINA Global initiative for asthma HST Home Sleep Testing ICS Inhaled ILD Intersititial lung disease LABA Long acting beta agonist LAM Lymphangioleiomyomatosis LAMA Long Acting Muscarinic Antagonist LCH Langerhan' Cell Histiocytosis LDH Lactate Dehydrogenase LIP Lipoid interstitial pneumonia LPA Line probe assay LTOT Long Term Oxygen Therapy LTRA receptor antagonists Mcg/ μg Microgram MDR Multi-drug resistant TB MGIT Mycobacterial growth indicator tube mMRC Modified Medical Research Council MRA Mandibular Repositioning Appliances MRI Magnetic Resonance Imaging NIV Non-invasive ventilation NSCLC Non Small Cell Lung Cancer NSIP Non Specific Interstitial Pneumonia OCS Oral corticosteroids OCST Out of Centre Sleep Testing OHS Obesity Hypoventilation Syndrome OSA Obstructive Sleep Apnoea PaO2 Partial pressure of Oxygen in arterial blood PAP Positive Airway Pressure PBD Post PDE4 Phosphodiesterase 4 PEEP Positive End Expiratory Pressure PEFR rate PET Position Emission Tomography

18 PM Portable Monitoring pMDI Pressurized Metered Dose Inhaler PSG Polysomnography PSP Primary Spontaneous Pneumothorax RAST Radio allergosorbent test RB ILD Respiratory Interstitial Pneumonia RDI - Respiratory Disturbance Index RERA Respiratory Effort Related Arousal RR TB Rifampicin resistant TB RS TB Rifampicin sensitive TB SABA Short acting beta agonist SAMA Short Acting Muscarinic Antagonist SCLC Small Cell Lung Cancer SDB Sleep Disordered Breathing SDGs Sustainable deveolpment goal SLE Systemic lupus erythematosus SLI Second line injectable SLIT Sublingual immunotherapy SL-LPA Second line Line Probe Assay SMART Single maintainance and reliever therapy Spo2 Peripheral capillary Oxygen saturation SSP Secondary Spontaneous Pneumothorax TBNA Trans Needle Aspiration TRA Tongue Retaining Appliances UAO Upper Airway Obstruction UIP Usual Interstitial Pneumonia ULCT Unattended Limited Channel Testing UPPP UvuloPalatoPharyngoPlasty USG Ultrasonography VATS Video Assisted Thoracoscopic Surgery WRDT WHO approved rapid diagnostic test XDR Extremely drug resistant TB

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Section I Asthma

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section I

Section I 1. Asthma Asthma is a heterogeneous disease characterized by chronic airway and is defined by variable symptoms of , , chest tightness and/or , and is associated with variable expiratory airflow limitation. Both symptoms and airflow limitation characteristically vary over time and in intensity. The usual triggering factors are exercise, allergen or irritant exposure, change in weather or viral respiratory infections. 1.1. When to suspect asthma Asthma is suspected in a person with history of wheeze, shortness of breath, chest tightness and cough that is often worse at night or in the early morning. It may be associated with a triggering factor. The symptoms may improve spontaneously or with treatment. There may be similar history of respiratory symptoms or allergic rhinitis or eczema in the family. Diagnostic criteria for asthma 1. More than one type of the characteristic respiratory symptoms (wheeze, shortness of breath, chest tightness, cough) • Vary over time and in intensity. • Often worse at night or on waking. • Triggered by exercise, laughter, allergens, cold air, strong smells, drugs. • May appear or worsen with viral infections. 2. Evidence of variable expiratory airflow limitation • A fixed cut off of FEV1/FVC <0.75 for older subjects and <0.8 for younger individuals (lower 5th percentile of values from reference population) may be used to diagnose airflow obstruction. • An increase in FEV1 of >12% and >200 mL from baseline, 10–15 minutes after 200–400 mcg or equivalent in adults and increase in FEV1 of >12% predicted in children. • An average daily diurnal PEF variability >10% in adults and average daily diurnal PEF variability >13% in children. • A fall in FEV1 from baseline of ≥ 20% on bronchial provocation test.

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from next p viral e r if - STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section I

Figure 1.1. Diagnosis of Asthma

Adapted from: Global Initiatives for Asthma guidelines 1.3. general principles of asthma management The long-term goals of asthma management are to • Achieve good symptom control (day to day, occupational and recreational) without any functional impairment • Minimize future risk of exacerbations and mortality from exacerbation, fixed airflow limitation and side-effects of treatment. • Achieve and maintain control of daytime as well as nocturnal

25 Section I STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES

symptoms. • Maintain normal activity levels, including exercise, with normal or near normal pulmonary function. 1.4. Categories of asthma medications The pharmacological options for long-term treatment of asthma fall into three main categories. • Controller medications are used for regular maintenance treatment. They reduce airway inflammation, control symptoms, and reduce future risks of exacerbations and decline in lung function. • Reliever (rescue) medications are provided to all patients for as- needed relief of symptoms during worsening asthma or exacerbation (also recommended for short-term prevention of exercise-induced bronchoconstriction). Success of asthma treatment aims at reducing and, ideally, eliminating the need for reliever treatment. • Add-on therapies may be considered when patients have persistent symptoms and/or exacerbations despite optimized treatment with high dose controller medications and treatment of modifiable risk factors. Table 1.1. Dosage of commonly used inhaled corticosteroids

Drug dosage (mcg) Drug Low Medium High Beclomethasone 100 - 200 >200-400 >400 dipropionate

Budesonide 200-400 >400-800 >800

Fluticasone furoate 100 200

Fluticasone propionate 100-250 >250-500 >500 Ciclosonide 80-160 >160-320 >320 Momentasone 110-220 >220-440 >440 Triamcinolone 400-1000 >1000-2000 >2000

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1.5. Control-based asthma management In control-based asthma management, step wise assessment of pharmacological and non-pharmacological treatment should be done, that includes assessment, treatment and review of both symptom control and future risk (of exacerbations and side-effects). Assessment Before initiating controller treatment, • Record evidence for the diagnosis of asthma. • Record the patient's level of symptom control and risk factors, including lung function. • Schedule an appointment for a follow-up visit. After initiating controller treatment • Review patient's response after 3 months, or earlier depending on clinical urgency. • Step up / down treatment based on symptom control. Once symptom control is achieved for 3 months, treatment may be stepped down in order to find the patient's minimum effective treatment. Symptom control assessment There are several numerical scores to assess the severity of asthma, most commonly used being asthma control questionnaire. As per the GINA guidelines 2018, the symptom control is assessed by the table below. Asthma symptom control: In the past 4 weeks, did the patient have l Daytime asthma symptoms more than twice a week? l Any night waking due to asthma? l Reliever needed for symptoms more than twice/week? l Any activity limitation due to asthma? Well controlled – none of these Partly controlled – 1-2 of these Uncontrolled – 3-4 of these

27 Section I STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES

1.6. Assessment of risk factors Potentially modifiable independent risk factors for flare-ups (exacerbations) l Uncontrolled asthma symptoms l High SABA use (with increased mortality if >1 x 200-dose canister/month) l Inadequate ICS: not prescribed ICS; poor adherence; incorrect inhaler technique l Low FEV1, especially if <60% predicted l Major psychological or socioeconomic problems l Exposures: ; allergen exposure if sensitized l Co morbidities: obesity; rhinosinusitis; confirmed food l or blood l Pregnancy Other major independent risk factors for exacerbations l Ever intubated or in intensive care unit for asthma l ≥1 Severe exacerbation in last 12 months Risk factors for developing fixed airflow limitation l Lack of ICS treatment l Exposures: tobacco smoke; noxious chemicals; occupational exposures l Chronic mucus hypersecretion; sputum or blood eosinophilia Risk factors for medication side-effects l Systemic: frequent OCS; long-term, high dose and/or potent ICS; also taking P450 inhibitors

l Local: high-dose or potent ICS; poor inhaler technique 1.7. Treatment Recommended options for initial controller treatment in adults and adolescent Patients need no controller medication or as required reliever medications (SABA) when l Asthma symptoms or need for SABA less than twice a month; l There is no waking due to asthma in last month; l There are no risk factors for exacerbations,including no exacerbations in the last year

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Patients need low dose Inhaled Corticosteroids and as required reliever medications (SABA) when 1) Asthma symptoms are infrequent, but the patient has one or more risk factors for exacerbations 2) Asthma symptoms occur or there is need for SABA between atleast twice a month Patients need Medium to high dose Inhaled Corticosteroids or Low dose ICS + LABA when 1) Patient has troublesome asthma symptoms most days 2) There is waking up due to asthma once a week or more(especially if any risk factors exist) Patients need a Short course of Oral Corticosteroids and start of regular controller medications; High dose Inhaled Corticosteroids or moderate dose ICS + LABA when 1) Initial asthma presentation is with severely uncontrolled asthma, or with an acute exacerbation Add-on tiotropium improves lung function and increases the time to severe exacerbation l Sputum-guided treatment: for patients with persisting symptoms and/or exacerbations despite high-dose ICS or ICS/LABA, treatment may be adjusted based on eosinophilia (>3%) in induced sputum where facility is available. Chest X ray is not routinely recommended in the diagnosis of asthma. In severe asthma, this strategy leads to reduced exacerbations and/or lower doses of ICS. Assess risk factors at diagnosis and periodically, particularly for patients experiencing exacerbations. Measure FEV1 at start of treatment, after 3–6 months of controller treatment to record the patient's personal best lung function, then periodically for ongoing risk assessment l Methylxanthines may be used as an add-on therapy in patients who remain uncontrolled on the moderate to high ICS/LABA combination. Whenever used as an add-on to ICS, low-dose (200-400 mg/day) sustained release formulations of theophylline is

29 Section I STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES

preferred. l SABA is the agent of choice for rescue medication in asthma. SAMA is a less preferred alternative/add-on to SABA as reliever medication l Oral beta agonists should not be used as rescue medications. Use of SiT (single inhaler therapy)/ SMART using an ICS/LABA combination (formoterol-based) as both maintenance and reliever medication is preferred whenever feasible. l Inhaler technique and adherence must be ensured. 1.8. Reviewing response and adjusting treatment The frequency of visits depends upon the patient's initial level of control and their response to treatment. For most controller medications, improvement begins within days of initiating treatment, but the full benefit may only be evident after 3–4 months. In severe and chronically under-treated disease, it may take longer. Ideally, patients should be seen 1–3 months after starting treatment and every 3–12 months thereafter. After an exacerbation, a review visit within 1 week should be scheduled. Stepping up asthma treatment Asthma is a variable condition, and periodic treatment adjustments by the clinician and/or the patient may be needed. It can either be a sustained or short term step up or can be day to day adjustment l Sustained step up (for at least 2–3 months) can be tried when the initial treatment has failed (provided, inhaler technique and adherence are satisfactory; and modifiable risk factors such as smoking have been addressed) any step-up should be regarded as a therapeutic trial, and the response reviewed after 2–3 months. If there is no response, treatment should be reduced to the previous level, and alternative treatment options or referral considered. l Short-term step up (for 1–2 weeks)by increasing maintenance ICS dose for 1–2 weeks; for example, during viral infections or seasonal allergen exposure. l Day-to-day adjustment: for patients prescribed combination /formoterol or beclometasone/formoterol as maintenance and reliever treatment, the patient adjusts the number of as-needed doses of ICS/formoterol from day to day

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according to their symptoms, while continuing the maintenance dosage.

Figure 1.2. Treatment of patients diagnosed with Asthma

Step1 – As needed SABA as reliever

Step2 - Low dose ICS (controller) with as needed SABA (reliever) Leucotriene receptor antagonists and low dose theophylline (as other controllers)

Step3 – Low dose ICS/LABA (controller) plus as needed SABA (reliever) Or Medium or high dose ICS or Low dose ICS + LTRA/ theophylline (as other controllers)

Step 4 – Low dose ICS/LABA or as needed SABA (reliever) And medium or high dose ICS/LABA (controller) Add tiotropium or high dose ICS + LTRA/ theophylline (as other controllers)

Step 5 –Consider add-on treatment (tiotropium, anti IgE, anti IL-5) as controller Add low dose oral corticosteroids (as other controllers) Low dose ICS / LABA or as needed SABA (reliever)

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Stepping down treatment when asthma is well controlled Once good asthma control has been achieved and maintained for 3 months and lung function has reached a plateau, treatment can often be successfully reduced, without loss of asthma control. l Choose an appropriate time (no respiratory infection, patient not travelling, not pregnant). l Stepping down ICS doses by 25–50% at 3 month intervals is feasible and safe for most patients, while continuing the second controller. l Actively engage the patient in the process; ask them to document their asthma status (symptom control, lung function and risk factors),and schedule a follow-up visit. l Provide a written asthma action plan and instructions for how and when to resume their previous treatment if their symptoms worsen.If treatment is stepped down too far or too quickly, exacerbation risk may increase even if symptoms remain Q reasonably controlled

l Complete cessation of ICS is associated with a significant risk of exacerbations; hence ICS need to be continued long term. Controller medication may be stopped only if patient has been totally asymptomatic for 6 – 12 months and there are no risk factors for exacerbation. This requires close follow up. 1.9. Other therapies Allergen Immunotherapy Allergen-specific immunotherapy may be an option if allergy plays a prominent role, e.g. asthma with allergic rhino-conjunctivitis. Sublingual immunotherapy (SLIT) can be considered in house dust mite sensitive patients with allergic rhinitis (FEV1>70%) who have exacerbations despite ICS treatment. Vaccinations causes significant morbidity and mortality in the general population, and the risk can be reduced by annual vaccination. Patients with moderate-severe asthma are advised to receive an influenza vaccination every year, or when vaccination of the general population is advised.

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Treating other modifiable risk factors Some patients continue to experience exacerbations even with maximal doses of current treatment. If a patient gets one exacerbation, there is high risk of getting another in next one year. Hence optimising asthma management includes addressing modifiable risk factors.

Table 1.2. Managing risk factors for optimal control of Asthma

Risk factor Treatment strategy • Encourage smoking cessation by Exposure to tobacco smoke patient/family; provide advice and resources • Consider higher dose of ICS if asthma poorly.

Low FEV1, especially if <60% Consider trial of 3 months’ treatment with high- Predicted dose ICS and/or 2 weeks’ OCS • Exclude other lung disease, e.g. COPD • Refer for expert advice if no improvement Obesity •Document BMI Strategies for weight reduction • Distinguish asthma symptoms from symptoms due to deconditioning, mechanical restriction, and/or sleep apnea. Major psychological problems Arrange mental health assessment Help patient to distinguish between symptoms of anxiety and asthma; provide advice about management of panic attacks Major socio economic problems Identify most cost-effective ICS-based regimen Confirmed food allergy Appropriate food avoidance; injectable epinephrine Allergen exposure if sensitized Consider trial of simple avoidance strategies; consider cost Consider step up of controller treatment.The efficacy of allergen immunotherapy in asthma is limited. Sputum eosinophilia Increase ICS dose independent of level of symptom control Medications Avoid the medications triggering the asthma attack. Gastro esophageal reflux disease Empirical trial of anti-reflux medication, such as a proton pump inhibitor or motility agent, may be considered. If the symptoms do not resolve, specific investigations such as 24-hour pH monitoring or may be considered. Allergic rhinitis Treatment with Intranasal corticosteroids

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1.10. Evaluation of difficult to treat ASTHMA

l Patients whose asthma symptoms are inadequately controlled, despite optimal step 4 therapy for a period of 1-3 months, can be considered to have difficult to treat asthma. l Check inhaler technique and adherence, and environmental exposures, smoking, address comorbidities. l Avoidance of exposure to allergens. Role of Anti- IGE and anti IL-5 in Asthma These agents have a role to play in the management of difficult to control Asthma, not responding to all other steps described above. However in view of extremely high cost, their use may be initiated only after consultation and concurrence with an expert committee at a Government Medical College. Role of Bronchial Thermoplasty in Asthma As of now, good quality evidence is lacking for recommending bronchial thermoplasty in the routine management of bronchial asthma. Role of Immunotherapy in Asthma Single allergen immunotherapy may provide a modest benefit to patients with mild-to-moderate asthma with demonstrable skin allergy to that antigen. To be decided upon only after approval of institute's expert committee. It is contraindicated in patients with poorly controlled asthma and in those with FEV1< 70%. Role of Patient Education and Pulmonary Rehabilitation l Optimal self management which involves a combination of patient education, self-monitoring, regular physician review, and self management using a written asthma action plan is strongly recommended in the management of asthma. l Pulmonary rehabilitation therapy in asthmatics reduces symptoms, improves exercise capacity and quality of life. Role of Vaccination and Antibiotics in the prevention of Asthma Exacerbation l Current evidence is insufficient to routinely recommend influenza or pneumococcal vaccination for patients with asthma. l Antibiotics are not recommended in the prevention of asthma exacerbations

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1.11. Management of Asthma in special situations Asthma & Pregnancy l Most medications used for asthma have negligible effects on the foetus. l Adequate asthma control in pregnancy should be attempted with routinely available asthma medications as in the non-pregnant state (including systemic steroids whenever indicated). l It is advisable to delay the objective confirmation of the diagnosis until after delivery. l Asthma during lactation should be managed similar to asthma during pregnancy. l Caution should be exercised while using theophylline during pregnancy and lactation. Exercise induced asthma l Pre-treatment with bronchodilator agents (SABA,SAMA, and LABA) as well as anti-inflammatory agents (LTRA but not ICS) is effective in attenuating the fall in FEV1 associated with EIA. l Regular use of ICS or LTRAs is effective in prevention of exercise-induced bronchospasm. l Regular use of LABA as prophylaxis for EIA should be avoided as long-term regular administration of LABA induces tolerance and may cause increase in adverse effects. Aspirin-exacerbated l It starts with and anosmia, and progresses to chronic rhinosinusitis with nasal polyps that re-grow rapidly after surgery. An acute asthma attack develops within minutes to 1–2 hours of ingestion of Aspirin or other NSAID. l Aspirin challenge (oral, bronchial or nasal) is the gold standard for diagnosis. Bronchial (inhalational) and nasal challenges with lysine aspirin are safer than oral challenges and may be safely performed in allergy centers. l Avoid aspirin or NSAID-containing products and other medications that inhibit cyclooxygenase-1 . Where an NSAID is indicated, a COX-2 inhibitor (e.g. celocoxib,oretoricoxib), or paracetamol (acetaminophen), may be considered with appropriate health care

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provider supervision and observation for at least 2 hours after administration. l ICS are the mainstay of asthma therapy in AERD, but OCS are sometimes required; LTRA may also be useful Occupational Asthma l Asthma may be induced or aggravated by exposure to allergens or other sensitizing agents. Hence a detailed history about work history, exposures and hobbies should be taken. PEF monitoring at and away from work is often used to help confirm the diagnosis. l Both removal of exposure and reduction of exposure improve symptoms of occupational asthma. l Removal of exposure appears to be better than reduction of exposure. Elderly l It is difficult to diagnose asthma in elderly due to poor perception of airflow limitation; acceptance of dyspnea as being 'normal' in old age; and reduced activity. l The presence of co-morbid diseases also complicates the diagnosis. l In older people with a history of smoking or biomass fuel exposure, a diagnosis of COPD and asthma–COPD overlap syndrome (ACOS) should be ruled out. Asthma action plan l Identify and avoid asthma triggers l Monitor your breathing l Identify and treat attacks early l Take your medication as prescribed. l Pay attention to increasing quick-relief inhaler use l Get vaccinated for influenza and pneumonia. 1.12. Acute exacerbation of Asthma Evaluation and management Exacerbations of asthma are episodes characterised by acute aggravation in symptoms of shortness of breath, cough, wheezing or chest tightness and progressive decline in lung function. It represents a change from the patient's usual status that is sufficient to require a change in treatment.

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Exacerbation may occur in a patient with previous diagnosis of asthma or occasionally the first presentation. Mimickers of an acute asthmatic attack 1) Acute exacerbation of COPD 2) Acute left heart failure 3) Pulmonary thromboembolism 4) Pneumothorax 5) Hyperventilation 6) 7) Foreign body inhalation Assessment of severity of asthmatic attack Objective assessments 1) Measurement of lung volumes 2) Oxygen saturation 3) Arterial oxygen saturation not routinely recommended 4) Chest x-ray not routinely recommended unless there is suspicion of cardiac involvement or pneumothorax. The severity of an asthma exacerbation is defined on a combination of and the extent of accompanying cardio-respiratory dysfunction into non-severe, severe and life-threatening. Factors that increase the risk of asthma-related death Patients with one or more of these risk factors should be encouraged to seek urgent medical care early in the course of an exacerbation. v A history of near-fatal asthma requiring intubation and v Hospitalization or emergency care visit for asthma in the past year v Currently using or having recently stopped using oral corticosteroids (a marker of event severity) v Not currently using inhaled corticosteroids v Over-use of SABAs, especially use of more than one canister of salbutamol (or equivalent) monthly v A history of psychiatric disease or psychosocial problems v Poor adherence with asthma medications and/or poor adherence with (or lack of) a written asthma action plan v Food allergy in a patient with asthma

37 Section I STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES

Table 1.3. Site of management of patients with exacerbation of Asthma

Severity Symptoms Sign/investigations Place of management Non- severe Not fulfilling criteria Out-patient for severe or life- threatening asthma Severe Inability to complete Use of accessory muscles ED/ ward (presence of a sentence, of respiration, two or more of agitation. Respiratory rate more than the following) 30/min Heart rate >110/min Pulses paradoxus>25mmHg Silent chest PEF <60% of predicted PaO2<60% of predicted Or SPo2 < 92% Life threatening Alteration in mental , ICU status , Paradoxical breathing, PaCO2>40mmhg with worsening of PH, heart rate <60/min

Figure 1.3 Treatment

Assess the patient Rule out alternate diagnosis. Assess the severity

Mild or moderate Severe or life threatening

If worsening

SABA 4-10 puffs by MDI with ED / ward/ ICU spacer to be repeated every Inhaled SABA, SAMA and steroids 20 min for one hour. Steroids- Controlled oxygen therapy prednisolone 1mg/kg max 50mg in adultsControlled oxygen therapy If worsening

To continue SABA as required To reassess after one hour

2038 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section I

Controlled oxygen therapy (if available) Oxygen therapy should be titrated against pulse oximetry (if available) to maintain oxygen saturation at 93–95% (94–98% for children 6–11 years, >95% in pregnancy). Controlled or titrated oxygen therapy gives better clinical outcomes than high-flow 100% oxygen therapy .Patient should be monitored for deterioration, somnolence or fatigue. Inhaled short-acting beta2-agonists Inhaled SABA ( Salbutamol) therapy should be administered frequently for patients presenting with acute asthma. The most cost-effective and efficient delivery is by pMDI with a spacer. Evidence is less robust in severe and near-fatal asthma. (Salbutamol 4-6 puffs of 100 μg every 15 min or nebulisation 2.5mg salbutamol every 15 min or >4 nebulisation per hour or; levosalbutamol 1.25mg) Levosalbuamol has similar efficacy and safety as compared to salbutamol in acute asthma. In patients unable to use MDI with spacer, drugs can be delivered via a nebulizer. Once stabilized patient should be switched over to spacer from nebulizer. Systemic corticosteroids Oral cortico steroids should be given promptly, especially if the patient is deteriorating, or had already increased their reliever and controller medications before presenting. The recommended dose for adults is 1 mg prednisolone/kg/day or equivalent up to a maximum of 50 mg/day, and 1–2 mg/kg/day for children 6–11 years up to a maximum of 40 mg/day. OCS should usually be continued for 5–7 days. Inhaled corticosteroids Inhaled steroids do not provide any additional benefit when used along with systemic corticosteroids and hence not recommended in management of acute asthma. Other treatments Antibiotics Evidence does not support a role of antibiotics in asthma exacerbations unless there is strong evidence of lung infection (e.g. fever and purulent sputum or radiographic evidence of pneumonia). Aggressive treatment with corticosteroids should be implemented before antibiotics are considered.

39 Section I STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES

Epinephrine Intramuscular epinephrine (adrenaline) is indicated in addition to standard therapy for acute asthma associated with anaphylaxis and angioedema. It is not routinely indicated for other asthma exacerbations. ( SAMA) l For adults and children with moderate-severe exacerbations, treatment in the emergency department with both SABA ( Salbutamol or levosalbutamol) plus ipratropium (2 puffs of 20 μg every 4hourly ; nebulization with 500 μg once then 250 μg four to six hourly) l Use of SAMA was associated with fewer hospitalizations and greater improvement in PEF and FEV1 compared with SABA alone. l No benefit noted with SAMA in children. and theophylline Intravenous aminophylline and theophylline should not be used in the management of asthma exacerbations, in view of their poor efficacy and safety profile, and the greater effectiveness and relative safety of SABA. But they may be used in exceptional circumstances such as type 2 or patients on mechanical ventilation with intense bronchospasm causing ineffective delivery of nebulized drugs. Magnesium Intravenous magnesium sulphate is not recommended for routine use in asthma exacerbations. When administered as a single 2 g infusion over 20 minutes, it reduces hospital admissions in some patients, including adults with FEV1 <25–30% predicted at presentation; adults and children who fail to respond to initial treatment and have persistent ; and children whose FEV1 fails to reach 60% predicted after 1 hour of care. Leukotriene receptor antagonists There is limited evidence to support a role for oral or intravenous LTRAs in acute asthma, hence not recommended. ICS/LABA combinations The role of these medications in the emergency department or hospital is unclear hence not recommended.

2040 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section I

Sedatives Sedation should be strictly avoided during exacerbations of asthma because of the respiratory depressant effect of anxiolytic and hypnotic drugs. An association between the use of these drugs and avoidable asthma deaths has been reported. Heliox Not routinely used in acute asthma exacerbation. Non-invasive ventilation (NIV) There is no recommendation for NIV in asthma exacerbation. If NIV is tried, the patient should be monitored closely (Evidence D). It should not be attempted in agitated patients, and patients should not be sedated in order to receive NIV. Mechanical ventilation in management of The absolute indications of MV in severe acute asthma include coma, respiratory or cardiac arrest and refractory hypoxemia while the relative indications include inadequate response to initial management, , fatigue, somnolence and cardiovascular compromise.

Table 1.4.

Setting Recommendation Mode 8 -12/min Tidal volume 4 -6ml/Kg I:E ratio 1:4 or lower Waveform Square waveform

Inspiratory flow 100 -120 l/min FiO2 Titrate to maintain PaO2> 60m m Hg or SpO2 >/= 89% Avoid hyperoxia PEEP Upto 5cm H2O Plateau pressure <30 cm H20

41 Section I STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES

1.14. Discharge following IP treatment of patient with acute Asthma

l A patient with severe acute asthma is considered fit for discharge from the medical facility when he/she is clinically stable for at least 24 hours. l PEF has improved to more than 60-80% of baseline. l The patient should be able to eat and get adequate sleep, should be able to comfortably use the inhaled medication with requirement of inhaled short-acting drugs no more than every 4 hours l Oxygen saturation has improved to >94%. l Adequate home support. At the time of discharge, step up or initiate the controller medication after checking the inhaler technique. Continue the reliever as and when required. Steroids may be continued orally for 5-7 days. Advise follow-up after a week.

2042 Section II Allergic rhinitis

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section II

Section II 2. Allergic rhinitis Rhinitis is defined as inflammation of the nasal mucosa and is characterized by sneezing, nasal congestion, nasal itching, and . The eyes, ears, sinuses, and throat can also be involved. It is an extremely common condition, affecting approximately 20% of the population. Allergic rhinitis, even though not a life threatening condition can significantly impair quality of life. Systemic effects, including fatigue, sleepiness, and malaise, can occur from the inflammatory response. Allergic rhinitis can frequently lead to significant impairment of quality of life. Symptoms such as fatigue, drowsiness, and malaise can lead to impaired work and school performance, missed school or work days, and traffic accidents. Allergic rhinitis involves inflammation of the mucous membranes of the nose, eyes, eustachian tubes, middle ear, sinuses, and . The nose invariably is involved, and involvement of other organs may vary according to severity. Inflammation of the mucous membranes is triggered by (IgE) in response to an extrinsic allergen. 2.1. Classification of allergic rhinitis Duration 1 Intermittent – symptoms are present less than 4 days a week or for less than 4 weeks. 2 Persistent – symptoms are present at least 4 days a week and for at least 4 weeks. Severity 1 Mild – none of the following is present. 2 Moderate-severe – at least one of the following is present. a) Sleep disturbance b) Impairment of daily activities, leisure and/or sport c) Impairment of school or work d) Troublesome symptoms 2.1.1Evaluation Obtaining a detailed history is important in the evaluation of allergic rhinitis. Important elements include an evaluation of duration, and time course of symptoms; possible triggers, response to medications, comorbid conditions, family history of

45 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section II

allergic diseases, environmental and occupational exposures. A thorough history may help identify specific triggers, suggesting an allergic etiology for the rhinitis. Symptoms that can be associated with allergic rhinitis include sneezing, itching of nose, eyes, ears and palate, rhinorrhea, postnasal drip, congestion and headache. Significant complaints of congestion, particularly if unilateral, might suggest the possibility of structural obstruction, such as a , foreign body, or deviated septum. Trigger factors This might include exposure to pollen outdoors, mold spores while doing yard work, specific animals, or dust while cleaning the house. Irritant triggers such as smoke, pollution, and strong smells can aggravate symptoms in a patient with allergic rhinitis. Response to treatment Response to treatment with supports the diagnosis of allergic rhinitis, although sneezing, itching, and rhinorrhea associated with can also improve with antihistamines. Response to intranasal corticosteroids supports the diagnosis of allergic rhinitis, although some cases of nonallergic rhinitis (particularly the nonallergic rhinitis with syndrome [NARES]) also improve with nasal steroids. Physical Signs The mucosa of the nasal turbinates may be swollen and have a pale, bluish- graycolor. Some patients may have predominant erythema of the mucosa, which can also be observed with , infection, or vasomotor rhinitis. While pale, boggy, blue-gray mucosa is typical for allergic rhinitis, mucosal examination findings cannot definitively distinguish between allergic and nonallergic causes of rhinitis.Thin and watery secretions are frequently associated with allergic rhinitis, while thick and purulent secretions are usually associated with .Nasal examination may reveal deviation of septum or polyps. Laboratory Studies Allergy testing provides knowledge of the degree of sensitivity to a particular allergen. The most commonly used methods of determining allergy to a particular substance are allergy skin testing and in vitro diagnostic tests. Testing for reaction to specific allergens can be helpful to confirm specific allergic triggers. If specific

2046 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section II allergic triggers are known, then appropriate avoidance measures can be recommended. It is essential to know which allergens a patient is sensitive to in order to perform allergen immunotherapy (desensitization treatment). In vitro allergy tests, ie, RAST, allow measurement of the amount of specific IgE to individual allergens in a sample of blood. The amount of specific IgE produced to a particular allergen approximately correlates with the allergic sensitivity to that substance. When selecting allergens, identify allergens that are present locally and are known to cause clinically significant allergic disease. Total serum IgE This is a measurement of the total level of IgE in the blood. While patients with allergic rhinitis are more likely to have an elevated total IgE level than the normal population, this test is neither sensitive nor specific for allergic rhinitis. As many as 50% of patients with allergic rhinitis have normal levels of total IgE, while 20% of nonaffected individuals can have elevated total IgE levels. Total blood eosinophil count. As with the total serum IgE, an elevated eosinophil count supports the diagnosis of allergic rhinitis, but it is neither sensitive nor specific for the diagnosis. Imaging Studies Radiography While radiographic studies are not needed to establish the diagnosis of allergic rhinitis, they can be helpful for evaluating possible structural abnormalities or to help detect complications or comorbid conditions, such as sinusitis or hypertrophy. CT scanning Coronal CT scan images of the sinuses can be very helpful for evaluating acute or chronic sinusitis. CT scanning may also help delineate polyps, turbinate swelling, septal abnormalities (eg, deviation), and bony abnormalities (eg, concha bullosa). MRI For evaluating sinusitis, MRI images are generally less helpful than CT scan images, largely because the bony structures are not seen as clearly on MRI images. However, soft tissues are visualized quite well, making MRI images helpful for diagnosing malignancies of the upper airway.

47 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section II

Other Tests Nasal cytology Rhinoscopy: Nasal provocation testing Treatment The management of allergic rhinitis consists of 3 steps (1) Environmental control measures and allergen avoidance, (2) Pharmacological management, and (3) Immunotherapy. Environmental Control Environmental control measures and allergen avoidance involve both the avoidance of known allergens and avoidance of nonspecific, or irritant, triggers. Pharmacotherapy Pharmacologic options for the treatment of allergic rhinitis include intranasal corticosteroids, oral and topical antihistamines, decongestants, intranasal cromolyn (Nasalcrom), intranasal , and leukotriene receptor antagonists. Intranasal corticosteroids are the mainstay of treatment of allergic rhinitis. The adverse effects most commonly experienced with the use of intranasal corticosteroids are headache, throat irritation, epistaxis, stinging, burning, and nasal dryness. The second-generation oral antihistamines such as desloratadine, levocetirizine, fexofenadine, and loratadine are effective in controlling symptoms and have better side effect profile. Compared with oral antihistamines, intranasal antihistamines offer the advantage of delivering a higher concentration of medication to a specific targeted area, resulting in fewer adverse effects. Oral and topical decongestants improve the nasal congestion associated with allergic rhinitis. There is a chance thatpatients may develop rhinitis medicamentosa or have rebound or recurring congestion. Immunotherapy (desensitization) Immunotherapy is a long-term process. Therapy should be continued for 3-5 years. Success rates have been demonstrated to be as high as 80- 90% for certain allergens. Sublingual immunotherapy (SLIT) is currently

2048 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section II

increasing in use, particularly in Europe. SLIT can produce significant clinical improvement in elderly patients with allergic rhinitis caused by house dust mites (HDMs). [13] Surgical Care Surgical care is not indicated for allergic rhinitis but may be indicated for co morbid or complicating conditions, such as chronic sinusitis, severe septal deviation (causing severe obstruction), nasal polyps, or other anatomical abnormalities. The value of turbinectomy is not established. 2.2. References 1. Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy ClinImmunol. Jul 2001;108(1 Suppl):S2-8. 2. Meltzer EO. The prevalence and medical and economic impact of allergic rhinitis in the United States. J Allergy ClinImmunol. Jun 1997;99(6 Pt 2):S805-28. 3. Bozek A, Ignasiak B, Filipowska B, Jarzab J. House dust mite sublingual immunotherapy: a double-blind, placebo-controlled study in elderly patients with allergic rhinitis. ClinExp Allergy. Feb 2013;43(2):242-8.

49

Section III CHRONIC OBSTRUCTIVE PULMONARY DISEASE

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section III

Section III 3. Diagnosis & managementof chronic obstructive pulmonary disease Chronic Obstructive Pulmonary Disease (COPD) - is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. 3.1. When to suspect COPD? A diagnosis of COPD should be considered in persons having chronic symptoms of cough, sputum production, shortness of breath, and/or wheezing, especially among those with prolonged exposure to risk factors for the disease. COPD in Indian females are increasing due to exposure to biomass fuels. Females are more susceptible to effects of tobacco smoke than males. 3.2. Risk factors for COPD

Table 3.1. Risk factors for COPD

Established Probable

Tobacco smoking Indoor Environmental tobacco smoke Outdoor air pollution Exposure to biomass fuel Genetic factors Occupational exposure to dust/ smoke Advancing age Alpha-1 antitrypsin deficiency Intrauterine growth retardation Low Socioeconomic Poorly controlled long standing Asthma Severe childhood respiratory infection Tuberculosis Poor nourishment HIV

A diagnosis of COPD should not be excluded in the absence of physical signs

53 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section III

3.3. Diagnosis of COPD Spirometry should be performed in all patients of age > 35 yrs with symptoms suggestive of COPD A Post-bronchodilator FEV1/FVC < 0.7 should be used as the criteria for diagnosis of COPD. Spirometry should not be used as a screening tool in asymptomatic individuals to detect airflow obstruction PEF should not be routinely used for screening, diagnosis, or monitoring of COPD Classification of severity of COPD Classification of severity of the disease should be done for all COPD patients based on the FEV1 and exacerbation frequency Level of patient's disability due to symptoms should be assessed using modified Medical Research Council (mMRC) dyspnoea questionnaire or the COPD assessment test (CAT) Classification of Severity of Airflow Limitation in COPD In patients with post bronchodilator FEV 1/FVC < 0.70 GOLD 1: Mild - FEV1 >/= 80% predicted GOLD 2: Moderate - 50%=/< FEV 1 < 80% predicted GOLD 3: Severe - 30%=/< FEV 1< 50% predicted GOLD 4: Very Severe - FEV1< 30% predicted *Based on Post-Bronchodilator FEV 1 Combined COPD assessment In the GOLD -2019 revised assessment scheme (see Figure), the impact of COPD on an individual patient is assessed by combining the symptomatic assessment using mMRC or COPD Assessment Tool (CAT), with the patient's spirometric classification and/or risk of exacerbations. The number provides information regarding severity of airflow limitation (spirometric grade 1 to 4) while the letter (groups A to D) provides information regarding symptom burden and risk of exacerbation which can be used to guide therapy

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Figure 3.1. Diagnosis of COPD

GRADE FEV1 (% predicted) Gold 1 >/=80 Gold 2 50-79 Gold 3 30-49 Gold 4 <30

exacerbration history groups

Atleast one exacerbration requiring hospitalisation or C D 2 or more exacerbration a year Maximun of one exacerbraion a year which does not require hospitalisation A B mMRC 0-1 mMRC OF 2 OR MORE SYMPTOMS Cat score less than 10 Cat score of 10 or more

3.4. Additional investigations in COPD 1. All new COPD suspects with cough of more than 2 weeks' duration should undergo sputum AFB examination as per RNTCP. 2. Pulse Oximetry & ABG – To screen for hypoxemia especially when there is clinical suspicion and FEV1 < 50%. ABG recommended if SPO2 < 92%. 3. Chest X-ray Diagnosis of COPD should not be made on the basis of a chest radiograph. Chest radiograph may be done during the initial evaluation of COPD to look for comorbidities, complications, and alternative diagnosis. 4. Special investigations like HRCT scan, lung volumes, DLCO, and exercise testing should be done in situations of diagnostic difficulty or

55 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section III

whenever clinically indicated. 5. 6MWT may be used for monitoring of exercise capacity in COPD. 6. Testing for alpha-1 antitrypsin deficiency is not routinely recommended. It may be done in young patients with lower lobe emphysema.  COPD patients should be routinely evaluated and appropriately treated for comorbid conditions such as Cardiovascular diseases, Osteoporosis, Skeletal muscle dysfunction, Cachexia, Respiratory infections, Anxiety and Depression, Diabetes, Lung cancer and Bronchiectasis These comorbid conditions may influence the mortality and hospitalizationsand should be looked for routinely, and treated appropriately 3.5. Treatment options 3.5.1. Management of stable COPD Includes Pharmacological and Non-Pharmacological therapies Pharmacotherapy – l Inhaled therapy is now established as the mainstay of treatment for patients with stable COPD. l The choice of inhaler device will depend on availability, cost, the prescribing physician, and the skills and ability of the patient. l It is essential to ensure that inhaler technique is correct and to recheck this at each visit. A . – a) Antimuscarinic agents Generally, Antimuscarinic agents are preferred over beta-2 agonists, in COPD, because they have found to be superior in symptom relief as well as reducing number of exacerbations. l Short-acting antimuscarinic agent (SAMA) like iptratropium can be used as rescue medication to relieve patient symptoms. l Long term SAMA monotherapy on regular basis is not recommended. l Long-acting antimuscarinic agents (LAMA) are useful in stable COPD (FEV1 < 80%) to control symptoms and decrease the risk of exacerbations. Eg tiotropium, aclidinium, glycopyrronium bromide and umeclidinium l ·LAMA should be preferred over SAMA

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Inhaled drugs are well tolerated. l The main side effect is dryness of mouth. l Occasional urinary symptoms have been reported b) Beta2 -Agonists l Short-acting beta-agonist (SABA) can be used to relieve symptoms of dyspnea as and when needed. The effect of SABAs usually wears off within 4-6hrs l Long term SABA monotherapy on regular basis is not recommended l Long-acting beta-agonist (LABA) monotherapy is not recommended. Long acting Beta 2 agonists, salmeterol and formetrol need to be given twice daily Ultra long acting Indacaterol is given once daily B. Inhaled Corticosteroids COPD-associated inflammation has limited responsiveness to corticosteroids. Regular treatment with ICS does not modify the long-term decline of FEV1 nor mortality in patients with COPD.So use of ICS in COPD have a beneficial effect in subgroup of COPD patients with l one exacerbation per year & AEC ≥300 eos inophils / μL l ≥2 moderate exacerbation spery ear or atleast one severe exacerbation requiring hospitalization in the prior year & eos inophil counts ≥ 100cel ls/μL Prolonged use of ICS has shown to increases risk of pneumonia in COPD l Long-term monotherapy with oral or inhaled corticosteroids is not recommended in COPD. Dosage of inhaled corticosteroids has already been described in chapter 1. Please see table 1.1. In patients of severe COPD (FEV1 < 60%), triple therapy (ICS + LABA + LAMA ) may be used in those who are symptomatic despite single or dual bronchodilator therapy and has shown to have better symptom control and reduction of exacerbations. Blood eosinophil count & Inhaled use l Recent studies have shown that blood eosinophil counts predict the magnitude of the effect of ICS in preventing future

57 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section III

exacerbations l GOLD 2019 guidelines suggest that that an absolute eosinophil count (AEC) > 300 cells/μL identifies the patients with the greatest likelihood of treatment benefit with ICS l ICS containing regimens have little or no effect at a blood eosinophil count < 100 cells/μL Methylxanthines l There is only evidence for a modest bronchodilator effect compared with placebo in stable COPD. l Clearance of the drug declines with age. l Addition of theophylline to salmeterol produces a greater improvement in FEV1 and breathlessness than salmeterol alone. l Adverse effects. Toxicity is dose-related, which is a particular problem with derivatives because their therapeutic ratio is small and most of the benefit occurs only when near-toxic doses are given l Methylxanthines are not recommended as first line They can be used l As alternative in patients noncompliant with inhalers for any reason. l As add-on therapy in patients continuing to have symptoms despite optimum inhaled therapy. Sustained release preparations are preferred. Roflumilast (PDE 4 Inhibitor)may be used in frequent to ICS, when FEV1 <50% and chronic bronchitis. PDE 4 Inhibitors should always be used in combination with a bronchodilator Combination of ICS/Bronchodilator Therapy l ICS + LABA -more effective than individual components in improving lung function,health status, decreasing exacerbations in moderate exacerbations. An ICS/LABA combination prescribed once daily does not show relevant differences in efficacy compared to BD dosing. Sustained release preparations are preferred. May be used in frequent exacerbators as an add-on or substitute to ICS, and in patients with chronic bronchitis.

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Combination of bronchodilators Available combinations: SABA + SAMA – Salbutamol + ipratropium LABA + LAMA - Formeterol + Tiotropium Ultra LABA + Ultra LAMA - Inadacaterol + Glycopyronium Combining bronchodilators with different mechanisms and durations of action may increase the degree of bronchodilation with a lower risk of side- effects compared to increasing the dose of a single bronchodilator. Combinations of a LABA and LAMA in a single inhaler improve lung function greater than long acting bronchodilator monotherapy effects. Such a combination is found to decrease exacerbations to a greater extent than an ICS/LABA combination. Combination of ICS/Bronchodilator Therapy More effective than individual components in improving lung functions, health status, decreasing exacerbations in moderate to severe COPD with frequent exacerbations. An ICS/LABA combination OD does not show relevant differences in efficacycompared to BD dosing 3.5.1. Other pharmacological treatments a. Vaccines Influenza and Pneumococcal vaccination. Influenza vaccination can reduce serious illness and death in COPD patients. The strains are adjusted each year for appropriate effectiveness and should be given once each year. l Pneumococcal polysaccharide vaccine is recommended for COPD patients 65yrs and older and also in younger patients with significant comorbid conditions such as cardiac disease. l Vaccines reduce the incidence of community acquired pneumonia in COPD patients younger than 65yrs with an FEV1<40% predicted b. Alpha 1 Antitrypsin Augmentation Therapy l Young patients with severe hereditary alpha 1 antitrypsin deficiency and established emphysema may be candidate for alpha 1 augmentation therapy. Very expensive and is not recommended for patients with COPD that is unrelated to alpha 1

59 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section III

antitrypsin deficiency l It should be prescribed only after discussion with an expert committee. c.Antibiotics May be prescribed for treating all exacerbations of COPD especially when patients present with purulent expectoration. Recent studies have shown that regular use of some antibiotics may reduce exacerbation rate. Azithromycin (250 mg/day or 500 mg three times per week) or Erythromycin (500 mg two times per day) for one year in patients prone to exacerbations reduced the risk of exacerbations. But patients on long term azithromycin should be cautioned about increased incidence of bacterial resistance, prolongation of QTc interval, and impaired hearing tests d. Mucolytics: In COPD patients not receiving inhaled corticosteroids, regular treatment with mucolytics such as erdosteine, carbocysteine and N-acetylcysteine may reduce exacerbations and modestly improve health status e. Antitussives Regular use not recommended f. Vasodilators Nitric oxide contraindicated in stable COPD Others drugs - Nedocromil, leukotriene modifiers like montelukast not adequately tested in COPD Symptom control and palliative care Even when receiving optimal medical therapy many patients with COPD continue to experience distressing breathlessness, impaired exercise capacity, fatigue, and suffer panic, anxiety and depression. Such patients should be referred to palliative care. Treatment with opioids (low dose morphine) has been found to be beneficial. 3.5.2. Non pharmacological therapies 1. Smoking Cessation Most important intervention for COPD patients who smoke regardless of disease severity . Greatest capacity to influence natural history 2. Physical activity Daily physical activity recommended for all COPD patients.

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3. Pulmonary Rehabilitation Improves exercise tolerance and decreases dyspnoea and fatigue Components of Pulmonary Rehabilitation Programme l Exercise training. l Smoking Cessation l Patient Education l Assessment and Follow-up l Nutritional support 4. Identify and reduce the exposure to risk factors like environmental, occupational and indoor and outdoor air pollution. 3.5.3. . Other treatments

l Oxygen therapy l Ventilatory Support l Surgical treatments

Table 3.2. INITIAL Pharmacological treatment of stable COPD

>2 moderate Gp C Gp D LAMA or exacerbations or >1 LAMA+LABA* or leading to LAMA ICS+LABA** hospitalisation 0 or 1 moderate Gp B Gp A exacerbations A long acting (not leading to A bronchodilator Bronchodilator hospitalisation) (LAMA or LABA

mMRC 0 – 1; CAT<10 mMRC > 2; CAT > 10

* For highly symptomatic patients ** If Eosinophils > 300

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3.6. Follow-up pharmacological management Patient on maintenance treatment should be periodically followed up and treatment options altered, on the basis of improvement or worsening of dyspnea/exercise limitation and frequency of exacerbations. If a change in treatment is considered necessary then select the corresponding algorithm for dyspnea or exacerbations Follow up pharmacological management should be guided by the principles of first review and assess, then adjust if needed: Ø Review- Review symptoms (dyspnea) and exacerbation risk. Ø Assess - Assess inhaler technique and adherence, and the role of non-pharmacological approaches Ø Adjust Adjust pharmacological treatment, including escalation or de-escalation. Ø Any change in treatment requires a subsequent review of the clinical response, including side effects.

Dyspnea Table 3.3. Adjusting the medications for COPD based on symptoms

Current treatment Action advised

Symptomatic on LABA or LAMA LABA + LAMA Switching inhalerdevice or molecules can also be considered Not better with LABA + LAMA Dyspnea due to other causes should be investigated Consider triple combination On LABA + ICS LABA + LAMA + ICS

Stopping ICS: This can be considered if there are adverse effects (such as pneumonia) or areported lack of efficacy

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Exacerbations

Table 3.4 Management of COPD exacerbations

Current treatment Action advised

Persistent exacerbations History or findings Escalation to either on LABA / LAMA alone suggestive of asthma LABA/LAMA or LABA/ICS /ACO Patients with one exacerbation LABA/ICS per year & ≥ 300 eosinophils/μL ≥ 2 moderate exacerbations LABA/ICS per year or at least one severe exacerbation requiring hospitalization in the prior year & eosinophil counts ≥ 100 cells/μL

Persistent AEC > 100 cells/μL LABA+ ICS + LAMA exacerbations on LABA + LAMA AEC < 100 cells/μL with an FEV1 < 50% predicted Add roflumilast and chronic bronchitis

AEC < 100 cells/μL Long term macrolides And former smokers

63

Section IV Community acquired Pneumonia

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section IV

Section IV 4. Community acquired Pneumonia 4.1. Introduction These guidelines refer to the management of adults with pneumonia in Indian settings. There is a need for a guideline in Indian setting because our social and economic factors are different from western setting, population affected by pneumonia is different, microbial pathogens differ and resistance pattern of organisms to drugs vary considerably. 4.2. Definition Pneumonia is defined as inflammation of lung parenchyma due to an infectious agent. It is broadly classified as. 1) Community acquired (CAP). 2) Hospital acquired pneumonia (HAP). 3) Pneumonia in immune-compromised Host 4) Community acquired pneumonia is the pneumonia that develops in a community setting or is diagnosed within 48 h of admission to a hospital.Hospital acquired pneumonia is defined as pneumonia that occurs 48 hours or more after hospital admission, which was not incubating the infection at the time of admission. Pneumonia in immune-compromised hosts is considered separately as these hosts are infected with rarer and unusual organisms apart from infection with common organisms. Aspiration pneumonia is the pneumonia that develop after a witnessed aspiration. 4.3. Diagnosis of pneumonia Patients with pneumonia usually presents with fever, rigor and chills, cough, sputum production, pleuritic and dyspnea. Extra pulmonary symptoms include headache, diarrhoea, myalgia, arthralgia and other gastro intestinal symptoms. On examination , findings of consolidation, , may be observed. Chest radiographic patterns are nonspecific but a lobar consolidation is usually associated with acute . The presence of radiological infiltrate in a patient presenting with typical clinical features is diagnostic of pneumonia.

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Table 4.1: Common pathogens causing pneumonia and their clinical and epidemiological features are summarized below.

4.4. Investigations l Routine Chest X-ray and microbiological investigations are not required for Out Patients. But may be required if they fail to respond to therapy. l All hospitalized patients should have a chest X-ray taken, since a diagnosis of pneumonia cannot be reliably established in the absence of infiltrates.

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l Laboratory tests like complete blood count including ESR, Blood urea Nitrogen, creatinine, Blood glucose, Serum electrolytes, Liver Function Tests, O2 Saturation and ABG are also done. l Gram stain and culture of sputum- If patients are unable to bring adequate sputum then induction of sputum should be done with hypertonic saline. Fewer than 10 squamous epithelial cells and >25 polymorphonuclear per low power (×100) field are required in a Gram stain for subsequent culture. l Sputum can also be testedwith Acid-fast stain for mycobacteria and Immunofluorescence for Legionella, Pneumocystis and . l Blood culture- It is taken in cases of severe CAP and in cases of host defect like chronic liver diseases, asplenia, leucopenia. It should be taken before starting antibiotics. Ideally 2 samples of 20 ml blood 30 min apart should be taken from 2 separate body sites. l Acute and convalescent serum sample after 3-6 weeks if the patient responds poorly- Useful in case of infections with atypical pathogens. l ·Other cultures: Pleural fluid gram stain and culture, Endotracheal aspirate culture, Bronchoscopic retrieval of specimen ( PSB and BAL). l Antigen testing: Urinary antigen detection for S. pneumoniae and L. pneumophila serogroup-1 in cases of severe pneumonia.

4.5. Risk Stratification l Patients with CAP should be risk stratified. l Initial assessment should be done with CRB-65. l Accordingly, patients can be managed as either out-patient or in- patient (ward or ICU).

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Table 4.2: CRB 65 Scoring system for risk stratification of pneumonia

CRB-65

Criteria Score*

Confusion 1

Respiratory rate ≥30/min 1 Low blood pressure(Diastolic blood pressure ≤60 mmHg or 1 Systolic blood pressure ≤90 mmHg) Age ≥65 years 1 *If the score is >1, patients should be considered for admission. l Clinical judgement should be applied as a decision modifier in all cases.The following features may indicate severity necessitating hospitalization. l Leukopenia (WBC count<4000 cells/mm3) l Thrombocytopenia (platelet count<100,000 cells/mm3) l Hypothermia (core temperature< 36ºC) l Hypoxemia (SaO2 < 90% and PaO2 < 60 mm Hg) l Presence of multilobar infiltrates

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Figure 4.1: Algorithmic approach for the diagnosis and management of CAP.

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Criteria for admission to ward or ICU l Patients selected for admission can be triaged to the ward (non- ICU / ICU) based upon the major / minor criteria. (ATS criteria ) l If any major criterion or ≥ 3 minor criteria are fulfilled, patients should generally be admitted to the ICU. Table 4.3. Criteria for admission

Major criteria Invasive mechanical ventilation Septic shock with the need for vasopressors Minor criteria Respiratory rate > or = 30 breaths/min PaO2/FiO2 ratio < or = 250 Multi-lobar infiltrates Confusion/disorientation Uremia (BUN level > or = 20 mg/dL) Leukopenia (WBC count < 4000 cells/mm 3) Thrombocytopenia (platelet count <100,000 cells/mm3 Hypothermia (core temperature <36 0 C) Hypotension requiring aggressive fluid resuscitation

Antibiotics l Antibiotics should be administered as early as possible; l Timing is more important in severe CAP. l For those patients referred to hospital with suspected CAP and where the illness is considered to be life threatening, general practitioners should administer antibiotics in the community. l Amoxicillin 1 g orally is the preferred agent Antibiotic Therapy in the Out-patient Setting l Therapy should be targeted towards coverage of the most common organisms, namely Streptococcus pneumoniae

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l Out-patients should be stratified as those with or without comorbidities. Recommended antibiotics A) for out-patients without comorbidities l oral β-lactams e.g. Amoxicillin 500-1000 mg thrice daily or l oral macrolides (preferably Azithromycin) B) For out-patients with comorbidities l ·Oral combination therapy is recommended:- β-lactams plus macrolides. l ·Duration of antibiotic treatment in out-patients is for five days. l ·Fluoroquinolonesshould be kept as reserve drug and not be used for empirical treatment in view of the high prevalence of tuberculosis in this country. Antibiotic in the Hospitalised non-ICU Setting l The recommended regimen is combination of aβ-lactam plus a macrolide l (preferredbetalactams include crystalline penicillin, cefotaxime, ceftriaxone andamoxicillin-clavulanic acid) l treatment duration for in-patients is for seven days l In case of hypersensitivity to β-lactams, respiratory fluoroquinolones (e.g. Levofloxacin 750mg daily) may be used if tuberculosis (TB) is not a diagnostic consideration. Antibiotic Therapy in ICU Setting 1. For patients without risk factors for Pseudomonas aeruginosa, the recommended regimen is l β-lactam (cefotaxime, ceftriaxone or amoxicillin-clavulanicacid) plus l a macrolide 2. If P. aeruginosais an aetiological consideration, l an anti-pneumococcal antibiotic should be given l (e.g. cefepime, ceftazidime, cefoperazone, piperacillin - tazobactam, Cefoperazone - sulbactam, imipenem or meropenem). l Combination therapy may be considered with the addition of aminoglycosides / antipseudomonalfluoroquinolones (e.g.ciprofloxacin).

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3.For community-acquired methicillin-resistant Staphylococcus aureusinfection addvancomycin or linezolid. l The use of linezolid in India should be reserved because of its potential use in extensively drug-resistant TB. 4. For suspected influenza l Early treatment (within 48 h of the onset of symptoms) with oseltamivir or zanamivir is recommended. l Antimicrobial therapy should be changed according to specific pathogen isolated. l For those with high severity microbiologically-undefined pneumonia, 7–10 days treatment is proposed. l This may need to be extended to 14 or 21 days according to clinical judgement and development of complications. l Diagnostic/therapeutic interventions should be done for complications, e.g. thoracentesis, chest tube drainage, etc., as and when required Switch from intravenous to oral therapy (De-escalation) l Patients should be switched from intravenous to oral therapy when they are hemodynamically stable and improving clinically, are able to ingest medications, and have a normally functioning gastrointestinal tract. l Patients should be discharged as soon as they are clinically stable. Table 4.4. Dosages of antibiotics

Amoxicillin 0.5-1 g thrice daily (PO or IV) Co-amoxiclav 625 mg thrice a day to 1 g twice daily (PO) / 1.2 g thrice daily (IV) Azithromycin 500 mg daily (PO or IV) Ceftriaxone 1-2 g twice daily (IV) Cefotaxime 1 g thrice daily (IV) Cefepime 1-2 g two to three times a day (IV) Ceftazidime 2 g thrice daily (IV) Piperacillin-tazobactam 4.5 g four times a day (IV) Imipenem 0.5-1 g three to four times a day (IV) Meropenem 1 g thrice daily (IV)

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Duration of Antibiotics CAP should be treated be treated for a minimum of 5 days. For patients with severe pneumonia, 10 days of treatment is proposed. This should be extended to 14- 21 days where Legionella, Staphylococcal or Gram negative enteric bacilli pneumonia are suspected or confirmed. Patients can be switched over from parenteral to oral therapy when they are: l Hemodynamically stable l Improving clinically l Able to ingest medications l Have a normally functioning gastrointestinal tract. Adjunctive Therapies

l Correction of dehydration with IV fluids, correction of hypoxemia with oxygen administration important supportive therapies to be considered in appropriate settings. l Steroids are not recommended for use in non-severe CAP. l Steroids should be used for septic shock or acute respiratory distress syndrome (ARDS) secondary to CAP according to the prevalent management protocols for these conditions. l No role of other adjunctive therapies (anticoagulants, immunoglobulin, granulocyte-colony-stimulating factor, statins, probiotics, chest physiotherapy, antiplatelet drugs, over-the counter cough medications, β2-agonists) in the routine management of CAP. l CAP-ARDS and CAP leading to sepsis and septic shock should be managed according to the standard management protocols for these conditions. l Non-invasive ventilation may be used in patients with CAP and acute . Role of Immunisation and Smoking Cessation for Prevention of CAP

l Routine use of pneumococcal vaccine among healthy immunocompetent adults for prevention of CAP is not recommended. l Pneumococcal vaccine may be considered for the prevention of CAP in special populations who are at high risk for invasive

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pneumococcal disease. l Influenza vaccination should be considered in adults for the prevention of CAP. l Smoking cessation should be advised for all current smokers. Failure to respond Non responding pneumonia is a situation in which an inadequate clinical response is present despite adequate antibiotic treatment. There will be persistence of symptoms and <50% radiological clearance after 2 weeks with radiological infiltrates persisting after 30 days. Failure to respond may be due to agent factors, host factors or due to extend of disease. At this stage a review of diagnosis should be done. Other causes which should be evaluated include: l Resistant microorganism l Nosocomial superinfection l Spread of pneumonia l Drug fever l Non-infectious etiologies l Post obstructive pneumonia. In addition to microbiologic diagnostic procedures Chest CT, thoracocentesis and bronchoscopy should be considered at this stage. 4.6. Diagnosis and management of hospital-acquired pneumonia (HAP) / ventilator-associated pneumonia (VAP) Definition Hospital Acquired Pneumonia (HAP) Pneumonia diagnosed 48 hrs or more after hospital admission. Ventillator Associated Pneumonia(VAP) Pneumonia diagnosed 48 hrs or more after endotracheal intubation Clinical diagnosis of HAP/VAP can be done using modified Centers for Disease Control and Prevention (CDC) criteria.

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Table 4.5: Modified Centers for Disease Control and Prevention (CDC) criteria for diagnosis of HAP/VAP

Chest radiographic opacities (new, progressive or persistent infiltrate or cavitation)

AND

At least two of the following:

1. Fever >38 °C or >100.4 °F

2. Leukopaenia (<4000 WBC/μL) or leukocytosis (≥12000 WBC/μL)

3. Altered mental status with no other recognised cause in the elderly

4. New onset of purulent sputum, or change in character of sputum, or increased respiratory secretions, or increased suctioning requirements 5. Worsening gas exchange (e.g., desaturations, increased oxygen requirements, or increased ventilator demand) 6. New onset or worsening cough, or dyspnoea, or tachypnoea

7. Rales or bronchial breath sounds

Risk stratification l Gram-negative are the most common pathogens causing HAP/VAP in the Indian setting l The risk stratification regarding acquisition of multidrug-resistant (MDR) pathogen should be individualized

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Figure 4.2: Approach to HAP

Risk Factors for Multi drug- Resistant Pathogens Risk factors for MDR VAP l Prior intravenous antibiotic use within 90 d l Septic shock at time of VAP l ARDS preceding VAP l Five or more days of hospitalization prior to the occurrence of VAP l Acute renal replacement therapy prior to VAP onset Risk factors for MDR HAP or MRSA VAP/HAP or MDR Pseudomonas VAP/HAP l Prior intravenous antibiotic use within 90 d Microbiological methods to diagnosis of HAP and VAP VAP:- 1. Non-invasive sampling with semi-quantitative cultures are

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recommended to diagnose VAP l Non-invasive respiratory sampling refers to endotracheal aspiration. l Invasive respiratory sampling includes bronchoscopic techniques (ie, bronchoalveolar lavage [BAL], protected specimen brush [PSB]) and blind bronchial sampling (ie, mini-BAL). HAP:- Patients with suspected HAP has to be treated according to the results of microbiologic studies performed on respiratory samples obtained noninvasively, rather than being treated empirically. Use of bio markers for initiation of antibiotic therapy 1. To decide whether or not to initiate antibiotic therapy, clinical criteria alone is recommended rather than using serum PCT plus clinical criteria . 2. Where available, serum procalcitonin levels<0.5 ng/mL may help in differentiating bacterial HAP/VAP from other non-infective aetiologies, and may help in decisions for antibiotic cessation. Initial treatment of HAP and VAP l All hospitals should regularly generate and disseminate a local antibiogram, ideally one that is specific to their intensive care population. VAP :- Antibiotics Recommended for Empiric Treatment of Clinically Suspected VAP l In patients with suspected VAP, coverage for S. aureus, Pseudomonas aeruginosa, and other gram-negative bacilli is recommended in all empiric regimens. l an agent active against MRSA recommended only in patients withany of the following: i. a risk factor for antimicrobial resistance ii. patients in units where the prevalence of MRSA is not known l An agent active against methicillin sensitiveS. aureus (MSSA) is recommended for the empiric treatment of suspected VAP I. in patients without risk factors for antimicrobial resistance

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l For MRSA:- either vancomycin or linezolid is recommended. l for MSSA :-a regimen including piperacillin-tazobactam, cefepime, levofloxacin, imipenem or meropenem is recommended. l Two anti -pseudomonal antibiotics from different classes are recommended only in patients with any of the following: i. a risk factor for antimicrobial resistance ii. patients in an ICU where local antimicrobial susceptibility rates are not available. l One antibiotic active against P. aeruginosa is recommended i. in patients without risk factors for antimicrobial resistance l Aminoglycosides is to be avoided if alternative agents with adequate gram-negative activity are available. l Colistin to be avoided if alternative agents with adequate gram- negative activity are available.

Table 4.6. Antibiotics With MRSA Activity

Glycopeptides

Vancomycin 15 mg/kg IV q 8– 12h

(consider a loading dose of 25–30 mg/kg × 1 for severe illness)

Or

Oxazolidinones

Linezolid 600 mg IV q 12h

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Table 4.7. Antibiotics WithAntipseudomonal Activity β-Lactam–Based Agents

Antipseudomonalpenicillins

Piperacillin-tazobactam 4.5 g IV q6h

Cephalosporins

Cefepime 2 g IV q8h

Ceftazidime 2 g IV q8h

Carbapenems

Imipenem500 mg IV q6h

Meropenem1 g IV q8h

Monobactams

Aztreonam2 g IV q8h

Table 4.8. Gram-Negative coverage With AntipseudomonalActivity - Non-β-Lactam–Based Agents

Fluoroquinolones

Ciprofloxacin 400 mg IV q8h

Levofloxacin 750 mg IV q24h

Aminoglycosides

Amikacin 15–20 mg/kg IV q24h

Gentamicin5–7 mg/kg IV q24h

Tobramycin5–7 mg/kg IV q24h

Polymyxins

Colistin5 mg/kg IV × 1 (loading dose)

followed by 2.5 mg × (1.5 × CrCl + 30) IV q12h (maintenance dose)

Polymyxin B2.5–3.0 mg/kg/d divided in 2 daily IV doses

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HAP:- Antibiotics Recommended for Empiric Treatment of Clinically Suspected HAP (Non-VAP) Recommendations 1. For patients being treated empirically for HAP, an antibiotic with activity against S. aureus is recommended l an antibiotic with activity against MRSA is recommended for patients with HAP who are being treated empirically and have either a risk factor for MRSA infection l For patients with HAP who are being treated empirically and have no risk factors for MRSA infection and arenot at high risk of mortality, we suggest prescribing anantibiotic with activity against MSSA. l For patients with HAP who are being treated empirically, antibiotics with activity against P. aeruginosa and other gram-negative bacilli is recommended. Recommended Initial Empiric Antibiotic Therapy for Hospital-Acquired Pneumonia (Non-Ventilator-Associated Pneumonia)

Table 4.9. Treatment for those not at High Risk of Mortality and no suspicion of MRSA

One of the following:

·Piperacillin-tazobactam 4.5 g IV q6h

·Cefepime 2 g IV q8h

·Levofloxacin 750 mg IV daily

·Imipenem 500 mg IV q6h

·Meropenem 1 g IV q8h

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Table 4.10. Not at High Risk of Mortality but With Factors Increasing the Likelihood of MRSA

One of the following: · Piperacillin-tazobactam 4.5 g IV q6h OR · Cefepime or ceftazidime 2 g IV q8h OR · Levofloxacin 750 mg IV daily · Ciprofloxacin 400 mg IV q8h OR · Imipenem 500 mg IV q6h · Meropenem 1 g IV q8h OR · Aztreonam 2 g IV q8h Plus: · Vancomycin 15 mg/kg IV q8–12h with goal to target 15–20 mg/mL trough level (consider a loading dose of 25–30 mg/kg × 1 for severe illness) OR · Linezolid 600 mg IV q12h

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Table 4.11. High Risk of Mortality Or Receipt of IV Antibiotics During the Prior 90 days

Two of the following, but avoid 2 β-lactams: · Piperacillin-tazobactam 4.5 g IV q6h OR · Cefepime or ceftazidime 2 g IV q8h OR · Levofloxacin 750 mg IV daily · Ciprofloxacin 400 mg IV q8h OR · Imipenem 500 mg IV q6h · Meropenem 1 g IV q8h OR · Amikacin 15–20 mg/kg IV daily · Gentamicin 5–7 mg/kg IV daily · Tobramycin 5–7 mg/kg IV daily OR · Aztreonam 2 g IV q8h Plus: · Vancomycin 15 mg/kg IV q8–12h with goal to target 15–20 mg/ml trough level (consider a loading dose of 25–30 mg/kg IV × 1 for severe illness) OR · Linezolid 600 mg IV q12h

Role of Inhaled Antibiotics in the Treatment of VAP l Aerosolised antibiotics (colistin and tobramycin) may be a useful adjunct to intravenous antibiotics in the treatment of MDR pathogens l Aerosolised antibiotics should not be used as monotherapy and should be used concomitantly with intravenous antibiotics.

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Pathogen specific therapy Treatment for HAP/VAPdue to MRSA l either vancomycin or linezolid rather than other antibiotics HAP/VAP due to P. aeruginosa l the choice of an antibiotic for definitive therapy has to be based upon the results of antimicrobial susceptibility testing HAP/VAP Due to Extended-Spectrum β-Lactamase (ESBL)–Producing Gram- Negative Bacilli l the choice of an antibiotic for definitive (not empiric) therapy has to be based upon the results of antimicrobial susceptibility testing and patient-specific factors. HAP/VAP Due to Acinetobacter Species l Treatment with either a carbapenem or ampicillin/ sulbactamif the isolate is susceptible to these agents. l if caused by Acinetobacter species that is sensitive only to polymyxins, intravenous polymyxin (colistin or polymyxin B) , and adjunctive inhaled colistin. HAP/VAP Due to Carbapenem-Resistant Pathogens l If caused by a carbapenem-resistant pathogen that is sensitive only to polymyxins, intravenous polymyxins (colistin or polymyxin B) and adjunctive inhaled colistin are recommended Length of therapy l For patients with VAP, a 7-day course of antimicrobialtherapy rather than a longer duration is recommended. l For patients with HAP, a 7-day course ofantimicrobial therapy is recommended. l For patients with HAP/VAP,antibiotic therapy should be de- escalated rather than fixed. l If cultures are sent after initiation of antibiotics,and there is clinical improvement with subsequent cultures being sterile, antibiotics should be continued for seven days followed by the assessment of clinical pulmonary infection score (CPIS) on the 7th day.

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Table 4.12. CPIS scoring for pneumonia

l If CPIS is <6, antibiotics can be stopped while if it is ≥6,treatment should be continued for 10 to 14 days. Other Good Practices to be followed in the ICU l Stress ulcer prophylaxis: l Early enteral feeding: l Enteral feeding is superior toparenteral nutrition and should be usedwhenever tolerated and in those without anycontraindications to enteral feeding. Deep venous thrombosis (DVT) prophylaxis: l DVTprophylaxis with unfractionated heparin (5000U thrice a day) or a low molecular weight heparin should be used if no contraindications. Glucose control: l A plasma glucose target of 140-180 mg/dL is recommended in most patients with HAP/VAP, rather than a more stringent target (80-110 mg/dL) or a more liberal target (180 -200 mg/dL). Blood products: l ·Red cells should be transfused at ahaemoglobin threshold of <7 gm/dL except inthose with myocardial ischaemia and pregnancy. l Platelet transfusion is indicated in patients withplatelet count <10,000/μL, or <20,000/μL if there is active bleeding. l Fresh frozen plasma is indicated only if there is a documented abnormality in the coagulation tests and there is active bleeding or if a procedure is planned.

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4.7.References 1) Guidelines for Diagnosis and Management of Community and Hospital Acquired Pneumonia in Adults: Joint ICS/ NCCP (I) Recommendations 2012 2) BTS guidelines for the management of community acquired pneumonia in adults: update 2009 3) Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults 2007 4) Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society 5) Guidelines for Diagnosis and Management of Community and Hospital Acquired Pneumonia in Adults: Joint ICS/ NCCP (I) Recommendations 2012 6) BTS guidelines for the management of community acquired pneumonia in adults: update 2009

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Section V Bronchiectasis

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section V

Section V 5. Bronchiectasis Bronchiectasis refers to abnormal, irreversibly dilated and thickened airways. It represents the end stage of a variety of pathologic processes that cause destruction of bronchial wall and its surrounding supporting tissue. 5.1. Clinical features l Chronic cough with sputum production (occur in more than 90%), Dyspnea (72%), hemoptysis (45-51%), fever, chest pain l Exacerbation of bronchiectasis : either a change in one or more of the common symptoms of bronchiectasis (increasing sputum volume or purulence, worsening dyspnea, increased cough, declining lung function, increased fatigue/malaise) or the appearance of new symptoms (fever, , hemoptysis, requirement for antibiotictreatment) l The number of infective exacerbations per annum should be noted including frequency and nature of antibiotic usage l Psychosocial symptoms : patients have increased anxiety and depression scoresincreased fatigue , lower quality of life. 5.2. Investigations Investigations are done to confirm the diagnosis of bronchiectasis and also to identify theunderlying cause of it. In approximately 40-50% patients even after extensive evaluation nospecific cause is found (Idiopathic). Investigations into underlying cause can changemanagement, while sometimes have important treatment and /or prognostic implications(eg: cystic fibrosis, immune deficiency, ciliary dyskinesia). l Complete blood count with differential count, ESR, CRP l specimen for microbiology: Send sputum for bacterial, mycobacterial and fungal culture & sensitivity, Gram staining accordingly based onclinical suspicion, before starting antibiotics. l When atypical mycobacterial infection is suspected, bronchoscopy with bronchial washings may be done if sputum culture negative.

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Chest x-ray l A baseline chest x-ray should be done in all patients. HRCT chest l HRCT CHEST is the gold standard investigation for diagnosis of bronchiectasis l Routine repeat chest x-ray or HRCT is not necessary; repeat imaging should beconsidered when there is clinical need. l In cases of humoral immune deficiency, repeat HRCT at intervals may be necessary todetect asymptomatic progression. 5.3. Investigations to determine the underlying cause of bronchiectasis l Raised Serum IgE , skin prick testing , peripheral blood eosinophilia positive specific IgE and IgG to aspergillus and aspergillus precipitins to rule out ABPA . l To rule out underlying connective tissue disorder: RA, ANA and ANCA (if clinically relevant). l To rule out primary Immunodeficiency: v Screening measurement of serum IgG, IgA, IgM levels with electrophoresis in allpatients. l Second line immunological investigations are performed in appropriate clinicalcircumstances. Cystic fibrosis should be evaluated a) Unless a confident alternative cause can be identified, all children withbronchiectasis will need investigation to exclude Cystic fibrosis b) In adults, investigations should also be considered in those with:– l age at presentation <40 years and no other identified cause l persistent isolation of S aureus in the sputum l features of malabsorption l male primary infertility l upper lobe bronchiectasis l a history of childhood steatorrhoea. c) The screening investigations should include two sweat chloride measurement and CFTR genetic mutation analysis.

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Ciliary dyskinesia should be evaluated a) Ciliary investigations should be considered in adults only if there is a history of chronic upper respiratory tract problems or . Factors favouring investigation include: l symptoms since childhood l childhood chronic otitis media l predominantly middle lobe bronchiectasis l infertility or situs anomalies. a) Screening tests is nasal nitric oxide test. Nasal niric oxidelevels< 100 parts per billion indicates need to test further ciliary function test b) Confirmatory test to assess the structure and function of cilia(ciliary beatfrequency / pattern tests and electron microscopy studies) Gastro intestinal investigations If gastric aspiration is suspected as a cause l Investigations chosen normally include one or more of 24 h oesophageal pHmonitoring, barium studies,or the identification of foam-laden macrophages onbronchoscopic samples. Bronchoscopy l Bronchoscopy can identify and be used to remove foreign bodies in the endobronchialtree and can show anatomical abnormalities of the bronchi. l In adults with localized disease, bronchoscopy may be indicated to exclude proximalobstruction l When atypical mycobacterial infection is suspected, bronchoscopy with bronchialwashings significantly increases the yield of mycobacterial cultures above that ofsputum culture alone. Lung function tests l Pre and post bronchodilator spirometry . All adults with bronchiectasis should havemeasures of FEV1, FVC and PEF. l Repeat lung function may be done annually. 5.4. Management l General approach and treatment of the specific underlying cause l Education for patients and parents of children with bronchiectasis

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l Airway clearance v Physiotherapy and exercise v Mucolytic and hyperosmolar therapies l Pulmonary rehabilitation l Immunisation l Airway drug therapy v Bronchodilators v Anti-inflammatory therapy l Antibiotic therapy l Surgical management Management of complications General approach and treatment of the specific underlying cause l Identify and treat underlying cause(immunodeficiency, foreign body, aspiration) l To maintain or improve pulmonary function and reduce exacerbations and improvequality of life l Patients with primary or secondary immune deficiency should be under joint care with a clinical immunologist. l Patients with CF should be referred to a CF specialist centre. 5.5. Patient education l Explain treatment approaches including airway clearance techniques, airway therapiesand management of infections. l Explain how to recognise an exacerbation l Explain the usefulness of sending a sputum sample for culture and sensitivity to aidappropriate management with antibiotics. Patients who should have regular follow-up in secondary care Include: l All children with bronchiectasis l Patients with chronic P aeruginosa, opportunist mycobacteria or methicillin-resistant Saureus colonisation l Deteriorating bronchiectasis with declining lung function l Recurrent exacerbations (>3 per year) l Patients receiving prophylactic antibiotic therapy (oral or nebulised) l Patients with bronchiectasis and associated rheumatoid arthritis, immune deficiency, inflammatory bowel disease and PCD

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l Patients with ABPA l Patients with advanced disease and those considering transplantation Chest physiotherapy and postural drainage (Airway clearance techniques & exercise) l All patients with bronchiectasis should be taught chest physiotherapy and posturaldrainage of secretions accordingly based on anatomical segments affected. l The active cycle of breathing techniques and oscillating positive expiratory devices (plus postural drainage and the forced expiration technique) may be considered l Airway clearance therapy should be for 20-30 min once or twice daily. This may alterwith periods of infective exacerbation. l Effectiveness and acceptability to the patient of the airway clearance technique shouldbe reviewed within approximately3 months of the initial visit Adjuncts to airway clearance l Sterile water inhalation, nebulized hypertonic saline may be used before airwayclearance to facilitate clearance. When nebulised hypertonic saline is first administered,watch for bronchoconstriction in susceptible patients l Nebulization with beta 2 agonists enhance sputum clearance. l NIV/intermittent positive pressure breathing may be used to augment tidal volume and reduce the work of breathing in those patients who are becoming fatigued and finding their standard airway clearance difficult. Pulmonary rehabilitation l Pulmonary rehabilitation should be offered to individuals who have breathlessness affecting their activities of daily living. Inspiratory muscle training can be used in conjunction with conventional pulmonary rehabilitation to enhance the maintenance of the training effect

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Vaccination l Pneumococcal vaccination and yearly influenza vaccination are advised Airway pharmacotherapy Bronchodilators and anti inflammatory drugs 1. Beta 2 agonist: if PFT shows airway obstruction which is reversible with betaagonist may be used. May also be used in management of coexistent asthmaand bronchiectasis 2. Anticholinergics : no evidence of benefits of its use in children, some adults maygain a useful response 3. Methylxanthines : have no routine role in bronchiectasis 4. Inhaled steroids : should not be used in children with bronchiectasis(outside of use for those patients with additional asthma). In adults, may be used in a selected subset of patients 5. Oral steroids and Leukotriene receptor antagonist: no evidence of role of oralsteroids in bronchiectasis without other indications like ABPA, chronic asthma, COPD andinflammatory bowel disease. Antibiotic therapy l Antibiotics should be given for exacerbations that present with an acute deteriorationwith worsening symptoms ( cough, increased sputum volume or change in viscosity,increased sputum purulence with or without increasing wheeze, breathlessness,hemoptysis ) and/or systemic upset l Patients with an infective exacerbation of bronchiectasis should be assessed for the need for inpatient or outpatient treatment. Inpatient treatment recommendations a) Unable to cope at home b) Development of cyanosis or confusion c) Breathlessness with respiratory rate ≥25/min d) Circulatory failure e) Respiratory failure f) Temperature ≥ 38˚C g) Unable to take oral therapy h) IV therapy required in patients with clinical failure with oral therapy

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Recommendations for antibiotic usage l Before starting antibiotics, a sputum sample should be sent off for culture. l Empirical antibiotics should be started whilst awaiting sputum microbiology. l If there is no previous bacteriology, first-line treatment is amoxicillin 500 mg three times a day or clarithromycin500 mg twice daily (in patients that are penicillin-allergic) for 14days l High-dose oral regimens (eg, amoxicillin 1 g three times a day or amoxicillin 3 g twice daily) may be needed in patients with severe bronchiectasis chronically colonised with H influenzae. l Antibiotics can be modified subsequently once the pathogen is isolated only if there isno clinical improvement and the treatment should then be guided by antibioticsensitivity results. l Failure to respond to an antibiotic course should prompt a repeat sputum culture. l Intravenous antibiotics should be considered when patients are particularly unwell, have resistant organisms or have failed to respond to oral therapy (this is most likely toapply to patients with P aeruginosa). l There is no evidence to support the routine use of antiviral drugs in exacerbations l In patients who culture Psuedomonas aeruginosa that is sensitive to ciprofloxacin, monotherapy with oral respiratory flouroquinolone can be used as first-line treatment if tuberculosis has been ruled out l In patients who have not responded to oral ciprofloxacin, monotherapy with an antipseudomonal intravenous antibiotic should be considered l Combination antibiotics should be used for infections due to strains of Psuedomonas aeruginosa that are resistant to one or more antipseudomonal antibiotics (including ciprofloxacin) or if the clinician suspects the patient will require many subsequent antibiotic courses to reduce the development of drug resistance.

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Third generation cephalosporin (ceftazidime) and aminoglycoside (gentamycin) for 14 days Long term antibiotics l Patients having ≥ 3 exacerbations per year requiring antibiotic therapy or patients with fewer exacerbations that are causing significant morbidity should be considered for long term antibiotics. P aeruginosa colonised patients: Use inhaled colistin for patients with chronic P aeruginosa infection. Inhaled gentamycin may be considered as a second line alternative. Azithromycin or Erythromycin may be considered as alternative if the patient does not tolerate inhaled antibiotics. Macrolides may also be considered as an additive treatment to inhled antibiotics for patients with high exacerbation frequency. Non P. aeruginosa colonised patients. Use Azithromycin or Erythromycin as first choice. Consider inhale gentamycin as an alternative. Consider doxycycline as an alternative in patients intolerant of macrolides or in whom they are ineffective. Eradication algorithm for psuedomonas aeruginosa in adults For patients with new or first isolation of P. aeruginosa, eradication treatment may be considered. First line treatment is ciprofloxacin 500-750 mg bd for 2 weeks. Alternative choice is intravenous antipseudomonal beta lactum ± an intravenous aminoglycoside for 2 weeks. This should be followed by a 3 month course of nebulised colistin, gentamycin or tobramycin. Risk and benefits of an eradication treatment should be discussed, like likelihood of achieving sustained eradication, risk of developing chronic infection and the risk of adverse events to eradication treatment. 5.6. Role of surgery l Lung resection surgery may be considered in patients with localised disease in whomsymptoms are not controlled by medical treatment. l Surgical option decided by expert committee in a tertiary care centre

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Lung transplantation for bronchiectasis l Consider transplant referral in bronchiectasis patients below 65 years, if the FEV1 is < 30% with significant clinical instability or if there is rapid clinical deterioration despite optimal medical management. l Earlier referral for transplant may be considered in patients with poor lung function and the following additional factors- massive hemoptysis, severe secondary pulmonary , ICU admissions or respiratory failure requiring NIV. Massive hemoptysis l Haemoptysis is a potentially life-threatening complication of bronchiectasis. l Bronchial artery embolisation and/or surgery may be required in the management of massive haemoptysis. Treatment of Respiratory Failure Consider long term oxygen therapy for patients with respiratory failure, using the same eligibility criteria as for COPD. Consider domiciliary NIV with humidification for patients with associated hypercapnia, especially where it is associated with recurrent hospitalisation.

99

Section VI Pleural Diseases

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Section VI 6. 6.1. Pleural effusion Pleural effusion is abnormal collection of fluid in the . Management of unilateral pleural effusion ­ Clinical assessment and history ­ Initial diagnostic imaging 1. Chest x ray preview The posteroanterior (PA) chest x-ray is abnormal in the presence of about 200 ml of pleural fluid. However, only 50 ml of pleural fluid can produce detectable posterior costophrenic angle blunting on a lateral film. 2. Ultrasonography Bedside ultrasound guidance significantly increases the likelihood of successful pleural fluid aspiration and reduces the risk of iatrogenic pneumothorax ,organ puncture. ­ Pleural aspiration A diagnostic pleural fluid sample should be aspirated with a fine-bore (21G) needle and preferably USG guided. Pleural fluid studies sent for protein, LDH, Gram stain, cytology and microbiological culture, ADA andsugar Appearance : The appearance of the pleural fluid and any odour should be noted. Investigations to be sent for all aspiration 1. Biochemistry: LDH and protein 2. Microscopy and culture 3. Cytological examination and differential cell count. 4. Pleural fluid ADA 5. Sugar Tests sent only in selected cases 1. pH in non-purulent effusions when pleural infection is suspected. 2. Acid-fast bacilli and TB culture when there is clinical suspicion of TB pleuritis. 3. Triglycerides and cholesterol to distinguish from pseudochylothorax in milky effusions.

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4. Amylase useful in suspected pancreatitis-related effusion. 5. Haematocrit Diagnosis of haemothorax. Differentiation into exudative and transudative causes Light's criteria: pleural fluid is an pleural fluid is an exudate if one or more of the following criteria are met: 1. Pleural fluid protein divided by serum protein is >0.5 2. Pleural fluid lactate dehydrogenase (LDH) divided by serum LDH is >0.6 3. Pleural fluid LDH >2/3 the upper limits of laboratory normal value for serum LDH. Transudative pleural effusion e.g are: Left ventricular failure, liver disease, renal disease Treat the cause in a transudative effusion l Exudative pleural effusion common causes are Tuberculosis, malignancy, parapneumonic effusions, , rheumatoid arthritis Differential count Lymphocytic pleural effusion If differential count of more than 50%, Causes of lymphocytic pleural effusion are Tuberculosis, Malignancy, Lymphoma, Cardiac failure, Rheumatoid effusion. -predominant pleural effusion when differential count of neutrophils is more than 80% of the total common causes-parapneumonic effusion, Pulmonary embolism, Acute tuberculosis, empyma. Eosinophilic pleural effusion When eosinophil count more than or equal to 10%. Causes are: Air or blood in the pleural space, Parasitic disease ,Churg strauss syndrome, Pulmonary infarction, Lymphoma. pH In non-purulent effusions, when pleural infection is suspected, pleural fluid pH should be measured. In a parapneumonic effusion, a pH of <7.2 indicates the need for tube drainage. Malignant effusion low pH is associated with shorter survival, more extensive disease, lower chance of successful pleurodesis.

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Glucose A low pleural fluid glucose level (<3.4 mmol/l) may be found in complicated parapneumonic effusions, empyema, rheumatoid pleuritis , oesophageal rupture. Amylase Routine measurements of pleural fluid amylase or its isoenzymes are not warranted. It can be useful in suspected cases of oesophageal rupture or effusions associated with pancreatic diseases. Cytology Malignant effusions can be diagnosed by pleural fluid cytology in about 60% of cases. The yield from sending more than two specimens (taken on different occasions) is very low and should be avoided. Immunocytochemistry should be used to differentiate between malignant cell types and can be very important in guiding oncological therapy. Immunohistochemistry useful to differentiate between pleural mesothelioma, and metastatic adenocarcinoma as both are morphologically similar. But if possible pleural tissue should be obtained by biopsy. Computed tomography (ct) CT scans should be performed in the investigation of all undiagnosed exudative pleural effusions and can be useful in distinguishing malignant from benign pleural effusion A CT scan should be requested for complicated pleural infection when initial tube drainage has been unsuccessful and surgery is to be considered. In a pleural effusion, a contrast-enhanced CT scan taken before full drainage of the fluid as pleural abnormalities will be better visualised. CT also distinguishes empyemas from lung abcesses. Magnetic resonance imaging (mri) MRI is not used as a routine investigation of pleural effusion, but may be used to accurately assess pleural disease. Distinction of morphological features of pleural malignancy by MRI is equal CT and assessment of diaphragmatic and chest wall involvement is superior. In patients for whom contrast is contraindicated and to assess response of pleural mesothelioma to chemotherapy.

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6.3. Invasive investigations Percutaneous pleural biopsy When investigating an undiagnosed effusion where malignancy is suspected pleural biopsy can be done Thoracoscopy Thoracoscopy is the investigation of choice in exudative pleural effusions where a diagnostic pleural aspiration is inconclusive and malignancy is suspected. Local anaesthetic thoracoscopy and video assisted thoracoscopy are avaliable Bronchoscopy Diagnostic bronchoscopy is performed for undiagnosed pleural effusion, whose radiology suggests the presence of a mass or loss of volume or when there is a history of haemoptysis, possible aspiration of a foreign body or a trapped lung with a suspicion of a proximal lung mass., it should be done after pleural drainage 6.4. Specific conditions and tests Tuberculous pleurisy Lymphocytic pleural effusion with high ADA is highly suggestive of tuberculosis. Pleural biopsies can be taken if still inconclusive, they should be sent for both histological examination and culture to improve the diagnostic sensitivity. Connective tissue diseases Rheumatoid arthritis and systemic lupus erythematosus (SLE) are the most common causes. Rheumatoid arthritis-associated pleural effusions: very low glucose level of <1.6 mmol/l (29 mg/dl). Elevated pleural fluid antinuclear antibodies (ANA) and an increased pleural fluid to serum ANA ratio is suggestive of SLE pleuritis, is also seen in malignant effusion. But not routinely done. l Pleural effusions due to pulmonary embolism: in appropriate clinical setting pulmonary embolism should be ruled out with the help of other specific investigation.

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Chylothorax and pseudochylothorax: If a chylothorax or pseudochylothorax is suspected, pleural fluid should be tested for cholesterol crystals and chylomicrons and the pleural fluid triglyceride and cholesterol levels measured. Chylothorax causes occurs due to the thoracic duct involvement trauma, tumor etc Pseudochylothorax causes are Tuberculosis, rheumatoid arthritis. Figure 6.1 Diagnostic algorithm for the investigation of a unilateral pleural effusion

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Figure 6.2. Diagnostic algorithm for the management of patients with pleural infection

Involve respiratory physician nutrition and DVT prophylaxis

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6.5. Indications for pleural fluid drainage in pleural infection 1. Patients with frankly purulent or turbid/cloudy pleural fluid on sampling 2. The presence of organisms identified by Gram stain and/or culture from a non-purulent pleural fluid sample. 3. Pleural fluid pH <7.2 in patients with suspected pleural Infection. 4. Poor clinical progress during treatment with antibiotics alone should lead to prompt patient review, repeat pleural fluid sampling and probably chest tube drainage. 5. Patients with a loculated pleural collection should receive early chest tube drainage. 6. Large non-purulent effusions could be drained by aspiration and/or chest tube if required for symptomatic benefit. Antibiotics l All patients should receive antibiotics targeted to treat the bacterial profile of modern pleural infection and based on local antibiotic policies and resistance patterns. l Antibiotics to cover anaerobic infection should be used in all patients except those with culture proven . l Macrolide antibiotics are not indicated unless there is objective evidence for or a high clinical index of suspicion of 'atypical' pathogens. l Where possible, antibiotic choice should be guided by bacterial culture results and advice from a microbiologist. l Penicillins, penicillins combined with b-lactamase inhibitors, metronidazole and cephalosporins penetrate the pleural space well. Aminoglycosides should be avoided. l Empirical antibiotic treatment for hospital-acquired empyema should include treatment for MRSA and anaerobic bacteria. l Intravenous antibiotics should be changed to oral therapy once there is clinical and objective evidence of improvement in sepsis. l Intrapleural antibiotics are not recommended. l Prolonged courses of antibiotics may be necessary and can often be administered as an outpatient after discharge

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Intrapleural fibrinolytics Not recommended routinely l Patients with persistent sepsis and a residual pleural collection should undergo further radiological imaging. l Patients should receive surgical treatment if they have persisting sepsis in association with a persistent pleural collection, despite chest tube drainage and antibiotics. Malignant Pleural Effusion Malignant pleural effusions are generally managed by oncologist respiratory opinion may be seeked if a pleurodesis or a indwelling pleural catheter needed. 6.6. Pneumothorax CLASSIFICATION: 1. PRIMARY SPONTANEOUS PNEUMOTHORAX [PSP]: occurring in healthy people 2. SECONDARY SPONTANEOUS PNEUMOTHORAX [SSP];occur in those with underlying lung pathology Imaging Initial diagnosis v Standard erect PA chest x-ray Standard erect chest x-rays in inspiration are recommended for the initial diagnosis of pneumothorax, rather than expiratory films. v Supine and lateral decubitus x-rays. These imaging techniques have mostly been employed for trauma patients who cannot be safely moved. v Ultrasound scanning Specific features on ultrasound scanning are diagnostic of pneumothorax but, to date, the main value of this technique has been in the management of supine trauma patients. v CT scanning l small pneumothoraces and in size estimation. l surgical emphysema and bullous lung disease l aberrant chest drain placement or additional lung pathology

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6.7. Treatment Options For Pneumothorax If the patient is severely dyspnoeic, hypoxic or with underlying lung pathology an immediate intercostal tube drainage insertion should be done Other modalities are needle aspiration, high flow oxygen, Failure of a pneumothorax to re-expand or a persistent air leak should prompt early referral to a respiratory physician, preferably with in 24hr. Such patients may require prolonged chest drainage with complex drain management (suction, chest drain repositioning) and liaison with thoracic surgeons. Management Of SSP All patients with SSP should be admitted to hospital for at least 24 h and receive supplemental oxygen Those with a persistent air leak should be discussed with a thoracic surgeon. Patients with SSP but unfit for surgery, medical pleurodesis may be appropriate. Discharge And Follow-up l Patients should be advised to return to hospital if increasing breathlessness develops. l All patients should be followed up by respiratory physicians until full resolution. l Air travel should be avoided until full resolution. l Diving should be permanently avoided unless the patient has undergone bilateral surgical pleurectomy and has normal lung function and chest CT scan postoperatively. Medical Chemical Pleurodesis Chemical pleurodesis can control difficult or recurrent pneumothoraces but, since surgical options are more effective, it should only be used if a patient is either unwilling or unable to undergo surgery. Agents: l Tetracycline: dose is 1500mg l Doxycycline l Minocycline l Talc l Betadine

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Referral To Thoracic Surgeons In cases of persistent air leak or failure of the lung to reexpand, an thoracic surgical opinion should be sought. Indications are: l Second ipsilateral pneumothorax. l First contralateral pneumothorax. l Synchronous bilateral spontaneous pneumothorax. l Persistent air leak (despite 5-7 days of chest tube drainage) or failure of lung re-expansion. l Spontaneous haemothorax. l Professions at risk (eg, pilots, divers). l Pregnancy Tension Pneumothorax Tension pneumothorax is a medical emergency that requires heightened awareness in a specific range of clinical situation eg ventilated patients on ICU,trauma patient,. Resuscitation patients acute presentations of asthma and chronic obstructive pulmonary disease, blocked, clamped or displaced chest drain. Treatment is with oxygen and emergency needle decompression or a chest drain may need to be inserted if there is an initial treatment failure

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Figure 6. 3. Management of spontaneous pneumothorax

Ref : BTS pleural disease guidelines 2010

113

Section VII Sleep disordered breathing

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Section VII 7. Sleep-disordered breathing (SDB) Sleep disordered breathing refers to abnormal respiratory pattern during sleep, characterised by apnoea, or respiratory effort related arousals (RERAs) or central sleep apnoea which includes Cheyne-Stokes breathing or central hypoventilation leading to an altered gas exchange. Obstructive sleep apnoea (OSA) is defined as the occurrence of an average 5 or more episodes of obstructive respiratory events (, hypopnoeas or RERAs) per hour of sleep with either sleep related symptoms or comorbidities or 15 such episodes without any sleep related symptoms or co-morbidities. 7.1. Overlap syndrome, obesity-hypoventilation and Pickwickian syndromes l Overlap syndrome is defined as the co-occurrence of both chronic obstructive pulmonary disease and OSA in the same individual. l Obesity-hypoventilation syndrome consists of obesity, sleep- disordered breathing, hypoxia and chronic hypercapnia during wakefulness in the absence of other known causes of hypercapnia. l Historically, OHS was first described as Pickwickian syndrome in a case report in 1956. This patient resembled a character depicted by Charles Dickens in “The Posthumous Papers of the Pickwick Club as he was obese and had hyper-somnolence. 7.2. Diagnosis of OSA When to suspect OSA l Patients undergoing routine health check-up with , daytime sleepiness, obesity, hypertension and motor vehicular accidents need to be screened l High risk cases such as congestive heart failure, diabetes mellitus, coronary artery disease, stroke, metabolic syndrome, nocturnal dysrhythmias should undergo a comprehensive sleep evaluation. l and preoperative cases should also have a comprehensive sleep evaluation. l Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study.

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l High risk cases, even if asymptomatic, can be referred for a sleep study. l Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA, if snoring, daytime sleepiness or obesity irrespective of the presence or absence of co morbidities are noted The role of ESS and pre-test screening questionnaires in the diagnosis of OSA l ESS Epworth sleepiness scale can be used as a tool to measure the quality of life with regard to Excessive Daytime Sleepiness (EDS), likelihood of long-term compliance to continuous positive airway pressure (CPAP) and to evaluate the treatment response rather than to screen for OSA . l Both Berlin questionnaire and modified Berlin questionnaire are moderately accurate to screen for OSA . l STOP Bang questionnaire is the most appropriate questionnaire for screening preoperative cases. l It may also be used for pre-test probability assessment before portable monitoring because of ease of administration and high sensitivity. 7.3. Various levels of sleep studies Level 1: Fully attended polysomnography (7 channels) in a laboratory setting Level 2: Unattended polysomnography (7 channels) Level 3: Limited channel study (using 4–7 channels) Level 4: One or two channels usually using oximetry as one of the parameters “Gold standard” for diagnosis for OSA l Level 1 study or in-hospital, in-laboratory, technician-attended, overnight polysomnography (PSG) is the “Gold standard” for evaluation of sleep-disordered breathing .

11820 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section VII Portable monitoring (PM) / out of center sleep testing (OCST) / home sleep testing (HST)/ unattended limited channel testing (ULCT) in diagnosis of OSA l Laboratory attended PSG is not necessary in all patients suspected to have OSA. l Portable monitoring or OCST with type 3 or type 4 devices (which should at least include airflow, oxygen saturation and respiratory effort) is adequate for diagnosis when used in conjunction with comprehensive sleep evaluation and in patients with high pre-test probability of moderate to severe OSA without co-morbid sleep disorders or medical disorders like pulmonary disease, neuromuscular disease, or congestive heart failure. Sleep study in preoperative evaluation l The incidence of postoperative desaturation, respiratory failure, postoperative cardiac events and intensive care unit transfers is higher in patients with OSA l Portable monitoring is preferable as it reduces the likelihood of delay in surgery, inconvenience and high cost of in-laboratory PSG. l Alternatively, in a case with high likelihood of OSA, sleep study may be deferred if it is not feasible or causes delay in surgery. l Instead, a standby CPAP with a close monitoring may be advised. l Patients with known OSA must be advised to use CPAP in the perioperative period. 7.4. Diagnostic criteria for OSA The diagnostic criteria for OSA are the presence of (A and B) or C A. Presence of one or more of the following: a. Complaints of sleepiness, non refreshing sleep, fatigue, or symptoms of insomnia. b. Waking up with breath holding, gasping or choking. c. Habitual snoring, interruptions in breathing, or both during sleep as reported by patient's bed partner or other observer. d. Co-existing morbidities such as hypertension, type 2 diabetes mellitus, coronary artery disease, congestive heart failure, atrial fibrillation, stroke, mood disorder, or cognitive dysfunction. B. PSG or OCST (out of center sleep testing) demonstrates

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a. Five or more obstructive respiratory events (apneas, , or RERAs) per hour of sleepduring a PSG or per hour of monitoring with OCST. OR C. PSG or OCST demonstrates a. Fifteen (15) or more obstructive respiratory events (apneas, hypopneas, or RERAs) per hour ofsleep during a PSG or per hour of monitoring with OSCT, even in the absence of symptoms. OSA Severity Grading l OSA severity, based on the frequency of abnormal respiratory events during sleep is graded as l Up to 5 apnoea / hypopnoea events per hour is normal a) mild: 5 to <15 events/hr of sleep b) moderate: 15–30 events/hr of sleep and c) severe: > 30 events/hr of sleep. Methods to prescribe PAP (Positive airway pressure) therapy l Full-night PSG with attended manual CPAP titration is regarded as the gold standard for prescription of CPAP. l However, split-night study, i.e., initial PSG followed by 3 hours of continuous positive airway pressure (CPAP) titration may be performed if AHI is >40 events/hr during first 2 hours or between 20-40 events/hr with clinical judgment regarding definitiveness of prescribing CPAP therapy l The process of BPAP titration in OSA management is initiated in two situations, i.e., after maximal CPAP has not resolved the respiratory events or less commonly as a primary PAP strategy. l Certain autoPAP devices can be tried during attended titration with PSG or in an unattended way to determine a fixed PAP level in patients with moderate to severe OSA without significant co- morbid illness such as CHF, COPD, central sleep apnea or hypoventilation syndromes. 7.5. Medical management of OSA The role of behavioural therapy in OSA The following measures have shown modest improvement in OSA and

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should be considered as adjuncts to PAP therapy: l Smoking cessation l Avoidance of alcohol, sedatives and nicotine l Treatment of nasal obstruction l Weight loss l Positional therapy during sleep l Sleep hygiene, avoidance of sleep deprivation The role of pharmacotherapy in OSA l There is no role of pharmacotherapy in OSA, however modafinil and armodafinil are the only agents approved for EDS for poor response despite use of adequate PAP therapy. PAP therapy and its role in OSA l PAP therapy is the mainstay of treatment of OSA, however, patient compliance is a major issue. Therefore, proper patient counselling is necessary to ensure adequate compliance. l PAP creates a pneumatic splint in the upper airway which prevents collapse of the pharyngeal airway, acting at all potential levels of obstruction. l PAP therapy improves quality of life in terms of significant reduction in daytime sleepiness, improvement in quality of life, driving performance, neuro-cognitive performance and cardiovascular outcomes including overall mortality The indications for PAP therapy PAP is indicated based on PSG results showing: l AHI or RDI> or = 15 events/hour Or l AHI or RDI > or = 5 but <15 events/hour with any one of the following symptoms: Excessive daytime sleepiness Neurocognitive impairment Hypertension Coronary artery disease Cardiac arrhythmias Pulmonary hypertension History of stroke

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Role of oral appliances in OSA l OAs are indicated for use in patients with mild to moderate OSA who prefer oral appliances to CPAP or l who do not respond to CPAP or who fail treatment attempts with CPAP or behavioural measures Types of oral appliances l Two types of oral appliances are available l Mandibular repositioning appliance (MRA) and l Tongue retaining appliances (TRA). These have defined indications and contra-indications with modest efficacy. 7.6. Surgical treatment of OSA Who should undergo surgical treatment for OSA? l Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy. l Patients with BMI > or = 35kg/m2 should undergo bariatric surgery rather than site directed surgery How is the level of obstruction evaluated preoperatively? l Of the various methods available, fibre-optic nasopharyngoscopy with Mueller's manoeuvre (FNMM) is found to predict response to UPPP. l Other investigations like cephalometry, acoustic analysis, somnofluoroscopy are outdated. l CT and MRI do not predict level of obstruction consistently and hence are not recommended for routine use Role of nasal and nasopharyngeal surgery l Nasal surgery (correction of anatomical defects) alone is not a useful method of treatment of moderate to severe sleep apnea l Nasal surgery improves the compliance with PAP and also enhances its effectiveness in patients who have nasal obstruction Maxillo-mandibular surgery l Maxillo-mandibular surgeries which include maxillo-mandibular advancement, genioglossus advancement, distraction osteogenesis are recommended only in the subset of patients with the specific anatomical abnormalities and intolerance to PAP

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therapy . Uvulopalatopharyngoplasty (UPPP) l It is recommended in patients with retropalatal obstruction and PAP therapy intolerance Multi-level surgery l Multi-level surgery is done in patients who have failed PAP therapy and other conservative measures with documented multi-level obstruction Bariatric surgery l Bariatric surgery is indicated in patients with BMI > or = 35kg/m2. l Gastric bypass is the most successful procedure and gastric banding is the least effective procedure for treating OSA Epworth sleepiness scale l Epworth sleepiness scale (ESS) is a simple, self-administered measurement of sleep propensity during daytime in adults that requires the subject to rate the probability of dozing off in eight different situations that are met in day-to-day life on a scale of 0–3. l Thus, the sum of the score can vary from 0 to 24. l ESS score >10 is defined as excessive daytime sleepiness and has a sensitivity of 49% and specificity of 80% for predicting OSA. Situation l Watching TV l Sitting and reading l Sitting, inactive in a public place (e.g. a theatre or a meeting) l As a passenger in a car for an hour without a break l Lying down to rest in the afternoon when circumstances permit l Sitting and talking to someone l Sitting quietly after a lunch without alcohol l In a car, while stopped for a few minutes in the traffic 0 = would never doze 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing References: 1. INOSA guidelines 2014

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Section VIII Hemoptysis

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section VIII

Section VIII 8. Haemoptysis Hemoptysis or spitting / coughing out of blood is a life threatening emergency which also creates a lot of anxiety in patients and bystanders. The various common causes of Hemoptysis include 1. Tuberculosis / Post – TB sequelae 2. Bronchiectasis 3. Lung cancer 4. and other infections (e.g. fungal) 5. Pulmonary embolism 6. Lung trauma 7. Systemic diseases like bleeding disorders 8.1. Management Always differentiate between hemoptysis and hemetemesis before starting the management Initial approach – resuscitation and protecting the airway Second step – localizing the site and cause of bleeding, Final step – application of definitive & specific treatments to prevent recurrent bleeding. Hemoptysis should be monitored in an intensive care unit if massive (>100ml per hour or >500ml in 24 hrs) 8.2. Airway protection and resuscitation l Airway - Suction to prevent & aspiration. l If large volume bleeding continues or the airway is compromised - Intubation with as large an endotracheal tube as is possible to allow adequate suctioning and access for bronchoscopy l Breathing – Correct / Prevent Hypoxia l Circulation – Connect IV lines, Blood loss should be treated with volume resuscitation, blood transfusion, and correction of coagulopathy. When the site of bleeding is known, one simple, initial bedside manoeuvre is to place the involved side in a dependent position in order to protect the uninvolved lung If the bleeding can be localised to the right or left lung, unilateral lung intubation may protect the non-bleeding lung.

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It may be possible to protect the nonbleeding lung from spillage by using of one of the following techniques for intubation and mechanical ventilation: unilateral lung ventilation using a standard, single-lumen endotracheal tube advanced into the right or left mainstem or independent lung ventilation using a double-lumen endotracheal tube. 8.3. Drugs used l Sedatives and anti-tussives – preferred drugs are morphine / pethedine as these are very good antitussives. However in case of non-availability of morphine a codeine containing cough syrup can be given. l The antifibrinolytic agent IV/Oral tranexamic acid( 1 gm TDS) or ethamsylate 500mg QID may be used. l All patients with massive hemoptysis should have known or suspected coagulation abnormalities rapidly reversed. l For patients with massive hemoptysis, flexible bronchoscopy at the bedside as the initial intervention to assess and attempt to control the bleeding. l Bronchoscopic strategies to control pulmonary hemorrhage include balloon tamponade, iced saline lavage, administration of a topical vasoconstrictor or a topical coagulant, laser therapy, APC and electrocautery. l When FOB fails Rigid bronchoscopy can be tried with ballon tamponade,electrocutery or APC l For patients with massive hemoptysis who continue to bleed despite a bronchoscopic intervention and are stable enough to leave the intensive care unit for a procedure, bronchial artery embolization rather than surgery during active bleeding episode.

12820 Section IX Pumonary embolism

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section IX

Section IX 9. Pulmonary embolism The diagnostic approach to PE should be targeted toward the patient population being studied. For outpatients, the use of a clinical prediction rule coupled with D-dimer testing or the use of the PERC criteria can prioritize patients for imaging studies. In patients with a low or intermediate clinical likelihood of PE, a negative D- dimer study is sufficient to exclude the diagnosis, assuming a highly sensitive assay is used. PERC = Pulmonary Embolism Rule-out Criteria l age < 50 years. l pulse < 100 beats min. l SaO2 >or= 95% l no hemoptysis. l no estrogen use. l no surgery/trauma requiring hospitalization within 4 weeks. l no prior venous thromboembolism (VTE) l no unilateral leg swelling. Table 9.1 The Revised Geneva Clinical Prediction Variable Score Age>65y 1 Previous DVT or PE 3 Surgery (GA) or lower limb fracture within 1m 2

Active malignancy 2

Symptom

· Unilateral lower limb pain 3 · Hemoptysis 2 Clinical Signs · Heart rate: 75-94/min 3 · >95/min 5 · Pain on lower limbdeep venous palpitation or unilateral oedema 4

Total score

0-3 Low

4 to 10 Moderate

>10 High

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Table 9.2. The Wells' Clinical Prediction Score Variable Score DVT symptoms/signs 3 PE like or more likely than alternative 3 diagnosis Heart rate> 100 1.5 Immobilisation / surgery previous 4 wk 1.5 Previous DVT or PE 1.5 Hemoptysis 1

Malignancy 1

Total score <2 Low 2 to 6 Moderate >6 High

Dichotomized score <=4 PE unlikely >4 PE likely

An imaging study (CT pulmonary angiogram) should be performed in all patients with a high probability of disease without going for D-dimer test, And in those with a low or intermediate probability having positive D-dimer test. 9.1. Treatment Initial approach to patients with suspected PE (Pulmonary Embolism) is to stabilize the patient while clinical evaluation and definitive diagnostic testing are ongoing. Stratify the risk Assess hemodynamic stability. Hemodynamically Stable PE A heterogenous group ranging from patients with small PE and stable BP(low risk) to patients with larger PE who have RV dysfunction and borderline BP

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(submassive PE). Obtain peripheral intravenous access with or without intravenous fluidsGive oxygen supplementation Start empiric anticoagulation depending upon the clinical suspicion for PE, risk of bleeding, and expected timing of definitive diagnostic tests Hemodynamically Unstable PE(Massive PE) Presenting with defined as systolic pressure <90 mmHg for a period >15 minutes, hypotension requiring vasopressors, or clear evidence of shock. A small percentage of patients with PE present with hemodynamic instability or shock (approximately 8 percent; ie, “massive” PE). Initial support should focus upon restoring perfusion with intravenous fluid resuscitation and vasopressor support, as well as oxygenation and, if necessary, stabilizing the airway with intubation and mechanical ventilation. When portable perfusion scanning or CTPA is not available or is unsafe,bedside echocardiography (transthoracic or transesophageal) to obtain a presumptive diagnosis of PE (right ventricle enlargement/hypokinesis, regional wall motion abnormalities that spare the right ventricular apex [McConnell's sign], or visualization of clot) prior to the empiric administration of systemic thrombolytic therapy (ie, reperfusion therapy). If bedside echocardiography is delayed or unavailable, the use of thrombolytic therapy as a life-saving measure should be individualized; if not used, the patient should receive empiric anticoagulation. Hemodynamic support The precise threshold that warrants hemodynamic support depends upon the patient's baseline blood pressure and whether there is clinical evidence of hypoperfusion (eg, change in mental status, diminished urine output). Small volumes of intravenous fluid (IVF), usually 500 to 1000 mL of normal saline, followed by vasopressor therapy, should perfusion fail to respond to IVF. Intravenous fluid IV Fluid isthe first-line therapy for patients with hypotension. However, in patients with right ventricular (RV) dysfunction, limited data suggest that aggressive fluid resuscitation is not beneficial, and may be harmful. The rationale for limiting IVF administration comes from preclinical studies and one small observational study in humans, which reported that small

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volumes of IVF increase the cardiac index in patients with PE, while excessive amounts of IVF result in RV overstretch (ie, RV overload), RV ischemia, and worsening RV failure. The patient's volume status should be carefully assessed as this could influence the approach to fluid administration. Vasopressors Intravenous vasopressors are administered when adequate perfusion is not restored with IVF. Norepinephrine is generally preferred. Empiric anticoagulation (Initiation of anticoagulation before confirmation) The administration of empiric anticoagulation depends upon the risk of bleeding, clinical suspicion for PE and the expected timing of diagnostic tests Low risk for bleeding – Patients without risk factors for bleeding, having a three-month bleeding risk of <2 percent; empiric anticoagulation to be considered in the following patient groups: l A high clinical suspicion for PE (eg, Wells score >6) l A moderate clinical suspicion for PE (eg, Wells score 2 to 6), in whom the diagnostic evaluation is expected to take longer than four hours l A low clinical suspicion for PE (eg, Wells score <2), if the diagnostic evaluation is expected to take longer than 24 hours Unacceptably high risk for bleeding For patients with absolute contraindications to anticoagulant therapy (eg, recent surgery, hemorrhagic stroke, active bleeding) or those assessed by their physician to be at an unacceptably high risk of bleeding (eg, aortic dissection, intracranial or spinal cord tumors), empiric anticoagulation should not be administered. The diagnostic evaluation should be expedited so that alternate therapies (eg, inferior vena cava filter, embolectomy) can be initiated if PE is confirmed. Typically, menstruation, epistaxis, and the presence of minor hemoptysis are not contraindications to anticoagulation but should be monitored during anticoagulant therapy.

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The optimal agent for empiric anticoagulation Depends upon the presence or absence of hemodynamic instability, the anticipated need for procedures or thrombolysis, and the presence of risk factors and comorbidities. As an example, low molecular weight heparin(LMWH) may be chosen for patients with hemodynamically stable PE who do not have renal insufficiency in whom rapid onset of anticoagulation needs to be guaranteed (ie, therapeutic levels are achieved with four hours). In contrast, unfractionated heparin is preferred by most experts in patients who are hemodynamically unstable in anticipation of a potential need for thrombolysis or embolectomy. Direct thrombin and factor Xa inhibitors should not be used in hemodynamically unstable patients. DEFINITIVE THERAPY For patients in whom the diagnostic evaluation excludes pulmonary embolism (PE)), anticoagulant therapy should be discontinued if it was initiated empirically, and alternative causes of the patient's symptoms and signs should be sought. For patients in whom the diagnostic evaluation confirms PE, an approach that is stratified according to whether the patient is hemodynamically stable or unstable. At any time, the strategy may need to be redirected as complications of PE or therapy arise. Hemodynamically stable patients For those in whom the risk of bleeding is low, anticoagulant therapy is indicated. For those who have contraindications to anticoagulation or have an unacceptably high bleeding risk, placement of an inferior vena cava (IVC) filter should be performed. For hemodynamically stable (ie, normotensive) patients with intermediate- risk/submassive PE who are anticoagulated, should be monitored closely for deterioration. Thrombolysis and/or catheter-based therapies may be considered on a case-by-case basis when the benefits are assessed by the clinician to outweigh the risk of hemorrhage. Examples of such patients include those who have a large clot burden, severe RV enlargement/dysfunction, high oxygen requirement, and/or are severely tachycardic.

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Options for anticoagulation Unfractionated heparin (UFH) Low molecular weight (LMW) heparin Fondaparinux Oral factor Xa inhibitors or direct thrombin inhibitors Direct oral anticoagulants – Rivaroxaban and apixaban are the only direct oral anticoagulants that have been studied and approved by regulatory agencies as monotherapy (ie, no pre-treatment with heparin is necessary) for the treatment of patients with VTE. They may be preferred in those who wish to avoid the burden of injections in whom convenience or oral medication is a personal preference. Importantly, LMW heparin (or UFH) should be administered if there is a delay in obtaining these anticoagulants (eg, availability needs to be assured). When prescribing the direct thrombin inhibitor dabigatran, or the factor Xa inhibitor edoxaban, a short course of heparin (typically LMW heparin) be administered for five days prior to transitioning to oral therapy (ie, dual therapy) since their efficacy as monotherapeutic agents has not been studied or approved. LMW heparin Subcutaneous LMW heparin may be preferred in those in whom oral anticoagulation is not feasible (eg, poor oral intake, malabsorption) or for those in whom rivaroxaban or apixaban are unavailable (eg, too costly). -Fondaparinux – Subcutaneous fondaparinux is an acceptable alternative to subcutaneous LMW heparin (eg, for those who prefer once daily injections; heparin induced thrombocytopenia [HIT]). Warfarin -When chosen as the long term anticoagulant it must be co- administered with heparin so that full anticoagulation is assured. Heparin stopped when INR reaches 2.5 and warfarin alone to be continued.INR periodically monitored warfarin dose adjusted to maintain INR between 2-3. Dosing LMWH Dosing is typically weight-based and renally-adjusted, and all are administered subcutaneously.

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Typical starting doses are: Enoxaparin 1 mg/kg twice daily (preferred); alternatively, 1.5 mg/kg once daily can be used in selected non-obese inpatients; for home treatment, the twice daily regimen is better studied and therefore preferred by many experts. Dalteparin 200 units/kg once daily Fondaparinux As an alternative to LMW heparin, fondaparinux is an acceptable anticoagulant for most nonpregnant patients with newly diagnosed VTE (eg, patients with HIT). Dosing Fondaparinux is typically dosed according to patient weight as 5 mg once daily (<50 kg), 7.5 mg once daily (50 to 100 kg), and 10 mg (>100 kg). The dose should be reduced to 1.5 mg once daily in patients with creatinine clearance (CrCl) in the range of 20 to 50 mL/minute. No dosage reduction is required for patients with mild renal impairment (CrCl >50 mL/minute) Dosing oral drugs Typical initial doses in those with normal renal function are: Rivaroxaban 15 mg twice daily (for the first three weeks) then 20 mg daily to complete 3 months Apixaban 10 mg twice daily (for first seven days) then 5 mg bd to complete 3months. Edoxaban 60 mg once daily (and 30 mg once daily in patients with a body weight below 60 kg) (after an initial 5 to 10 days of parenteral anticoagulation) Dabigatran 150 mg twice daily (after an initial 5 to 10 days of parenteral anticoagulation) Duration of anticoagulation Typically three months (eg, transient VTE risk factors), or up to 6 or 12 months in some cases (eg, persisting risk factors, or unprovoked VTE). Indefinite anticoagulation Select patients with PE are candidates for indefinite anticoagulation. Patient selection depends upon the nature of the event (ie, provoked or unprovoked), the presence of risk factors (eg, transient or persistent), the estimated risk of bleeding and recurrence, as well as patient preferences

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and values (eg, occupation, life expectancy, burden of therapy) Outpatient anticoagulation In select patients with PE, outpatient therapy can be administered by giving the first dose of anticoagulant in the hospital or urgent care center, with the remaining doses given at home. The decision to treat as an outpatient should be made in the context of the patient's clinical condition, understanding of the risk-benefit ratio, and their preferences. -No requirement for supplemental oxygen -No requirement for narcotics for pain control -No respiratory distress -Normal pulse and blood pressure -No recent history of bleeding or risk factors for bleeding -No serious comorbid conditions (eg, ischemic heart disease, chronic lung disease, liver or renal failure, thrombocytopenia, or cancer) -Normal mental status with good understanding of risk and benefits, are not needle averse (if low molecular weight (LMW) heparin chosen), and have good home support (eg, do not live alone, have access to a telephone and physician, can return to the hospital quickly if there is clinical deterioration) -Absence of concomitant deep venous thrombosis (a high clot burden in the lower extremities may increase the risk of death or warrant additional therapy) Inferior vena cava filter For most patients with PE in whom anticoagulation is contraindicated, or patients in whom the risk of bleeding is unacceptably high, IVC filter should be placed. Similarly, an IVC filter is appropriate in patients who develop contraindications while on anticoagulation; however, placement in this population depends upon the planned duration of anticoagulation and risk of recurrence when anticoagulation is discontinued. Retrievable filters are preferred, such that once the contraindication has resolved, the filter can be removed and patients should be anticoagulated. Hemodynamically unstable patients In patients with PE who are hemodynamically unstable or who become unstable due to recurrence despite anticoagulation

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Thrombolytic therapy is indicated provided there is no contraindication Embolectomy is appropriate for those in whom thrombolysis is either contraindicated or unsuccessful (surgical or catheter-based) Thrombolytic therapy — Systemic thrombolytic therapy is a widely accepted treatment for patients with PE who present with, or whose course is complicated by, hemodynamic instability. Continuous infusions — Intravenous thrombolytic infusion regimens are the most common method of administering thrombolytics. Common regimens that are approved by the FDA include: tPA (alteplase) – 100 mg intravenously over two hours. -Streptokinase – 250,000 units intravenously over the initial 30 minutes, then 100,000 units/hour for 24 hours. Monitor closely for hypotension, anaphylaxis, asthma, and allergic reactions. Mild adverse reactions may respond favorably to a decreased infusion rate. -Urokinase – 4400 units/kg intravenously over the initial 10 minutes, then 4400 units/kg per hour for 12 hours. The FDA-approved infusion duration for tPA of two hours, being much shorter than for SK or UK, has been the main reason why this drug is commonly chosen. An activated partial thromboplastin time (aPTT) can be measured when infusion of the thrombolytic therapy is complete. Heparin should be resumed without a loading dose when the aPTT is less than twice its upper limit of normal. If the aPTT exceeds this value, the test should be repeated every four hours until it is less than twice its upper limit of normal, at which time heparin should be resumed. Catheter-directed thrombus removal with or without thrombolysis can also be administered in select patients (eg, those at high risk of bleeding, those with shock who will likely die before systemic thrombolysis can take effect (eg, within hours), and those who have failed systemic thrombolysis For those in whom systemic thrombolysis is unsuccessful, the optimal therapy is unknown. Options include repeat systemic thrombolysis, catheter-directed thrombolysis, or catheter or surgical embolectomy, the choice of which is dependent upon available resources and local expertise.

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Embolectomy Embolectomy is indicated in patients with hemodynamically unstable PE in whom thrombolytic therapy is contraindicated. It is also a therapeutic option in those who fail thrombolysis. Emboli can be removed surgically or using a catheter. The choice between these options depends upon available expertise, the presence or absence of a known diagnosis of PE, and the anticipated response to such therapies. Special populations In general, the initial approach to the treatment of PE as well as the treatment of life- threatening PE in special populations are similar to that in the general population. However, definitive therapy may differ in hemodynamically stable patients with malignancy, pregnancy, and heparin-induced thrombocytopenia. Patients with malignancy In hemodynamically stable patients with malignancy and PE, LMW heparin is the preferred agent for all phases of anticoagulation. Patients who are pregnant For most pregnant women with hemodynamically stable PE, adjusted- dose subcutaneous LMW heparin is the preferred agent for initial and long-term anticoagulation due to its favorable fetal safety profile . Patients with heparin-induced thrombocytopenia For patients with PE and heparin-induced thrombocytopenia (HIT), all forms of heparin are contraindicated (eg, unfractionated and LMW heparin). Fondaparinux can be used. Immediate anticoagulation with a fast-acting non heparin anticoagulant (eg, argatroban) is indicated.

14020 Section X Interstitial Lung Disease

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Section X 10. Interstitial Lung Disease 10.1. Diagnosis and management of interstitial lung diseases ILD (interstitial lung diseases) refers to a heterogeneous collection of distinct lung disorders that tend to be grouped together because they share clinical, radiological, and pathologic features. 10.2. Classification of interstitial lung diseases Broadly classified into 1. Aetiology known 2. Aetiology unknown Aetiology known l Inorganic exposure – Asbestos, Silica, Hard Metals, Coal Dust l Organic exposure- Birds, Hay, Mould, Mycobacteria l Connective tissue disease- Scleroderma, Polymyositis, Dermatomyositis, Rheumatoid Arthritis, Sjogrens Syndrome l Drugs- Amiodarone, Methotrexate, Nitrofurantoin, Chemotherapy. l Smoking- DIP, RB-ILD, LCH Aetiology unknown 1. Idiopathic interstitial pneumonias l Major idiopathic interstitial pneumonias Chronic fibrosing- l Idiopathic l Idiopathic nonspecific interstitial pneumonia Smoking related l Respiratory bronchiolitis–interstitial lung disease l Desquamative interstitial pneumonia Acute or sub acute l Cryptogenic organizing pneumonia l Acute interstitial pneumonia l Rare idiopathic interstitial pneumonias v Idiopathic lymphoid interstitial pneumonia v Idiopathic pleuroparenchymal fibroelastosis

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l Unclassifiable idiopathic interstitialpneumonias

2. GRANULOMATOUS- . 3. RARE FORMS OF ILD- LAM, VASCULITIS 10.3. Diagnosis of interstitial lung diseases The multidisciplinary approach is now considered the ''gold standard'' for diagnosing interstitial lung disease. It is based on the following: 1. Detailed history & clinical examination 2. Physiological evaluation 3. Radiology 4. Serologic evaluation 5. Pathologic evaluation Detailed history include chronology of symptoms, smoking history, occupation, hobbies, travel, family history, drugs, past medical history, connective tissue symptoms, h/o radiotherapy 10.4. Physiological evaluation Spirometry l All patients with ILD should have a baseline spirometry. l For evaluation, prognostication, & assessment of treatment response. l FVC & DLCO are reliable measures of disease severity. Exercise testing l 6 Minute Walk test (6MWT) - distance covered during 6MWT and desaturation to 88%- prognostic indicators. l For monitoring and assessment of treatment response Radiology Chest radiography l Specificity 50% l It is widely used for monitoring patients with ILD. High resolution computed tomography (HRCT) l Most essential component in diagnosis of ILD. l Specificity and positive predictive value > 90%

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l In the appropriate clinical setting, appearances on the HRCT scan may be sufficiently characteristic to preclude the need for BAL or lung biopsy and histopathological confirmation. Blood investigations l Initial tests in cases of suspected ILD should include a l full differential blood cell count, l serum urea, electrolytes and creatinine, l Liver function tests. l Erythrocyte sedimentation rate(ESR), C-reactive protein (CRP) Baseline cardiac investigations l ECG l ECHO Based on clinical context: l Autoantibody testing,creatine kinase l Serum calcium, serum angiotensin converting enzyme (ACE), urinary calcium,tuberculin test l Precipitating antibodies

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Table 10.1. Hrct patterns for making diagnosis

Indeterminate for UIP Probable UIP UIP Alternate Dignosis

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Table 10.2. Histopathological patterns & features

Probable UIP Indeterminate for Alternate Dignosis UIP UIP

Table 10.3. Auto antibody testing in evaluation of ILD

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Table 10.4. Diagnosis of IPF

Role of bronchoscopy in ILD Bronchoalveolar lavage (BAL), trans bronchial lung biopsy (TBLB), endobronchial biopsy l Diagnosis is uncertain after clinical assessment and HRCT scanning. l BAL helpful in diagnosis of ILDs like sarcoidosis, h y p e r s e n s i t i v i t y p n e u m o n i t i s , L C H , a l v e o l a r proteinosis, and to exclude infection/malignancy. l TBLB – helpful in diseases with Bronchocentric involvement like sarcoidosis,HP l Endobronchial biopsy: in suspected sarcoidosis l BAL/TBLB should be performed before the initiation of treatment. Role of surgical lung biopsy in ILD l Surgical lung biopsy is required in cases of ILD, ifintegration of clinical, radiological and, where appropriate, BAL/TBLB data don't lead to a confident diagnosis. l The principal factors influencing the decision to proceed to a surgical biopsy are the degree of confidence in the clinical diagnosis including the HRCT appearances and the patient's age, functional status and wish to proceed once informed about the risks versus benefit of the procedure. l In appropriate clinical setting, patients may be referred to a tertiary care centre for decision regarding surgical biopsy.

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l Surgical lung biopsy, when required, should be performed before the initiation of treatment. It can be done either by VATS or Open lung biopsy.

Figure 10.1. Algorithm for diagnosis of ILD

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10.5. General management strategies in ILD l All patients with ILD should have access to a multidisciplinary team based in a regional centre with expertise in ILD. l Referral to a regional ILD clinic should be made if there are perceived difficulties in diagnosis and/or management, but a tailored shared care model is advocated. l Patients with ILD who are current smokers should receive opportunistic smoking cessation advice from healthcare professionals and this advice should be recorded in the clinical notes. l Patients with ILD should have access to a local pulmonary rehabilitation programme. l Patients with clinically significant resting hypoxemia (resting SpO2<88%) should receive long term oxygen therapy. l Adult immunisation with annual influenza vaccine and pneumococcal vaccine is also recommended.

Table 10.5. Treatment approach and monitoring strategy

Pulmonary hypertension in ILD: Pulmonary hypertension should be considered in patients with ILD who have either breathlessness or lung dysfunction (reduced TLCO or desaturation on exercise) that seem disproportionate to the extent of parenchymal lung disease. Transthoracic echocardiography is a suitable screening tool. Long-term warfarin therapy may be prescribed in patients with CTD-associated hypertension.

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ILD presenting with acute respiratory failure The two most common scenarios in which ILD presents with acute respiratory failure are 1. Rapid deterioration in a patient with previously diagnosed ILD. Eg: acute exacerbation of IPF 2. Initial presentation with rapidly progressive disease. Eg: acute interstitial pneumonia, fulminant COP Decision on admission to ICU On a case by case basis. Compare previous CXRs and HRCT; Evidence of extensive fibrotic change or a pattern of disease typical of IPF usually indicates that invasive ventilation is highly unlikely to have a successful outcome. Pre-emptive counselling of patients that palliation or non-invasive supportive therapy rather than invasive ventilation is appropriate is an important component of management. In management of pre-existing ILD, non ILD processes such as pulmonary oedema, malignancy, drug induced lung disease and infection has to be excluded. Pharmacological management l Intravenous corticosteroid therapy is the initial treatment of choice. v Methyl prednisolone 750mg or 1g given on three consecutive days and maintanence therapy of 0.5-1mg/kg depending on clinical response. v Assess response after 5-7 days. l Intravenous cyclophosphamide- second line. v Dose: 600-650mg/m2 l In suspected vasculitis – IV cyclophosphamide first choice. Follow up Follow up of ILD patients is recommended every 3 -6 months with clinical assessment, spirometry, DLCO and 6MWT.Timing of follow up HRCT to be decided by the treating physician.

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Management of specific ILDs Idiopathic pulmonary fibrosis (IPF) IPF is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, limited to the lungs, and associated with the histopathology and/or radiologic pattern of UIP. Diagnostic criteria The diagnosis of IPF requires: multidisciplinary discussion 1. Exclusion of other known causes of interstitial lung disease (ILD) (e.g., domestic and occupational environmental exposures, connective tissue disease, and drug toxicity). 2. The presence of a UIP pattern on high-resolution computed tomography (HRCT) in patients not subjected to surgical lung biopsy. 3. Specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy. 10.6. Treatment recommendations A. Pirfenidone- dose: 400 to 800 mg TID, l A/E: photosensitivity, fatigue, stomach discomfort, and anorexia. B. Anti- Acid Therapy-Proton pump inhibitors/H2 receptor blockers C. Nintedanib – dose: 150 mg BD, l Adverse effect - Diarrhoea Treatment Not Recommended l Anticoagulation with Warfarin l Imatinib l Combination prednisone,azathioprine, and N-acetylcysteine l Selective endothelin receptor antagonist (Ambrisentan) l Phosphodiesterase-5 inhibitor (). l Dual endothelin receptor antagonists (macitentan, bosentan) l N-acetylcysteinemonotherapy. Nonpharmacologic Therapies Long term oxygen therapy-In patients with clinically significant resting hypoxemia (SpO2 of < 88%) Lung transplantation Referral to a transplant centre should be made if the disease is advanced (TLCO <40% predicted) or progressive (>10% decline in FVC or >15% decline in

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FVC) during 6 months of follow-up. Decision regarding transplantation should be made by an expert panel in a tertiary care centre. Pulmonary Rehabilitation Pulmonary rehabilitation recommended in majority of patients. Mechanical Ventilation may be used as a bridge therapy prior to lung transplantation. Pulmonary hypertension In patients with moderate to severe pulmonary hypertension documented by right heart catheterization (i.e., mean pulmonary artery pressure >35 mm Hg), a trial of vaso-modulatory therapy may be indicated. Acute exacerbation of IPF Criteria l Previous or concurrent diagnosis of IPF l Unexplained worsening or development of dyspnoea within 30 days. l HRCT with new B/L GGO and/or consolidation superimposed on a background consistent with UIP pattern l No evidence of pulmonary infection by ET aspirate or BAL l Exclusion of alternative causes including: left heart failure, pulmonary embolism and identifiable cause of lung injury. Treatment High dose corticosteroid with or without immunosuppressive agents in combination with a broad spectrum of antimicrobial coverage. Non specific interstitial pneumonia (NSIP) For exposure related NSIP related to drugs or inhalations, cessation of the offending agent is the treatment. Idiopathic NSIP can have 3 clinical profiles 1) NSIP /IPF Clinical presentation and the distribution of disease on HRCT scanning is similar to that of IPF but ground glass attenuation tends to be more extensive than in IPF and honeycombing is rarely present. Treatment is similar to that of IPF and is based on the hope of slowing orpreventing

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disease progression in most cases rather than achieving regression of disease. 2) NSIP/COP Initial high-dose steroid regimen is recommended.Steroid dose of 1 mg/kg of oral prednisolone for several months and then assessed for evidence of objective response on PFT or HRCT. Long-term treatment may be required to prevent progression of fibroticdisease. 3) NSIP/HSP Similar to that of HSP; the introduction and continuation of treatment calibrated against disease behaviour. Immunosuppresants like Azathioprine,Cyclophosphamide, mycophenolate mofetil may be considered in a minority of cases. 10.7. Connective tissue disease related ILD Rheumatoid arthritis is the most common CTD associated with ILD, while systemic sclerosis is much less prevalent than RA but is more commonly complicated by ILD. NSIP is the predominant histological diagnosis in CTDs. In the diagnosis of CTD ILD, a rheumatologist should also be included in the multidisciplinary discussion team Rheumatoid arthritis ILD in RA may result from the disease itself or as a consequence of its treatment (eg: methotrexate-induced ). A significant smoking history also increase the risk of developing ILD. Treatment 1. Oral corticosteroids (Tab prednisolone 0.5 mg/kg/day) a. May be started at a dose of 0.5mg/kg/day b. May be tapered off to 10mg /day or 20mg alternate day as a maintenance dose. 2. Immunosuppressant – a. Cyclophosphamide (1 – 1.5mg/kg) b. Azathioprine (2.5mg/kg/day) c. D-penicillamine (125-250mg/day) In case of non-responsiveness to steroid. 3. Cyclosporin A (5mg/kg/day)has been useful as a steroid-sparing agent.

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4. Anti-TNF alpha therapy in severe case of RA-ILD Treatment of methotrexate induced pneumonitis Withdrawal of methotrexate Oxygen therapy Corticosteroids Cyclophosphamide is used in severe cases. 10.8. Polymyositis-dermatomyositis Treatment l Corticosteroids, usually with oral prednisolone (0.75–1.0 mg/kg/day) with gradual tapering. l Fulminant disease may require high-dose intravenous methylprednisolone (1.0 g/day for 3 days). l Immunosuppressant or cytotoxic agents, cyclophosphamide (1 - 1.5mg/kg), tacrolimus (0.075mg/kg daily), mycophenolatemofetil (dose 1-3gm/d) l Rituximab v If not responding to steroids. Systemic sclerosis Treatment 1) Low-dose corticosteroid therapy (prednisolone 10 mg daily) 2) Immunosuppressive agent- oral cyclophosphamide, at a dose of 1.0–1.5 mg/kg. Sjogren's syndrome Treatment 1. Corticosteroids are the main mode of treatment. 2. Cytolytic therapy such as Azathioprine (2.5mg/kg/day) or Cyclophosphamide (1 -1.5mg/day) may be used. 3. Cyclosporine (5mg/kg/day) is recommended in steroid – resistant cases. 4. Rituximab, an anti- CD20 antibody may be recommended in selected patients.

155 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES SectionX Systemic lupus erythematosis Treatment – 1) Low dose steroids 2) Azathioprine (2.5mg/kg/d) &mycophenolatemofetil (1-3g/d)- depending upon underlying histology) Sarcoidosis Sarcoidosis is a multisystem disorder characterized by noncaseating granulomatous inflammation at sites of disease. Treatment Tr e a t m e n t s h o u l d b e c o n s i d e r e d f o r p a t i e n t s w i t h : a) Deteriorating lung function over 3–6 month intervals; b) Deteriorating radiological changes; c) Significant pulmonary symptoms of cough, shortness of breath, chest pain or haemoptysis. Treatment 1. Corticosteroids is the main form of treatment. Treatment varies from between 15–40 mg prednisolone / prednisone and 4– 32 mg methylprednisolone given for 3–24 months.Alternate day therapy is also used 2. Bisphosphonates should be given to prevent and treat steroid induced osteoporosis 3. Immunosuppressive drugs can be used both as treatment and as steroid-sparing agents. These include methotrexate, cyclosporin A, h y d r o x y c h l o r o q u i n e , a z a t h i o p r i n e , c h l o r a m b u c i l , cyclophosphamide, leflunamide, pentoxifylline, thalidomide, infliximab and etanercept. 4. Lung transplantation- lung transplantation has been considered in end stage sarcoidosis. Cryptogenic Organising Pneumonia (COP) Corticosteroid therapy has been the rule, with the occasional addition of azathioprine, Cyclophosphamide or cyclosporine in refractory cases. Recommended corticosteroid regimen is Prednisolone 0.75 mg/kg for 4 weeks followed by 0.5 mg/kg for 4 weeks, 20 mg daily for 4 weeks; 10 mg daily for6 weeks; 5 mg daily for 6 weeks and gradually tapered off

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Hypersensitivity pneumonitis Avoidance of allergen is most important mode of treatment Persisting symptoms despite antigen withdrawal are an indication to introduce oral corticosteroids (0.5 mg/kg/day) until symptoms and radiographic changes have resolved. Pulmonary langerhan's cell histiocytosis An uncommon smoking related ILD that primarily affects young adults and is characterised by abnormal organ infiltration by Langerhans's cells. It may be associated with systemic manifestations like aneurysmal bone cyst,diabetesinsipidus etc. l Investigations- Apartfrom routine Investigations for ILD(HRCT,PFT,DLCO), Bronchoscopy and BAL Langerhans cell > 5% l Birbeck granule in EMS, CD 1a/S100 Ag +ve. Langerin in Birbeck granule: (CD 207+). Definitive diagnosis: Based on clinicopathological evidence with microscopic examination and atleast one of the following Immunological staining LANGERIN, CD1a ,Birbeck granules on EMF Treatment: l Smoking cessation – first step l Watchful waiting in a- or minor symptomatic patient. l Systemic steroid therapy in symptomatic patients. l Chemotherapy (eg: cladribine) in progressive disease. l RADIOTHERAPY for symptomatic bone lesions may be palliative l LUNG TRANSPLANTATION: for selected patients with end stage disease or severe pulmonary hypertension. l PLEURODESIS: in patients with recurrent pneumothorax. 10.9. Pulmonary lymphangioleiomyomatosis LAM is a multisystem disorder, predominantly affecting women, which is characterised by cystic lunglesions,abdominalangiomyolipomas[AML], lymphatictumours and chylous effusions.

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l Investigations-In addition to the usual investigations for ILD, VEGF D > 800 pg/mm in blood. l Circulating LAM cell - (in blood, pleural fluid etc.) react with HMB 45. Treatment: LAM is considered to be a low-grade malignancy and drugs targeting signalling pathways that are considered important in the pathogenesis of the disease may turn out to be effective. General measures l Educate patient. l Weight control. l Avoidance of sports martial arts. l Avoidance of oestrogen containing drugs & phytoestrogen food. Targeted therapies l Anti estrogen therapy: oopherectomy, progesterone and gonadotropin releasing analogues l Mtor C1 Inhibitors: Sirolimus, Everolimus l Starting dose of sirolimus is 2mg/d l Mtor C2 Inhibitors: Simvastatin l Matrix Metalloproteinase Inhibitors: Doxycycline l Inhibitors Of Autophagy: Hydroxychloroquine l Aromatase inhibitor: LETROZOLE l VGEF inhibitors Treatment of complications Pneumothorax: Chemical sclerosis, pleurectomy, mechanical abrasion and talc poudrage are most effective Chylous Effusion and Lymhangioleiomyomas: Low fat diet, pleura peritoneal or peritoneal-venous shunts, sirolimus Angiomyolipomas: Selective embolization of tumor, sirolimus Lung Transplantation: considered when FEV1 and DLCO are less than 30% predicted and the patient is on continuous supplemental oxygen and unable to carry out activities of daily living or surgical pleurodesis by video assisted thoracoscopy.

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Respiratory bronchiolitis interstitial lung disease Diagnosis is based on typical HRCT finding in a current smoker or who recently quit smoking. Investigations- in addition to radiology and spirometry BAL: pigment laden macrophages. TREATMENT l Smoking cessation Desquamative interstitial pneumonia Rare disease Affect smokers in 4th to 5th decade. Association with Infection, Organic dust exposure, Marijuana addicts, mutation in SP-C,SP-B. TREATMENT l Good prognosis on smoking cessation. l Progressive & symptomatic cases - Corticosteroids x 6-9 m. l Macrolide as steroid sparing agent. l Lung transplantation Lymphoid interstitial pneumonia l Female >50 yr. l Associations: Immune deficiency, HIV, Autoimmune diseases (Sjogrens,thyroiditis), Idiopathic (<20%). Treatment l Idiopathic /CTD-LIP -potential benefit for Corticosteroids (1mg/kg over 8-12 weeks and taper over several months) &Immunosuppressive (cyclosporine or azathioprine) l HIV LIP – HAART, Corticosteroids trial may be given General management strategies in ild l All patients with ILD should have access to a multidisciplinary team based in a regional centre with expertise in ILD. l Patients with ILD who are current smokers should receive opportunistic smoking cessation advice from healthcare professionals and this advice should be recorded in the clinical notes.

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l Patients with ILD should have access to a local pulmonary rehabilitation programme. l Patients with clinically significant resting hypoxemia (resting SpO2<88%) should receive long term oxygen therapy.

16020 Section XI Long Term Oxygen Therapy

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section XI

Section XI 11. Long-term Oxygen Therapy LTOT can be defined as oxygen used for at least 15 h per day in chronically hypoxemic patients. Chronic hypoxaemia is defined as a PaO2 ≤ 54.75 mmHg or, in certain clinical situations, PaO2 ≤60kPa. LTOT is delivered via an oxygen concentrator. LTOT addresses specific physiological inclusion criteria as outlined below: 11.1. Use of long-term oxygen therapy in patients with chronic obstructive pulmonary disease Ø Patients with stable chronic obstructive pulmonary disease (COPD) and a resting PaO2 ≤ 54.75 mmHg or SaO2 at or below 88% should be assessed for long-term oxygen therapy (LTOT) which offers survival benefit and improves pulmonary haemodynamics Ø LTOT should be ordered for patients with stable COPD with a resting PaO2 between 55mmHg and 60 mmHg or SaO2 88% with evidence of peripheral oedema, polycythaemia Ø (Haematocrit >55%) or pulmonary hypertension. Ø LTOT should be ordered for patients with resting hypercapnia if they fulfil all other criteria for LTOT. 11.2. LTOT in patients with ILD Ø LTOT should be ordered for patients with interstitial lung disease (ILD) with a resting PaO2 ≤54.75 mmHg. Ø LTOT should be ordered for patients with ILD with a resting PaO2 ≤60 mmHg in the presence of peripheral oedema, polycythaemia (haematocrit ≥55%) or evidence of pulmonary hypertension. Ø Patients with ILD who experience severe breathlessness could be considered for palliative oxygen therapy. LTOT in patients with pulmonary hypertension Ø LTOT should be ordered for patients with pulmonary hypertension, including idiopathic pulmonary hypertension, when the PaO2 is ≤ 60 mmH.

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LTOT in patients with neuromuscular or chest wall Disorders Ø Non-invasive ventilation (NIV) should be the treatment of choice for patients with chest wall or neuromuscular disease causing type 2 respiratory failure. Additional LTOT may be required in case of hypoxaemia not corrected with NIV 11.3. Assessment of patients for LTOT Patients with a resting stable oxygen saturation (SpO2) of ≤ 92% should be referred for a blood gas assessment in order to assess eligibility for LTOT. In patients with clinical evidence of peripheral oedema, polycythaemia (haematocrit ≥55%) or pulmonary hypertension, referral for LTOT assessment may be considered at SpO2 levels ≤94% to identify patients with a resting PaO2 ≤60 mmHg Patients should undergo formal assessment for LTOT after a period of stability of at least 8 weeks from their last exacerbation. Patients should not normally have LTOT ordered at the time of an acute exacerbation of their underlying condition. However, if home oxygen is ordered (e.g. at hospital discharge), it should be limited to patients with a SpO2 of ≤92%, who are breathless, and unable to manage off oxygen. Assessment using arterial blood gases and capillary blood gases Ø Patients being assessed for LTOT should undergo initial assessment for suitability using arterial blood gases (ABG) sampling. Ø Patients assessed for LTOT during a period of apparent clinical stability should undergo two ABG measurements at least 3 weeks apart, before the need for LTOT can be confirmed. Ø Patients undergoing LTOT assessment should be reassessed with ABG after oxygen titration is complete to determine whether adequate oxygenation has been achieved without precipitating respiratory acidosis and/or worsening hypercapnia. Ø For oxygen titration during LTOT assessment, capillary blood gases (CBG) sampling can be used in place of ABG sampling for re-measuring PaCO2 and pH at different oxygen flow rates. Ø For oxygen titration during LTOT assessment, cutaneous capnography can be used in place of ABG sampling for re-

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measuring PaCO2 alone but not pH at different oxygen flow rates. Assessment using pulse oximetry Ø Patients potentially requiring LTOT should not be assessed using pulse oximetry alone. Ø Ambulatory and nocturnal oximetry may be performed to allow more accurate flow rates to be ordered for exercise and sleep, respectively. LTOT hours of use Ø LTOT should be ordered for a minimum of 15 h per day, and up to 24 h per day may be of additional benefit. LTOT flow rates Ø Patients eligible for LTOT should be initiated on a flow rate of 1 L/min and titrated up in 1 L/min increments until SpO2 >90% at 20 minutes intervel. An ABG should then be performed to confirm that a target PaO2 ≥60 mm Hg at rest has been achieved. Ø Non-hypercapnic patients initiated on LTOT should increase their flow rate by 1 L/min during sleep in the absence of any contraindications. Ø Patients initiated on LTOT who are active outdoors should receive an ambulatory oxygen assessment to assess whether their flow rate needs increasing during exercise. Follow-up of LTOT patients Ø LTOT patients should receive follow-up at 3 months after LTOT has been ordered, which should include assessment of blood gases and flow rate to ensure LTOT is still indicated and therapeutic. Ø LTOT patients should receive follow-up visits at 6– 12 months after their initial 3-month follow-up, which can be either home based or in combination with hospital visits. Ø Follow-up visits should be conducted by a specialist home oxygen assessment team with the necessary skills to deliver patient education and manage withdrawal of home oxygen.

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Ambulatory Oxygen Therapy in patients eligible for LTOT AOT assessment should only be offered to patients already on LTOT if they are mobile outdoors. Ø AOT should be offered to patients for use during exercise in a pulmonary rehabilitation programme or during an exercise programme following a formal assessment demonstrating improvement in exercise endurance. Nocturnal oxygen therapy l Only in those with CF, Neuro-muscular disorders, OSA & ILD in ventilatory failure l Should be used along with NIV. Mode of delivery l Long term oxygen therapy may be delivered via oxygen concentrator or oxygen cylinder. l For long term use, oxygen concentrators pose definite advantage over cylinders. l In areas where electric supply is erratic, oxygen concentrator with battery backup & supportive high power UPS may be considered. l Accessories to be used – pulse oxymeter, UPS. l Nasal cannula is the first choice for oxygen administration.

16620 Section XII Tuberculosis

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Section XII 12. Tuberculosis Tuberculosis is not dealt in detail in this document as the RNTCP guidelines extensively cover the diagnosis and treatment of TB and it is expected that all doctors follow the RNTCP guidelines. A brief summary of the diagnosis and treatment of TB is provided in this chapter. Tuberculosis remains a major public health problem in India and the World with about 10.4 million new cases in the world every year. India is the highest TB country in the world with an incidence of 2.79 million and with 435,000 mortality every year. Kerala state has an annual notification of total TB patients of 20969 in the government sector and the private sector notified 26324 cases (TB India 2017). Worldwide the TB control strategy is now moving to the END TB strategy, and as part of this and the sustainable development goals (SDGs), many countries in the world, including India, are now moving towards TB elimination. One of the key targets for the END TB strategy is reduction of mortality due to TB. For this, early diagnosis of TB as well as early diagnosis of Rifampicin resistance is believed to be crucial. As such, the country is now moving towards “Universal DST”, which in the Indian context means offering at least Rifampicin resistance testing, primarily through CBNAAT, to all TB patients. Pulmonary TB is the major form of TB, however extrapulmonary TB is also not too uncommon. TB is suspected in persons with cough more than two weeks. However other symptoms like fever, weight loss, night sweats, hemoptysis, etc should also be kept in consideration. The diagnostic algorithm for Pulmonary and extra-pulmonary TB are given in the following pages. This is followed by an algorithm on evaluation for drug resistance.

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Figure 12.1. Diagnosis of Pulmonary TB

Figure 12.2. Diagnosis of Pulmonary TB

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12.3. Diagnosis of pediatric TB

12.1. Treatment of drug sensitive TB Only a single regime now. All patients with new or retreatment TB, if found to have drug sensitive TB, are started on a 6 month regime with two months (eight weeks) of INH, Rifampicin, pyrazinamide and ethambutol followed by four months (16 weeks) of INH, Rifampicin and ethambutol

Table 12.1 Drug dosages for drug sensitive TB

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This dosing schedule is likely to change in the 2019 update, hence please refer to the updated dosing schedule in the current RNTCP guidelines. 4 Regimes for drug resistant TB INH mono / poly resistant TB l For patients who are found to have H resistant and R sensitive TB, the regimen recommended regimen is Lfx R Z E for a period of 6 months. (injection free regimen-no separate IP and CP, for Pulmonary as well as Extra-pulmonary H mono/poly DR-TB patients) l Baseline SL-LPA must be done for all patients with H resistance to check for additional FQ resistance. Substitution of drug with Lzd, Cfz + Cs. MDR TB – short MDR regime 1. Inclusion criteria 1. RR-TB patients with no resistance to FQ/SLI 2. Exclusion criteria 1. FL-LPA (inhA), DST (Mfx 2.0 and Z) to be done and switch to longer regimen if any resistance detected. 2. Other exclusion criteria: Intolerance to drugs being used in the regimen, pregnancy, EPTB in PLHIV, Disseminated, Meningeal or CNS-TB. 3. In any early signs of failure or ADR observed, switch to longer regimen Regime Intensive phase (4-6) Mfxh Km Eto Cfz Z Hh E Continuation phase (5) Mfxh Cfz Z E Conventional regime Intensive phase (6-9) Km Lfx Eto Cs Z E Continuation phase (18) Lfx Eto Cs E This regime is likely to change in the 2019 RNTCP guidelines, hence please refer to

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the 2019 RNTCP guidelines when these are released. Patients are eligible for the two new drugs, Bedaquiline and Delamanid in the following scenarios l Patient not eligible for a shorter MDR-TB regimen for reasons of resistance, contraindication or tolerability l MDR/RR-TB with resistance to any/all FQ OR any/all SLI l XDR-TB l Mixed Pattern DR-TB including patients who are v failing any DR-TB regimen or v have drug intolerance or contraindications or v who return after interruption or v emergence of any exclusion criteria for shorter MDR-TB regimen or v with extensive or advanced disease and v others deemed at higher baseline risk for poor outcomes.

Figure 12.4. Drug sensitivity / resistance based regimes for TB

173

Section XIII Lung cancer

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section XIII

Section XIII 13. LUNG CANCER Preamble Lung cancer is usually managed by the oncologist in most institutions. Advanced centres use the services of tumour board for decision making in which a pulmonologist is a member. These guidelines are intended to provide information to the Pulmonologist on early diagnosis and proper referral to the concerned specialist. 13.1. Introduction About 90% of lung cancers are caused by smoking. Now that fewer men smoke, lung cancer deaths in men have decreased by more than a quarter. However, the number of women who smoke has risen and deaths from lung cancer in women have increased. Only about 5.5% of lung cancers are currently cured. Although the cure rate is rising slowly, the rate of improvement has been slower than for other common cancers. There is evidence that outcomes vary in different countries, which among other factors may be explained by variations in the standard of care. Recommendations are included on communication, diagnosis and staging, selection of patients with non-small-cell lung cancer (NSCLC) for treatment with curative intent, treatment for small-cell lung cancer (SCLC) with curative intent, managing endobronchial obstruction, managing brain metastases, smoking cessation, and follow-up and patient perspectives. Patient-centred care People with lung cancer should have the opportunity to make informed decisions about their care and treatment, in partnership with their healthcare professionals. If patients do not have the capacity to make decisions, healthcare professionals should interact with his close relatives. Good communication between healthcare professionals and patients is essential. It should be supported by evidence-based written information tailored to the patient's needs. Treatment and care, and the information patients are given about it, should be culturally appropriate. It should also be accessible to people with additional needs such as physical, sensory or learning disabilities. If the patient agrees, families and carers should have the opportunity to be involved in decisions about treatment and care. Families and carers should also be

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given the information and support they need. 13.2. Diagnosis and staging l Choose investigations that give the most information about diagnosis and staging with least risk to the patient. Think carefully before performing a test that gives only diagnostic pathology when information on staging is also needed to guide treatment. l Sputum cytology is rarely indicated and should be reserved for the investigation of patients who have centrally placed nodules or masses and are unable to tolerate, or unwilling to undergo, bronchoscopy or other invasive tests. l An X-ray should be performed in the first instance for all patients presenting with symptoms and signs suggestive of a primary or metastatic tumour. If the results are negative or inconclusive, either a bone scan or an MRI scan should be offered. Avoid bone scintigraphy when PET-CT has not shown bone metastases. l Patients with known or suspected lung cancer should be offered a contrast-enhanced chest CT scan to further the diagnosis and stage the disease. The scan should also include the liver and adrenals. l In the assessment of mediastinal and chest wall invasion CT alone may not be reliable. Other techniques such as ultrasound should be considered, where there is doubt. Surgical assessment may be necessary if there are no contraindications to resection. l Magnetic resonance imaging (MRI) should not routinely be performed to assess the stage of the primary tumour (T-stage) in NSCLC. MRI should be performed, where necessary to assess the extent of disease, for patients with superior sulcus tumours3. l EBUS-guided TBNA for biopsy of paratracheal and peri-bronchial intra-parenchymal lung lesions is a relatively safe choice. Ensure adequate samples are taken without unacceptable risk to the patient to permit pathological diagnosis including tumour sub-typing and measurement of predictive markers. l CT- or ultrasound-guided transthoracic needle biopsy is done in patients with peripheral lung lesions when treatment can be planned on the basis of this test. Biopsy any enlarged mediastinal

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nodes (≥ 10 mm maximum short axis on CT) or other lesions in preference to the primary lesion if determination of stage affects treatment. l Fibreoptic bronchoscopy is to be considered in patients with central lesions on CT where nodal staging does not influence treatment. Enlarged lymph nodes (≥ 10 mm maximum short axis on CT) may be simultaneously sampled with TBNA (non-ultrasound-guided) if required for diagnosis. l PET-CT is the preferred first test after CT showing a low probability of mediastinal malignancy (lymph nodes 10 mm maximum short axis on CT) for patients who are potentially suitable for treatment with curative intent. l Consider ultrasound with sampling of visible lymph nodes or non-ultrasound-guided TBNA to patients with a high probability of mediastinal malignancy (lymph nodes > 20 mm maximum short axis on CT). If neck ultrasound is negative, follow with non- ultrasound-guided TBNA, EBUS-guided TBNA or EUS-guided FNA. If non-ultrasound-guided TBNA is negative follow with EBUS-guided TBNA or EUS-guided FNA. l Evaluate PET-CT-positive mediastinal nodes by mediastinal sampling (except when there is definite distant metastatic disease or a high probability that N2/N3 disease is metastatic [for example, if there is a chain of lymph nodes with high 18F-deoxyglucose uptake]). l Confirm negative results obtained by EBUS-guided TBNA and/or EUS-guided FNA using surgical staging if clinical suspicion of mediastinal malignancy is high. l Confirm the presence of isolated distant metastases/synchronous tumours by biopsy or further imaging (for example, MRI or PET-CT) in patients being considered for treatment with curative intent. Consider MRI or CT of the head in patients selected for treatment with curative intent, especially in stage III disease. Multidisciplinary teams The care of all patients with a working diagnosis of lung cancer should be discussed at a lung cancer MDT meeting (Tumour board). Rapid access clinics

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should be provided where possible for the investigation of patients with suspected lung cancer, because they are associated with faster diagnosis and less patient anxiety. 13.3. Treatment Smoking cessation Inform patients that smoking increases the risk of pulmonary complications after lung cancer surgery. Advise patients to stop smoking as soon as the diagnosis of lung cancer is suspected and tell them why this is important. Offer nicotine replacement therapy and other therapies to help patients to stop smoking in line with Smoking cessation services and Varenicline for smoking cessation. Assessment before radiotherapy A clinical oncologist's in thoracic oncology should determine suitability for radiotherapy with curative intent, taking into account performance status and comorbidities. Surgery for non-small-cell lung cancer In patients with NSCLC who are medically fit and suitable for treatment with curative intent, lobectomy is the treatment of first choice. For patients with borderline fitness and smaller tumours (T1a–b, N0, M0), consider lung parenchymal-sparing operations (segmentectomy or wedge resection) if a complete resection can be achieved. More extensive surgery (bronchoangioplastic surgery, bilobectomy, pneumonectomy) are considered only when needed to obtain clear margins. Perform hilar and mediastinal lymph node sampling or en bloc resection for all patients undergoing surgery with curative intent. For patients with T3 NSCLC with chest wall involvement who are undergoing surgery, complete resection of the tumour should be the aim by either extrapleural or en bloc chest wall resection. Radiotherapy for non-small-cell lung cancer Radical radiotherapy is indicated for patients with stage I, II or III NSCLC who have good performance status (WHO 0,1) and whose disease can be encompassed in a radiotherapy treatment volume without undue risk of normal tissue damage. All patients should undergo pulmonary function tests (including lung volumes and transfer factor) before having radical radiotherapy for

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NSCLC. Patients who have poor lung function but are otherwise suitable for radical radiotherapy should still be offered radiotherapy, provided the volume of irradiated lung is small. Chemotherapy for non-small-cell lung cancer Chemotherapy should be offered to patients with stage III or IV NSCLC and good performance status (WHO 0,1 or a Karnofsky score of 80–100), to improve survival, disease control and quality of life. Chemotherapy for advanced NSCLC should be a combination of a single third-generation drug (docetaxel, gemcitabine, paclitaxel or vinorelbine) plus a platinum drug. Either carboplatin or cisplatin may be administered, taking account of their toxicities, efficacy and convenience. Patients who are unable to tolerate a platinum combination may be offered single-agent chemotherapy with a third-generation drug. Docetaxel monotherapy should be considered if second-line treatment is appropriate for patients with locally advanced or metastatic NSCLC in whom relapse has occurred after previous chemotherapy. Biological agents such as gefitinib or erlotinib may be considered for non- small-cell lung cancer having EGRF mutation detected in the histopathological specimen. Combination treatment for non-small-cell lung cancer Patients with stage I–III NSCLC who are not suitable for surgery need to be assessment by a clinical oncologist specialising in thoracic oncology for radiotherapy with curative intent. Consider chemoradiotherapy for patients with stage II or III NSCLC who are not suitable for surgery. Consider potential benefit in survival with the risk of additional toxicities before this treatment. Consider postoperative chemotherapy in patients with good performance status (WHO 0 or 1) and T2–3 N0 M0 NSCLC with tumours greater than 4 cm in diameter. Offer a cisplatin-based combination chemotherapy regimen for adjuvant chemotherapy. Ensure eligible patients have the benefit of detailed discussion of the risks and benefits of adjuvant chemotherapy. Treat Pancoast tumours in the same way as other types of NSCLC. Offer multimodality therapy according to resectability, stage of the tumour and performance status of the patient.

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Assessing patients with small-cell lung cancer All patients with small-cell lung cancer (SCLC) should be assessed by a thoracic oncologist within 1 week of deciding to recommend treatment. First-line treatment for limited-stage disease small-cell lung cancer Patients with limited-stage disease (T1–4, N0–3, M0) should receive four to six cycles of cisplatin-based combination chemotherapy. Consider substituting carboplatin in patients with impaired renal function, poor performance status (WHO 2 or more) or significant comorbidity. Concurrent chemoradiotherapy may be offered to patients with limited- stage disease (T1–4, N0–3, M0) and a WHO performance status of 0 or 1 if they present with disease that can be encompassed in a radical thoracic radiotherapy volume. Start the radiotherapy during the first or second cycle of chemotherapy. Sequential radical thoracic radiotherapy is given to patients with limited- stage disease SCLC (T1–4, N0–3, M0) who are unfit for concurrent chemoradiotherapy but who respond to chemotherapy. Surgical treatment for patients with small-cell lung cancer Consider surgery in patients with early-stage SCLC (T1–2a, N0, M0). First-line treatment for extensive-stage disease of small-cell lung cancer Platinum-based combination chemotherapy is preferred in patients with extensive-stage disease SCLC (T1–4, N0–3, M1a/b – including cerebral metastases) if they are clinically fit. Assess the patient's condition before each cycle of chemotherapy for extensive-stage disease SCLC and offer up to a maximum of six cycles, depending on response and toxicity. For patients with extensive-stage disease SCLC, thoracic radiotherapy should be considered after chemotherapy if there has been a complete response at distant sites and at least a good partial response within the thorax. Prophylactic cranial irradiation in small-cell lung cancer Prophylactic cranial irradiation is offered at a dose of 25 Gy in 10 fractions to patients with limited-stage disease SCLC and WHO performance status 2 or less, if their disease has not progressed on first-line treatment. Prophylactic cranial irradiation is given to patients with extensive-stage disease SCLC and WHO performance status 2 or less, if their disease has not progressed on first-line treatment.

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Second-line treatment for patients with small-cell lung cancer that has relapsed after first-line treatment SCLC that has relapsed after first-line treatment is assessment by a thoracic oncologist. Inform patients whose disease has not responded to first-line treatment that there is very limited evidence that second-line chemotherapy will be of benefit. Treatment with an anthracycline- containing regimen or further treatment with a platinum-based regimen to a maximum of six cycles is the choice in such situations. Offer radiotherapy for palliation of local symptoms to these patients. Supportive and palliative care Supportive and palliative care of the patient should be provided by general and specialist palliative care providers. Patients who may benefit from specialist palliative care services should be identified and referred without delay. Palliative radiotherapy Patients who cannot be offered curative treatment, and are candidates for palliative radiotherapy, may either be observed until symptoms arise and then treated, or be treated with palliative radiotherapy immediately. Managing endobronchial obstruction When patients have large airway involvement, monitor (clinically and radiologically) for endobronchial obstruction to ensure that treatment is g i ve n e a rl y. Offe r e xte rn a l b e a m ra d i o th e ra p y a n d /o r endobronchialdebulking or stenting to patients with impending endobronchial obstruction. Other palliative treatments Pleural aspiration or drainage should be performed in an attempt to relieve the symptoms of a pleural effusion. Patients who benefit symptomatically from aspiration or drainage of fluid should be offered talc pleurodesis for longer-term benefit. Non-drug interventions based on psychosocial support, breathing control and coping strategies should be considered for patients with breathlessness. Non-drug interventions for breathlessness should be delivered by a multidisciplinary group, coordinated by a professional with an interest in breathlessness and expertise in the techniques (for example, a nurse,

183 184 20 13.4. an experience thereafter completing Follow-up and swallowing, Other swallowing, administered. analgesic Hypercalcaemia, metastases Consider reduce Section XIII ST option Ensure ANDARD TREA palliative Of Of For Of Managing symptoms, fer fer fer to patients palsy cough. care provided physiotherapist Patients Opioids, treatment. symptoms Stent and of Patients for , protocol-driven palliative all dexamethasone the treatments and fered rather symptoms. fatigue with should that patients treatment patients care performance settings. minimum Managing should insertion patient TMENT GUIDELINES-RESPIRA brain good chemotherapy with patients including professionals. with such bone in than who and be whole-brain of a with bone an performance be metastases managed breathlessness superior troublesome are perspectives depression. to as relying present pain necessary referred should initial or a follow-up other know status. life codeine discuss metastasis to weight occupational inadequate, and expectancy patients specialist vena symptoms: and on radiotherapy by be with how to pathological status led loss, multidisciplinary an patients maintenance considered or radiotherapy hoarseness ongoing caval superior clinic, ear to morphine, by requiring with loss follow-up T therapist). single-fraction (WHO , contact a of OR nose obstruction weight lung more patients requesting Y symptomatic of DISEASES for care. vena fractures for and appetite, 0 cancer palliation due according dose patients should or than the loss, appointment the groups throat Although 1). Of should cava to or lung 3 for immediate fer clinical appointments recurrent loss months. following be radiotherapy depression specialist with symptomatic and brain obstruction that regular to cancer have considered of this the for symptomatic nurse include appetite, within metastases stage access support laryngeal whom failure relief for clinical appointments and specialist 6 advice. when should supportive should of response. to of weeks standard of to dif dif disease may reduce severe earlier it ficulty ficulty nurse nerve brain in they and be be be as all of STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section XIII specialist involved in their care between their scheduled hospital visits. The opinions and experiences of lung cancer patients and carers should be collected and used to improve the delivery of lung cancer services. Patients should receive feedback on any action taken as a result of such surveys. 13.5. References 1. Jaklitsch MT, Jacobson FL, Austin JHM, et al. The American association for thoracic surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups. J ThoracCardiovascSurg 2012;144:33-8 [PubMed] [Google Scholar] 2. 4. Brodowicz T, Ciuleanu T, Crawford J, et al. Third CECOG consensus on the systemic treatment of non-small-cell lung cancer. Ann Oncol 2012;23:1223-9 [PubMed] [Google Scholar] 3. Sørensen M, Pijls-Johannesma M, Felip E, et al. Small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21Suppl 5:v120-5 [PubMed] [Google Scholar] 4. National Collaborating Centre for Cancer. eds. Lung cancer. The diagnosis and treatment of lung cancer. London: National Institute for Health and Clinical Excellence, 2011. [Google Scholar]

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Section XIV Upper airway obstruction

STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section XIV

Section XIV 14. Upper airway obstruction 14.1. Major Airway Obstruction Major airway obstruction is an uncommon and potentially life threatening condition. It may be caused by a luminal compromise due to intrinsic pathology or by extrinsic compression. The upper airway is conventionally described as being made up of all the structures that conduct air between the carina and the nares. Within the upper airway pharyngeal airway do not have a bony support and is susceptible to collapse during sleep. 14.2. Causes of Benign and malignant airway obstruction Benign l Post-intubation l Post-tracheostomy l Anastomotic stricture (lung transplant, sleeve resection, airway resection) l Intrinsic airway tumors l Extrinsic airway tumors l Infalmmatory l Infectious l Foreign body 14.3. Malignant l Adjacent malignancies v Lung cancer v Thyroid cancer v Esopahgeal cancer v Mediastinal tumors l Primary airway tumors v Carcinoid tumor v Adenoid cystic carcinoma v Mucoepidermaoid carcinoma v Squamous cell carcinoma l Metastatic tumors v Breast cancer v Renal cell carcinoma

189 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section XIV

v Melanoma v Colorectal v Others Clinical presentation: UAO can have acute life threatening presentation resulting in asphyxia. Sometimes the manifestation is chronic with noisy breathing often misdiagnosed and treated as asthma. It can also be asymptomatic for long period of time. Commonest symptoms are breathlessness, noisy breathing. By the time exertional dyspnea develops UA diameter is already reduced to 8 mm. It becomes around 5 mm when the patient is having . Stridor is more predominant on inspiration and louder over the neck. History: l Dyspnea, onset and progression l Stridor l Positional variation of symptoms l Whether patient wakes at night with difficulty in breathing l Dysphagia, l H/o foreign body aspiration/ Recentintubation l Any h/o suggestive of anaphylaxis/ infection l H/o cancer l Drug overdose Examination: l Examine the patient in the position in which they are most comfortable. l Check vitals l Examine neck and oral cavity l Check for stridor, its respiratory phase and change with position.Inspiratory stridor suggests extrathoracic airway obstruction at or above the while expiratory stridor may be due tointrathoracic obstruction. Biphasic stridor is present in subglottic or tracheal stenosis.

19020 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section XIV

14.4. Management Initial management of UAO focus on securing the airway and stabilizing the patient. Adequate oxygenation Sometime bypassing the obstruction by translaryngeal intubation or tracheostomy is required. Fibre optic bronchoscope helps to assess the site of obstruction and its extend. It helps to clear out blood clot or mucous plug obstructing the major airway. Foreign bodies causing luminal obstruction can be taken out using grasping forceps or by cryoprobe. During the procedure there can be desaturation as the bronchoscope further compromises the already narrowed airway. With regard to securing the airway , maintaining ventilation, and controlling hemoptysis rigid bronchoscope is more useful than fibre optic bronchoscope. The UAO due to PITS can be dilated by serial passage of bronchoscopes. Intraluminal lesions can be mechanically debulked. Ablative procedures like endobronchial laser can be performed through rigid scope. UAO due to extraluminal lesion can treated by airway stent. For benign causes silicone stents are preferred.

191 STANDARD TREATMENT GUIDELINES - RESPIRATORY DISEASES Section XIV

Figure 14.1 Management of upper airway obstruction

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Department Of Health And Family Welfare Government Of Kerala Annexe II, Secretariat Thiruvananthapuram

Kerala-695001 February 2021 Kerala HEALTH