Asthma and Hypersensitivity Pneumonitis.pptx

Asthma and hypersensitivity pneumonia

1. Asthma, Hypersensitivity Pneumonitis

2. Asthma Asthma is a chronic inflammatory disorder of the airways in which breathing is periodically rendered difficult by widespread narrowing of the bronchi(reversible bronchoconstriction). Clinically characterized by recurrent paroxysms of wheezing, breathlessness, tightness of the chest & cough particularly at night & early in the morning. Characteristics of Asthma are; 1) Airflow narrowing 2) Bronchial hyper responsiveness & 3) Bronchial inflammation.

3. Characteristics of Asthma 1.Airflow Narrowing 2.Bronchial hyper 3.Bronchial inflammation responsiveness Muscle edema & viscid Increased tendency Inflammation of bronchial Bronchial secretion. f or airways to narrowing walls by T lymphocytes, (reversible spontaneously response to triggers. mast cells, eosinophils Or with treatment) associated edema, mucus plugging , smooth muscle hypertrophy & epithelial damage.

4. Classification of Asthma According to type of antigen Early-onset asthma(atopic/(allergic/extrinsic) Late-onset asthma(non-atopic/intrinsic) without evidence of allergen sensitization. According to agents or events that trigger bronchoconstriction Seasonal 6. Cough variant asthma Exercise induced Drug induced(aspirin) Occupational asthma Asthmatic bronchitis in smokers

5. Differentiating features of early-onset & late onset asthma Features Early-onset asthma Late-onset asthma Onset Early age usually begins in childhood Late age Individuals Atopic individuals Non-atopic individuals Role of external allergens Strong role No role Family Hx Positive Hx of asthma(eczema, urticarial, or hay fever Less common or absent Triggering events Environmental allergens(dusts, pollens, animal dander & foods) Respiratory infections due to vruses (rhinovirus, parainfluenza virus) Serum IgE level Increased Normal Skin hypersensitivity test to common inhalant allergens Positive Negative Response to provocation tests Positive Negative

6. Risk Factors & Triggers Involved in Asthma Endogenous Factors Environmental Factors Genetic predisposition Indoor allergens Atopy Outdoor allergens Airway hyper responsiveness Occupational sensitizers Gender Passive smoking Ethnicity Respiratory infections Obesity Diet Early viral infections Acetaminophen (paracetamol )

7. Risk Factors & Triggers Involved in Asthma(contd..) Triggers Allergens Upper respiratory tract viral infections Exercise and hyperventilation Cold air Sulphur dioxide and irritant gases Drugs ( β blockers, aspirin) Stress Irritants (household sprays, paint fumes)

8. Pathophysiology of Asthma Airway Inflammation Involves many cell types & inflammatory mediators Genetic predisposition to develop strong T H 2 reactions against environmental antigens. T H 2 cells secrete cytokines promote allergic inflammation & stimulate B cells to produce IgE Important cells involved are Mast cells, eosinophils, dendritic cells & lymphocytes Mast cells Early reaction- bronchoconstriction, increased mucus production & vasodilation with increased vascular permeability Late phase reaction- inflammation & airway remodeling

9. Eosinophils Mediators release from eosinophils- LTC4 & basic proteins(major basic protein, eosinophil cationic protein and eosinophils peroxidase these are toxic to epithelial cells Dendritic cells & lymphocytes Release prostaglandin, thromboxane, LTC4, LTB4 & platelet activating factor.

10. Airway Remodelling Group of structural & functional changes in the bronchial wall due to repeated bouts of inflammation -increase in size & number of the submucosal glands -hypertrophy and/or hyperplasia of the bronchial wall smooth muscle -increased vascularity -deposition of subepithelial collagen with fibrosis & thickening of BM

11. Pathophysiology of Asthma

12. Pathophysiology of Asthma(Contd..)

13. Pathogenesis of Asthma summarized Allergen & Sensitizers Environmental Factors Inflammatory cells -Mast cells -Eosinophils -T H 2 cells Mediators -Histamine & serotonin -Leukotrienes -Prostaglandins -Thromboxane -Platelet activating factor -Bradykinin -Adenosine -Oxygen free radicals -Complement fragments -Nitric oxide -Cytokines &chemokines Genetic predisposition Bronchial inflammation Bronchial hypersensitivity+Triggering factors Edema Bronchoconstriction Mucus production Airway narrowing Cough Wheeze Breathlessness Chest tightening

14. Clinical Features Studied under three headings: Episodic asthma Occurs as episodes with asymptomatic b/w asthmatic attacks Sudden onset of paroxysms of wheezing & dyspnoea May develop spontaneously or triggered by triggers Mild to severe & may last for hrs, days or even weeks

15. Severe acute asthma(Status Asthmaticus ) Most severe form of asthma Severe acute paroxysm persist for days & even weeks Bronchoconstriction & asthmatic symptoms doesn’t respond despite acute asthma therapy May cause severe airflow obstruction leading to severe cyanosis and even death

16. Chronic Asthma Chronic persistent symptoms include chest tightness, wheeze & breathlessness on exertion Episodes of spontaneous cough & wheeze worst during night Prone to repeated attacks of severe acute asthma, features resemble those of chronic bronchitis Physical signs During an attack -Inspection: increased RR with use of accessory muscles -Percussion: hyper-resonant -Auscultation: vesicular breath sounds with prolonged respiration, high pitched polyphonic inspiratory & expiratory rhonchi, very severe attacks results in silent chest

17. Investigations Diagnosis is mainly clinical & based on characteristic history There is no single satisfactory diagnostic test for asthma Lung Function Tests Spirometry: -Useful in assessing reversibility -Useful in confirming the airflow limitation with reduced FEV 1, FEV 1 /FVC ratio & PEFR. -Asthma can be diagnosed if there is >15% improvement in FEV 1 or PEFR after inhalation of bronchodilator. PEFR (Peak expiratory flow rate): -PEFR measurements to be done on waking, prior to taking bronchodilator & before bed after a bronchodilator -Diurnal variation in PEFR of >20% is considered diagnostic

18. Airway hyper responsiveness(AHR): To detect the presence of airway hyper responsiveness Useful in patients whom cough is the only main symptom Contraindicated in individuals with poor lung function(FEV <1.5L) Indirect challenge tests: Release endogenous mediators that cause contraction of airway smooth muscle(exercise eucapnic voluntary hyperpnea , ultrasonically nebulizer hypertonic saline & dry powder mannitol)

19. Imaging Chest X-ray -Usually normal between attacks -Hyperinflated lungs during acute episode or chronic severe disease -helpful in excluding complications(pneumothorax, lobar collapse etc.) High-resolution CT -may show areas of bronchiectasis(complication) & thickening of bronchial walls

20. Measurement of Allergic Status Skin prick tests -performed by intradermal injections of common allergens(house dust mite, cat fur, grass pollen) & checking for development of wheal and flare reaction. Positive in allergic asthma. Elevated serum IgE levels: Measurement of total & allergen specific IgE in serum.

21. Blood & Sputum tests May show increased numbers of eosinophils in PS( >0.4×10⁹) But sputum eosinophils more specific diagnostic finding-may reveal Curshmann spirals, Creola bodies & Charcot- Layden crystals) 5. Trial of Corticosteroids Patients with severe airflow limitation should be given a trial of corticosteroids Prednisolone 30mg/day orally given for 2weeks with lung function measured before & immediately after the course Substantial improvement in FEV(>15%) confirms the presence of reversible airflow obstruction, indicates inhaled steroids are beneficial.

22. ABG Analysis Hypoxia & hypocarbia during an acute attack Hypercarbia during severe acute asthma

23. Differential Diagnosis of Asthma Disease Features COPD H/O significant smoking, Airflow obstruction less reversible, Reduced diffusing capacity of lung for CO Bronchiectasis May be secondary to many disorders, produces copious purulent sputum, CT is usually diagnostic Reactive airways viral syndrome Transient, usually resolves after several weeks Rhinosinusitis Usually nasal congestion & post nasal drip, Common co-morbid illness accompanying asthma GERD Usually have other GI symptoms, Common co-morbid illness accompanying asthma Congestive Heart Failure Exertional dyspnoea, Moist basilar rales, S3 gallop, orthopnoea, pink frothy/blood tinged sputum, Echo is helpful Laryngeal dysfunction Stridor, Laryngoscope helpful, May co-exist with asthma Upper airway obstruction Flow-volume loop helpful, Endoscopy diagnostic Recurrent episodes of bronchospasm Carcinoid tumors , recurrent pulmonary emboli, Churg-strauss syndrome

24. Management Avoid Identified Aggravating Factors -Important in the management of atopic & occupational asthma -Avoid causative allergens such as pets, moulds, certain food stuffs Control of Risk factors causing exacerbation -Active & passive smoking should be avoided -Control if associated rhinitis & GERD -Control obesity -Individuals intolerant to aspirin should avoid NSAIDs -Avoid inadequate use of inhaled corticosteroids -Avoid overuse of inhaled short acting β -agonists(>one canister of 200doses/ mnth ) -Follow proper inhalation techniques

25. Desensitization or Immunotherapy -Repeated sub-cutaneous injections of gradually increasing doses of the extracts of allergens Drug therapy -To control or suppress clinical manifestations

26. Drug therapy in Asthma Bronchodilators β ₂-adrenoreceptor agonists -Most widely used bronchodilator -Divided into short acting β ₂ agonists(salbutamol, levosalbutamol , terbutaline) & long acting β ₂ agonists( bambuterol , salmeterol, formoterol). Catecholamines : used are adrenaline, isoprenaline & isoetharine -Adrenaline most commonly used agent in this group, useful in children.

27. Salbutamol, levosalbutamol , terbutaline , fenoterol -Highly selective for β ₂- adrenoreceptors & act predominantly on respiratory tract -Powerful & rapidly but short acting bronchodilators-relaxes bronchial smooth muscles -ROA: Active by inhalation, oral, IV, Sc routes but preferred route is inhalation, extremely effective as it rapidly decreases airflow obstruction -Dose: Salbutamol- 2 to 4mg TID orally or two puffs of 100mcg each as required Terbutaline - 2.5 to 5mg TID or two puffs of 100mcg each as required Levosalbutamol - Two puffs of 50mcg each as required -Side effects: tremor & palpitations are main untoward effects. Tachycardia is less with levosalbutamol .

28. Bambuterol : -Long acting β ₂-adrenoreceptor agonist converted into terbutaline in the body -Dose: 10-20mg once in a day orally -Side effects: More than inhaled β -agonists include tachycardia, palpitation & tremors. d. Salmeterol & formoterol : -Highly selective, potent & long-acting β ₂-adrenoreceptor agonist -Once or twice daily by inhalation(aerosol or dry powder) -Uses: routinely used in place of short acting β ₂-stimulants when pt requires regular β ₂-stimulants therapy, used as an add on therapy along with ICS. -Formoterol has rapid onset of action hence suitable for immediate control of symptoms. -Dose: Salmeterol- two puffs of 25mcg each two to three times a day Formoterol- two puffs of 6mcg each one to three times a day

29. Methylxanthines -These are beneficial as add-on therapy in patients not controlled with ICS -Less effective than long acting inhaled β 2 -agonists Theophylline -Medium potency bronchodilator - Actions :1)improves movement of airway mucus 2)improves diaphragm contractility & 3)reduces the release of mediators - ROA : IV, oral or as suppository. Therapeutic plasma concns . from 10-20mcg/ml. - Dose : 100-200mg(plain preparation) TID/day & 300mg BID/day or 450-600mg OD for sustained-release preparation - Side effects : Nervousness, nausea, vomiting, anorexia & headache. When plasma levels exceed 30mcg/mL, seizures & cardiac arrhythmia can occur . - Precautions : Theophylline clearance decreased in elderly, liver disease, CHF & with concurrent use of erythromycin, allopurinol & cimetidine. Clearance is increased in concurrent use of phenobarbitone & phenytoin and smokers.

30. Aminophylline -Effective with oral, IV & as a suppository -Preferred route of administration is intravenous & have some role in the management of status asthmaticus -MOA: inhibition of phosphodiesterase in airway smooth muscle cells which increases cAMP. -Dose: Loading dose of 5mg/kg slowly IV over 20min followed by maintenance of 0.5mg/kg/hr as a continuous IV infusion. If patient already on theophylline loading dose is preferably withheld. -rapid infusion can lead to sudden death due to cardiac arrhythmias. Doxophylline -MOA: As that of aminophylline, it has better safety profile than theophylline. -Also inhibits PAF-induced bronchoconstriction & subsequent production of thromboxane A 2. -Dose: 400mg twice a day.

31. Anticholinergics Antimuscarinic bronchodilators: Less effective than beta2 agonists. May be useful during asthma exacerbations but less useful in stable asthma

32. Controller Therapies Inhaled corticosteroids(ICS) Most effective controllers for asthma MOA : Most effective anti-inflammatory agents which reduces number of inflammatory cells as well as their activation in airways. Decrease bronchial hyper-responsiveness & relieve or prevent airflow obstruction. Also reverse β₂ -receptor down regulation produced by long term use. Uses : Beneficial in treating asthma of any severity & age, now given as 1 st line therapy for persistent asthma. Dose : usually given twice daily. Higher doses in severe cases. -Beclomethasone dipropionate (200µg), budesonide (200µg) or fluticasone(125µg) as aerosols or dry powder form. - Ciclesonide in a dose of 80-160µg once a day. Others- flunisolide & mometasone

33. Advantages : -Rapid improvement of symptoms & lung function. -Prevention: Effective in preventing exercise induced asthma & nocturnal exacerbations and also prevent severe exacerbations. -Reduces airway hyper-responsiveness -Reduces number of courses of oral corticosteroid therapy. Disadvantages : -do not cure the underlying condition -effects in acute asthma are not immediate & may take 6hrs or more after 1 st dose, so its necessary to continue vigorous O2 & bronchodilator therapy during this period. Majority of pts respond to corticosteroids but few may show little or no response. Side effects : -Local : Hoarseness & oropharyngeal candidiasis, these can be minimized by the use of spacing devise along with metered- dose inhaler & gargling with water after use. -Systemic : Long term use may result in osteoporosis, skin thinning & adrenal suppression.

34. Systemic corticosteroids Oral corticosteroids & steroid sparing agents -OCS: necessary in patients controlled by inhaled corticosteroids -Dose: Prednisolone started as single morning dose of 40-60mg/day orally, thereafter dose reduced by half every 6hrs. Methyl prednisolone 40-125mg every 6hrs. -Steroid sparing agents: Low doses of Methotrexate (15mg weekly) reduce dose of oral steroids. Cyclosporine also improves lung function in few steroid dependent asthmatics.

35. Parenteral corticosteroids -Corticosteroids used IV for the treatment of acute severe asthma -Dose: Hydrocortisone: Loading dose 4mg/kg IV followed by 2-3mg/kg every 6hrs Methyl prednisolone: 40-125mg every 6hrs Indications for corticosteroids in Asthma -Acute asthma which doesn’t respond to or even worsen despite bronchodilator therapy -Severe acute asthma(status asthmaticus )

36. Cromones (anti-inflammatory drugs) Inhibit degranulation of mast cells , preventing release of mediators Used as a prophylactic treatment of asthma(ex. Sodium cromoglycate , cromolynt , nedocromil & ketotifen ) Sodium cromoglycate : Administered as an inhalation. Useful in children with atopic asthma & few cases of non-atopic asthma. Nedocromil sodium: given as an inhalation 4mg 2-4 times daily Ketotifen : antihistaminic that inhibits release of mediators, useful in the prophylactic treatment at a dose 1-2mg BID orally(SE-drowsiness & weight gain)

37. Anticholinergics -Currently used anticholinergics are Ipratropium bromide & tiotropium . -administered as aerosol or in dry powder form. Ipratropium also given as nebulisation. - Use s: Patients with co-existent heart disease in whom methylxanthines & β₂ adrenoreceptor agonists causes significant tachycardia. - Dose : Ipratropium- two puffs of 20µg each QID/day, 250-500µg nebulisation Tiotropium - two puffs of 9µg each once a day - Side effects : Dryness of mouth & bitter taste.

38. Leukotriene modifiers Include leukotriene receptor antagonists ( montelukast , zafirlukast , pranlukast ) & 5-lipoxygenase inhibitors( Zileuton ) Uses : used as add-on therapy -who do not respond to the conventional agents -who require high doses of ICS Dose : Zafirlukast - 20mg BID Montelukast - 10mg once a dayin the evening Side effects : uncommon include headache, abdominal pain, skin rashes, angioedema, pulmonary eosinophilia & arthralgia. Zileuton may cause liver damage.

39. Anti- IgE -Monoclonal Antibodies - Omalizumab, recombinant humanized monoclonal antibody against IgE that neutralizes free circulating IgE without binding to cell-bound IgE . Inhibits IgE mediated reactions. -useful in patients with allergic asthma -Disadvantage: very expensive, 3-4mnth trial therapy to show objective benefit. -S/C injection once every 2-4weeks. -Side effects: very rarely produces anaphylaxis. Anti-TNF therapy (infliximab or etanercept ): beneficial in severe corticosteroid refractory asthma.

40. Miscellaneous -PPI used in symptomatic GERD & sub optimally controlled asthma. Bronchial Thermoplasty -Invasive procedure for severe asthma -controlled thermal energy is delivered to airway wall during a series of bronchoscopies. -Risks: Lung collapse, bleeding & additional breathing problems related to bronchoscope. -Benefits: Pt may use rescue inhalers less often & able to engage in strenuous physical activity than before.

41. General measures in Asthmatics Avoid: -opiates, sedatives & tranquilizers in acute ill patients with asthma β -blockers & parasympathetic agonists. - Expectorants & Mucolytic agents have no significant role. Prevention/treatment of exercise induced asthma Prevention of episode by inhalation of 2 metered doses of salbutamol or terbutaline a few minutes before exercise. Regular use of sodium cromoglycate or leukotriene modifiers is often needed. Assessment of Asthma control Features of controlled Asthma Daytime symptoms develop 2 times or less/week No limitation of daily activities including exercise No awakening in the night due to symptoms Need for short-acting β -agonists twice or less/week No exacerbations

42. Global Initiative for Asthma (GINA) severity Grades Assessment of Asthma control Complications of asthma Pneumonia Collapse of part or all of the lung Respiratory failure Status asthmaticus. Characteristics Controlled asthma Partly controlled asthma Uncontrolled asthma Daytime symptoms >twice/ wk No Any one or two Characteristics present Any 3 or > characteristics present Limitation of activities No Nocturnal symptoms No Need for rescue medicine >twice/ wk NO

43. Stepwise management of Chronic Asthma Step Management Step 1 (only for intermittent/less frequent symptoms) Short-acting inhaled β₂ -agonist as required(required in all steps) Step 2: Daily symptoms Regular inhaled preventer therapy Low-dose ICS up to 800µg daily or Leukotriene receptor antagonists Step 3: Severe symptoms Inhaled corticosteroids & long acting inhaled β₂ -agonist Continue inhaled low-dose ICS+ long acting β₂ -agonist or Medium or high dose ICS or Low-dose ICS + LTRA or Low-dose ICS + sustained release oral theophylline Step 4: Severe symptoms uncontrolled with high dose ICS High dose ICS & regular bronchodilators Medium or high dose ICS(up to 2000µg daily) + long acting β₂ -agonist May add LTRA May add sustained release oral theophylline Step 5: Severe symptoms deteriorating Regular oral corticosteroids Add oral corticosteroids(prednisolone 40mg daily) Consider anti- IgE ( Omaliumab ) Step 6: Severe symptoms deteriorating in spite of prednisolone Hospital admission

44. Stepwise management of Asthma GINA 2015 STEP1 STEP2 STEP3 STEP4 STEP5 Preferred controller choice Consider low-dose ICS Low dose ICS Low dose ICS/LABA Medium/High dose ICS/LABA Refer for add-on Rx eg . Anti IgE Other controller options - Leukotriene receptor antagonists Low dose theophylline Medium/high dose ICS Low dose ICS+LTRA (or+Theophylline) Add tiotropium High dose ICS+LTRA (or+Theophylline) Add tiotropium Add low dose OCS Reliever As needed short-acting beta2-agonist As needed short-acting beta2-agonist As needed SABA or low-dose ICS/formoterol As needed SABA or low-dose ICS/formoterol As needed SABA or low-dose ICS/formoterol

45. Acute severe asthma is the term used for an exacerbation of asthma that has not been controlled by the use of standard medication. Treatment at Home -Give high concentration of oxygen(40-60%) if available -Bronchodilator therapy: Nebulized salbutamol 5mg or terbutaline 10mg every 20min for 3 doses -Salbutamol/terbutaline through metered dose inhalers(4-8puffs with a spacer every 20min for 3 doses) followed by 4 to 8 puffs every 2-4hrs. -Corticosteroids: hydrocortisone succinate 200mg IV, oral prednisolone 60mg. -Admit to hospital if there is no response within 1hr or pt becomes drowsy Treatment of Severe Acute Asthma(Status Asthmaticus)

46. Management in Hospital -Initial assessment: take brief Hx, perform rapid examination & assess severity. -Administer high conc. Of oxygen(40-60%) Assessment of severity of Asthma Mild-moderate exacerbation FEV₁ of PEFR ≥50% Pt talks in sentences in one breath Pulse ≤120bpm SaO ₂ ≥ 90% Severe exacerbation FEV₁ of PEF ≤ 50% of predicted normal Pt talks in words or phrases but unable to complete a sentence in one breath Tachycardia: pulse ≥ 110bpm, pulsus paradoxus >25mm Hg RR ≥ 25breaths/min Loud wheezes or silent chest SaO ₂ <90% or PaO ₂ <60 mm Hg Life threatening asthma Exhaustion, confusion, drowsy or coma Silent chest, cyanosis or feeble respiratory effort Bradycardia or hypotension

47. Exacerbations of Asthma Increased symptoms, deterioration in lung function & an increase in airway inflammation. Precipitating factors: Viral infections, moulds, pollens & air pollution Treatment of Mild-moderate exacerbation - β₂ -agonists every 20min for 3 doses -Oral corticosteroids if no response - pt is reassessed every hour

48. Treatment of Severe Exacerbation -High concn of oxygen(40-60%) - Bronchodilators: -Nebulized(in oxygen) salbutamol(5mg) or terbutaline (10mg) or levosalbutamol (1.25-2.5mg) immediately & repeated after few minutes if no response - β₂ -agonist(SC or IV) in very sick pts - Terbutaline (0.25-0.5mg) SC or IV(0.1-10µg/kg/min) -Epinephrine (adrenaline) 0.2-0.5mg as 1:1000 solution SC every 20min - add nebulized ipratropium bromide 0.5mg to nebulized salbutamol 5mg/ terbutaline 10mg who don’t respond in 15-30min every 20min for 3 doses. -Aminophylline Iv Loading dose of 5mg/kg/ hr as an infusion to those who don’t respond to nebulized bronchodilators

49. Corticosteroids -Hydrocortisone sodium succinate 100mg IV then repeated 4-6hrly for 24hrs -Oral prednisolone 40-60mg of loading dose followed by 40-60mg/day in single or two divided doses for 2 weeks. Antibiotics indicated if there is respiratory infection If no improvement with above measures, endotracheal intubation & mechanical ventilation is indicated. -Indications for intubation: Cardiac or respiratory arrest, severe hypoxia( PaO ₂ <60 mmHg), hypercarbia (PaCO₂ >50mmHg), acidosis(pH <7.3). Non-invasive ventilation with continuous positive pressure of BiPAP machines & tight fitting mask used in cooperative & alert pts who have impending respiratory failure. Helium 70-80% with oxygen may be useful as it reduces airway resistance & improves efficacy of bronchodilators.

50. Drug Induced asthma Most common due to aspirin followed by ibuprofen, indomethacin, naproxen, phenylbutazone , mefenamic acid. Drugs that can cause bronchospasm: Adenosine, prostaglandin analogues, beta blockers, cholinergic drugs, streptomycin, pentazocine , penicillin Non-pharmacological agents: Tartrazine , sulphating agents Safe NSAIDS: Acetaminophen, sodium salicylate, choline salicylate, salicylamide , propoxyphene. Mechanism: decreased production of PGE2 & enhanced production of LTB4 Associations: Nasal polyps, vasomotor rhinitis, hyperplastic rhino sinusitis( Samter’s triad)

51. Aspirin induced Asthma: Cutaneous form-associated with urticaria & angioedema Respiratory form-resulting in rhinoconjunctivitis & bronchospasm Diagnosis: Bronchial challenge with Lysine-Aspirin Drug Rx of AIA: treat the underlying asthma & strict avoidance of aspirin & cross reacting NSAIDS

52. Hypersensitivity Pneumonitis(Extrinsic Allergic Alveolitis ) Immune lung disease that occur secondary to inhalational exposure to a variety of antigens leading to widespread diffuse inflammatory reaction in the alveoli & small airways(bronchioles) Pathogenesis -An immune mediated condition that develops in response to inhaled antigens that are small enough to deposit in distal airways & alveoli. -It involves T H 1 & T H 17 lymphocyte subsets.

53. Examples of Hypersensitivity pneumonitis Disease Sources of antigen Antigen Farming/food processing Farmer’s lung Grain, mouldy hay Thermophilic actinomycetes , fungus Bagasssosis Sugarcane Thermophilic actinomycetes Mushroom worker’s lung Mushroom Thermophilic actinomycetes , spores Coffee worker’s lung Coffee beans Coffee bean dust Malt worker’s lung Aspergillus species (clavatus) Mouldy barley Miller’s lung Infested wheat flour Sitophilus granaries Tobacco grower’s lung Tobacco Aspergillus species Birds & other animals Bird fancier’s lung Avian droppings Protein in avian excreta, feathers Other occupational & environmental exposures Humidifier fever & air conditioner lung Humidifiers & air conditioners Several microorganisms Wood worker’s lung Wood dust Alternaria species

54. Clinical features Depend on type, intensity & duration of exposure to offending agent. Clinical forms: -Most of the patients (80-95%) are non-smokers Acute form Onset: 4-8hrs following exposure to the causative agent Symptoms: fever, chills, cough & malaise. resolution: resolve within hrs to days if there is no further exposure Subacute form Onset of respiratory symptoms & systemic symptoms more gradual. Chronic form More gradual onset of symptoms than subacute form with progressive dyspnoea, cough, fatigue, weight loss & clubbing of the fingers. Complications: long-standing disease leads to diffuse pulmonary interstitial fibrosis, pulmonary hypertension resulting in cor-pulmonale

55. Investigations Chest x-ray : may show diffuse micronodular shadowing particularly in upper zones, advanced cases show honeycomb lung HRCT: reticular & nodular changes with ground glass opacity Blood: raised ESR & neutrophilia Lung function tests: shoe a restrictive ventilatory defect. Bronchoscopy with BAL: increased T lymphocytes & granulocytes. Most often CD4:CD8 ratio <1 Lung biopsy: show chronic inflammatory cells, ill-defined non- caseating granulomas & fibrosis in late stages. Provocation test: 4-10hrs after exposure to the inhaled antigen, respiratory or systemic findings(fever, leucocytosis), reduced diffusing capacity, diminished VC, increased radiographic abnormalities , worsening alveolar-arterial oxygen pressure suggests a positive response.

56. Treatment Prevention: identification & avoidance of the offending agent Corticosteroids: some role in subacute & chronic forms. - Prednisolone 1mg/kg/day orally for 1-2weeks followed by gradual tapering over the next 4-6 weeks, not useful in established fibrosis Oxygen therapy: in severely hypoxemic individuals.

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