Hypersensitivity Pneumonitis DR S H HASHEMI 1 INTRODUCTION

Hypersensitivity Pneumonitis DR. S. H. HASHEMI 1

INTRODUCTION § HP known as extrinsic allergic alveolitis § Granulomatous, interstitial, bronchiolar and alveolar-filling lung diseases § Caused by repeated exposure and subsequent sensitization to a variety of organic and chemical antigens. 2

ETIOLOGY q. Three main categories: Ø Microbial agents § Bacteria § Farmer’s lung § Bagassosis § Mushroom worker’s lung § Fungi § Wood pulp worker’s lung § Cheese washer lung § Ameba § Humidifier lung ØAnimal proteins Ø Chemicals §Avian proteins § Isocyanate § Bird breeder’s lung § TDI, MDI, HDI §Urine, Serum, Pelts § TMA § Animal handler’s § Trimellitic lung anhydride §Wheat weevil lung 3

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PATHOGENESIS q Immunology: § Cell-mediated immunity § Repeated inhalation of antigens → sensitization → immunology response(type III, IV) → influx of neutrophiles → shift T lymphocytes (~70%)(predominantly of CD 8)(↓CD 4/CD 8 ) § BAL → activated T lymphocytes § Lung biopsy: § Interstitial mononuclear cell infiltration § Granulomatous inflammatory response § Antibodies in HP are Ig. G class 5

PATHOGENESIS. . . q Host factors: § Host susceptibility or resistance factors may influence individual responses to inhaled antigens. § Non smokers > smokers § No association with HLA q Exposure factors: § § § Ag concentration Duration of exposure Frequency & intermittency of exposure Particle size Use of respiratory protection § Farmer's lung disease: winter § Bird breeder's lung: summer 6

CLINICAL FEATURES q. Acute HP: § Fever , chills , myalgia , cough , dyspnea (4 -12 h after heavy exp. ) § Ph/E : basilar rales , peripheral leukocytosis § Recurrent febrile episodes (most frequent presentation) 7

CLINICAL FEATURES. . . q. Subacute and chronic HP: § Temporal relationship between symptoms and exposure is difficult to elicit. § Insidious onset of respiratory symptoms § Non-specific systemic symptoms § Malaise, fatigue, weight loss, cough, dyspnea, low grade fever § Ph/E: normal or basilar crackles & wheezing § End-stage disease: cyanosis & right-sided HF 8

L/D § § § ↑ ↑ ↑ Specific Ig. G ( no sensitive , no specific ) ESR & CRP Ig. M , Ig. A, Ig. G ACE ANA 9

PFT § There is no single characteristic pattern of pulmonary function abnormalities. § Acute HP : restrictive pattern § Subacute and chronic HP : air way obstruction or mixed § ↓ DLCO (most sensitive physiologic test in early HP ) § Methacholine challenge test : increased non-specific bronchial hyper-reactivity 10

CXR q Acute HP: § Diffuse ground glass opacification § Fine nodular or reticulonodular pattern( lower lung field) § Consolidation ( rarely ) q Subacute HP: § Reticulonodular pattern q Chronic HP: § § § Fibrosis with upper lobe retraction Reticular opacity Volume loss Honeycombing Mediastinal lymphadenopathy (up to 50%) 11

Ground glass pattern § Most common in acute HP (but may also be seen in subacute and chronic HP) § Middle lung zone § PFT: restrictive , ↓DLCO § May resolve with removal from exposure 12

Acute HP: pigeon breeder’s lung shows ground-glass haziness and associated air-trapping 13

Airspace consolidation § Only reported in acute HP § Bilateral ill-defined areas of consolidation 14

Subacute HP: bilateral alveolar and reticular pattern 15

Centrilobular nodules § Round, poorly defined, less than 5 mm in diameter § Typically centrilobular § Profuse throughout the lung, but a middle to lower lung zone predominance. § Most frequent HRCT finding in HP § Centrilobular nodules + ground glass opacification are highly suggestive for HP. § PFT : normal 16

Fibrosis § § Chronic HP (subacute HP) Irregular linear opacities Traction bronchiectasis Honeycombing 17

Emphysema § Chronic HP § Emphysema occurred more commonly than fibrosis in chronic farmer’s lung. 18

Chronic HP: upper lobe fibrosis 19

Chronic HP: farmer’s lung disease showing bibasilar end-stage fibrosis 20

HRCT § § § Sensitivity of HRCT is significantly better than CXR Ground glass Centrilobular nodules Fibrosis Emphysema Mediastinal lymphadenopathy (> 20 mm ) 21

§Centrilobular ground-glass nodules uniformly distributed throughout the lung. Lobular air-trapping also frequently present. 22

Multiple low density ill-defined centrilobularnodules 23

§Extensive areas of grand-glass attenuation. Decreased perfusion (arrows)representing associated air-trapping. 24

Chronic HP: Honeycombing, intralobular and septal fibrosis, architectural distorsion 25

Mosaic pattern § Patchwork of regions of differing attenuation § Due to patchy areas of ground glass or airtrapping 26

Histopathology § Classic triad: § Cellular bronchiolitis § Lympho-plasmocytic interstitial infiltration § Non-necrotizing granulomas 27

Diagnosis Ø Temporal relationship between symptoms and certain activities is often the first clue to the diagnosis of HP 28

Diagnostic criteria q Required § § Appropriate exposure Dyspnea on exertion Inspiratory crackles Lymphocytic alveolitis q Supportive Recurrent febrile episodes Infiltration on CXR Decreased DLCO Precipitating antibodies Granulomatous on lung biopsy § Improvement with contact avoidance § § § 29

DDx 30

Comparison HP& Inhalation fever 31

Comparison HP& Inhalation fever. . . 32

Comparison HP& Inhalation fever. . . 33

PROGNOSIS § The clinical course of HP is variable § Acute HP generally resolves without sequelae § But progressive impairment may occur with recurrent attacks or with a single severe attack. § Subacute or chronic forms of HP present with insidious symptoms § More subtle clinical abnormalities § Frequently recognized later in the disease course § Long-term mortality rates for patients with chronic HP range from 1% to 10%. 34

Prognostic factors § Age § Duration of exposure after onset of symptoms § Time of exposure prior to diagnosis 35

TREATMENT § Cornerstone of therapy → removal from exposure § Respirators are used when removal from exposure is impossible. § Oxygen (hypoxemic patients) § Airflow limitation: § Inhaled steroids § β-agonists § Oral corticosteroids (40– 60 mg/day of oral prednisone) in severe or progressive disease. § In refractory cases: § Cyclophosphamide & Azathioprine 36

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