Hypersensitivity Pneumonitis DR.S.H.HASHEMI

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.

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

PATHOGENESIS Immunology: Cell-mediated immunity Repeated inhalation of antigens → sensitization → immunology response(type III,IV) → influx of neutrophiles → shift T lymphocytes (~70%)(predominantly of CD8)(↓CD4/CD8 ) BAL → activated T lymphocytes Lung biopsy: Interstitial mononuclear cell infiltration Granulomatous inflammatory response Antibodies in HP are IgG class

PATHOGENESIS . . . Host factors: Exposure factors: Host susceptibility or resistance factors may influence individual responses to inhaled antigens. Non smokers > smokers No association with HLA 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

CLINICAL FEATURES 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)

Subacute and chronic HP: CLINICAL FEATURES . . . 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

L/D ↑ Specific IgG ( no sensitive , no specific ) ↑ ESR & CRP ↑ IgM , IgA, IgG ↑ ACE ↑ ANA

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

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

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

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

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

Subacute HP: bilateral alveolar and reticular pattern

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

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

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

Chronic HP: upper lobe fibrosis

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

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

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

Multiple low density ill-defined centrilobularnodules

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

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

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

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

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

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

DDx

Comparison HP& Inhalation fever

Comparison HP& Inhalation fever . . .

Comparison HP& Inhalation fever . . .

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%.

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

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