Hypersensitivity Pneumonitis (HP) By : ziba Loukzadeh, M.D Occupational Medicine department Yazd University of Medical Sciences

Definition Immune (hypersensitive) response 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 Microbial agents Animal proteins Low molecular weight chemicals

Microbial agents Bacteria Fungi Ameba -Bagassosis -Farmer’s lung -Bagassosis -Mushroom worker’s lung Fungi -Wood pulp worker’s lung -Cheese washer lung Ameba -Humidifier lung

Bacteria cause occupation Agent source Major antigen Farmer's lung Agriculture worker Moldy hay thermoactinomycet Mushroom worker's Mushroom worker Compost Bagassosis Bagass worker Moldy sugarcane

Animal proteins Avian proteins : Bird breeder’s lung Urine ,Serum ,Pelts : Animal handler’s lung Wheat weevil : Wheat weevil lung

Chemicals Isocyanate HP TDI , MDI , HDI TMA HP Trimellitic anhydride

Pathogenesis Immunology Repeated inhalation of antigens sensitization immunology response(type III,IV) influx of neutrophiles shift T lymphocytes (~70%)(predominantly of CD8) Antibodies in HP are IgG class Response delay by 3-8 hours

Pathogenesis (cont’) Host factors -Polymorphism in TNF-α gene -Non smokers > smokers -Polymorphism in TNF-α gene -No association with HLA

Pathogenesis (cont’) Exposure factors: -Ag concentration -Duration of exp. -Frequency & intermittency of exp. -Particle size -Use of respiratory protection Farmer's lung disease: winter Bird breeder's lung: summer Indirect exposure

Clinical features Acute HP : fever ,chill ,myalgia ,cough & dyspnea + basilar rales in Ph/E (4-12 h after heavy exp. ) Recurrent febrile episodes (most frequent presentation) Subacute & chronic HP : insidious onset of respiratory symptoms ,malaise , fatigue , weight loss + basilar rales ,wheezing cyanosis ,right sided HF in Ph/E

DDx Inhalation fevers others granulomatous disorder(Sarcoidosis) immunologic disease (Asthma) infection fibrotic lung disease (IPF)

Comparison HP& Inhalation fever Feature HP Inhalation fever Example Farmer`s lung disease Metal fume fever Etiology Thermoactinomyces Zinc fume fever pathophysiology Hypersensitive reaction Cytokine- mediated (??) Exposure dose Low dose High dose Sensitization required Yes No

Comparison HP& Inhalation fever (cont´) Feature HP Inhalation fever Fever Yes Flu-like syndrome Cough Expected Not necessary Dyspnea Not typically Chest exam Rales normal

Comparison HP& Inhalation fever (cont´) Feature HP Inhalation fever CXR Alveolar infiltration No PFT Decreased DLCO&volums Minimal change BAL Lymocytosis Inincreased Neutrophiles Chronic sequle ~yes None Natural Hx Reccurent or progressive Complete recovery within 3 day

Lab. studies Precipitin Ab: Helpful but not specific, not sensitive, not hallmark Leukocytosis ,mild elevation of ESR ,CRP , IgG , IgA ,IgM ,ACE ,ANA

PFT Normal (early dis.) Restrictive Obstructive Mixed decreased DLCO (most sensitive physiologic test in early HP )

CXR Acute : diffuse ground glass ,fine nodular or reticulonodular pattern (lower lung ) Subacute : reticulonodular pattern Chronic : fibrosis ,reticular opacity, honey combing mediastinal lymphadenopathy (up to 50%)

HRCT Ground glass Centrilobular nodules Airspace consolidation Mosaic patten Fibrosis Emphysema

Normal CXR

Histopathology Classic triad : cellular bronchiolitis lymphoplasmocytic interstitial infiltration non-necrotizing granuloma

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

diagnosis environmental history: pets and other domestic animals hobbies such as gardening and lawn care recreational activities, for example, use of hot tubs and indoor swimming pools use of humidifiers, cool mist vaporizers, and humidified air conditioners moisture indicators such as leaking, flooding, or previous water damage to carpets and furnishings

Diagnostic criteria Required appropriate exposure Supportive dyspnea on exertion inspiratory crackles lymphocytic alveolitis Supportive recurrent febrile episodes infiltrative on CXR decreased DLCO precipitating antibodies granulomatous on lung biopsy improvement with contact avoidance

Treatment Best treatment : Removal from exp. Preferred approach : Elimination of Ag. Oral corticosteroid : in severe or progressive disease O2 ,inhaled steroid & B-agonist in airflow limitation