Hypersensitivity Pneumonitis

(HP)

By : ziba Loukzadeh, M.DOccupational Medicine

departmentYazd 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 agentsBacteria

-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 thermoactinomycet

Bagassosis Bagass worker

Moldysugarcane

thermoactinomycet

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 -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

feverFever Yes Yes

Flu-like syndrome

Yes Yes

Cough Expected Not necessary

Dyspnea Yes Not typically

Chest exam Rales normal

Comparison HP& Inhalation fever

(cont´)Feature HP Inhalation

feverCXR Alveolar

infiltrationNo

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%)

HRCTGround glass Centrilobular nodules Airspace consolidation Mosaic pattenFibrosis 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

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