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

2. 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

3. Etiology Microbial agents Animal proteins
Low molecular weight chemicals

4. 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

5. 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

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

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

8. 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

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

10. 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

11. 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

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

13. 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

14. 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

15. 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

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

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

18. 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%)

19. HRCT Ground glass Centrilobular nodules Airspace consolidation
Mosaic patten
Fibrosis
Emphysema

21. Normal CXR

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

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

30. 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

31. 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

32. 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