1. Hypersensitivity Pneumonitis
DR.S.H.HASHEMI

2. 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.

3. 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

5. 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

6. 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

7. 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)

8. 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

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

10. 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

11. 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%)

12. 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

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

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

15. Subacute HP: bilateral alveolar and reticular pattern

16. 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

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

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

19. Chronic HP: upper lobe fibrosis

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

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

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

23. Multiple low density ill-defined centrilobularnodules

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

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

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

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

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

29. 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

30. DDx

31. Comparison HP& Inhalation fever

32. Comparison HP& Inhalation fever . . .

33. Comparison HP& Inhalation fever . . .

34. 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%.

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

36. 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