Hypersensitivity pneumonitis is an immune system disorder causing lungs to become inflamed due to allergic reactions to inhaled microorganisms, plant and animal proteins, or chemicals. In this presentation "Hypersensitivity Pneumonitis" has been described including their Causes, Diagnosis, Management, etc. For more information, please contact us: 9779030507.

1. Hypersensitivity Pneumonitis:
Approach to diagnosis
Surinder K. Jindal
(Emeritus-Professor Pulm Med, PGIMER, Chandigarh)
Medical Director, Jindal Clinics, Sec 20 D, Chandigarh
www.jindalchest.com

2. Agenda
• Introduction
• Epidemiology
• Immuno-pathogenesis
• Clinical Features
• Diagnosis
• ImmunoCAP™ for specific IgG – HP Panel

3. Hypersensitivity Pneumonitis
• Hypersensitivity Pneumonitis (HP) or extrinsic allergic alveolitis is a complex
group of immunologically-mediated alveolar and interstitial lung disorders caused
by repeated inhalation of an airborne allergen.
• Several different kinds of environmental, occupational and recreational organic
antigens, and low-molecular weight chemical agents are responsible
• Occurs in a person
i. Previously sensitized by exposure to the antigen;
ii. Does not depend on the constitutional makeup
ii. Develops predominantly in non-atopic persons who become sensitized due to
repeated exposure.

4. Acute vs. Chronic forms
• Acute allergic alveolitis develops from exposure to high concentration of antigen;
repeated exposure to smaller amounts is likely to cause chronic disease.
• The bacterial and fungal antigens found in the internal environment offer ideal
circumstances for their proliferation.
• HP induced by chemicals is relatively less common, compared to those induced by
microbial and animal proteins. Isocyanates such as toluene diisocyanate (TDI),
diphenylmethane diisocyanate (MDI), hexamethylene diisocyanate (HDI) and 1,5
naphthalene diisocyanate (NDI), used in the production of polyurethane polymers,
are the commonly reported chemicals responsible for HP.

5. Exposure Antigens Diseases
• Mouldy hay Th actinomycetes Farmer’s lung
• Mouldy bagasse Th actinomycetes Bagassosis
• Mouldy compost Mushroom
& mushroom Th actinomycetes worker’s dis
• Contaminated barley Aspergi clavatus Malt worker’s lung
• Compost Aspergillus spp. Compost lung
• Esparto grass Aspergillus spp. Esparto dust lung
• Soy sauce brewing Aspergillus spp. Soy sauce lung
• Contaminated
humidifiers, air Th actinomycetes Ventilator lung
conditioners,
heating systems
• Domestic birds Bird proteins Bird fancier’s lung
• Pigeon droppings Serum, feathers, droppings Pigeon breeder’s dis
• Parakeets Serum, feathers, droppings Budgerigar fancier’s

6. Exposure Antigens Diseases
• Silkworm larvae Silkworm larvae proteins Sericulturist’s lung
• Grains Grain weevil Grain lung
• Isocyanates Altered proteins H. pneumonitis
• Wood cutting Plant protein Woodman’s disease
• Contaminated
metal working fluid Pseudomonas spp Machine operator’s
• Detergent enzymes Bacillus subtilis Detergent worker’s
(washing powder lung)
• Contaminated Cladosporium spp,
basement Penicillium spp Basement lung
• Contaminated
hot tub water Myco avium complex Hot-tub lung
• House dust Trichosporum asahii Japanese summer
House dust H.P

7. Pathogenesis
• The pathogenesis of HP is complex and for all three clinical phenotypes.
There are 3 essential components of disease development:
i. Repeated antigen exposure,
ii. Immunologic sensitization of the host to the antigen, and
iii. Immune-mediated damage to the lung.

8. Pathogenesis –Delayed sensitivity
• The sensitization results from an earlier exposure to antigen (organic dust). Following an
intense re-exposure to such an antigen, there is interaction of the antigen and the “memory”
system. There is formation of precipitins and complement fixing antibodies and they form
immune complex aggregates of antigen-antibody
• The demonstration of precipitins and a delay of three-to-eight hours before the onset of
symptoms following exposure to the antigen suggest that the pulmonary and systemic
disturbances are as a result of an immune complex-mediated Arthus reaction. The immune
complexes are not demonstrable in the alveolar septa or in the granuloma.
• A delayed type hypersensitivity reaction also responsible for the development of chronic
disease- presence of a higher proportion of lymphocytes in the bronchopulmonary lavage
fluid

9. Pathology
• Acute HP: Characterized by diffuse alveolar damage with necrosis. There is an acute
inflammatory infiltrate.
• Subacute form is best described from a pathological view point, characterized by the irregular
areas of patchy consolidation with a centriacinar distribution. There are interstitial
lymphocytic infiltrates, cellular bronchiolitis and loosely formed non-necrotizing granulomas.
The small and poorly circumscribed granulomas consist of the aggregates of lymphocytes,
plasma cells, macrophages and multinucleated giant cells. Presence of eosinophils and
neutrophils is not characteristic.
• Chronic H.P. Interstitial fibrosis with honeycomb changes in the These changes are similar,
irrespective of the causative antigens.

10. Clinical Features: Chronic HP
• In chronic condition, the level of antigen exposure is generally much lower and persistent.
• Respiratory manifestations develop slowly over months or years without any discrete attack
suggesting the antigen as an offending agent. Presents as an Interstitial Lung Disease (ILD)
• Signs & Symptoms:
- Increasing breathlessness,
- Nonproductive cough
- Fever is usually absent.
Examination reveals the presence of tachypnea and bibasilar crackles. Digital clubbing is
uncommon.

11. HP as an ILD
Inflammation, damage and fibrosis in the
acinar regions of lungs.
Involvement of air spaces , vessels, airways,
?pleura - i.e. diffuse involvement ILD is a
general category that includes many
different lung conditions.
Ch HP is an important cause of ILD –
frequently resembles IIPs or UIP
Type II Alveolar Cell
Type I Alveolar Cell
Alveolar Space
ce
Alveolar Space
Alveolar Space
ce
Alveolar Space
Interstitium
 Fibroblasts
 Capillaries
 Collagen and elastic fibres
 Smooth muscle
 Lymphatics
 Alv. Epithelium
 Capillary endothelin

12. Epidemiology of HP - ILD
• The worldwide prevalence of HP is unknown.
• Incidence, prevalence, and attack rates vary widely and depend on the populations
studied, the nature and intensity of antigen exposure, the case definition chosen.
• In Europe, HP constitutes 4% to 13% of all interstitial lung diseases.
• Epidemiologic studies of agricultural workers and bird fanciers suggest that HP is
quite common in some high-risk occupational settings.
• Avian proteins are the most common antigen associated with HP in the
pediatric population.

13. Prevalence of HP in India
Singh S et al. Interstitial Lung Disease in India. Results of a Prospective Registry. AJRCCM 2016

14. Causative Agents
• Specific agents that cause HP can simply be organized into three major categories of
causal antigens:
Microbial agents, animal proteins, and low-molecular-weight chemicals
200 plus
Causative
Agents trigger
HP
Causative
Agents found in
India

15. Birds as a cause of HP
• Flying birds such as pigeons and parakeets produce the largest amount of bloom
and are the birds most often associated with HP
• Extremely potent inducers of immunologic lung disease
• These antigens can also be highly resistant to degradation
• Even with extensive cleanup following removal of birds from indoor environments,
antigen exposure may persist for months to years, perhaps explaining the lack of
improvement in some patients with this form of HP
• Antigenic similarity across various bird species mandates a thorough removal of all
bird and feather products for a patient with bird fancier’s lung.

16. DIAGNOSIS of
Hypersensitivity Pneumonitis

17. Clinical Features
• Acute condition: fever, chills, dyspnea, myalgias, arthralgias, headache, cough and chest
tightness, 4 to 8 hours following a heavy exposure to the antigens. The symptoms peak in 6 to
24 hours following the exposure. Generally, the attack is self-limited and resolves in 1 to 3
days, following removal of the patient from the source of antigens.
• The continued exposure results in the persistence of symptoms.
• Physical examination usually reveals the presence of fever, tachypnea and bi-basilar crackles.
• Subacute HP. Slowly progressive symptomatology - Discrete attacks of symptoms following
heavy antigen exposure; clinical features develop insidiously over a period of weeks; Cough
and dyspnea are prominent; acute presentation if exposure persists.
• Chronic HP: Presents as a chronic ILD

18. Chest Radiology
• The chest radiograph may be normal especially if obtained during an asymptomatic phase. In an
established and symptomatic case, the radiograph shows the presence of patchy or diffuse
infiltrates.
Acute HP: Fine micronodular pattern or diffuse patchy ground-glass opacity. These shadows
resolve completely following cessation of exposure. HP is not associated with pleural effusions
or thickening, and hilar or mediastinal lymphadenopathy. HRCT is highly sensitive than the
plain chest radiographs; characteristically shows small, indistinct nodules, ground glass
infiltrates and air-trapping.
Subacute form: Small nodules and fine linear opacities.
Chronic HP: Advanced cases exhibit pulmonary fibrosis with linear interstitial opacities,
distortion, volume loss, and honeycombing. Predominantly noted in the upper lobes. There is
evidence of pleural effusion or thickening.
HRCT shows multiple, centrilobular nodules throughout the lung fields. Emphysematous
changes may also be seen

19. Pulmonary Function Tests
• Pulmonary function tests may be normal or show restrictive, or mixed restrictive
and obstructive defects.
• Acute HP: Restrictive defect with a decreased forced vital capacity, total lung
capacity and diffusion capacity. Mild obstructive defect may be seen due to
bronchiolitis obliterans. The diffusing capacity is generally decreased. Arterial
hypoxemia is evident especially after exercise.
• Subacute HP: PFT may be within normal limits.
• Chronic HP: Both restrictive and obstructive defects. There is decreased diffusion
capacity and hypoxemia.
• HP should be considered in differential diagnosis in nonsmoking individuals
presenting with airflow limitation.

20. Other tests: Skin tests, BAL, Bx
Skin tests demonstrate immediate or delayed type of hypersensitivity against the suspected antigens. often there
are nonspecific reactions.
Inhalation challenge tests for suspected antigens may be helpful in confirming the diagnosis.
Bronchoalveolar lavage (BAL) fluid shows the presence of neutrophils initially, later replaced by lymphocytes
(CD8+ lymphocytes)
During acute HP, there is increase in erythrocyte sedimentation rate and the inflammatory markers, such as the
C-reactive protein. BAL lymphocytosis may persist for a long period of time after removal of antigen
exposure.
Lung biopsies from patients with chronic HP: Chronic interstitial inflammation with infiltration of plasma
cells, macrophages and lymphocytes found adjacent to the bronchioles. There are poorly formed,
noncaseating granulomas without any necrosis. There may be bronchiolitis, bronchiolitis obliterans and
sometimes with organizing pneumonia. In addition, there are varying degrees of interstitial fibrosis.
Transbronchial lung biopsies may fail to provide sufficient material for the histopathologic study, open lung
biopsy is preferred in such a situation.

21. Serum Antibodies
• Exposure to an antigen is confirmed by the presence of elevated titers of serum
antibodies (IgG, IgM and IgA). They can be demonstrated by utilizing ELISA,
indirect immunofluorescence, complement fixation, latex agglutination or agar-
diffusion methods.
• The presence of antibody merely indicates the occurrence of exposure and
sensitivity and not necessarily the disease.
• The serum antibodies tend to disappear following the cessation of exposure to
antigen.
• Several different cytokines involved in the disease pathogenesis have been
demonstrated to rise in HP. At present, they have no role in the diagnosis or clinical
assessment of disease.

22. Diagnosis of
HP
• Lung function – PFT
• Imaging studies – CXR and HRCT
• Bronchoalveolar Lavage
• Other Includes:
• CRP, ESR
• Specific IgG levels
• Rheumatoid factor
• Antinuclear antibodies etc.

23. ImmunoCAP™ specific IgG –Bird Fanciers hypersensitivity
Pneumonitis
Bird Fancier's
hypersensitivity
pneumonitis
Specific IgG
against Pigeon
serum proteins,
feathers and
droppings –
ImmunoCAP Ge91
Cut-off for IgG ImmunoCAP Ge91 –
30mgA/l1,2
Sensitivity Specificity
100% 84.62%
1. Khan S, Roy Chowdhury S, Ghosh S, Sengupta A, Ramasubban S, Sen D. Quantitation of avian IgG antibodies with clinico-
radiological tests in the diagnosis of Bird Fancier’s hypersensitivity pneumonitis. Pulmo Face. 2015 Nov 1;15:48.
2. Bhattacharyya P, Dasgupta S, Paul M, Saha D, Sengupta S, Bhattacharyya PP. High-resolution computerized tomography changes in
diffuse parenchymal lung disease from chronic hypersensitivity pneumonitis related to bird antigen. Lung India. 2018 May 1;35(3):215
Technical features ImmunoCAP Specific IgG
• Measuring range: 2.0–200 mgA/l
• Accurate and reproducible test results
• Large panel of standardized, high-quality allergens available

24. ImmunoCAP™ specific IgG
ImmunoCAP™ Hypersensitivity Pneumonitis Panel includes
1. Pigeon serum proteins, feathers
and droppings
1. Penicillium chrysogenum (P. notatum)
2. Cladosporium herbarum
3. Aspergillus fumigatus
4. Mucor racemosus
5. Alternaria alternata
Fungi
Animal Proteins

25. Summary
• Hypersensitivity Pneumonitis is a complex of immunologically-mediated lung
disorders caused by repeated inhalation of an airborne allergen.
• Several different kinds of environmental, occupational and recreational organic
antigens, and low-molecular weight chemical agents are responsible.
• Acute allergic alveolitis develops from exposure to high concentration of antigen;
repeated exposure to smaller amounts is likely to cause chronic disease.
The following features are most helpful for diagnosis:
– Symptoms after exposure to a potential HP antigen,
– Positive antibody testing to the offending antigen with ImmunoCAP™
Hypersensitivity Pneumonitis Panel

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