Presentation by S.K Jindal on Hypersensitivity Pneumonitis: Approach to diagnosis | Jindal Chest Clinic

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
SurinderK. Jindal
(Emeritus-Professor PulmMed, PGIMER, Chandigarh)
Medical Director, JindalClinics, Sec 20 D, Chandigarh
www.jindalchest.com

2. Agenda
•Introduction
•Epidemiology
•Immuno-pathogenesis
•ClinicalFeatures
•Diagnosis
•ImmunoCAP™forspecificIgG–HPPanel

3. Hypersensitivity Pneumonitis
•HypersensitivityPneumonitis(HP)orextrinsicallergicalveolitisisacomplex
groupofimmunologically-mediatedalveolarandinterstitiallungdisorderscaused
byrepeatedinhalationofanairborneallergen.
•Severaldifferentkindsofenvironmental,occupationalandrecreationalorganic
antigens,andlow-molecularweightchemicalagentsareresponsible
•Occursinaperson
i.Previouslysensitizedbyexposuretotheantigen;
ii.Doesnotdependontheconstitutionalmakeup
ii.Developspredominantlyinnon-atopicpersonswhobecomesensitizeddueto
repeatedexposure.

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
•ThepathogenesisofHPiscomplexandforallthreeclinicalphenotypes.
Thereare3essentialcomponentsofdiseasedevelopment:
i.Repeatedantigenexposure,
ii.Immunologicsensitizationofthehosttotheantigen,and
iii.Immune-mediateddamagetothelung.

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
•AcuteHP:Characterizedbydiffusealveolardamagewithnecrosis.Thereisanacute
inflammatoryinfiltrate.
•Subacuteformisbestdescribedfromapathologicalviewpoint,characterizedbytheirregular
areasofpatchyconsolidationwithacentriacinardistribution.Thereareinterstitial
lymphocyticinfiltrates,cellularbronchiolitisandlooselyformednon-necrotizinggranulomas.
Thesmallandpoorlycircumscribedgranulomasconsistoftheaggregatesoflymphocytes,
plasmacells,macrophagesandmultinucleatedgiantcells.Presenceofeosinophilsand
neutrophilsisnotcharacteristic.
•ChronicH.P.InterstitialfibrosiswithhoneycombchangesintheThesechangesaresimilar,
irrespectiveofthecausativeantigens.

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
acinarregions of lungs.
Involvement of air spaces , vessels, airways,
?pleura -i.e. diffuse involvement ILDis a
general category that includes many
different lung conditions.
Ch HP is an important cause of ILD –
frequently resembles IIPs or UIPType 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
•TheworldwideprevalenceofHPisunknown.
•Incidence,prevalence,andattackratesvarywidelyanddependonthepopulations
studied,thenatureandintensityofantigenexposure,thecasedefinitionchosen.
•InEurope,HPconstitutes4%to13%ofallinterstitiallungdiseases.
•EpidemiologicstudiesofagriculturalworkersandbirdfancierssuggestthatHPis
quitecommoninsomehigh-riskoccupationalsettings.
•AvianproteinsarethemostcommonantigenassociatedwithHPinthe
pediatricpopulation.

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
•SpecificagentsthatcauseHPcansimplybeorganizedintothreemajorcategoriesof
causalantigens:
Microbialagents,animalproteins,andlow-molecular-weightchemicals
200 plus
Causative
Agents trigger
HP
Causative
Agents found in
India

15. Birds as a cause of HP
•Flyingbirdssuchaspigeonsandparakeetsproducethelargestamountofbloom
andarethebirdsmostoftenassociatedwithHP
•Extremelypotentinducersofimmunologiclungdisease
•Theseantigenscanalsobehighlyresistanttodegradation
•Evenwithextensivecleanupfollowingremovalofbirdsfromindoorenvironments,
antigenexposuremaypersistformonthstoyears,perhapsexplainingthelackof
improvementinsomepatientswiththisformofHP
•Antigenicsimilarityacrossvariousbirdspeciesmandatesathoroughremovalofall
birdandfeatherproductsforapatientwithbirdfancier’slung.

16. DIAGNOSIS of
Hypersensitivity Pneumonitis

17. Clinical Features
•Acutecondition:fever,chills,dyspnea,myalgias,arthralgias,headache,coughandchest
tightness,4to8hoursfollowingaheavyexposuretotheantigens.Thesymptomspeakin6to
24hoursfollowingtheexposure.Generally,theattackisself-limitedandresolvesin1to3
days,followingremovalofthepatientfromthesourceofantigens.
•Thecontinuedexposureresultsinthepersistenceofsymptoms.
•Physicalexaminationusuallyrevealsthepresenceoffever,tachypneaandbi-basilarcrackles.
•SubacuteHP.Slowlyprogressivesymptomatology-Discreteattacksofsymptomsfollowing
heavyantigenexposure;clinicalfeaturesdevelopinsidiouslyoveraperiodofweeks;Cough
anddyspneaareprominent;acutepresentationifexposurepersists.
•ChronicHP:PresentsasachronicILD

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.
HRCTshows 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
Skintestsdemonstrateimmediateordelayedtypeofhypersensitivityagainstthesuspectedantigens.oftenthere
arenonspecificreactions.
Inhalationchallengetestsforsuspectedantigensmaybehelpfulinconfirmingthediagnosis.
Bronchoalveolarlavage(BAL)fluidshowsthepresenceofneutrophilsinitially,laterreplacedbylymphocytes
(CD8
+
lymphocytes)
DuringacuteHP,thereisincreaseinerythrocytesedimentationrateandtheinflammatorymarkers,suchasthe
C-reactiveprotein.BALlymphocytosismaypersistforalongperiodoftimeafterremovalofantigen
exposure.
LungbiopsiesfrompatientswithchronicHP:Chronicinterstitialinflammationwithinfiltrationofplasma
cells,macrophagesandlymphocytesfoundadjacenttothebronchioles.Therearepoorlyformed,
noncaseatinggranulomaswithoutanynecrosis.Theremaybebronchiolitis,bronchiolitisobliteransand
sometimeswithorganizingpneumonia.Inaddition,therearevaryingdegreesofinterstitialfibrosis.
Transbronchiallungbiopsiesmayfailtoprovidesufficientmaterialforthehistopathologicstudy,openlung
biopsyispreferredinsuchasituation.

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
•Lungfunction–PFT
•Imagingstudies–CXRandHRCT
•BronchoalveolarLavage
•OtherIncludes:
•CRP,ESR
•SpecificIgGlevels
•Rheumatoidfactor
•Antinuclearantibodiesetc.

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 –
30mg
A/l
1,2
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 mg
A/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.Penicilliumchrysogenum(P. notatum)
2.Cladosporiumherbarum
3.Aspergillusfumigatus
4.Mucorracemosus
5.Alternariaalternata
Fungi
Animal Proteins

25. Summary
•HypersensitivityPneumonitisisacomplexofimmunologically-mediatedlung
disorderscausedbyrepeatedinhalationofanairborneallergen.
•Severaldifferentkindsofenvironmental,occupationalandrecreationalorganic
antigens,andlow-molecularweightchemicalagentsareresponsible.
•Acuteallergicalveolitisdevelopsfromexposuretohighconcentrationofantigen;
repeatedexposuretosmalleramountsislikelytocausechronicdisease.
Thefollowingfeaturesaremosthelpfulfordiagnosis:
–SymptomsafterexposuretoapotentialHPantigen,
–PositiveantibodytestingtotheoffendingantigenwithImmunoCAP™
HypersensitivityPneumonitisPanel

26. THANK YOU