Hypersensitivity Pneumonitis

Extrinsic Allergic Alveolitis
Martha Burk MD, MS

Definition
“…a group of immunologically mediated lung diseases in which the repeated inhalation of certain finely dispersed antigens of a wide variety, mainly including organic particles or low molecular weight chemicals, provokes a hypersensitivity reaction with granulomatous inflammation in the distal bronchioles and alveoli of susceptible subjects”

Bourke et al Eur Respir J 2001

Epidemiology
 First recognized in grain workers in 1713  Prevalence difficult to assess
 Not

caused by a single etiologic agent  A complex syndrome varying in
Intensity  Clinical presentation
 Lack

of agreement on diagnostic criteria

Causative Antigens The Simple List
 Bacteria  Fungi  Animal proteins  Insect proteins  Amoebae  Chemicals  Medications  Soybean hulls

Causative Agent Source
Thermophilic actinomycetes Aspergillus Aureobasidium sp Alternaria sp Candida albicans Mixed ameba, fungi, bacteria Moldy hay, plant materials, compost Animal bedding Ubiquitous Contaminated water Wood, wood pulp Saxophone mouthpiece Cold mist and other humidifiers, air conditioners Metal working fluids Paints, plastics Plastics

Disease
Farmer’s Lung Dog house disease Sauna-taker’s disease Wood worker’s lung Sax lung Nylon plant Office worker’s Air conditioner’s lung Ventilation pneumonitis Machine operator’s lung Paint refinisher’s lung Chemical worker’s lung Plastic worker’s lung Epoxy worker’s lung Hard metal lung disease Berylliosis
Patel et al J Allergy Clin Immunol 2001

Bacteria, fungi Isocyanates Anhydrides

Cobalt Berylliosis

Worksite-related Agents Organic Antigens
Farmer’s lung

Antigen
Micropolyspora faeni
Aspergillus species Streptomyces albus Sacharopolyspora rectivirgula

Malt worker’s lung Wood worker’s lung

Aspergillus species Penicillium chrysogenum
Alternaria species Merulius lacrymans Saccharomonospora viridis Cryptostroma corticale Aureobasidium pullulans Wood dust

Cheese worker’s lung Sugar cane worker’s lung (Bagassosis) Detergent worker’s lung Cork worker’s lung Coffee worker’s lung Cotton worker’s lung (Bysinnosis) Wheat worker’s lung Metal worker’s lung

Penicillium casei Thermoactinomyces vulgaris Bacillus subtilis Penicillium frequentens Coffee bean dust Bract of cotton flower Wheat weevil Rapid growing mycobacteria
www.lungcancerfrontiers.com

Inorganic Antigens Associated with HP
Paints, resins, plastics Insulation, polyurethane Vineyard sprayer’s lung (fungicide) Pesticide/insecticide

Non-microbial
Diisocyanates Trimellitic anhydride Copper sulfate Pyrethrum

Home or Work-related Agents
Humidifier lung

Organic Antigens Microbial
Acanthamoebae castellani Acanthamoebae polyphaga Naegleria gruberi Thermoactinomyces candidus

Bird breeder’s lung (budgies, pigeons) Rodent handler’s lung Hot tub/spa lung

Bird droppings Urinary antigens, serum, pelts Mycobacterium avium complex

Inorganic Antigens Associated with HP
Polyurethane foam insulation

Non-microbial
Diisocyanates

How much antigen are we talking about?

Airborne Fungi In Industrial Environments
 Study of six industrial facilities  Poultry house  Swinery  Feed preparing and storing house at swinery  Grain Mill  Wooden panel factory  Organic waste recycling facility  Samples collected by multiple methods
Lugauskas et al Ann Agric Environ Med 2004

 Grain Mill  49 species of 20 fungal genera isolated

Penicillium, Aspergillus, Mucor, Alternaria, Cladosporium, Rhizopus and others

 Poultry House  31 species of 13 fungal genera

Aspergillus, Penicillium, Rhizopus, Trichophyton

 Swinery  33 species from 15 fungal genera

Aspergillus, Penicillium, Cladosporium, Zygomycetes

 Food processing and storing house  35 fungal species from 18 genera

Aspergillus, Zygomycetes, Staphylotrichum

 Wood panel factory  21 fungal species from 10 genera

Paecilomyces, Rhizopus*

 Organic waste recycling facility  40 fungal species from 21 genera

Penicillium, Aspergillus, Cladosporium, Geotrichum

Rhizopus cause of ODTS among wood trimmers

Inciting antigens are ubiquitous! So why doesn’t everyone exposed to these environments develop hypersensitivity pneumonitis?

Antigen Qualities
 Size
 1-5

microns, usually <3 microns  Inhaled into distal bronchial tree and alveoli
 Induce an IgG response
 IgE

sometimes formed as well

 Many are capable of stimulating the

complementary cascade
 Delayed

cellular response

Environmental Factors
 Antigen concentration  Duration of exposure  Frequency/intermittency of exposure  Particle size  Antigen solubility  Use of airway protection  Variability in work practice

Hypersensitivity pneumonitis: current concepts Eur Respir J 2001 18:81s-92s

Genetic Susceptibility
 Approximately 5-15% of exposed individuals develop

disease
  

~4% budgerigar’s fanciers ~8% pigeon breeders ~4% farmers

 Males affected > females  Familial forms of HP documented
 

No confirmed genetic factors May represent undetected common exposures

 Ethnicity may matter  Pigeon fancier’s disease worse in Mexican Americans compared with Caucasian Americans  Higher prevalence of HLA-DR7 in Mexican Americans  HLA-DPB1 associated with more severe disease in

beryllium exposure

Hypersensitivity pneumonitis: current concepts Eur Respir J 2001 18:81s-92s

Additional Factors
 Occurs more frequently in nonsmokers  Onset may be triggered by
 Non-specific  Infections

lung inflammation

Mycoplasma
– Case studies of HP development after Mycoplasma infection

Influenza A common in lower airways of patients presenting with acute HP

Inhibitory Effect of Nicotine
 Fewer inflammatory diseases in smokers  Sarcoidosis  Ulcerative colitis  Radiation pneumonitis  In vivo and in vitro experimental HP in rats

Nicotine associated with dose-dependent decreases in
 

Macrophage, lymphocytes and neutrophils IFN gamma, TNF

 Smokers develop fewer antibodies when exposed to

antigens

  

Yet, if they do develop HP
More insidious More chronic Worse prognosis
Blanchet et al Am J Resp Crit Care Med 2004

Occupational Respiratory Disease Surveillance
Sex Yr No. of Deaths Under-lying Cause (%) M 31 28 14 31 28 24 35 25 31 36 283 F 10 8 4 15 8 13 16 13 7 21 115 W 38 34 17 44 36 32 49 38 37 56 381 Race B 1 1 1 5 2 1 1 12 O 2 2 1 5 1524 2 2 2534 1 1 1 1 3 3 10 3544 1 1 2 1 3 1 2 11 Age Group (yrs) 4554 3 2 2 4 2 6 5 2 2 9 37 5564 8 4 2 7 5 4 7 6 3 5 51 6574 11 11 3 14 8 7 11 8 10 11 94 7584 15 11 7 14 12 14 16 14 17 19 139 85 + 2 5 1 5 9 5 6 7 6 8 54 Median Age (yrs)

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 TOTAL

41 36 18 46 36 37 51 38 38 57 398

63.4 72.2 77.8 52.2 75.0 62.2 76.5 71.1 63.2 64.9 67.1

73.0 73.5 72.5 71.5 76.5 75.0 73.0 76.0 78.5 74.0 74.0

Table 8-1. Hypersensitivity pneumonitis: Number of deaths by sex, race, and age, and median age at death, U.S. residents age 15 and over, 1990-1999
CDC National Instititute for Occupational Safety and Health

Hypersensitivity pneumonitis:

Number of deaths, crude and age-adjusted mortality rates, U.S. residents age 15 and over, 1979-1999

CDC National Instititute for Occupational Safety and Health

Immunopathogenesis
 Acute phase  Inhaled Ag binds IgG Ab  Macrophage activated and release IL-8, IL-6
   

Chemotactic for monocytes/macrophage Differentiation of CD4+ TH0 cells to TH1 cells Differentiation of B cells to plasma cells (IL-6) Maturation of CD8+ cells into cytotoxic cells

TH1 cells secrete TNF alpha -> fever

 Subacute phase  Macrophage develop into epithelioid cells and multinucleated giant cells  Lymphoid follicles with plasma cells develop in lesions  Chronic phase

Macrophage express TGF beta
 

Fibrosis Angiogenesis
Patel et al J Allergy Clin Immunol 2001

Ag

Memory cells
Stimulates

T cell
Activates

Cytotoxic cells

Lymphocyte
Stimulates

Helper cells

Chemokines

Lymphokines Ab formation

Over-expressed In rat models of HP

IFN gamma key to granuloma formation in mouse models

Opal and DePalo Chest 2000 Gudmundsson et al J Immunology 1998 Patel et J Allergy Clin Immunol 2001

Key Players In Fibrosis
Angiotensin II
TGF-β Macrophage TNF-α IL-1 Neutrophils

TGF-β TNF−α
Alveolar Epithelial Cell

Fibroblast
IFN-γ

Angiotensin II TGF-β

Lymphocyte

Fibroblast Proliferation Extracellular Matrix Formation

Clinical Features

Classification Systems
Classical
Acute

Boyd
Acute progressive

Cormier
Active

Selman
Active
Nonprogressive and intermittent

Subacute

Acute intermittent nonprogressive Nonacute Residual

Active
Progressive and intermittent

Chronic

Chronic
Progressive Nonprogressive

J Allergy Clin Immunol 1989;89:839

Clin Allergy 1982;12(suppl):53

Clin Pulm Med 1996;3:72

Interstitial Lung Disease
Schwarz, MI, King, TE Jr, (Eds) 4th Ed, Hamilton, BC Decker 2003 UpToDate

Acute
 Abrupt onset
        

 Clinical
Diffuse rales  Tachypnea  Central cyanosis

Cough Dyspnea Chest tightness Fevers Chills Malaise Myalgias Anorexia Nausea/vomiting

 Labs
Leukocytosis  Restrictive pattern on PFTs  Positive serum precipitins

 Sx 4-8 hrs after high level  Radiographs

exposure  Sx subside over hours -days

 Prognosis good

complete recovery in 7-10 days Kupeli, et al Postgrad Med 2003

1-5mm bilateral pulmonary nodules  Bilateral consolidation  Ground glass infiltrates

Non-neoplastic Disorders of the Lower Respiratory Tract 2002 American Registry of Pathology and the Armed Forces Institute of Pathology

Acute HP

London Southbank University@myweb.lsbu.ac.uk

www.emedicine.com

Differential Diagnosis Acute stage
        

Acute tracheobronchitis, bronchiolitis, pneumonia Acute endotoxin exposure Organic dust toxic syndrome Allergic bronchopulmonary aspergillosis Reactive airways dysfunction syndrome Acute Respiratory Distress Syndrome Aspiration pneumonitis Bronchiolitis obliterans organizing pneumonia Diffuse alveolar damage

Patel et al J Allergy Clin Immunol 2001

Subacute
 More insidious onset  Dyspnea  Cough  Occurs after weeks to  Exam  Diffuse rales  Hypoxia  Labs
 

months of exposure  Prognosis good

Restrictive defect Hypoxemia

 Radiographs  Air trapping  Micronodules

Kupeli, et al Postgrad Med 2003 Non-neoplastic Disorders of the Lower Respiratory Tract 2002 American Registry of Pathology and the Armed Forces Institute of

Differential Diagnosis
 Subacute stage
        

Recurrent pneumonia ABPA Granulomatous lung diseases Infection – mycobacteria, fungi Pneumoconiosis Langerhans’ cell histiocytosis Churg-Strauss syndrome Wegener’s granulomatosis Sarcoidosis
Patel et al J Allergy Clin Immunol

Chronic
 Sx occur over 4-12  Labs

months
Dyspnea  Fatigue  Cough

Same as for prior stages

 Pathology
Fibrosis  Patchy alveolar infiltrate

 

 Prognosis is poor  Inciting antigen

Mononuclear cells Bronchocentric pattern

unlikely to be isolated

Non-necrotizing granulomas  Bronchiolitis obliterans  Organizing pneumonia

 Radiographs

Honeycombing

Kupeli, et al Postgrad Med 2003 Non-neoplastic Disorders of the Lower Respiratory Tract 2002 American Registry of Pathology and the Armed Forces Institute of Pathology

Chronic HP

www.emedicine.com Hayakawa et al Respirology 2002

Differential Diagnosis
Chronic stage
   

Idiopathic pulmonary fibrosis Chronic obstructive pulmonary disease with pulmonary fibrosis Bronchiectasis/bronchiolectasis Mycobacterium avium complex

Patel et al J Allergy Clin Immunol 2001

Clinical Course
 Acute illness resolves in weeks if

recognized early and patient exposure to antigen is eliminated  Subacute or chronic illness
 More

insidious symptoms  Increased risk of emphysema, fibrosis, asthma  Avian sensitivity associated with poor prognosis similar to interstitial lung disease
5 year mortality 50%  Clubbing on exam portends a worse prognosis

Diagnostic Criteria
Major
    

History of symptoms compatible with HP

Appear or worsen within hours after antigen exposure
History, Environmental investigation, Serum Ab or BAL Ab

Evidence of exposure to antigen

BAL lymphocytosis Histologic findings compatible with HP Compatible radiographic findings Basilar crackles Decreased diffusion capacity Decreased O2 saturation with rest or activity
Synopsis of Diseases of the Chest 3rd ed

Minor
  

1. Known exposure to offending antigen
A.History of appropriate exposure
B. Environmental tests confirm Ag presence C. Positive serum IgG to Ag

2. Compatible clinical, radiologic, physiologic findings Definite
A. Respiratory (+/- constitutional) Si/Sx B. Compatible CXR/CT findings C. Altered PFTs, gas exchange

3. BAL with lymphocytosis A.Low CD4/CD8
B. Positive specific imm response to Ag A. Reexposure to environment B. Lab exposure to suspected Ag

Probable Subclinical Sensitization

1,2,3 1,2,4A 1,2A,3,5 1,2A,3 1,3A 1

4. Positive inhalation challenge test 5. Compatible histopathology
A. Poorly formed, noncaseating granulomas B. Mononuclear infiltrate Atlas of Nontumor Pathology
Travis, et al 2002 American Registry of Pathology and the Armed Forces Institute of Pathology

Diagnostic Value to History/Exam
 Multicenter trial studying consecutive patients

presenting with a pulmonary syndrome for which HP was considered in the differential diagnosis  Objective: Identify diagnostic criteria and develop clinical prediction rule
     

History of exposure to Ag Presence of precipitating Ab Recurrent episodes of Sx Inspiratory crackles on exam Sx occurring 4-8 hrs after exposure Weight loss

 400 patients in derivation cohort  261 patients in validation cohort  HRCT and BAL defined presence or absence of HP
Lacasse et al Am J Respir Crit Care Med 2003

Significant Predictors of HP
Variables
Exposure Precipitating Abs present Recurrent episodes Inspiratory rales Sx 4-8 hrs after exposure Weight loss Sensitivity 86%

OR
38.8 5.3 3.3 4.5 7.2 2.0 Specificity 86%

CI
11.6-129.6 2.7-10.4 1.5-7.5 1.8-11.7 1.8-28.6 1.0-3.9

Rules do not apply to subacute or chronic forms HP
Lacasse et al Am J Respir Crit Care Med 2003

Pulmonary Function
 Classically, a restrictive pattern
 Decreased

FEV1 and FVC  Decreased total lung capacity  Decreased diffusion capacity
 Concomitant bronchiolitis may result in

obstructive defect  Hypoxemia  Bronchial hyperreactivity

Chest Radiography
CXR
 Acute
  

CT
 Acute
  

Fine micronodular pattern Diffuse ground-glass opacity Normal Interstitial fibrosis

Profuse centrilobular micronodules Ground-glass opacities Evidence of air trapping Honeycombing Poorly defined nodules Fibrosis Lobar volume loss

 Chronic

 Chronic
   

Imaging of Diseases of the Chest 3rd ed Armstrong et al Mosby London 2000

Ground Glass Opacities

www.emedicine.com

Bronchoalveolar Lavage
 Immediate (within 48 hours)  Neutrophils  Days later

T lymphocyte predominant alveolitis
 

CD8+ predominant CD4/CD8 usually < 1.0 Few disease processes > 50%

 

20-70% lymphocytes

Increased mast cells, usually > 1%

 Problem  Lymphocytic response seen in asymptomatic patients with antigen exposure, and patients with organic dust toxic syndrome
Atlas of Nontumor Pathology Non-Neoplastic Disorders of the Lower Respiratory Tract Hypersensitivity pneumonitis: current concepts Eur Respir J 2001 18:81s-92s

Histopathology
 Cellular bronchiolitis  Interstitial lymphocytic

infiltrate

Usually bronchocentric

 Scattered, small, poorly

formed non-necrotizing granulomas  Large histiocytes with foamy cytoplasm  Fibrosis

Indistinguishable from other causes in advanced disease

Approximately 80% of subacute and chronic cases have this triad

Differential Diagnosis
Table Modified from Atlas of Nontumor Pathology Histologic Hypersensitivity Sarcoidosis feature Pneumonitis
Granulomas Frequency Morphology Distribution Intraluminal fibrosis Lymphocyte infiltrates Dense fibrosis BAL lymphocytosis
2/3 open biopsies 100% of cases

LIP

5-10% cases; Well formed or poorly formed Random

Poorly formed Mostly random, some peribronchiolar 2/3 open biopsies Mild-moderate Peribronchiolar Advanced cases CD8>CD4
(CD4/CD8 < 1.0)

Well formed Lymphangitic, peribronchiolar, perivascular Very rare Absent or minimal Advanced cases CD4>CD8
(> 3.5 has a PPV 75%)

Unusual Extensive, diffuse Unusual Usually B cells

Non-neoplastic Disorders of the Lower Respiratory Tract

Predictive Value of BAL Cell Differentials
in the Diagnosis of Interstitial Lung Disease (ILD)
 Retrospective evaluation  3,975 BALF samples from 3,118 pts  Collected January 1997 – November 2003  Determine pre-test and post-test probabilities  Relative frequencies of diagnoses based on available information (prior to BAL) were used as pre-test probabilities  Post-test probabilities determined using Bayes’ rule based on cell differentials and the CD4/CD8 ratio

Eur Respir J 2004; 24: 1000-1006

Probability of ILD as a function of CD4/CD8 in suspected ILD
n CD4/CD8 Sarcoidosis UIP EAA 239 112 66 33.7 15.8 9.3 Pre-test 9.1 * 13.6 27.3 * Post-test <0.5 0.5-3.5 40.3 12.2 17.2 * >3.5 69.1 *** 5.2 * 12.5

p<0.05; *** p<0.001 Versus the respective a priori value

Likelihood of EAA rose 3x with a CD4/CD8 <0.5
Eur Respir J 2004; 24: 1000-1006

Probability of ILD as a function of lymphocytes and CD4/CD8 in suspected ILD when the percentage of granulocytes was low
(eosinophils <2% and neutrophils <4%) Post-test Lymph % and CD4/CD8 Sarcoidosis UIP EAA n 182 25 35 Pretest 45.2 6.2 8.7
<30 Low High 30-50 Low High Low >50 High

28.6 86.1 56.1 *** *** 9.4 1.4 *** 5.6 0.0 3.5 17.5 *

86.5 *** 0.0 2.7

33.3 3.0 39.4 ***

55.6 0.0 29.6 ***

Likelihood of EAA rose nearly 4x independently of CD4/CD8 when lymphocytes were very high and granulocytes were low

•p<0.05; *** p<0.001 •Low CD4/CD8 <3.5

Eur Respir J 2004; 24: 1000-1006

Probability of ILD as a function of lymphocytes and CD4/CD8 in suspected ILD when the percentage of granulocytes was high
(eosinophils >1% and neutrophils >3%) Lymph % and CD4/CD8 Sarcoidosis UIP Pretest 18.6 28.3 Post-test
<30 Low High 30-50 Low High >50 Low High

n 57 87

13.9 44.4 23.1 * 34.2 22.2 11.5

50.0 * 6.3

21.4 0.0*

0.0 0.0

EAA

31

10.1

3.0*

5.6

34.6 ***

37.5 ***

50.0 ***

50.0

Likelihood of EAA rose nearly 5x independently of CD4/CD8 when lymphocytes were very high and granulocytes were high

p<0.05; *** p<0.001 Low CD4/CD8 <3.5

Eur Respir J 2004; 24: 1000-1006

Who Gets HP?

Farmers

Farmers moving hay into a barn, [between 1895 and 1910] Bartle Brothers Glass plate negative Reference Code: C 2-10232-1729

 Thermophilic actinomycetes

Hay, grain, compost, manure Pigeon, duck, turkey, quail Contaminated air conditioning systems Contaminated air conditioning systems

 Avian proteins

 Amoebae (Naegleria, Acanthamoeba)

 Thermophilic actinomycetes

Bird Fanciers

www.ryancordell.com

Bird Fanciers
 Avian proteins  Case study  67 yo 150+ pack-yr smoker www.ladygouldianfinch.com  Raised budgerigars 1980-88  Diagnosed as IPF 1988  1994 diagnosed with Bird Fancier’s Lung
 

Lymphocytic alveolitis and organizing pneumonia by TBBx Serum precipitins positive for bird antigens Developed low grade fever and increased dyspnea Bronchocentric alveolitis on CT/chest Patient acquired feather duvet
Inase et al Internal Medicine 2004

Disease stable until 2000
  

Nursing Home Aviary

Factory Workers
 Metalworking fluid aerosols  Pseudomonas fluorescans  Mycobacterium avium complex  Cheese mold

www.groupnch.com www.defra.gov.uk

Penicillium

 Plastics and resins  Anhydrides  Paint catalysts, adhesives, and foam  Diisocyanates  Contaminated ventilation systems

Naegleria, Acanthamoebae

Patients With H/O Medication Use
 Amiodarone  Gold  Procarbazine  Minocycline  Chlorambucil  Sulfasalazine  Beta blockers  HMG co-A Reductase inhibitors

Others
 Wood workers  Alternaria species  Malt workers

Aspergillus

 Bathtub refinishers

 Domestic engineers  Ventilation systems, compost, chemicals, greenhouses  Office employees

and Paint refinishers
Diisocyanates

Ventilation systems

 Lab workers  Rat urinary proteins

 Anybody!  Household mold  Air conditioning  Saunas, Hot tubs  Birds  Goose down

Diagnostic Approach
 Detailed history and physical exam

Patient may not associate symptoms with antigen exposure  Symptoms may be delayed for hours  Temporal relationship weaker with chronic forms

 Positive precipitating antibodies
      

Once thought to be hallmark Demonstrates immune response Lack sensitivity and specificity for HP Serve as markers for antigen exposure Poorly standardized antigens Improper quality controls More sensitive, but less specific

 Enzyme-linked immunosorbent assay  Bronchoscopy  Lung biopsy  No single clinical or laboratory feature is diagnostic

Occupational History
 Current and previous occupations  Description of job processes  Chemical exposure  Symptom improvement away from work?  Similar symptoms in coworkers?  Use of respiratory protection at work

Environmental History
 Pets (especially birds)  Hobbies and recreational activities  Presence of humidifiers, swamp coolers, indoor       

vented dryers Use of hot tubs, saunas Visible fungal growth in household/workplace History of flooding or water damage to walls and carpets History of recent renovation/remodeling Similar symptoms in home occupants Feather pillows, comforters, bedding, jackets Use of air fresheners, spray cleaners

www.brickleyenv.com

www.indoorairpro.com

Treatment
 Antigen avoidance  Responsible antigen may be difficult to isolate  Multiple antigens may be involved  Half-lives of animal dander, proteins measured in years  Exposure may be unavoidable  Disease may progress in spite of antigen avoidance  Corticosteroids
    

0.5 mg/kg/d for severe, acute episodes Subacute episodes may benefit from 1 mg/kg/day 2-4 weeks Improved short term effect No difference in long term effects (5 years)

 Role of inhaled steroids and beta agonists unclear  May provide symptomatic relief UpToDate
Monkare Eur J Respir Dis 1983 Kokkarinen et al Am Rev Respir Dis 1992 Patel et al J Allergy Clin Immunol 2001

Value of steroids
Monkare Eur J Respir Dis 1983  93 pts with Farmer’s lung studied prospectively
 

No impact on lung function or work capacity Minor improvements in radiographic changes

Kokkarinen et al Am Rev Respir Dis 1992  36 pts in double blind, placebo control  20 received prednisolone x 8 wks  16 received placebo  1 month follow up

Steroids improved DLCO No statistical significance between groups Symptoms recurred
– 6 pts receiving steroids – 1 pt in placebo group

5 year follow up
 

Summary of HP
 Antigen exposure is necessary but insufficient  Important exposures occur at home

Pet birds, feathers, humidifiers, indoor molds and bacteria Nonspecific symptoms Variable clinical presentation Variable radiographic findings Lack of a “gold standard” diagnostic test

 Challenging to diagnose
   

 Immunopathogenesis remains unclear  Can be improved with antigen avoidance, and

steroids in severe, acute cases  Unrecognized/untreated it may lead to development of asthma, emphysema or interstitial fibrosis

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