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 Disease
Thermophilic actinomycetes Moldy hay, plant Farmer’s Lung
materials, compost
Aspergillus Animal bedding Dog house disease
Ubiquitous
Aureobasidium sp Contaminated water Sauna-taker’s disease
Alternaria sp Wood, wood pulp Wood worker’s lung
Candida albicans Saxophone mouthpiece Sax lung
Mixed ameba, fungi, bacteria Cold mist and other Nylon plant Office
humidifiers, air worker’s Air conditioner’s
conditioners lung
Ventilation pneumonitis
Bacteria, fungi Metal working fluids Machine operator’s lung
Isocyanates Paints, plastics Paint refinisher’s lung
Anhydrides Plastics Chemical worker’s lung
Plastic worker’s lung
Epoxy worker’s lung
Cobalt Hard metal lung disease
Berylliosis Berylliosis
Patel et al J Allergy Clin Immunol 2001
Worksite-related Agents Organic Antigens Antigen

Farmer’s lung Micropolyspora faeni

Aspergillus species
Streptomyces albus
Sacharopolyspora rectivirgula
Malt worker’s lung Aspergillus species

Wood worker’s lung Penicillium chrysogenum

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

Cheese worker’s lung Penicillium casei

Sugar cane worker’s lung (Bagassosis) Thermoactinomyces vulgaris

Detergent worker’s lung Bacillus subtilis

Cork worker’s lung Penicillium frequentens

Coffee worker’s lung Coffee bean dust

Cotton worker’s lung (Bysinnosis) Bract of cotton flower

Wheat worker’s lung Wheat weevil

Metal worker’s lung Rapid growing mycobacteria

www.lungcancerfrontiers.com
Inorganic Antigens Associated with HP Non-microbial

Paints, resins, plastics Diisocyanates

Insulation, polyurethane Trimellitic anhydride

Vineyard sprayer’s lung (fungicide) Copper sulfate

Pesticide/insecticide Pyrethrum
Home or Work-related Agents Organic Antigens
Microbial
Humidifier lung Acanthamoebae castellani
Acanthamoebae polyphaga
Naegleria gruberi
Thermoactinomyces candidus

Bird breeder’s lung (budgies, pigeons) Bird droppings

Rodent handler’s lung Urinary antigens, serum, pelts

Hot tub/spa lung Mycobacterium avium complex

Inorganic Antigens Associated with HP Non-microbial

Polyurethane foam insulation 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 lung inflammation
 Infections
 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 Race Age Group (yrs)
No. of Under-lying Median
Yr
Deaths Cause (%) 15- 25- 35- 45- 55- 65- 75- 85 Age (yrs)
M F W B O
24 34 44 54 64 74 84 +

1990 41 63.4 31 10 38 1 2 - 1 1 3 8 11 15 2 73.0

1991 36 72.2 28 8 34 - 2 2 - 1 2 4 11 11 5 73.5

1992 18 77.8 14 4 17 1 - - 1 2 2 2 3 7 1 72.5

1993 46 52.2 31 15 44 1 1 - 1 1 4 7 14 14 5 71.5

1994 36 75.0 28 8 36 - - - - - 2 5 8 12 9 76.5

1995 37 62.2 24 13 32 5 - - 1 - 6 4 7 14 5 75.0

1996 51 76.5 35 16 49 2 - - 3 3 5 7 11 16 6 73.0

1997 38 71.1 25 13 38 - - - - 1 2 6 8 14 7 76.0

1998 38 63.2 31 7 37 1 - - - - 2 3 10 17 6 78.5

1999 57 64.9 36 21 56 1 - - 3 2 9 5 11 19 8 74.0

TOTAL 398 67.1 283 115 381 12 5 2 10 11 37 51 94 139 54 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
 Memory cells
Ag Stimulates
T cell
Activates
Cytotoxic cells

Helper cells
Lymphocyte

Stimulates
Chemokines

Lymphokines

Ab formation
Over-expressed
In rat models of HP

IFN gamma key to

granuloma formation Opal and DePalo Chest 2000
Gudmundsson et al J Immunology 1998
in mouse models Patel et J Allergy Clin Immunol 2001
Key Players In Fibrosis
Angiotensin II
TGF-β
Macrophage TNF-α TGF-β
IL-1
Neutrophils
TNF−α
Alveolar
Epithelial Cell

Fibroblast
IFN-γ Angiotensin II
TGF-β
Lymphocyte
Fibroblast Proliferation
Extracellular Matrix Formation
Clinical Features
Classification Systems
Classical Boyd Cormier Selman
Acute Acute progressive Active Active
Nonprogressive
and intermittent
Subacute Acute intermittent Active
nonprogressive Progressive and
intermittent
Chronic Nonacute Residual Chronic
Progressive
Nonprogressive
J Allergy Clin Clin Allergy Clin Pulm Med Interstitial Lung
Immunol 1982;12(suppl):53 1996;3:72 Disease
1989;89:839 Schwarz, MI, King, TE Jr,
(Eds) 4th Ed, Hamilton,
BC Decker 2003

UpToDate
Acute
 Abrupt onset  Clinical
 Cough  Diffuse rales
 Dyspnea  Tachypnea
 Chest tightness  Central cyanosis
 Fevers  Labs
 Chills  Leukocytosis
 Malaise  Restrictive pattern on
 Myalgias PFTs
 Anorexia  Positive serum
 Nausea/vomiting precipitins
 Sx 4-8 hrs after high level  Radiographs
exposure  1-5mm bilateral
pulmonary nodules
 Sx subside over hours
 Bilateral consolidation
-days  Ground glass infiltrates
 complete recovery in 7-10
days Kupeli, et al Postgrad Med 2003
 Prognosis good 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  Exam
 Dyspnea  Diffuse rales
 Cough  Hypoxia

 Occurs after weeks to  Labs

months of exposure  Restrictive defect
 Prognosis good  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  Same as for prior stages
 Dyspnea  Pathology
 Fatigue  Fibrosis
 Cough  Patchy alveolar infiltrate
 Prognosis is poor  Mononuclear cells
 Bronchocentric pattern
 Inciting antigen
 Non-necrotizing
unlikely to be isolated 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
 Evidence of exposure to antigen
 History, Environmental investigation, Serum Ab or BAL Ab
 BAL lymphocytosis
 Histologic findings compatible with HP
 Compatible radiographic findings
Minor
 Basilar crackles
 Decreased diffusion capacity
 Decreased O2 saturation with rest or activity
Synopsis of Diseases of the Chest 3rd ed
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 1,2,3
A. Respiratory (+/- constitutional) Si/Sx 1,2,4A
B. Compatible CXR/CT findings 1,2A,3,5
C. Altered PFTs, gas exchange
Probable 1,2A,3
3. BAL with lymphocytosis Subclinical 1,3A
A.Low CD4/CD8 Sensitization 1
B. Positive specific imm response to Ag
4. Positive inhalation challenge test
A. Reexposure to environment
B. Lab exposure to suspected Ag
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 OR CI
Exposure 38.8 11.6-129.6
Precipitating Abs present 5.3 2.7-10.4
Recurrent episodes 3.3 1.5-7.5
Inspiratory rales 4.5 1.8-11.7
Sx 4-8 hrs after exposure 7.2 1.8-28.6
Weight loss 2.0 1.0-3.9

Sensitivity 86% Specificity 86%

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 CT
 Acute  Acute
 Fine micronodular pattern  Profuse centrilobular
 Diffuse ground-glass micronodules
opacity  Ground-glass opacities
 Normal  Evidence of air trapping
 Chronic  Chronic
 Interstitial fibrosis  Honeycombing
 Poorly defined nodules
 Fibrosis
 Lobar volume loss

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
 20-70% lymphocytes
 Few disease processes > 50%
 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 LIP
feature Pneumonitis
Granulomas
Frequency 2/3 open biopsies 100% of cases 5-10% cases;
Well formed or
poorly formed
Morphology Poorly formed Well formed Random
Distribution Mostly random, some Lymphangitic,
peribronchiolar peribronchiolar,
perivascular
Intraluminal 2/3 open biopsies Very rare Unusual
fibrosis
Lymphocyte Mild-moderate Absent or minimal Extensive, diffuse
infiltrates Peribronchiolar

Dense fibrosis Advanced cases Advanced cases Unusual

BAL CD8>CD4 CD4>CD8 Usually B cells

lymphocytosis (CD4/CD8 < 1.0) (> 3.5 has a PPV 75%)

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 Pre-test Post-test
CD4/CD8 <0.5 0.5-3.5 >3.5
Sarcoidosis 239 33.7 9.1 40.3 69.1
* ***
UIP 112 15.8 13.6 12.2 5.2
*
EAA 66 9.3 27.3 17.2 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 % Pre-
<30 30-50 >50
and n test
CD4/CD8 Low High Low High Low High

Sarcoidosis 182 45.2 28.6 86.1 56.1 86.5 33.3 55.6

*** *** ***
UIP 25 6.2 9.4 5.6 3.5 0.0 3.0 0.0

EAA 35 8.7 1.4 0.0 17.5 2.7 39.4 29.6

*** * *** ***
•p<0.05; *** p<0.001
Likelihood of EAA rose nearly 4x independently of •Low CD4/CD8 <3.5
CD4/CD8 when
lymphocytes were very high
and granulocytes were low
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 % Pre- Post-test

and n test <30 30-50 >50
CD4/CD8 Low High Low High Low High

Sarcoidosis 57 18.6 13.9 44.4 23.1 50.0 21.4 0.0

* *
UIP 87 28.3 34.2 22.2 11.5 6.3 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 p<0.05; *** p<0.001
independently of CD4/CD8 when Low CD4/CD8 <3.5
lymphocytes were very high
and granulocytes were high
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
 Avian proteins
 Pigeon, duck, turkey, quail
 Amoebae (Naegleria, Acanthamoeba)
 Contaminated air conditioning systems
 Thermophilic actinomycetes
 Contaminated air conditioning systems
Bird Fanciers

www.ryancordell.com
Bird Fanciers
 Avian proteins
 Case study
 67 yo 150+ pack-yr smoker
 Raised budgerigars 1980-88 www.ladygouldianfinch.com

 Diagnosed as IPF 1988

 1994 diagnosed with Bird Fancier’s Lung
 Lymphocytic alveolitis and organizing pneumonia by TBBx
 Serum precipitins positive for bird antigens
 Disease stable until 2000
 Developed low grade fever and increased dyspnea
 Bronchocentric alveolitis on CT/chest
 Patient acquired feather duvet

Inase et al Internal Medicine 2004

Nursing Home Aviary
Factory Workers
 Metalworking fluid aerosols
 Pseudomonas fluorescans
www.groupnch.com
 Mycobacterium avium complex
 Cheese mold 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  Domestic engineers
 Alternaria species  Ventilation systems,
compost, chemicals,
 Malt workers
greenhouses
 Aspergillus  Office employees
 Bathtub refinishers  Ventilation systems
and Paint refinishers  Anybody!
 Diisocyanates  Household mold
 Lab workers  Air conditioning
 Rat urinary proteins
 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
 Enzyme-linked immunosorbent assay
 More sensitive, but less specific
 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
 5 year follow up
 No statistical significance between groups
 Symptoms recurred
– 6 pts receiving steroids
– 1 pt in placebo group
Summary of HP
 Antigen exposure is necessary but insufficient
 Important exposures occur at home
 Pet birds, feathers, humidifiers, indoor molds and bacteria
 Challenging to diagnose
 Nonspecific symptoms
 Variable clinical presentation
 Variable radiographic findings
 Lack of a “gold standard” diagnostic test
 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