Professional Documents
Culture Documents
Pneumonitis
Extrinsic Allergic Alveolitis
Pesticide/insecticide Pyrethrum
Home or Work-related Agents Organic Antigens
Microbial
Humidifier lung Acanthamoebae castellani
Acanthamoebae polyphaga
Naegleria gruberi
Thermoactinomyces candidus
Helper cells
Lymphocyte
Stimulates
Chemokines
Lymphokines
Ab formation
Over-expressed
In rat models of HP
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
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
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
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
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
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
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