Clinical Features

  • Definition of HP is controversial
  • Cormier and Schuyler:
    • HP is an inappropriate immune response to inhaled antigens that causes: shortness of breath, a restrictive lung defect, interstitial infiltrates seen on lung imaging (CXR and high-resolution CT) caused by the accumulation of large numbers of activated T lymphocytes in the lungs. The disease is sometimes further characterized by episodic bouts of fever a few hours after exposure.

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  • During the acute phase, respiratory symptoms (e.g. cough, dyspnea) are common but not universal, and chest imaging may be normal

  • Features of HP may vary based on the causative antigen
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  • Pathophysiology unclear: immune complex-mediated (serum precipitins) vs. cellular mediated disease (lymphocytic cell infiltration and granuloma formation in lungs)

Causative Antigens and Sources


Farming

Environmental source
Major causative antigen
Moldy hay, grain, silage
Thermophilic actinomycetes, such as Faenirecti virgula (also known as Micropolyspora faeni or Saccharopolyspora rectivirgula)
Fungus, such as Aspergillus umbrosus
Moldy on pressed sugar cane (bagassosis, very rare cases)
Thermoactinomyces sacchari, T. vulgaris
Tobacco plants (tobacco grower's lung; "Blackfat" tobacco)
Aspergillus sp
Scopulariopsis brevicaulis
Mushroom worker's lung
Mushroom spores
Thermophilic actinomycetes
Potato riddler's lung (moldy hay around potatoes)
Thermophilic actinomycetes
T. vulgaris
F. rectivirgula
Aspergillus sp
Paprika slicer's lung (moldy paprika pods)
Mucor stolonifer
Wine maker's lung (mold on grapes)
Botrytis cincrea
Cheese washer's lung (moldy cheese)
Penicillium casei
Aspergillus clavatus
Coffee worker's lung
Coffee-bean dust
Tea grower's lung
Tea plants

Ventilation and water-related contamination

Environmental source
Major causative antigen
Humidifier fever
Thermoactinomyces (T vulgaris, T sacchari, T candidus)
Klebsiella oxytoca
Naegleria gruberi
Acanthamoeba polyphaga
Acanthamoeba castellani
Unventilated shower
Epicoccum nigrum
Hot-tub lung (mists; mold on ceiling and around tub)
Cladosporium sp
Mycobacterium avium complex
Sauna taker's lung
Aureobasidium sp, other sources
Summer-type pneumonitis
Trichosporon cutaneum
Lifeguard lung
Aerosolized endotoxin from pool-water sprays and fountains
Contaminated basement (sewage) pneumonitis
Cephalosporium

Birds and poultry handling

Environmental source
Major causative antigen
Bird fancier's lung (parakeets, budgerigars, pigeons)
Droppings, feathers, serum proteins
Poultry worker's lung (feather plucker's disease)
Serum proteins (chicken products)
Turkey handling disease
Serum proteins (turkey products)
Canary fancier's lung
Serum proteins
Duck fever
Feathers, serum proteins

Veterinary work and animal handling

Environmental source
Major causative antigen
Laboratory worker's lung (rats, gerbils)
Urine, serum, pelts, proteins
Pituitary snuff taker's disease
Dried, powdered neurohypophysis (bovine and porcine pituitary proteins)
Furrier's lung (sewing furs; animal fur dust)
Animal pelts
Bat lung (bat droppings)
Bat serum protein
Fish meal worker's lung
Fish meal
Coptic lung (mummy handler's lung)
Cloth wrappings of mummies
Mollusc shell HP
Sea-snail shell
Pearl oyster shell pneumonitis
Oyster shells

Grain and flour processing

Environmental source
Major causative antigen
Grain measurer's lung
Cereal grain (Sporobolomyces)
Grain dust (mixture of dust, silica, fungi, insects, and mites)
Miller's lung (dust-contaminated grain)
Sitophilus granarius (ie, wheat weevil)
Malt worker's disease (moldy barley)
Aspergillus fumigatus, Aspergillus clavatus

Milling and construction

Environmental source
Major causative antigen
Wood dust pneumonitis (oak, cedar, and mahogany dust, pine and spruce pulp)
Alternaria sp
Bacillus subtilis
Sequoiosis (moldy wood dust)
Graphium
Pullularia
Trichoderma sp.
Aureobasidium pullulans
Maple bark disease (moldy maple bark)
Cryptostroma corticale
Wood trimmer's disease (contaminated wood trimmings)
Rhizopus sp, Mucor sp
Wood pulp worker's disease (oak and maple trees)
Penicillium sp
Suberosis (moldy cork dust)
T. viridis
Penicillium glabrum
Conidia
Composter's lung
T. vulgaris
Aspergillus
Dry rot lung
Merulius lacrymans
Thatched-roof lung (huts in New Guinea)
Saccharomonospora viridis (dead grasses and leaves)
Esparto dust ("Stipatosis"; Stipa tesnacissima is a grass of the graminea family)
Aspergillus fumigatus
T. actinomycetes

Plastic manufacturing, painting, electronics industry, and other chemicals

Environmental source
Major causative antigen
Chemical HP
Diphenylmethane diisocyanate (MDI)
Toluene diisocyanate (TDI)
Detergent worker's lung (washing powder lung)
Bacillus subtilis enzymes
Pauli's reagent alveolitis
Sodium diazobenzene sulfate
Vineyard sprayer's lung
Copper sulfate (bordeaux mixture)
Pyrethrum (pesticide)
Pyrethrum
Epoxy resin lung
Phthalic anhydride (heated epoxy resin)
Bible printer's lung
Moldy typesetting water
Machine operator's lung
Pseudomonas fluorescens
Aerosolized metal working fluid

Textile workers

Environmental source
Major causative antigen
Byssinosis ("brown lung") (unclear if a true cause of HP; asthma is common)
Cotton mill dust (carding and spinning areas of cotton, flax, and soft-hemp)
"Velvet" worker's lung
Unknown (? nylon velvet fiber, tannic acid, potato starch)
Upholstery fabric (nylon filament, cotton/polyester, and latex adhesive)
Aflatoxin-producing fungus, Fusarium sp
Lycoperdonosis (lycoperdon puffballs)
Puffball spores

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Differential Diagnosis

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Note:
  • "Inhalation fevers" include:
    • Organic dust toxic syndrome (grain fever) - exposure to grain dust containing endotoxin or mycotoxins
    • Humidifier fever - exposure to bioaerosols from humidifiers, air conditioners
    • Metal fume fever - exposure to Zn or Al oxides, usually in welders
    • Other: Silo unloader's fever, wood-trimmer's disease, Polymer fume fever, textile mill fever, Pontiac fever (exposure to aerosols containing Legionella)


Diagnosis


Predictors of HP

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probability_of_HP.png


Diagnostic Criteria

  • A number of diagnostic criteria recommendations for HP have been published but none of these sets of criteria have been validated
Investigator---
Major criteria
Minor criteria
Cormier
1. Appropriate exposure
2. Inspiratory crackles
3. Lymphocytic alveolitis (if BAL is done)
4. Dyspnoea
5. Infiltrates on chest radiographs (or HRCT)
1. Recurrent febrile episodes
2. Decreased DLCO
3. Precipitating antibodies to HP antigens
4. Granulomas on lung biopsy (usually not required)
5. Improvement with contact avoidance or appropriate treatment
Schuyler
1. Symptoms compatible with HP
2. Evidence of exposure to appropriate antigen by history or detection in serum and/or BAL fluid antibody
3. Findings compatible with HP on chest radiograph or HRCT
4. BAL fluid lymphocytosis
5. Pulmonary histological changes compatible with HP
6. Positive "natural challenge"
1. Bibasilar rales
2. Decreased DLCO
3. Arterial hypoxaemia, either at rest or during exercise
Terho
1. Exposure to offending antigens (revealed by history aerobiological or microbiologic investigations of the environment, or measurements of antigen-specific IgG antibodies
2. Symptoms compatible with HP present and appearing or worsening some hours after antigen exposure
3. Lung infiltrations compatible with HP visible on chest X-ray
1. Basal crepitant rales
2. Impairment of the diffusing capacity
3. Oxygen tension (or saturation) of the arterial blood either decreased at rest, or normal at rest but decreased during exercise
4. Restrictive ventilation defect in the spirometry
5. Histological changes compatible with HP
6. Positive provocation test whether by work exposure or by controlled inhalation challenge
Richerson
1. The history and physical findings and pulmonary function tests indicate an interstitial lung disease
2. The X-ray film is consistent
3. There is exposure to a recognized cause
4. There is antibody to that antigen



Testing


Specific IgG Antibodies
  • May be useful as supportive evidence; positive serum antibodies is a significant predictor of HP (odds ratio 5)
  • Not always identifiable in patients with HP, probably signifying that some antigens causing HP are still unknown
  • False-negative results may be seen in acute and chronic HP cases
  • Majority of individuals exposed to an HP antigen develop a high titer of serum precipitating antibodies to the antigen but only 1–15% develop the disease
    • For example, 10% develop antibodies to farmer's lung antigen Saccharopolyspora rectivirgula but 0.3% develop disease.
  • The antigens to be tested needs to be determined locally according to the prevalent antigens and patient's history
  • These antigens cover most cases of HP:
    • Pigeon and parakeet sera
    • Dove feather antigen
    • Aspergillus sp.
    • Penicillium
    • S. rectivirgula
    • Thermoactinomyces viridans

Hypersensitivity Pneumonitis Panel by Precipitin
  • Aspergillus Fumigatus #1,2,3,6
  • Aureobasidium pullulans
  • Pigeon Serum
  • Micropolyspora faeni
  • Thermoactinomyces vulgaris #1
  • Aspergillus flavus
  • Saccharomonospora viridis
  • Thermoactinomyces candidus
  • Thermoactinomyces sacchari

Johns Hopkins DACI Reference Lab - Precipitins
  • Thermophilic actinomyces: 3 antigens
  • Aspergillus fumigatus: 5 antigens
  • Pigeon serum:1 antigen
  • Aureobasidium pullulans: 1 antigen
  • Parakeet droppings: 1 antigen
  • P6 Cockatiel droppings: 1 antigen
  • Parrot (Blue Front) droppings: 1 antigen

HP Panel Serology (IBT labs Fluorescence Enzyme Immunoassay; Units Reported: mcg/mL of specific IgG)
  • Micropolyspora faeni IgG
  • Thermoactinomyces vulgaris IgG
  • Aspergillus fumigatus IgG
  • Penicillium Chrysogenum/notatum IgG
  • Alternaria tenuis/alternata IgG
  • Tricoderma viride IgG
  • Aureobasidium pullulans IgG
  • Phoma betae IgG


CT Scan
HP_CT_lung.png
  • Chest X-ray may be normal in 10%
  • CT patterns are not specific for HP but HP may be considered in the differential diagnosis when these patterns are present.
    • Ground-glass opacities can be seen desquamative interstitial pneumonitis, PCP pneumonia, BOOP, bronchoalveolar carcinoma, alveolar proteinosis and alveolar haemorrhage.
    • When ground-glass opacities are associated with poorly defined, centrilobular micronodules and mosaic attenuation or expiratory air trapping, the diagnosis of HP is further supported


Bronchoalveolar Lavage
  • Can provide support for diagnosis of HP.
    • A normal number of lymphocytes rules out all but residual disease. An increase in the total cell count with a remarkable elevation in the percentage of T lymphocytes (often >50%) characterizes HP.
    • Elevated lymphocytes does notdefinitively establish the diagnosis
      • Asymptomatic, exposed individuals can have increased BAL lymphocytes (due to normal inflammatory response or mild self-limited alveolitis)
      • Many other diseases (sarcoidosis, interstitial pneumonia associated with collagen vascular disease, silicosis, BOOP, HIV pneumonitis and drug-induced pneumonitis) are characterized by an alveolar lymphocytosis
      • Increased lymphocytes in a patient with interstitial lung disease of unknown origin should direct the clinician towards the possible diagnosis of HP
    • A predominance of CD8+ T cells and a CD4+/ CD8+ ratio lower than 1 is often (but notalways) observed in HP whereas a high CD4+/CD8+ ratio is associated with sarcoidosis (CD4/CD8 ratio >4 has 100% positive predictive value for sarcoidosis).
      • Exceptions:
        • CD4/CD8 ratio can be increased in HP to levels as high as those seen in sarcoidosis
        • Low CD4+/CD8+ ratio may be associated with chronic HP and to asymptomatic individuals with HP whereas a predominance of CD4+ T cells is related to the acute phase of the disease.
        • CD4+/CD8+ ratio may depend on the type/amount/duration of antigen exposure.
      • Overall, the evaluation of CD4+ and CD8+ T cell subsets is not recommended for clinical practice, because a growing body of evidence has shown that these subsets and their ratio diverge according to a number of situations, including the type of inhaled antigen, the intensity of exposure, smoking, and the clinical stage


PFTs
  • Typical physiological profile of acute HP is a restrictive pattern with low DLCO
  • Decreased DLCO is not always present in HP (in one study, up to 22% with HP had normal DLCO)


HP Diagnostic Algorithm
HP algorithm.png


Treatment

  • Avoidance of the offending antigen
  • Corticosteroid
    • Help control symptoms of acute or subacute disease but do not seem to affect the long-term outcome
    • The dose of corticosteroids to be given is unclear and based on expert opinion
      • Most recommend 50 mg of oral prednisone daily; others suggest that 20 mg would be sufficient
      • 2-4 weeks of prednisone 0.5 mg/kg/day may be appropriate in acute phase; subacute HP might require higher doses for several months


References