AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a complex syndrome of varying intensity, clinical presentation, and natural history, rather than a single uniform disease.

First described in Iceland in 1874 and termed heykatarr, HP is caused by sensitization to repeated inhalation of dusts containing organic antigens. These dusts can be derived from a variety of sources, such as dairy and grain products, animal dander and protein, wood bark, and water reservoir vaporizers. The most common antigens are thermophilic actinomycetes and avian proteins; the most common diseases are farmer's lung and bird fancier's lung.

HP is characterized by diffuse inflammation of lung parenchyma and airways in previously sensitized patients. Based on the length and intensity of exposure and subsequent duration of illness, clinical presentations of HP are categorized as acute, subacute (intermittent), and chronic progressive.

Pathophysiology

Pathologically, acute HP is characterized by poorly formed noncaseating interstitial granulomas and mononuclear cell infiltration in a peribronchial distribution with prominent giant cells.

The subacute, or intermittent, form produces more well-formed noncaseating granulomas, bronchiolitis with or without organizing pneumonia, and interstitial fibrosis.

Chronic forms reveal additional findings of chronic interstitial inflammation and alveolar destruction (honeycombing) associated with dense fibrosis. Cholesterol clefts or asteroid bodies are present within or outside granulomas.

The pathologic features of chronic HP, often associated with a poor prognosis, have the following 3 patterns of fibrosis.

• Predominantly peripheral fibrosis in a patchy pattern with architectural distortion and fibroblast foci similar to usual interstitial pneumonia (UIP)
• Homogeneous linear fibrosis similar to fibrotic nonspecific interstitial pneumonia (NSIP)
• Irregular predominantly peribronchiolar fibrosis

Thus, chronic HP may mimic UIP or fibrotic NSIP. If no areas of subacute HP are present, giant cells, poorly formed granulomas, or Schaumann bodies (if identified) may lead to the correct diagnosis. The finding of peribronchiolar fibrosis may also be helpful (Churg, 2005).

Pathogenesis

Most patients have circulating immunoglobulin G antibodies that are specific for the offending antigen. The antibody (called precipitating antibody) reacts with a specific antigen to form a precipitation. However, approximately 50% of asymptomatic persons exposed to the sensitizing antigen also have these antibodies.

Although initially thought to be an immunocomplex-mediated process, subsequent studies showed that cell-mediated immunity is more important.

Early response to the antigen is characterized by an increase in neutrophils in the alveoli and small airways followed by an influx of mononuclear cells. These cells release proteolytic enzymes, prostaglandins, and leukotrienes. The production and release of interleukins, cytokines, growth factors, and various other mediators from T lymphocytes and macrophages play important roles in HP pathogenesis.

Frequency

United States

Resistance or susceptibility to infection following exposure varies. Incidence also varies considerably. Studies document 8-540 cases per 100,000 persons per year for farmers and 6000-21,000 cases per 100,000 persons per year for pigeon breeders. High attack rates are documented in sporadic outbreaks. Approximately 52% of office workers exposed to an infected humidifier were infected, and 27% of workers at a molding plant for polyurethane foam parts were infected.

Prevalence varies by region, climate, and farming practices. HP affects 0.4-7% of the farming population. Reported prevalence among bird fanciers is estimated to be 20-20,000 cases per 100,000 persons at risk.

International

The prevalence of farmer's lung in the United Kingdom is reported to be 420-3000 cases per 100,000 persons at risk, in France is 4370 cases per 100,000 persons at risk, and in Finland is 1400-1700 cases per 100,000 persons at risk.

One epidemiologic study revealed that the estimated incidence of interstitial lung disease was 7.6 per 100,000 per year. Out of all interstitial lung diseases, the most frequent was idiopathic pulmonary fibrosis (38.6%), followed by sarcoidosis (14.9%), cryptogenic organizing pneumonia (10.4%), interstitial lung disease associated with collagen vascular diseases (9.9%), HP (6.6%), and unclassified in 5.1% of cases (Xaubet, 2004).

Mortality/Morbidity

• Most patients recover completely after the inciting exposure ceases.
• Bird fancier's disease has a worse prognosis than farmer's lung.
• The outcomes of other varieties of HP are more variable.

Sex

One epidemiological study revealed the male to female ratio was 1.2:1.

Age

In the same study, the mean age of the patients with HP in Spain was 61 years ±0.7 years.

CLINICAL

Section 3 of 11  

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History

The clinical presentation of HP is categorized as acute, subacute, or chronic, according to duration of illness.

• Acute HP
• • The acute form may develop 4-6 hours following heavy exposure to an inciting agent. Symptoms often resolve spontaneously within 12 hours to several days upon cessation of exposure.
  • Patients abruptly develop fever, chills, malaise, cough, chest tightness, dyspnea, headache, and malaise.
• Subacute (intermittent) HP
• • Patients may gradually develop a productive cough, dyspnea, fatigue, anorexia, and weight loss.
  • Findings may be present in patients who experience repeated acute attacks.
• Chronic HP
• • Patients often lack a history of acute episodes.
  • They have an insidious onset of cough, progressive dyspnea, fatigue, and weight loss.
  • Removing exposure results in only partial improvement.

Physical

Physical examination findings vary according to clinical presentation.

• Patients with acute HP present with fever, tachypnea, and diffuse fine bibasilar crackles upon auscultation.
• Patients with subacute HP present similarly to patients with acute disease, but symptoms are less severe and last longer.
• Patients with chronic HP present with muscle wasting and weight loss. Clubbing is observed in 50% of patients. Tachypnea, respiratory distress, and inspiratory crackles over lower lung fields often are present.

Causes

More than 300 etiologies of HP have been reported from a wide range of exposures involving airborne antigens.

Selected Etiological Agents for HP

Reported occupations and major causative antigens are as follows:

• Farmers and cattle workers develop the most common form of HP.
• • The major causative antigen is thermophilic actinomycetes.
  • Farmer's lung must be distinguished from febrile toxic reactions to inhaled mold dusts (organic dust toxic syndrome). This nonimmunologic reaction occurs 30-50 times more commonly than HP.
• Ventilation workers and those exposed to water-related contamination may be exposed to microorganism-colonized forced-air systems, humidifiers, whirlpools, hot tubs, and spas. Antigens are various species of Thermoactinomyces or Cladosporium.
• Poultry and other bird handlers are commonly exposed to droppings, feathers, and serum proteins of pigeons, other birds, and fowl
• Veterinarians and animal handlers have significant contact with animals and organic antigens.
• Grain and flour processors and loaders are exposed to grain that may become colonized with a variety of microorganisms that are easily aerosolized. Exposure may lead to HP.
• Lumber mill workers and paper and wallboard manufacturers are exposed to wood products colonized with molds.
• Plastic manufacturers, painters, and electronics industry workers may be exposed to inciting agents that are synthetic in origin, possibly including diphenylmethane diisocyanate or toluene diisocyanate.
• Textile workers may have exposures that lead to lung injury characterized by diffuse alveolar damage or airway dysfunction (eg, byssinosis, nylon worker's lung). This is not a true form of HP.
• Conditions that mimic HP that occur from inhalation of organic agents but are not true forms of HP are as follows:
• • Patients with inhalation fever present with fever, chills, headaches, and myalgias without pulmonary findings (although mild dyspnea may occur). Onset is 4-8 hours following exposure, but no long-term sequelae occur.
  • Organic dust toxic syndrome results from exposure to bioaerosols contaminated with toxin-producing fungi (mycotoxins). Fever, chills, and myalgias occur 4-6 hours after exposure, and chest radiographs may show diffuse opacities. Bronchiolitis or diffuse alveolar damage may be present on lung biopsy specimens. These are not true forms of HP because no prior sensitization is required.
  • Chronic bronchitis can result from chronic obstructive pulmonary disease, which is the most common respiratory syndrome among agricultural workers. The prevalence of chronic bronchitis is 10%, compared with 1.4% for HP. Smoking and atopy have additive effects. An association may exist between chronic bronchitis and HP.
  • A case-control study investigated the agricultural practices and the microbiological composition of hay handled in patients with farmer's lung disease. The location, type of farm, and working conditions were similar to those of the control farms. However, the microbiological composition of hay differed. Significantly higher amounts of Eurotium amstelodami, Absidia corymbifera, mesophilic Streptomyces, thermophilic Streptomyces, and Saccharomonospora viridis were present in the hay. Farmer's lung resulted from handling hay with high amounts of these 5 microorganisms (Roussel, 2005).
  • Hypersensitivity pneumonitislike syndrome in patients exposed to aerosolized Mycobacterium avium complex (MAC) has been described. Hot tub lung is a term used to describe these hypersensitivity pneumonitislike cases because they have generally been associated with hot tub use (linked to the high levels of infectious aerosols containing organisms found in the water). Whether this pulmonary response to MAC represents true infection or classic HP remains controversial (Marras, 2005).

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Inhalation fever
Organic dust toxic syndrome
Chronic bronchitis

The diagnostic criteria for hypersensitivity pneumonitis (HP) were recently described. The following 6 significant predictors were identified:

• Exposure to a known offending antigen
• Positive precipitating antibodies to the offending antigen
• Recurrent episodes of symptoms
• Inspiratory crackles on physical examination
• Symptoms occurring 4-8 hours after exposure
• Weight loss

WORKUP

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Lab Studies

• Blood tests are of limited utility.
• • Leukocytosis and neutrophilia, elevated erythrocyte sedimentation rate, and increased levels of quantitative immunoglobulins and C-reactive protein are observed in many patients.
  • Precipitating immunoglobulin G antibodies against potential antigens indicate prior exposure and sensitization but do not necessarily represent disease. Many patients with clinical disease have no detectable antibodies, due either to testing with an inappropriate antibody or to cessation of exposure.

Imaging Studies

• Chest radiograph
• • In acute HP, a diffuse micronodular interstitial pattern (at times with ground-glass density in the lower and middle lung zones) may be observed. Findings are normal in approximately 10% of patients.
  • In subacute HP, micronodular or reticular opacities are most prominent in mid-to-upper lung zones.
  • In chronic HP, progressive fibrotic changes with loss of lung volume particularly affect the upper lobes. Nodular or ground-glass opacities are not present. Features of emphysema are found on significant chest films and CT scans.
• High-resolution CT scan
• • Ground-glass opacities or diffusely increased radiodensities are present in the acute phase of disease.
  • In subacute disease, diffuse micronodules, ground-glass attenuation, focal air trapping, and mild fibrotic changes are observed.
  • In chronic HP, several patterns may be observed, including multiple centrilobular nodules with some ground-glass attenuation, radiolucency or air trapping, extensive fibrosis and honeycombing, and traction bronchiectasis.

Other Tests

• Pulmonary function studies
• • A restrictive ventilatory pattern, with reduced forced vital capacity, total lung capacity, and preserved airflow, is observed in acute or subacute disease.
  • A restrictive (severe) or a mixed obstructive and restrictive pattern is common in chronic HP.
  • Diffusing capacity of lungs for carbon monoxide is reduced in all forms of HP.
  • Many patients have hypoxemia at rest, and all patients desaturate with exercise.

Procedures

• Inhalation challenge
• • Re-exposure to the environment of the supposed agent is sometimes recommended.
  • Patients develop fever, malaise, headache, crackles upon chest examination, and decreased forced vital capacity 8-12 hours after exposure.
• Bronchoalveolar lavage
• • Bronchoalveolar lavage may provide supportive information for the diagnosis of HP.
  • A marked bronchoalveolar lavage lymphocytosis (>20%) is nonspecific but helpful.
  • Elevation in the number of CD8⁺ T cells and a CD4⁺-to-CD8⁺ ratio of less than 1 is diagnostic.
  • Abnormalities from bronchoalveolar lavage fluid (both cellular changes and specific antibodies) may be found in asymptomatic individuals with antigen exposure.
• Lung biopsy
• • Histopathological confirmation of the diagnosis is required in many instances and should be attempted by performing transbronchial biopsies. Results are diagnostic in two thirds of cases, but, sometimes, surgical lung biopsy (ie, advanced disease) may be necessary.
  • Findings may reveal small, poorly formed noncaseating granulomas near respiratory or terminal bronchioles; these are associated with multinucleated giant cells.
  • Patchy mononuclear cell infiltration (lymphocytes and plasma cells) of alveolar walls may be present.
  • Large histiocytes with foamy cytoplasm may be present in the interstitium.

TREATMENT

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Medical Care

Environmental and host factors are responsible for the pathogenesis of HP. Emphasis on environmental control is the cornerstone of treatment. Measures to minimize antigenic exposure usually result in regression of disease, but treatment with corticosteroids is required in severe cases.

• Antigen avoidance
• • Once the environmental source of inhaled antigen has been identified, primary therapy is to avoid the inciting agent. Acute forms of disease remit without specific therapy.
  • When complete elimination of the allergen exposure is not possible, protective devices may be used. A patient with disease progression in the setting of ongoing exposure should be strongly advised to avoid the antigen. This may require drastic measures, such as relocation to a new job or home.
  • Farmer's lung carries the financial and emotional implications of leaving the farm. A change of employment or residence may be necessary, but these measures do not always guarantee improvement. The decision should not be taken lightly, and consultation with an expert may be required.
• Corticosteroid therapy
• • Corticosteroid therapy may accelerate the initial recovery in persons with severe disease; however, the long-term prognosis is not favorably affected. Prospective studies have shown significant resolution of symptoms with corticosteroid therapy at 1-2 months, but longer-term follow-up offered no advantage over antigen avoidance or placebo.
  • Corticosteroids are standard treatment for severely ill patients with all varieties of HP. The optimum dose and duration of therapy is uncertain. Treatment is initiated with prednisone (0.5-1 mg/kg as a single dose in the morning).
  • The initial dose is continued for 2-4 weeks and then tapered over a 4- to 8-week period while evaluating clinical response, pulmonary function, and radiographic improvement. Maintenance doses are not always required, particularly if the patient is removed from exposure.

Consultations

Consultation with a pulmonary specialist or an occupational medicine specialist experienced in treating HP is mandatory.

MEDICATION

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The acute form of HP abates without specific therapy. Corticosteroids are used to speed recovery in patients with severe symptoms or significant lung dysfunction. In those with chronic HP, corticosteroids are often used. The optimum dose and duration are not well established.

Drug Category: Corticosteroids

Decrease inflammation, suppress leukocyte migration, reverse increased capillary permeability, and dampen the immune system.

FOLLOW-UP

Section 8 of 11  

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Deterrence/Prevention

Reduce the chances of contracting HP by minimizing exposure to provocative antigens, reducing microorganism contamination in the environment, and/or using protective equipment.

Reduce the antigenic burden by altering the handling and storage of microbial antigens, wetting compost to decrease aerosolization, and using antibiotics to decrease fungal growth.

Facilities designed to reduce humidity and the presence of stagnant water discourage microbial overgrowth.

Preventive maintenance should be performed routinely on all heating, ventilation, and air-conditioning equipment. Water-damaged furnishings and carpeting should be removed.

When avoidance of causative antigens cannot be achieved easily, protective devices such as personal respirators may be used. Dust respirators do not provide protection, and helmet-type air purifying respirators are efficacious but cumbersome to wear.

Prognosis

Most patients experience total recovery of lung function, but this may take several years.

Most patients diagnosed with farmer's lung recover with only minor functional abnormalities; very few advance to disability. A significant number of farmers develop mild chronic lung impairment, which is predominantly obstructive airflow disease associated with mild emphysematous changes on high-resolution CT scan images.

Bird fancier's lung, although not as well studied, appears to have a much worse prognosis compared with farmer's lung. The poorer outcome may be due to higher antigenic exposure and persisting avian antigens in the home environment, even after birds are removed. These factors may account for the substantial 5-year mortality rate of 30%.

Patient Education

Education about and increased awareness of HP have resulted in changes in farming techniques and improved workplace and environmental hygiene, which has significantly reduced the prevalence of this disease.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Failure to maintain a high index of suspicion, resulting in misdiagnosis or delay in diagnosis
• Failure to carefully review a patient's occupational, avocational, or domestic exposure
• Failure to ask questions that reveal an etiologic, environmental, or occupational exposure
• Failure to consider hypersensitivity pneumonitis (HP) because of normal findings on the chest radiograph
• Failure to obtain adequate transbronchial biopsy specimens or an incorrect pathological interpretation because subtle findings were assumed insignificant

Special Concerns

• HP is a multifaceted group of immunologically mediated lung disorders that may mimic any interstitial disease. HP is caused by recurrent exposure to various environmental agents, many of which remain unidentified. Diagnosis of HP is a challenge and requires a combination of clinical, environmental, radiologic, physiologic, and pathologic findings. Treatment includes avoiding further exposure and, depending on the clinical form, the administration of a course of prednisone.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  A 60-year-old dairy farmer had an 8-year history of intermittent dyspnea. Chest radiograph shows bilateral reticulonodular interstitial infiltration secondary to subacute hypersensitivity pneumonitis.
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Media file 2:  Chest radiograph of a patient with chronic hypersensitivity pneumonitis from pigeon breeder's disease. Bilateral reticulonodular densities are present.
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Media type:  X-RAY

Media file 3:  High-resolution CT scan of lungs shows ground-glass opacification in the acute phase of hypersensitivity pneumonitis.
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Media type:  CT

Media file 4:  The chronic phase of hypersensitivity pneumonitis shows honeycombing in the right upper lung and traction bronchiectasis.
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Media type:  CT

Media file 5:  High-resolution chest CT scan of a patient with chronic hypersensitivity pneumonitis demonstrates centrilobular nodules. These nodules are unlike those of sarcoidosis, in which the nodules are subpleural and along bronchovascular bundles.
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Media type:  CT

Media file 6:  Light microscopy shows mononuclear infiltration and noncaseating granulomas usually observed in association with acute hypersensitivity pneumonitis, but it also can be observed in subacute and chronic disease.
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Media type:  Photo

Media file 7:  Giant cells are a characteristic feature of hypersensitivity pneumonitis.
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Media file 8:  Chronic hypersensitivity pneumonitis shows interstitial inflammation associated with fibrosis.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
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• Barbee RA, Callies Q, Dickie HA, Rankin J. The long-term prognosis in farmer''s lung. Am Rev Respir Dis. Feb 1968;97(2):223-31. [Medline].
• Bourke SJ, Banham SW, Carter R, et al. Longitudinal course of extrinsic allergic alveolitis in pigeon breeders. Thorax. May 1989;44(5):415-8. [Medline].
• Buschman DL, Gamsu G, Waldron JA Jr, et al. Chronic hypersensitivity pneumonitis: use of CT in diagnosis. AJR Am J Roentgenol. Nov 1992;159(5):957-60. [Medline].
• Churg A, Muller NL, Flint J, Wright JL. Chronic hypersensitivity pneumonitis. Am J Surg Pathol. Feb 2006;30(2):201-8.
• Cormier Y, Belanger J, Tardif A, et al. Relationships between radiographic change, pulmonary function, and bronchoalveolar lavage fluid lymphocytes in farmer''s lung disease. Thorax. Jan 1986;41(1):28-33. [Medline].
• D''Ippolito R, Chetta A, Foresi A, et al. Induced sputum and bronchoalveolar lavage from patients with hypersensitivity pneumonitis. Respir Med. Oct 2004;98(10):977-83. [Medline].
• Daman L, Lieberman P, Ganier M, Hashimoto K. Localized heat urticaria. J Allergy Clin Immunol. Apr 1978;61(4):273-8. [Medline].
• Fink JN. Hypersensitivity pneumonitis. Clin Chest Med. Jun 1992;13(2):303-9. [Medline].
• Fink JN, Ortega HG, Reynolds HY, et al. Needs and opportunities for research in hypersensitivity pneumonitis. Am J Respir Crit Care Med. Apr 1 2005;171(7):792-8.
• Ganier M, Lieberman P, Fink J, Lockwood DG. Humidifier lung. An outbreak in office workers. Chest. Feb 1980;77(2):183-7. [Medline].
• Gurney JW. Hypersensitivity pneumonitis. Radiol Clin North Am. Nov 1992;30(6):1219-30. [Medline].
• Hartman TE. The HRCT features of extrinsic allergic alveolitis. Semin Respir Crit Care Med. Aug 2003;24(4):419-26.
• Hendrick DJ, Faux JA, Marshall R. Budgerigar-fancier''s lung: the commonest variety of allergic alveolitis in Britain. Br Med J. Jul 8 1978;2(6130):81-4. [Medline].
• Klote M. Hypersensitivity pneumonitis. Allergy Asthma Proc. Nov-Dec 2005;26(6):493-5. [Medline].
• Krasnick J, Meuwissen HJ, Nakao MA, et al. Hypersensitivity pneumonitis: problems in diagnosis. J Allergy Clin Immunol. Apr 1996;97(4):1027-30. [Medline].
• Lacasse Y, Selman M, Costabel U, et al. Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med. Oct 15 2003;168(8):952-8. [Medline].
• Lee DK. Nicotine and hypersensitivity pneumonitis. Am J Respir Crit Care Med. Jul 15 2004;170(2):199-200; author reply 200. [Medline].
• Lynch DA, Rose CS, Way D, King TE Jr. Hypersensitivity pneumonitis: sensitivity of high-resolution CT in a population-based study. AJR Am J Roentgenol. Sep 1992;159(3):469-72. [Medline].
• Marras TK, Wallace RJ, Koth LL, et al. Hypersensitivity pneumonitis reaction to Mycobacterium avium in household water. Chest. Feb 2005;127(2):664-71.
• Monkare S. Influence of corticosteroid treatment on the course of farmer''s lung. Eur J Respir Dis. May 1983;64(4):283-93. [Medline].
• Moreno-Ancillol A, Dominguez-Noche C, Gil-Adrados AC, et al. Hypersensitivity pneumonitis due to occupational inhalation of fungi-contaminated corn dust. J Investig Allergol Clin Immunol. 2004;14(2):165-7. [Medline].
• Roussel S, Reboux G, Dalphin JC, et al. Farmer''s lung disease and microbiological composition of hay: a case-control study. Mycopathologia. Nov 2005;160(4):273-9.
• Salvaggio JE, Millhollon BW. Allergic alveolitis: new insights into old mysteries. Respir Med. Oct 1993;87(7):495-501. [Medline].
• Salvaggio JE. Inhaled particles and respiratory disease. J Allergy Clin Immunol. Aug 1994;94(2 Pt 2):304-9. [Medline].
• Selman M. Hypersensitivity pneumonitis: a multifaceted deceiving disorder. Clin Chest Med. Sep 2004;25(3):531-47, vi.
• Sharma OP, Fujimura N. Hypersensitivity pneumonitis: a noninfectious granulomatosis. Semin Respir Infect. Jun 1995;10(2):96-106. [Medline].
• Travaline JM, Kelsen SG. Hypersensitivity pneumonitis associated with hot tub use. Arch Intern Med. Oct 13 2003;163(18):2250; author reply 2250-1. [Medline].
• Xaubet A, Ancochea J, Morell F, et al. Report on the incidence of interstitial lung diseases in Spain. Sarcoidosis Vasc Diffuse Lung Dis. Mar 2004;21(1):64-70. [Medline].

Article Last Updated: Jun 1, 2006