eMedicine Specialties > Pediatrics: General Medicine > Pulmonology

Hypersensitivity Pneumonitis

Harold J Farber, MD, Associate Professor, Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine
Nidhy S Paulose Varghese, MD, Postdoctoral Fellow, Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine; Bettina C Hilman, MD, Consulting Staff, The Asthma and Allergy Center

Updated: Apr 14, 2008

Introduction

Background

Hypersensitivity pneumonitis (HP) refers to a group of disorders caused by a nonatopic immunologic response to an inhaled agent. In its acute or subacute form, HP may be a cause of recurrent pneumonitis. In its chronic form, HP may insidiously lead to pulmonary fibrosis and emphysema. Severe acute or subacute flares can be life threatening,¹ and recurrent or chronic disease can lead to permanent, severe lung damage.² Although rare, fatal cases of chronic HP have been reported in children.³

Hypersensitivity pneumonitides are classically considered occupational illnesses and have colorful names reflecting the associated occupation. Some of these illnesses and their associated causes include the following:⁴

• Farm worker's lung - Thermophilic actinomycetes and other pathogens
• Winemaker's lung - Botrytis cinerea
• Coffee worker's lung - Coffee bean dust
• Lifeguard's lung - Aerosolized endotoxin
• Poultry worker's lung - Avian antigens
• Laboratory worker's lung - Rodent antigens
• Miller's lung - Wheat weevil
• Woodworker's lung - Penicillium chrysogenum
• Detergent worker's lung - Bacillus subtilis
• Epoxy-resin lung - Phthalic anhydride

Pathophysiology

Numerous organic and inorganic antigens can cause HP. To cause pneumonitis, the antigen must penetrate into the small airways; therefore, its size must be within the respirable range (smaller than 5 μm). Implicated antigens include avian (bird) antigens, mammalian proteins, fungi and fungal spores, bacterial antigens, and small-molecular-weight chemicals.⁵ See Causes.

Immune responses

The immunopathogenesis of HP has not been well characterized. An exuberant production of antibody (especially immunoglobulin G [IgG]) against the offending antigen is frequently identified; however, the precipitating antibody alone is not sufficient to cause HP. A key role for T-cell mediated responses is suggested by the observations of CD8+ cytotoxic lymphocyte proliferation⁶ and greater percentages of natural killer T (NKT) cells in bronchoalveolar lavage fluid (BALF).⁷

Various cytokines have been identified in acute hypersensitivity pneumonitides, but their role is poorly understood; most research has focused on animal models, in vitro systems, and clinical observations. Interleukin (IL)-8 (a chemoattractant of neutrophils) is released by a cell line with properties of alveolar lung cells when stimulated by thermophilic bacteria.⁸ High levels of IL-8 are released by alveolar macrophages in patients with acute HP.⁹ Levels of tumor necrosis factor (TNF)-α (a proinflammatory cytokine produced by macrophages) became elevated in patients with acute farmer’s lung after an antigen challenge but were not elevated in unaffected farmers after antigen challenge.¹⁰

An important role for interferon-γ (a cytokine important in Th1 response) is suggested by the observation that interferon-γ knockout mice lack granulomatous inflammation in response to stimulation by thermophilic bacteria, whereas granulomatous inflammation develops in both knockout mice given interferon-γ replacement and wild-type mice.¹¹

Genetics

Familial clustering of cases suggests a genetic predisposition, but a clear genetic locus has not yet been identified. Likewise, associations with different human leukocyte antigen (HLA) phenotypes have been suggested, but no clear or consistent pattern has emerged.^12,13,14

Viral infections

Viral infections may play a role in triggering HP flares. Research in an animal model suggests that viral infection can augment inflammatory responses in HP.¹⁵ This is supported by the finding of respiratory viruses in the BALF of 9 of 13 patients during acute exacerbations of farmer’s lung.¹⁶

Frequency

The true prevalence of HP is unknown. Relatively few cases have been described in the pediatric literature.

United States

The frequency in children is unknown.

International

Acute HP in children is more common in areas where pigeon racing and pigeon breeding are popular. Chronic disease is more common in areas where caged birds are typical house pets.

Mortality/Morbidity

Mortality due to HP in childhood is uncommon; however, a fatal case has been reported.³  Significant morbidity can result if the child is not removed from the causative environment. 

Severe pulmonary fibrosis with honeycombing and spontaneous pneumothorax (end-stage lung disease) as a consequence of chronic HP has been described in an adolescent.²

In adults, chronic HP with pulmonary fibrosis and honeycombing is associated with high mortality rates.¹⁷

Age

See Mortality/Morbidity.

Clinical

History

A comprehensive environmental history and high index of suspicion are critical for diagnosis. Hypersensitivity pneumonitis (HP) should be considered in patients with chronic or recurrent cough, shortness of breath, or a history of recurrent acute respiratory symptoms without definite infectious triggers.

Inquire about specific exposures; the patient may not volunteer them. Because bird fancier’s lung is the most common HP in children, a specific inquiry must be made about bird exposure. Contact may not necessarily be in the home and may not be obvious. Exposures in or near the home, at school, as a part of hobbies, at the place of employment, or anywhere else the child spends time must be explored. Repeated questioning, home inspection, and/or inspection of sites where the child spends time may be needed to identify the causative antigen. 

Clues that strongly suggest the diagnosis of HP are as follows:¹⁸

• History of recurrent pneumonia, particularly with regularity or a pattern
• Other people at home or school who have similar symptoms
• Development of respiratory symptoms after the patient moves to a new home or new school
• Improvement of symptoms when the patient is away from home or school for an     extended period
• Contact with birds
• Water damage to the patient's home or school facility
• Use of a hot tub, sauna, or swimming pool

Manifestations of HP are classified as acute, subacute, or chronic. These classifications should be considered as points along a spectrum of illness rather than clearly delineated, discrete types of illness.¹⁹ In patients with acute disease, a temporal relation between the respiratory symptoms and antigenic exposure can usually be identified. In cases of subacute or chronic exposure, the association between antigenic exposure and development of disease may not be obvious. 

HP seems to be least common among active smokers of tobacco products. This relative infrequency might result from suppression of alveolar macrophage function.^20,21,22 However, a chart review of an outbreak of HP among metalworkers suggested that low disease rates among tobacco smokers may reflect a high proportion of false-negative results instead of a truly low rate of disease.²³ Another study suggests that HP may be most insidious and is most often associated with low survival rates when it occurs in smokers.²⁴

Physical

Acute HP is characterized by the abrupt onset (4-6 h after exposure) of fever, chills, malaise, nausea, dry cough, chest tightness, and dyspnea. Physical examination may reveal tachypnea and fine crackles localized to the lung bases; wheezing is unusual. The presentation is easily confused with that of an infectious pneumonia. Removal from exposure usually results in resolution of symptoms within hours to days.

Subacute HP is characterized by the gradual development of productive cough, dyspnea, fatigue, anorexia, weight loss, and low-grade fever. Physical examination and chest auscultation may reveal tachypnea and diffuse crackles. In patients with severe disease, cyanosis may be present.¹ Resolution of disease may take weeks to months after removal from exposure.

Chronic HP may be difficult to diagnose in its early stages. A chronic cough with a normal physical exam may be the first presentation. Over time, the disease may progress to dyspnea, fatigue, weight loss, and exercise intolerance. Auscultation of the chest may reveal crackles. An “inspiratory squawk” or “chirping rales” have been described.^25,26 Digital clubbing may be seen in the advanced stages of the disease.

Causes

Types and causes of hypersensitivity pneumonitis in children

A wide spectrum of respirable antigens can trigger HP, including avian antigens, rodent antigens, fungi, bacteria, and low molecular weight chemicals. Fungal spores can be present wherever sufficient humidity is present; for example, in piles of moldy hay (farmer's lung), in mold-contaminated ventilation systems (humidifier lung), or in old homes seasonally contaminated by mold (summer-type pneumonitis).^27,5 Mycobacterial antigens aerosolized by the mist that surrounds an operating hot tub can cause HP, colorfully described as hot-tub lung. 

Commonly Described Causes of HP²⁸

The most common type of HP in children is bird fancier's lung. Most often, the contact is with identified household pets, but, in many cases, the contact may be less obvious. HP has been reported after bird exposure from parental hobbies or occupations, including parental pigeon breeding,²⁹ pheasant raising,³⁰ and working on a turkey farm.³¹ Relevant exposures may be from nearby bird activity, with reported cases of HP resulting from birds congregating by a backyard pool,²⁹ goose droppings tracked inside from a contaminated outdoor environment,³² wild city pigeons nesting just outside the home,³³ birds nesting near the air intake of an air-conditioning system,³⁴ and neighbors engaged in bird breeding.³⁵ Live birds are not necessary to cause bird fancier's lung. Exposure to avian antigens from a feather duvet (feather duvet lung) has been linked to HP.^36,37

Exposure to mold–contaminated moist organic material is a frequent cause of HP. Farmer's lung has been reported among children living on farms, especially in children exposed to moist or moldy hay or grains.^38,39 Summer-type pneumonitis is classically described in the mid and southern parts of Japan, with onset during summer, resolution by mid-autumn, and recurrence the following summer. It is caused by fungal growth in older wooden homes stimulated by warm, moist summers.^40,27 This summer-type pneumonitis has been described outside of Japan where similar conditions occur.^41,42

Sources of mold in the child's environment may not be obvious. A compost heap in a play area caused HP in one child.⁴³ HP was diagnosed in a child exposed to moldy hay at a horseback-riding school.⁴⁴ A familial cluster of chronic HP was caused by mold that collected behind torn wallpaper and beneath worn carpets.⁴⁵  Mold that contaminated a basement shower caused HP in several children.⁴⁶  

Wherever aerosolized water is present, HP can occur. Mold contamination of humidifiers has led to the disease in adults and children.^47,48,49,50 Aerosolized endotoxin generated from a water spray in an indoor swimming pool has been implicated in lifeguard's lung.⁵¹ Hot-tub lung is believed to be a hypersensitivity reaction to contamination of hot-tub water by Mycobacterium avium intracellulare complex or mold in a hot tub.^52,53

Finding the source of contaminated water may take some investigation. Hot-tub lung has been described in teenagers who used their family's or friend's hot tub.⁵² A central humidification system that nebulizes water into the heating system caused a cluster of HP cases in a family.⁴⁷

Low molecular weight chemicals, such as isocyanates (eg, in spray paint and glue), phthalic anhydride (in epoxy resin), and pyrethrum (an insecticide), are thought to cause HP by combining with human proteins to form complete antigens.⁵⁴

To diagnose HP, the key lies in a detailed history. The clinician has to maintain a high index of suspicion. Reaching the diagnosis can be difficult because symptoms are often nonspecific and the available diagnostic tests are imperfect. However, taking appropriate, effective action to eliminate the inciting exposure can prevent substantial pulmonary morbidity.

Diagnostic criteria proposed for adults are generally appropriate for children. Nonetheless, many of these criteria require invasive tests or radiation exposure, and some of the testing is difficult to perform in young children.

The diagnosis of HP is generally considered to be confirmed if at least 4 major criteria and 2 minor criteria are present and if alternative diagnoses are excluded. These diagnostic criteria may be summarized as follows:⁵⁵

• Major diagnostic criteria
• Symptoms compatible with HP
• Evidence of exposure to an appropriate antigen apparent from the patient's history or from antibody detected in serum, BALF, or both
• Findings compatible with HP on chest radiography or high-resolution CT (HRCT) scanning
• Lymphocytosis observed in BALF
• Lung biopsy results that reveal histologic changes compatible with HP
• Positive finding from a natural challenge (ie, symptoms and laboratory abnormalities reproduced after exposure to the offending antigen
• Minor diagnostic criteria(almost always present but nonspecific)
• Bibasilar crackles
• Decreased capacity of the lung to diffuse carbon monoxide
• Hypoxemia whether patient is at rest or exercising

Differential Diagnoses

Other Problems to Be Considered

• Acute hypersensitivity pneumonitis (HP) closely resembles viral or bacterial infections of the lower respiratory tract.
• Bird exposure can place the patient at risk for psittacosis.
• Granulomatous lung diseases (eg, tuberculosis, histoplasmosis, coccidiomycosis, sarcoidosis) can also produce findings similar to those of subacute HP.⁵
• Lymphoid interstitial pneumonitis observed in patients with acquired immunodeficiency syndrome (AIDS) can manifest as dyspnea, crackles, interstitial infiltrates, and hypergammaglobulinemia. 
• For patients residing or working in a farm setting, organic toxic dust syndrome can be provoked by bacterial endotoxins or fungal toxins.⁵⁶
• Zamboni disease (a toxic reaction to nitrogen oxides emitted from an ice-smoothing machine operated in an indoor ice rink) can mimic acute or subacute HP.⁵⁷
• Differentiating chronic HP from idiopathic pulmonary fibrosis is particularly important because the prognosis for the former improves when the offending antigen is identified and eliminated. 
• Subacute and chronic HP has been misdiagnosed as asthma, a condition that can also cause cough, dyspnea, and exercise intolerance.²
• Chronic HP may be misdiagnosed as anorexia nervosa. Anorexia, weight loss, and exercise intolerance are manifestations of both diseases.
• Connective-tissue disease (eg, systemic lupus erythematosus) can cause noninfectious pneumonitis with fever and weight loss, but other clinical and laboratory features of the connective tissue disease are expected. 
• Drug-induced pneumonitis is considered separately from pneumonitis triggered by inhaled antigens. Medications most often implicated in drug-induced pneumonitis include gold salts, methotrexate, and amiodarone. Rare causes of drug-induced pneumonitis are the nonsteroidal anti-inflammatory drugs aspirin and ibuprofen; the anticonvulsants carbamazepine and phenytoin; the antibiotics nitrofurantoin and dapsone; the sulfonamides sulfasalazine and sulfadoxine; the antimalarial chloroquine; the immunosuppressants penicillamine and cyclophosphamide; and the cytotoxic agents azathioprine, bleomycin, chlorambucil, cyclophosphamide, mitomycin, and vinblastine. For additional details, see the eMedicine article Lung, Drug-Induced Disease.

Workup

Laboratory Studies

• Precipitating antibodies to the offending antigen are commonly present; however, this observation is considered marker of exposure and not the cause of the disease. It is also not specific to hypersensitivity pneumonitis (HP) because exposed persons without disease may have precipitating antibodies to the antigen.^58,59 Reports have attributed missed diagnoses to false-negative results of precipitin studies, although repeat testing showed true-positive findings of precipitin in many cases.⁶⁰
• A preliminary study suggested that precipitating antibody titers (as opposed to simply the presence or absence) may be of help in diagnosis.⁶¹ Among adult pigeon fanciers, those who reported respiratory symptoms within 4-8 hours of pigeon exposure had much higher precipitin levels to pigeon serum, feathers, and droppings than those who had no symptoms from pigeon exposure. Further validation and standardization of this test is necessary to better determine the sensitivity and specificity before it can be considered ready for routine clinical use.
• The erythrocyte sedimentation rate and C-reactive protein levels may be elevated, a rheumatoid factor may be present, and circulating immune complexes may be observed. However, these findings are not considered sufficiently specific to be useful for diagnosis.¹⁹
• Hypergammaglobulinemia is a common finding but is neither sensitive nor specific.

Imaging Studies

HRCT is more sensitive than chest radiography for revealing pneumonitis; however, normal radiographic results have been observed in subjects who meet other diagnostic criteria for HP.^62,63

• Acute HP: Chest radiography may reveal a fleeting, micronodular, interstitial pattern in the lower and middle lung zones; however, chest radiography often reveals normal results. Airspace consolidation can be seen in patients with acute disease, especially after exposure to causative antigens. HRCT usually reveals a patchy, ground-glass attenuation with small, poorly defined centrilobular nodules.
• Subacute HP: Radiographic findings are similar to those observed in acute disease, although abnormalities may be most prominent in the mid- to upper-lung zones, and focal emphysema may be seen in addition to mild fibrotic changes. As in acute HP, airspace consolidation can also be seen in subacute disease.
• Chronic HP: The most severe radiographic abnormalities are observed in the upper zones of the lungs. The most common abnormalities observed include centrilobular nodules, areas of linear opacity, and increased lung density. In advanced disease, evidence of lung damage due to pulmonary fibrosis and emphysema with honeycombing can be seen with HRCT. The centrilobular nodules on HRCT of the chest correlate with the granulomatous areas seen in lung biopsy specimens.⁶²

Other Tests

• Pulmonary function studies
  • Acute HP: Pulmonary function may be normal between acute episodes of HP. Normal diffusing capacity observed between exacerbations of acute or subacute HP does not exclude the diagnosis. Testing during acute episodes of HP reveals predominately restrictive changes; however, obstruction and bronchial hyperreactivity can also be seen. Obstruction alone does not preclude a diagnosis of HP. Hypoxemia can be seen in patients with active pneumonitis whether the affected patient is at rest or exercising.²⁸
  • Subacute HP: Pulmonary function testing may demonstrate mild hypoxemia, restriction and/or obstruction, and a reduced capacity for diffusing carbon monoxide.
  • Chronic HP: A reduced diffusing capacity of the lung for carbon monoxide may be the earliest abnormality observed. Pulmonary restriction, hypoxemia at rest, and/or desaturation during the 6-minute walk test indicates the presence of more advanced disease.
• Provocation challenge: The role of inhalation challenge is controversial because it can provoke clinically significant disease and standardized antigen preparations are not yet available. Because of the risk for the late-phase severe reactions, patients should be closely observed for at least 24 hours after the inhalation challenge is administered.⁶⁴
• Natural challenge: Patients may be accidentally re-exposed during a “natural” challenge. The development of signs and symptoms after the patient is re-exposed to the antigenic environment supports a diagnosis of acute or subacute HP.
• Skin testing:Skin testing is not helpful in assessing HP.⁶⁵
• Lung biopsy:If other measures are not adequate to establish the diagnosis, lung biopsy can be performed. In older children, transbronchial biopsy may be attempted before the more invasive transthoracic lung biopsy. Several biopsy specimens should be obtained from sites showing evidence of radiographic involvement. In patients with advanced disease, video-assisted thoracoscopic biopsy improves the diagnostic yield from that of transbronchial biopsy.⁶⁴

Procedures

Analysis of BALF is the most sensitive tool for alveolitis detection in patients with suspected HP. Analysis of BALF in HP typically reveals the following:⁶⁴

• Lymphocytosis (>20% of WBCs recovered)
• CD4+/CD8+ ratio reduced to less than 1
• Elevated proportion of neutrophils (may be elevated to >5%), especially after recent antigenic exposure or in advanced disease
• Elevated proportion of eosinophils (may be >5%), particularly in advanced disease

One study of BALF cytology reported that adults with HP have a greater percentage of NKT cells than adults with sarcoidosis (11% [range, 3-38%] vs 3% [range, 0-16%]).⁷  The NKT cells observed in patients with HP were predominantly of the CD8+CD56+ population. Although the clinical use of this observation remains to be determined, these data suggest that a high percentage of NKT cells in the BALF supports a diagnosis of HP, whereas a low percentage neither confirms nor excludes the diagnosis.

Histologic Findings

HP is a diffuse, predominantly mononuclear cell inflammation of the small airways and pulmonary parenchyma. The inflammation is often associated with poorly formed, nonnecrotizing granulomas.⁵⁵ A bronchiolocentric distribution of the interstitial inflammation is believed to result from the airway being the portal of entry for the offending agent. Histologic findings may include the following:⁶⁶

• Bronchiolocentric, chronic interstitial inflammation in which lymphocytes predominate
• Poorly formed, nonnecrotizing interstitial granulomas
• Foamy macrophages within airspaces
• Intra-alveolar foci of organizing pneumonia
• Dense fibrosis, honeycombing, and fibroblastic foci in advanced, chronic disease

Treatment

The key to effective treatment is identifying the offending antigen and eliminating further exposure. These goals can be hard to achieve because the offending antigen may not be obvious. Some antigens, such as avian antigens, may persist in the home environment for a long time, even after the source of the antigen or its source (the bird) is removed.¹⁸ Patients or their families may find it difficult to remove treasured pets, abandon hobbies, move to a new home, or give up income-producing activity.

Removal from exposure usually results in complete resolution of symptoms, although substantially more time is required in subacute than in acute disease. In many patients, complete resolution requires weeks to months. Permanent lung damage, continued progression, or both may be seen in advanced cases of chronic hypersensitivity pneumonitis (HP). 

Corticosteroids can speed resolution of HP, especially in its subacute and chronic forms, however corticosteroid therapy does not eliminate or reduce the need to identify the causative antigen and elimination of exposure to it.  If systemic corticosteroid therapy is used, the same dosage regimen should be continued until clinical improvement of pulmonary function is observed. The dosage should then be gradually tapered downward.  In advanced chronic disease, progression of pulmonary fibrosis and death can occur despite aggressive corticosteroid therapy. If the patient has risk factors for tuberculosis, tuberculin skin testing should be considered before corticosteroid therapy is started.

Antibiotic therapy is not indicated for treatment of HP. However, in many cases, antibiotic drugs are administered until a diagnosis of infectious pneumonia is ruled out.

Medical Care

See Treatment.

Consultations

Consulting a pediatric pulmonologist, an allergist, or both who have experience in treating HP can be helpful for confirming the diagnosis, for assessing complications, for educating the patient and family, and for providing long-term follow-up care for the patient.

Diet

No dietary restrictions are needed.

Activity

If the patient has pulmonary fibrosis, subpleural blebs, or airway obstruction, scuba diving is contraindicated because of the risk of pneumothorax. Otherwise, activity levels should be adjusted according to the patient's comfort; dyspnea causes most patients to spontaneously reduce their physical activity. If needed, tolerance of physical activity can be objectively assessed with 6-minute walk testing.

Medication

Systemic corticosteroid therapy speeds resolution of symptoms. Progression of pulmonary fibrosis and death can occur despite corticosteroid therapy. Corticosteroid therapy is not a substitute for identifying and eliminating the offending antigen.

Corticosteroids

These agents decrease inflammation, suppress leukocyte migration, reverse increased capillary permeability, and dampen the immune system.

Prednisone (Deltasone)

Decreases inflammation by reversing increased capillary permeability and suppressing PMN activity. Must be metabolized to the active metabolite prednisolone for effect.

Dosing

Adult

0.5-1 mg/kg/d PO for 4-8 wk; slowly taper as symptoms resolve

Pediatric

1-2 mg/kg PO initially, followed by 1 mg/kg/d PO, usually for 4 wk until clinically significant improvement; taper slowly as symptoms resolve; long courses may be needed to treat chronic disease

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin, may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia when coadministered with diuretics

Contraindications

Documented hypersensitivity; peptic ulcer disease; hepatic dysfunction; untreated tuberculosis infection, or other serious infection; systemic fungal infection; varicella infection

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may result from glucocorticoid use

Follow-up

The patient should be strongly advised to eliminate exposure to the offending antigen. In cases of severe disease, the patient may need to be moved to a new setting to avoid the offending antigen. In some cases, antigen avoidance may include interventions that are very disruptive to the individual’s life or the family’s life, such as moving from the home, changing occupations or both.

Corticosteroid doses and adverse effects must be monitored. Once a clinical response has been achieved, the acute dosing should be gradually tapered. Markers of clinical response consist of resolution of abnormalities on physical and radiologic examination, improvement in pulmonary function measures including vital capacity, diffusing capacity, and oxygen saturation. 

Further Inpatient Care

Monitor corticosteroid doses and adverse effects. Gradually taper dose after clinical response, radiologically visible clearing, and improved pulmonary function are achieved.

Further Outpatient Care

Monitor corticosteroid doses and adverse effects. Serial pulmonary function testing with assessment of lung volumes and diffusion capacity is indicated (if the patient is able to perform the maneuvers) to document resolution of abnormalities. Monitor adherence to recommendations to eliminate exposure to the offending antigen.

Deterrence/Prevention

The immediate family of children with chronic HP should be screened for subclinical disease because both the exposure and genetic predisposition may be shared.

Complications

Complications may include the following:

• Spontaneous pneumothorax
• Pulmonary fibrosis
• Emphysema
• Respiratory insufficiency or failure
• Cor pulmonale
• Death

Prognosis

Overall, the prognosis is good if the antigen is identified and the antigenic exposure is eliminated. In acute HP, removal from exposure generally results in improvement within 12 hours to several days. Complete resolution of clinical and radiographic findings may take several weeks.⁶²  Longer periods are needed for resolution of subacute disease. 

Digital clubbing, pulmonary fibrosis, and prolonged (>2 y) exposure all suggest permanent lung damage and a risk for disease progression. Reports have described this progression among adults with chronic HP despite a reduction or elimination of their antigenic exposures.

Patient Education

Educate the patient and his or her family about the importance of eliminating exposure to the offending antigen. 

Miscellaneous

Medicolegal Pitfalls

Failure to consider hypersensitivity pneumonitis (HP) in the differential diagnosis, resulting in misdiagnosis or delayed diagnosis, can have significant consequences secondary to treatment postponement.

Multimedia

Media file 1: Anteroposterior chest radiograph reveals a right-sided tension pneumothorax with mediastinal shift to the left in a female adolescent with severe chronic hypersensitivity pneumonitis (HP) resulting from bird exposure. Radiograph reveals diffuse haziness and increased interstitial markings of the underlying lung. Reprinted with permission from Farber and Budson, 2000.

Media file 2: High-resolution chest CT scan in the same patient as in Media file 1 reveals ground-glass attenuation, areas of nodular attenuation, and a thickened interstitium. A chest tube is evacuating the pneumothorax. Reprinted with permission from Farber and Budson, 2000.

Media file 3: Axial high-resolution chest CT scan (1-mm section) obtained at the level of the third thoracic vertebra reveals a persistent right pneumothorax and diffuse ground-glass attenuation through both lung fields. Areas of nodular attenuation, a thickened interstitium, and small subpleural cysts are most prominent on the superior section. Reprinted with permission from Farber and Budson, 2000.

Media file 4: Photomicrograph of a lung biopsy specimen reveals marked interstitial inflammation with lymphocytic predominance and a multinucleated giant cell (hematoxylin-eosin stain, original magnification 40X). Reprinted with permission from Farber and Budson, 2000.

Media file 5: Photomicrograph of a lung biopsy sample reveals interstitial fibrosis with active interstitial inflammation (hematoxylin-eosin stain, original magnification 10X). Reprinted with permission from Farber and Budson, 2000.

Media file 6: Photograph reveals precipitin lines produced by means of Ouchterlony immunodiffusion assay. Central wells contain the patient's serum. Peripheral wells contain serum or droppings from various birds. Reprinted with permission from Farber and Budson, 2000.

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Keywords

Hypersensitivity pneumonitis, HP, extrinsic allergic alveolitis, EAA, bird fancier's lung, pigeon fancier’s lung, bird breeder's lung, pigeon breeder's lung, farmer's lung, recurrent pneumonitis, pulmonary fibrosis, emphysema, hypersensitivity pneumonitides, farm worker's lung, thermophilic actinomycetes, winemaker's lung, Botrytis cinerea, coffee worker's lung, coffee bean dust, lifeguard's lung

aerosolized endotoxin, poultry worker's lung, avian antigens, laboratory worker's lung, rodent antigens, miller's lung, wheat weevil, woodworker's lung, Bacillus subtilis, epoxy-resin lung, Phthalic anhydride, spontaneous pneumothorax, end-stage lung disease, acute respiratory symptoms, pneumonia, digital clubbing, chronic cough, dyspnea, cyanosis, bird fancier's lung, pigeon breeder's lung, Aspergillus species, moldy hay, Mucor stolonifer, humidifier lung, hot-tub lung, sauna taker's lung, sewage pneumonitis, summer-type pneumonitis, Trichosporon species

Contributor Information and Disclosures

Author

Harold J Farber, MD, Associate Professor, Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine
Harold J Farber, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

Coauthor(s)

Nidhy S Paulose Varghese, MD, Postdoctoral Fellow, Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine
Nidhy S Paulose Varghese, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Bettina C Hilman, MD, Consulting Staff, The Asthma and Allergy Center
Bettina C Hilman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Chest Physicians, American Heart Association, American Medical Association, American Pediatric Society, American Thoracic Society, and Louisiana State Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Girish D Sharma, MD, Associate Professor, Department of Pediatrics, Rush University Medical Center, Rush Children's Hospital; Director of Pediatric Pulmonary Section and Rush Cystic Fibrosis Center
Girish D Sharma, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Royal College of Physicians of Ireland
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Charles Callahan, DO, Professor, Deputy Chief of Clinical Services, Walter Reed Army Medical Center
Charles Callahan, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American College of Osteopathic Pediatricians, American Thoracic Society, Association of Military Surgeons of the US, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

CME Editor

Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Associate Professor, Department of Clinical Pediatrics, State University of New York at Stony Brook
Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics, American Heart Association, and American Thoracic Society
Disclosure: Nothing to disclose.

Chief Editor

Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons
Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Merck Honoraria Speaking and teaching

This article has been extensively revised and updated from the original version by Lori R Johnson, MD; Bettina C Hilman, MD; Laurianne Wild, MD; and Harold J Farber, MD. Leland Fan, MD reviewed this version of the manuscript and provided helpful suggestions.

Fan LL. Hypersensitivity Pneumonitis in Children. Curr Opin Pediatr. 2002 Jun;14(3):323-6.

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