Pediatric Hypersensitivity Pneumonitis Workup

  • Author: Harold J Farber, MD; Chief Editor: Michael R Bye, MD   more...
 
Updated: Mar 1, 2010
 

Laboratory Studies

  • Precipitating antibodies to the offending antigen are commonly present in hypersensitivity pneumonitis (HP); however, this observation is considered marker of exposure and not the cause of the disease. It is also not specific to hypersensitivity pneumonitis because exposed persons without disease may have precipitating antibodies to the antigen.[59, 60] Reports have attributed missed diagnoses to false-negative results of precipitin studies, although repeat testing showed true-positive findings of precipitin in many cases.[61]
  • A preliminary study suggested that precipitating antibody titers (as opposed to simply the presence or absence) may be of help in diagnosis.[62] 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.[28]
  • Hypergammaglobulinemia is a common finding but is neither sensitive nor specific.
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Imaging Studies

Plain film chest radiography is a useful first step because it can provide a tool to assess for any other responsible illnesses. Normal radiographic results have been observed in subjects who meet other diagnostic criteria for hypersensitivity pneumonitis.[63, 64] An example of a chest radiograph in a patient with hypersensitivity pneumonitis is shown in the image below.

Anteroposterior chest radiograph reveals a right-sAnteroposterior 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.

High-resolution CT (HRCT) scanning of the chest is more sensitive than chest radiography for revealing pneumonitis but should not be relied on as the sole diagnostic test. Examples of HRCT scans in patients with hypersensitivity pneumonitis is shown in the images below.

High-resolution chest CT scan in the same patient High-resolution chest CT scan in the same patient as in the previous image 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. Axial high-resolution chest CT scan (1-mm section)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.
  • Acute hypersensitivity pneumonitis: 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 hypersensitivity pneumonitis: Radiographic findings are similar to those observed in acute disease, although abnormalities may be most prominent in the mid-lung to upper-lung zones, and focal emphysema may be seen in addition to mild fibrotic changes. As in acute hypersensitivity pneumonitis, airspace consolidation can also be seen in subacute disease.
  • Chronic hypersensitivity pneumonitis: 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.[63]
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Other Tests

  • Pulmonary function studies
    • Acute hypersensitivity pneumonitis: Pulmonary function may be normal between acute episodes of hypersensitivity pneumonitis. Normal diffusing capacity observed between exacerbations of acute or subacute hypersensitivity pneumonitis does not exclude the diagnosis. Testing during acute episodes of hypersensitivity pneumonitis reveals predominately restrictive changes; however, obstruction and bronchial hyperreactivity can also be seen. Obstruction alone does not preclude a diagnosis of hypersensitivity pneumonitis. Hypoxemia can be seen in patients with active pneumonitis whether the affected patient is at rest or exercising.[32]
    • Subacute hypersensitivity pneumonitis: Pulmonary function testing may demonstrate mild hypoxemia, restriction and/or obstruction, and a reduced capacity for diffusing carbon monoxide.
    • Chronic hypersensitivity pneumonitis: 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.[65]
  • 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 hypersensitivity pneumonitis.
  • Skin testing: Skin testing is not helpful in assessing hypersensitivity pneumonitis.[66]
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Procedures

  • Analysis of bronchoalveolar lavage (BAL) fluid (BALF) is the most sensitive tool for alveolitis detection in patients with suspected hypersensitivity pneumonitis. Analysis of BALF in hypersensitivity pneumonitis typically reveals the following:[65, 10]
    • Lymphocytosis (>20% of WBCs recovered)
    • 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
  • Analysis of bronchoalveolar lavage fluid in adults with hypersensitivity pneumonitis frequently reveals a CD4/CD8 ratio of less than 1. As stated above (see Pathophysiology), children naturally have a low CD4/CD8 ratio due to an elevated number of CD8 cells. Thus, this finding is neither sensitive nor specific for hypersensitivity pneumonitis in children.[67, 68]
  • One study of BALF cytology reported that adults with hypersensitivity pneumonitis have a greater percentage of natural killer T cells than adults with sarcoidosis.[8] The natural killer T cells observed in patients with hypersensitivity pneumonitis were predominantly of the CD8+CD56+ population. Although the clinical use of this observation has yet to be determined, these data suggest that a high percentage of natural killer T cells in the BALF supports a diagnosis of hypersensitivity pneumonitis, whereas a low percentage neither confirms nor excludes the diagnosis.
  • Induced sputum has been proposed as a noninvasive alternative to BAL. In adults with hypersensitivity pneumonitis, the distribution of T-cell subpopulations is similar in induced sputum and BALF; however the percentage of lymphocytes was substantially lower in the induced sputum.[69] Although lymphocytosis and elevated proportion of CD8+ cells on induced sputum is consistent with hypersensitivity pneumonitis, induced sputum should not be relied on to exclude the diagnosis.
  • Lung biopsy can be considered if the diagnosis cannot be established by other less-invasive methods. The role of transbronchial biopsy is controversial, with some authors advocating it as a less invasive test;[65] others are less enthusiastic because the diagnostic yield is poor and interpretation is not consistent.[70] The extent to which invasive testing should be performed should be based on the probability of the diagnosis, the impact on patient and family of making the diagnosis, and the need to rule out alternative diagnoses.[6] Examples of lung biopsy findings are shown in the images below. Photomicrograph of a lung biopsy specimen reveals 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. Photomicrograph of a lung biopsy sample reveals inPhotomicrograph 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.
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Histologic Findings

  • Hypersensitivity pneumonitis is a diffuse, predominantly mononuclear cell inflammation of the small airways and pulmonary parenchyma. The inflammation is often associated with poorly formed, nonnecrotizing granulomas.[71] 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:[72, 73]
    • Bronchiolocentric, chronic interstitial inflammation in which lymphocytes predominate
    • Poorly formed, noncaseating necrotizing interstitial granulomas
    • Foamy macrophages within airspaces
    • Intra-alveolar foci of organizing pneumonia
    • Dense fibrosis, honeycombing, and fibroblastic foci in advanced, chronic disease with potential upper lobe contraction.
  • Nonclassic and nonspecific pathology has been described in patients who otherwise met criteria for hypersensitivity pneumonitis. Cases of clinical hypersensitivity pneumonitis have been documented with biopsy results showing only nonspecific interstitial pneumonitis (NSIP) or a bronchiolitis obliterans organizing pneumonia (BOOP)–like picture.[10, 74]
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Contributor Information and Disclosures
Author

Harold J Farber, MD  Associate Professor, Section of Pediatric Pulmonology, Baylor College of Medicine, Texas Children's Hospital

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 Paulose Varghese, MD  Assistant Professor of Pediatrics, Division of Pulmonology, Baylor College of Medicine, Texas Children's Hospital

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.

Specialty Editor Board

Girish D Sharma, MD  Associate Professor of Pediatrics, Rush Medical College; Director, Section of Pediatric Pulmonology and Rush Cystic Fibrosis Center, Rush University Medical 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.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

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.

Mary E Cataletto, MD  Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Professor of Clinical Pediatrics, State University of New York at Stony Brook; Director of Children's Sleep Services, Winthrop University Hospital

Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians

Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Michael R Bye, MD  Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; Attending Physician, Pediatric Pulmonary Medicine, Morgan Stanley Children's Hospital of New York Presbyterian, Columbia University Medical Center

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: Nothing to disclose.

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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.
High-resolution chest CT scan in the same patient as in the previous image 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.
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.
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.
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.
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.
Table 1. Commonly Described Causes of Hypersensitivity Pneumonitis[32]
Exposure Disease Source of Antigen
AvianBird fancier's lung, pigeon breeder's lung, poultry worker's lungFeathers, droppings, serum proteins, intestinal mucins, avian immunoglobulin A
AgricultureFarmer's lung, Bagasse (sugar cane) lung, mushroom worker's lung, potato riddler's lung, paprika slicer's lung, wine maker's lung Thermophilic actinomycetes, Aspergillus species, and other fungi in moldy hay or grains; moldy sugar cane; mushroom spores and thermophilic actinomycetes; moldy hay around potatoes, thermophilic actinomycetes, and others; Mucor stolonifer (on moldy paprika pods); B cinerea (noble rot on grapes)
Water-based systemsHumidifier lung, hot-tub lung, sauna taker's lung, lifeguard's lung, sewage pneumonitisAerosolized molds, endotoxins, mycobacteria, thermophilic actinomycetes, Penicillium species, others
Home environmentSummer-type pneumonitis, mold-contaminated walls, humidifiers, wallpaperTrichosporon species, mold contamination in older and/or water-damaged homes
ChemicalsChemical worker's lung, epoxy-resin lung, pyrethrum pneumonitisExposure to chemicals in manufacturing, laboratories, spray paints, heated epoxy resins, insecticides
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