Pediatric Hypersensitivity Pneumonitis

Updated: May 20, 2016
  • Author: Harold J Farber, MD, MSPH; Chief Editor: Girish D Sharma, MD, FCCP, FAAP  more...
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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, hypersensitivity pneumonitis may be a cause of recurrent pneumonitis. In its chronic form, hypersensitivity pneumonitis may insidiously lead to pulmonary fibrosis and end-stage lung disease.

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 hypersensitivity pneumonitis have been reported in children. [3] Hypersensitivity pneumonitides are classically considered occupational illnesses and have colorful names reflecting the associated occupation. New sources of exposure causing hypersensitivity pneumonitis are continuing to be identified.

Some of these illnesses and their associated causes are as follows: [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

  • Wind instrument lung – Bacteria and/or mold contamination of wind instruments [5, 6, 7]

  • Feather duvet lung - Organic dust due to goose or duck feathers in duvets or pillows [8, 9, 10]



Numerous organic and inorganic antigens can cause hypersensitivity pneumonitis. To cause pneumonitis, the antigen must penetrate into the small airways; therefore, its size must be within the respirable range (< 5 mm). Implicated antigens include avian (bird) antigens, mammalian proteins, fungi and fungal spores, bacterial antigens, and small-molecular-weight chemicals. [11] See Causes.

Immune responses

Although much research has been done, how immune dysregulation causes the disease is still unclear. An exuberant production of antibody (especially immunoglobulin G [IgG]) against the offending antigen is frequently identified. However, many patients with precipitating antibodies against antigens associated with hypersensitivity pneumonitis have no disease, suggesting that the precipitating antibodies by themselves are not the cause of the disease. [12, 13]

Although bronchoalveolar lavage (BAL) fluid (BALF) from adults with hypersensitivity pneumonitis reveals a decreased CD4/CD8 ratio of T lymphocytes and increased natural killer cells, this finding has not been consistently demonstrated in pediatric studies. Healthy children tend to naturally have a CD8 predominance, and this does not appear to be significantly altered in children with hypersensitivity pneumonitis. However, in all ages, lymphocytosis appears to be present. [13, 14, 15]

An important role for Th1 immune response is suggested by the production and release of tumor necrosis factor (TNF), interferon-gamma, interleukin (IL)-12 and IL-18 by patients with hypersensitivity pneumonitis and animal models of hypersensitivity pneumonitis. [16, 17, 18] The inflammatory responses observed in chronic hypersensitivity pneumonitis differ from those of acute and subacute hypersensitivity pneumonitis. Patients with chronic hypersensitivity pneumonitis did not have as prominent a bronchoalveolar lavage lymphocytosis and had an increase of the CD4+:CD8+ ratio compared with those with subacute disease.

Cytokine profiles resembled more the Th2-like phenotype with BAL fluid demonstrating increased CXCR4 expression and decreased CXCR3 expression. Supernatants from antigen-specific–stimulated cells from chronic hypersensitivity pneumonitis produced higher levels of IL-4 and lower levels of IFN-gamma compared with subacute HP. [19]

IL-8 (a chemoattractant of neutrophils) is released by a cell line with properties of alveolar lung cells when stimulated by thermophilic bacteria. [20] High levels of IL-8 are released by alveolar macrophages in patients with acute hypersensitivity pneumonitis. [21] This corresponds to the BAL fluid neutrophilia observed immediately upon antigen challenge in acute hypersensitivity pneumonitis. [22]

A role for interferon-gamma is suggested by the observation that interferon-gamma knockout mice lack granulomatous inflammation in response to stimulation by thermophilic bacteria, whereas granulomatous inflammation develops in both knockout mice given interferon-gamma replacement and wild-type mice. [23]

Hypersensitivity pneumonitis seems to be least common among active smokers of tobacco products. This relative infrequency might result from suppression of alveolar macrophage function. [24, 25, 26] However, a review of an outbreak of hypersensitivity pneumonitis 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. [27] Another study suggested that hypersensitivity pneumonitis may be insidious and is most often associated with low survival rates when it occurs in smokers. [28]


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. [29, 30, 31] A study of BALF from children with hypersensitivity pneumonitis compared with healthy patients without lung disease showed an increase in lymphocytes expressing HLA-DR phenotype. [15]

Viral infections

Animal models have suggested that viral infections may play a role in triggering or augmenting hypersensitivity pneumonitis flares in genetically susceptible subjects. [32] Examination of BALF from persons with farmer’s lung showed respiratory viruses during acute exacerbations of farmer’s lung. [23]




United States

The frequency in children is unknown.


Acute hypersensitivity pneumonitis 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.

Summer-type hypersensitivity pneumonitis has been classically described in the southern and western parts of Japan and is associated with older housing and shady, damp, poorly ventilated rooms. Exacerbations in the summer are followed by remissions in the fall and winter. [33, 34] The causative agent has been identified as Trichosporon cutaneum. The fungus grows on warm, decaying organic matter. [35, 36] Although more common in adults, summer-type hypersensitivity pneumonitis has been reported in children. [37, 38, 39]


In contrast to the disease in adults, mortality due to hypersensitivity pneumonitis in childhood is uncommon. Fatal cases in childhood, however, have been reported. [3] Significant morbidity can result if the child is not removed from the causative environment because flares of acute hypersensitivity pneumonitis can be severe and life-threatening.

Progression of chronic disease can lead to pulmonary fibrosis and end-stage lung disease. Severe pulmonary fibrosis with honeycombing and spontaneous pneumothorax as a consequence of chronic hypersensitivity pneumonitis has been described in an adolescent. [2] Such clinical picture is associated with high mortality rates. [40]


See Mortality/Morbidity.