Abstract

Hypersensitivity pneumonitis (HP) is a complex syndrome caused by an exaggerated immune response to the inhalation of a large variety of organic particles. The most frequent antigens that cause HP pigeon breeders’ disease) and bacteria (Saccharopolyspora rectivirgula). However, fungi are also implicated in many cases, including occupational and nonoccupational outbreaks. The clinical course of the disease is highly variable and its diagnosis clinically challenging since no specific test or biomarker allows a consistent diagnosis. Therefore, a combination of symptoms, bronchoalveolar lavage findings, chest imaging, lab tests, and often biopsies are needed for an accurate diagnosis. Regardless of the cause or the responsible environment, the histopathology is similar and usually consists of a granulomatous interstitial bronchiolocentric pneumonitis characterized by the presence of poorly formed granulomas and a prominent interstitial infiltrate composed of lymphocytes, plasma cells, and macrophages. However, some patients may show a ‘‘nonspecific interstitial pneumonia’’ pattern, or even a usual interstitial pneumonia–like pattern. Importantly, patients with chronic HP may evolve to interstitial fibrosis or develop emphysematous changes, although the reason(s) for these different pathological responses are presently unclear. This review provides a general overview of HP, emphasizing its fungal etiologies, and also
examines the currently used clinical criteria for diagnosis and proposes an alternative classification. Challenges for future research include identification of biomarkers that may predict outcome and progression (primarily of chronic HP), and the need for a better understanding of the underlyingmolecular and geneticmechanisms of the disease.
Keywords: hypersensitivity pneumonitis; extrinsic allergic alveolitis; fungi; lung inflammation

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