Diagnostic, prognostic, and therapeutic challenges in patients with hypersensitivity pneumonitis

Hypersensitivity pneumonitis is an immune-mediated lung disease resulting from prolonged and/or repeated exposure to an inciting antigen. The official American Thoracic Society (ATS)/Japanese Respiratory Society/Latin American Thoracic Association clinical practice guideline for the diagnosis of hypersensitivity pneumonitis in adults and the European Respiratory Society/ATS statement for the update of the international multidisciplinary classification of the interstitial pneumonias represented a major step to reduce diagnostic uncertainty among clinicians. However, the diagnosis of hypersensitivity pneumonitis remains sometimes challenging due to the variability in clinical, radiological and pathological manifestations of hypersensitivity pneumonitis. Diagnostic challenges include the timely identification of the inciting antigen, the proper execution and interpretation of high-resolution computed tomography, the absence of a disease-specific, clinically applicable feature in bronchoalveolar lavage, the limited access to cryobiopsy in some centres, and the lack of pathognomonic findings at the clinical, imaging and pathology level. Accordingly, prognostic challenges also exist and include the clinical applicability of disease-specific biomarkers. In terms of treatment, there is a pressing need for studies aiming to identify endotypes that are more likely to benefit from immunomodulation, antifibrotics or a combination of both. This review article aims to present diagnostic, prognostic and therapeutic challenges in patients with hypersensitivity pneumonitis and highlight future perspectives in the field.