Diagnostic, prognostic, and therapeutic challenges in patients with Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP) is an immune-mediated lung disease resulting from prolonged and/or repeated exposure to an inciting antigen. The Official ATS/JRS/ALAT Clinical Practice Guideline for the Diagnosis of Hypersensitivity Pneumonitis in Adults and the ERS/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 HP remains sometimes challenging due to the variability in clinical, radiological, and pathologic manifestations of HP. Diagnostic challenges include the timely identification of the inciting antigen, the proper execution and interpretation of High-Resolution Computed Tomography (HRCT), the absence of a disease-specific, clinically applicable feature in bronchoalveolar lavage (BAL), the limited access to cryobiopsy in some centers, 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 aimed at identifying 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 HP and highlight future perspectives in the field.