B41-10 Nationwide Analysis of Fibrotic and Non-fibrotic Hypersensitivity Pneumonitis: Clinical Characteristics and Factors Associated With Pulmonary Function Decline

Rationale Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease caused by inhalation of diverse antigens. In Japan, summer-type HP and bird-related HP are the most common forms of acute and chronic HP, respectively. Most studies have classified HP as acute or chronic rather than fibrotic or non-fibrotic. A refined understanding of these phenotypes is essential for prognosis and treatment. To our knowledge, this is the first nationwide report providing detailed characterization of HP subtypes. We aimed to clarify disease features using cases registered in a nationwide epidemiological survey, focusing on differences between fibrotic and non-fibrotic forms. Methods Cases with at least moderate diagnostic confidence according to HP guidelines were included. Data were collected via an electronic system and included demographics, symptoms, findings, laboratory results, pulmonary function, radiologic findings, and bronchoalveolar lavage fluid (BALF) analysis. Longitudinal data on pulmonary function, prognosis, and treatment were recorded annually. Environmental exposure history and causative antigens were also assessed. For analysis of pulmonary function decline, only cases with follow-up testing for over one year were included. Results From 90 institutions, 255 non-fibrotic and 506 fibrotic HP cases were collected. Fibrotic HP patients were older, more often had chronic onset, and more frequently had unknown antigens, resulting in lower diagnostic confidence. Biomarkers KL-6 and SP-D were higher in fibrotic HP (p = 0.011 and p < 0.0001), and forced vital capacity (FVC) was lower (p = 0.036). BALF lymphocyte fractions were elevated in both groups (63% vs. 36%). HRCT more frequently showed honeycombing and traction bronchiectasis in fibrotic HP, while non-fibrotic HP exhibited ground-glass opacities and centrilobular nodules. Glucocorticoids were prescribed in 40% of non-fibrotic and 49% of fibrotic cases; antifibrotics in 24% of fibrotic cases, mainly nintedanib. In non-fibrotic HP, fungi were the most frequent antigens, followed by birds; in fibrotic HP, birds predominated, followed by fungi. Humidifier-related and occupational exposures were also observed. In fibrotic HP, slower annual FVC decline was associated with acute onset, antigen identification, higher BMI, and lower baseline FVC (Table). Conversely, glucocorticoid or antifibrotic use correlated with greater decline. Cluster analysis divided fibrotic HP into two groups: The cluster with more smokers, lower KL-6, fewer ground-glass opacities, younger age, and more chronic onset, showed a greater annual FVC decline. Conclusions We analyzed the largest HP cohort to date. Antigen identification was a key factor associated with pulmonary function decline. Early recognition of causative antigens may help prevent disease progression. This abstract is funded by: Japan Agency for Medical Research and Development (AMED): Grant Number JP23ek0410101h0002