Risk stratification of acute exacerbations by autoantibodies in patients with idiopathic interstitial pneumonia.

Although acute exacerbation of idiopathic interstitial pneumonia (AE-IIP) is a critical event, the detailed features of connective tissue diseases (CTD) that affect the incidence of AE-IIP have not been fully elucidated. This study aimed to clarify the CTD-related features that affect the incidence of AE-IIP. This was a post hoc analysis of a prospective and multicenter cohort study conducted between 2015 and 2020. Newly diagnosed patients with IIP were consecutively enrolled, and 74 autoimmune features and autoantibodies were comprehensively checked during IIP diagnosis. In total, 222 patients with IIP were enrolled. The median observation period was 36 months, during which 34 patients developed AE-IIP. In multivariate models adjusted for age, gender, and %predicted FVC, AE-IIP frequently occurred in patients positive for anti-cyclic citrullinated peptide (CCP) antibody (hazard ratio [HR]: 4.407, p = 0.004, q = 0.027), while it was less common in patients positive for antinuclear antibodies (ANA) ≥ 320 or polymyositis/dermatomyositis (PM/DM)- or systemic sclerosis (SSc)-related antibodies (HR < 0.001, p < 0.001, q < 0.001). A composite model consisting of these items stratified the incidence of AE-IIP (p < 0.001), which was closely related to the mortality. These results indicate that the presence of anti-CCP antibodies, ANA, or PM/DM/SSc-related antibodies, in addition to decreased lung function, could help determine the risk of AE-IIP in patients with IIP.