Prognostic Value of IPF/PPF/non-PPF Classification Beyond ILD-GAP Stage in Fibrotic ILD

Background Progressive pulmonary fibrosis (PPF) identifies patients with fibrotic interstitial lung disease (F-ILD) who show progressive disease behaviour resembling idiopathic pulmonary fibrosis (IPF). However, it remains uncertain whether classification as IPF, PPF, or non-PPF provides prognostic information beyond established baseline mortality predictors. We compared the prognostic performance of IPF/PPF/non-PPF classification with the interstitial lung disease–gender–age–physiology (ILD-GAP) stage and assessed whether IPF/PPF/non-PPF classification provided additional prognostic information. Methods This is a nationwide prospective cohort study of incident F-ILD patients diagnosed at all Danish tertiary ILD centres between 1 June 2016 and 31 May 2017. Patients with fewer than two pulmonary function tests or without registry linkage were excluded. Patients were retrospectively classified as IPF, PPF, or non-PPF according to the 2022 PPF criteria. Baseline ILD-GAP stage was calculated at diagnosis. Cox proportional hazards models were used to assess all-cause mortality, and Harrell’s C-index, time-dependent area under the receiver operating characteristic curve (AUC), and Akaike’s Information Criterion (AIC) were used to compare discrimination and relative model fit. Results Among 393 incident F-ILD patients, 362 were included: 165 with IPF, 113 developed PPF, and 84 were classified as non-PPF. During follow-up, 216 patients died. In unadjusted analysis, PPF and non-PPF were associated with lower mortality hazard than IPF (HR 0.7 and 0.68; p = 0.028 and 0.035); however, these associations attenuated after adjustment for ILD-GAP stage (HR 0.93 and 0.93; p = 0.64 and 0.69). ILD-GAP stage II–III remained strongly associated with mortality in the adjusted model (HR 2.60, 95% CI 1.95–3.47; p < 0.001). Harrell’s C-index was 0.54 for IPF/PPF/non-PPF classification, 0.62 for ILD-GAP stage, and 0.62 for the combined ILD-GAP and IPF/PPF/non-PPF classification model. Pairwise comparisons of Harrell’s C-index showed ILD-GAP stage discriminated mortality risk significantly better than IPF/PPF/non-PPF classification, with an absolute increase in C-index of 0.085 (95% CI 0.042 to 0.127; p < 0.001). Adding IPF/PPF/non-PPF classification to ILD-GAP stage did not improve discrimination (difference 0.001) Conclusions After adjustment for ILD-GAP stage, the IPF/PPF/non-PPF classification did not confer prognostic value. Higher ILD-GAP was strongly associated with increased mortality, and adding IPF/PPF/non-PPF classification to ILD-GAP did not improve discrimination.