Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease. Three trajectories of the clinical course of IPF (rapid, slow and non-progressing) have been described and associated with duration of symptoms. This was observed for 114 IPF patients and has not yet been validated1. It remains unclear whether these IPF trajectories represent clinical phenotypes or merely reflect duration of disease before diagnosis.We describe the association between duration of symptoms prior to IPF diagnosis and survival and lung function decline (FVC, DLCO) in the European MultiPartner IPF Registry (EMPIRE), to validate these three disease trajectories. Methods We analyze data from 3,178 incident IPF patients enrolled in EMPIRE between 2012-2022. For analysis, patients were classified according to symptom duration: 6 months, 6-24 months, and 24 months. Outcomes included overall survival, decline in forced vital capacity (FVC), and diffusion capacity for carbon monoxide (DLCO). Multivariate linear models were used to estimate annual decline for FVC and DLCO (adjusted for sex, age, FVC and DLCO at registry entry, use of antifibrotics, finger clubbing and smoking). Cox proportional hazards models were used for survival analysis. Results The mean duration of symptoms before diagnosis was 18 months (SD 22). In the unadjusted model the overall annual FVC decline was 126 mL (95% CI 100 to 151; p 0.001) and was 131 mL (95% CI 104 to 159; p 0.001) following adjustment. DLCO declined by 0.313 mmol/kPa/min (95% CI -0.380 to -0.246; p 0.001) in the unadjusted and 0.339 mmol/kPa/min (95% CI -0.411 to -0.267, p 0.001) in the adjusted model. The observed decline in FVC (p 0.001) and DLCO (p = 0.09) was most pronounced when symptoms lasted 24 months (FVC: 126mL; DLCO: 0.313 mmol/kPa/min), intermediate in those with duration of 6 - 24 months (FVC: 82mL; DLCO: 0.285 mmol/kPa/min), and smallest in those with duration 6 months (FVC: 52 mL; DLCO: 0.214 mmol/kPa/min).Overall survival differed between groups (p = 0.013), with the 6 months group showing best survival (HR 0.75), the 6-24 months group intermediate (HR 0.84) survival and the 24 months group worst survival (HR = 1.0). Conclusions We assume that, duration of symptoms before diagnosis of IPF appears to reflect more advanced disease rather than distinct IPF trajectories or clinical phenotypes. Footnotes Selman M, Carrillo G, Estrada A, et al. Accelerated variant of idiopathic pulmonary fibrosis: Clinical behavior and gene expression pattern. PLoS One. 2007;2(5). doi:10.1371/journal.pone.0000482 This abstract is funded by: None
Kamm et al. (2026) studied this question.