Prospective study of fibrosis in the lung endpoints (PROFILE): characteristics of an incident cohort of patients with idiopathic pulmonary fibrosis

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease. Prospective study of fibrosis in the lung endpoints (PROFILE) was a prospective, observational cohort study designed to better define the natural history of IPF, understand disease biology and identify biomarkers to support disease management and enhance clinical trial design. Methods Individuals with an incident diagnosis of IPF were recruited between 2010 and 2017 across two co-ordinating centres in the UK. Demographics, clinical measurements and blood samples were obtained at baseline, and 1, 3, 6, 12, 24 and 36 months. Disease progression events were defined as death or relative forced vital capacity (FVC) decline >10% at 12 months. Survival estimates were modelled using Cox proportional hazards; longitudinal lung function decline was estimated using mixed effect models, specified with restricted cubic splines, a random intercept for participant and random effect for study visit. All models were adjusted for baseline age, sex and continuous baseline percent predicted FVC (ppFVC). Results A total of 632 participants were recruited, 77.1% were male, and mean age at enrolment was 70.4 years (SD 8.4). Mean baseline ppFVC was 79.5% (SD 19.2), and mean percent predicted DL CO (ppDL CO ) was 45.7% (SD 15.1). A total of 304 (48.1%) participants met disease progression criteria at 1 year. Median survival was 3.7 years (95%CI 3.3 to 4.0). More severe baseline physiology, 12-month relative lung function decline ≥10%, older age and short telomeres were independent risk factors for mortality. Twelve-month estimated change in ppFVC was −5.28% (95% CI −6.34 to −4.22) with an average FVC decline of 186.9 mL (95% CI −225.4 to −148.5); 12-month estimated change in ppDL CO was −3.35% (95% CI −4.30 to −2.40). Conclusion The PROFILE cohort confirms that untreated IPF is inexorably progressive and inevitably fatal with a poor median survival from diagnosis.