Changes in Lung Function and Mortality Risk in Patients With Idiopathic Pulmonary Fibrosis.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with lung function decline and high mortality. What are the associations between thresholds of lung function decline and the risk of mortality in patients with IPF? The Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry enrolled patients with IPF that was diagnosed or confirmed at the enrolling center within the prior 6 months. Associations between time to first decline in FVC or diffusing capacity of the lungs for carbon monoxide (Dlco) of ≥ 2% predicted, ≥ 5% predicted, and ≥ 10% predicted (and ≥ 15% predicted for Dlco) and risk of subsequent death or lung transplantation was assessed using Cox proportional hazards models with a time-dependent covariate. Models were unadjusted or adjusted for FVC and Dlco % predicted, age, sex, smoking status, BMI, antifibrotic treatment (yes or no), and oxygen use at enrollment. Among 1,001 patients, median follow-up time was 38.4 months. Significant associations were observed between all thresholds of decline in FVC and Dlco % predicted and the risk of death or lung transplantation in unadjusted and adjusted analyses. In adjusted analyses, absolute declines in FVC of ≥ 2% predicted, ≥ 5% predicted, and ≥ 10% predicted were associated with 1.8-fold, 2.3-fold, and 2.7-fold increases in the risk of subsequent death or lung transplantation, whereas absolute declines in Dlco of ≥ 2% predicted, ≥ 5% predicted, ≥ 10% predicted, and ≥ 15% predicted were associated with 2.0-fold, 1.4-fold, 1.5-fold, and 1.9-fold increases in the risk of subsequent death or lung transplantation, respectively. For Dlco, but not FVC, the increase in risk generally was greater for patients meeting a threshold based on a relative rather than an absolute decline. Our results show that even small declines in FVC and Dlco % predicted inform prognosis in patients with IPF. ClinicalTrials.gov; No.: NCT01915511; URL: www. gov.