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

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with lung function decline and high mortality. RESEARCH QUESTION: What are the associations between thresholds of lung function decline and the risk of mortality in patients with IPF? STUDY DESIGN AND METHODS: 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. RESULTS: 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. INTERPRETATION: Our results show that even small declines in FVC and Dlco % predicted inform prognosis in patients with IPF. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01915511; URL: www. CLINICALTRIALS: gov.

Duke Scholars

Author Jamie Lynn Todd Medicine, Pulmonary, Allergy, and Critical Care Medicine

Author Megan Lee Neely Biostatistics & Bioinformatics, Division of Biostatistics

Author Scott Michael Palmer Jr. Medicine, Pulmonary, Allergy, and Critical Care Medicine

Author Daniel Wojdyla