Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis

作者：Miya Okada Paterniti, Youwei Bi, Dinko Rekić, Yaning Wang, Banu A. Karimi-Shah, Badrul Alam Chowdhury · 发表于：Annals of the American Thoracic Society · 年份：2017 · DOI：10.1513/annalsats.201606-458oc · 被引用次数：199 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Lung Cancer Treatments and Mutations、Respiratory and Cough-Related Research

RATIONALE: Exploration of FVC as it relates to mortality in idiopathic pulmonary fibrosis (IPF), a chronic, progressive, and ultimately fatal parenchymal lung disease, is important both clinically and to the current drug development paradigm. We evaluated the association between FVC decline and mortality in what is to our knowledge the largest well-characterized placebo cohort to date. Additionally, we sought to explore the risk of death caused by acute exacerbations and to further validate previously identified baseline predictors of mortality. OBJECTIVES: To validate and further characterize FVC decline, acute exacerbations, and previously identified baseline predictors as they relate to risk of death. METHODS: A total of 1,132 placebo subjects from six studies used for the clinical development of nintedanib and pirfenidone for the treatment of IPF were included in the present analysis. Deaths were captured as all-cause mortality. A stratified Cox proportional hazards model was used to test the association between baseline predictors, decline in FVC % predicted from baseline, acute exacerbations, and death. Decline in FVC % predicted and exacerbations were treated as time-varying covariates. RESULTS: Subjects were followed for a mean of 60 weeks. At baseline, age, smoking status, lower FVC % predicted, and lower diffusing capacity of the lung for carbon monoxide % predicted were associated with an increased risk of death. The risk of death was also increased for subjects ha...