Multi-dimensional Assessment of IPF Across a Wide Range of Disease Severity

Abstract

The pathophysiology of idiopathic pulmonary fibrosis (IPF) is complex, and its clinical course is difficult to predict. Perceived dyspnea, exercise capacity, and lung physiology have all been associated with mortality outcomes in IPF, but the significance of these relationships is unclear. We sought to investigate the correlation among these variables and their independent predictive capability in determining mortality outcomes. Four-hundred-thirty-seven patients diagnosed with IPF from three independent centers were included in the study. Medical Research Council Dyspnea Score (MRCDS), 6-min walk distance (6MWD), and pulmonary function tests were determined at baseline. The end-point was 18-month transplant-free survival. Correlations between MRCDS, 6MWD, forced vital capacity (FVC), and diffusing lung capacity for carbon monoxide were either very weak or weak. Calculation of variance inflation factors demonstrated absence of collinearity among these variables. Univariate regression analysis and c-statistics identified MRCDS, 6MWD, and FVC as significant predictors of 18-month transplant-free survival. Multivariate regression analysis retained MRCDS, 6MWD, and FVC as independent predictors of mortality. To ensure generalizability, we confirmed the results in subgroups of patients stratified according to baseline FVC, and further by considering lung transplant as a competing event to death. In a cohort of patients with IPF encompassing a wide range of disease severity, baseline perceived exertional dyspnea, exercise capacity, and lung function are weakly correlated to each other, translating in the absence of collinearity. MRCDS, 6MWD, and FVC are significant and independent predictors of outcome, suggesting that a multi-dimensional assessment of IPF is prognostically appropriate and advantageous.