Cardiopulmonary exercise testing provides prognostic information in advanced cystic fibrosis lung disease

Abstract

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease (ACFLD) is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2-years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1s (FEV1)  40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modelled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1 30.9±5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex and FEV1, revealed percent predicted peak oxygen uptake ( OV 2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional ten percent predicted were 0.60 (95% confidence interval, 0.43–0.90, P=0.008) and 0.60 (0.48–0.82, P<0.001). Tree-structured regression models, including a set of twelve prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak 49.2% predicted versus 10.9% for those with a Wpeak >49.2% predicted, P<0.001. Conclusions: CPET provides prognostic information in ACFLD and Wpeak appears to be a promising marker for LTX referral and candidate selection.