Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease.

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 (FEV 1 ) ≤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 (FEV 1 30.9±5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex and FEV 1 , revealed percent predicted peak oxygen uptake (V ̇O 2peak ) and peak work rate (W peak ) 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 W peak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a W peak ≤49.2% predicted versus 10.9% for those with a W peak >49.2% predicted, P<0.001. Conclusions: CPET provides prognostic information in ACFLD and W peak appears to be a promising marker for LTX referral and candidate selection.