Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease
Thomas Radtke, Don S. Urquhart, Julia Braun, Peter J. Barry, I. Waller, N. Petch, Meir Mei‐Zahav, Mordechai R. Kramer, T. Hua-Huy, Anh Tuan Dinh‐Xuan, J. Alastair Innes, Sara McArthur, Aleksandar Sovtić, Bojana Gojsina, Samuel Vergès, T. de Maat, Lisa Morrison, Jamie Wood, Samantha Crute, Craig A. Williams, Owen W. Tomlinson, Ronen Bar‐Yoseph, Alexandra Hebestreit, Bradley S. Quon, Eugenie Kwong, Zoe L. Saynor, Adam J. Causer, Anne L. Stephenson, Jane E. Schneiderman, Michelle Shaw, Tiffany Dwyer, Daniel Stevens, Natascha Remus, Benoît Douvry, Karla Foster, Christian Benden, Félix Ratjen, Helge Hebestreit
Abstract
Abstract Rationale Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease 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 1 second (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 modeled 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 percentage predicted peak oxygen uptake (V˙o2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% 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 11 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 advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection.