Hebestreit H; Hulzebos EH; Schneiderman JE; Karila C; Boas SR; Kriemler S; Switzerland; Dwyer T; Sahlberg M;
Urquhart DS; Lands LC; Ratjen F; Takken T; Varanistkaya L; Rücker V; Hebestreit A; Usemann J; Radtke T;

American Journal Of Respiratory And Critical Care Medicine [Am J Respir Crit Care Med] 2018 Oct 15. Date of Electronic Publication: 2018 Oct 15.

Rationale: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors is unclear.
Objectives: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake (VO2peak) following rigorous adjustment for other predictors.
Measurements and Main Results: Data from 10 CF-centers in Australia, Europe and North America were collected retrospectively. 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation (LTx) was analyzed using Cox proportional hazards regression. In addition, phenotyping using hirarchical Ward’s clustering was performed to characterize high risk subgroups. Cox regression showed – even after adjustment for sex, forced expiratory volume in 1s (%predicted), body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model – that VO2peak in %predicted, hazard ratio (HR) 0.964 [95%-CI: 0.944-0.986], peak work rate (%predicted, HR 0.969 [0.951-0.988], ventilatory equivalent for oxygen (VE/VO2peak) HR 1.085 [1.041-1.132], and carbon dioxide (VE/VCO2peak), HR 1.060 [1.007-1.115], all P<0.05) were significant predictors of death or LTx at 10 years follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high risk cluster characterized by poor lung function, nutritional status and exercise capacity.
Conclusions: In conclusion, CPET provides additional prognostic information to established predictors of death/LTx in CF. High risk patients may especially benefit from regular monitoring of exercise capacity and exercise counselling.