Hebestreit H; Hulzebos EHJ; Schneiderman JE; Karila C; Boas SR; Kriemler
S; Dwyer T; Sahlberg M; Urquhart DS; Lands LC; Ratjen F; Takken T;Varanistkaya L; Rucker V; Hebestreit A;
Usemann J; Radtke T; PrognosticValue of CPET in CF Study Group.

American Journal of Respiratory & Critical Care Medicine. 199(8):987-995,
2019 04 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 ( V. o2peak) following rigorous adjustment for
other predictors.

METHODS: Data from 10 CF centers in Australia, Europe, and North America
were collected retrospectively. A total of 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 was
analyzed using Cox proportional hazards regression. In addition,
phenotyping using hierarchical Ward clustering was performed to
characterize high-risk subgroups.

MEASUREMENTS AND MAIN RESULTS: Cox regression showed, even after
adjustment for sex, FEV1% predicted, body mass index (z-score), age at
CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates
in the model, that V. o2peak in % predicted (hazard ratio [HR], 0.964; 95%
confidence interval [CI], 0.944-0.986), peak work rate (% predicted; HR,
0.969; 95% CI, 0.951-0.988), ventilatory equivalent for oxygen (HR, 1.085;
95% CI, 1.041-1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007-1.115)
(all P < 0.05) were significant predictors of death or lung
transplantation at 10-year 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: CPET provides additional prognostic information to
established predictors of death/lung transplantation in CF. High-risk
patients may especially benefit from regular monitoring of exercise
capacity and exercise counseling.