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 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 ([Formula: see text]o_2peak) and peak work rate (W_peak) 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 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 advanced CF lung disease, and W_peak appears to be a promising marker for LTX referral and candidate selection.

Keywords: CF; lung transplantation; peak oxygen uptake; peak work rate; survival..

Figure 1.

Receiver operating characteristic curves for (A) percentage predicted peak oxygen uptake ($\dot{\text{V}}$o_2peak) and (B) percentage predicted peak work rate (W_peak). The optimal cutoff values for $\dot{\text{V}}$o_2peak and W_peak were 39.4% and 49.2% predicted, respectively. Area under the receiver operating characteristic curve (AUC) and 95% confidence intervals are shown. The gray dashed line indicates no discriminatory ability (AUC = 0.5). The red asterisk displays the optimal cutoff value for 2-year risk of death/lung transplant. Sensitivity = true-positive rate; 1 − specificity = false-positive rate.

Figure 2.

Kaplan-Meier survival curves for percentage predicted peak oxygen uptake ($\dot{\text{V}}$o_2peak) and peak work rate (W_peak). The figure shows the probability of death/lung transplant within 2 years (herein referred to as survival probability) after cardiopulmonary exercise testing for different groups of patients categorized according to $\dot{\text{V}}$o_2peak and W_peak cutoff values from receiver operating characteristic curves. The blue curves represent the groups of patients with (A) $\dot{\text{V}}$o_2peak >  39.4% predicted, or (B) W_peak > 49.2% predicted. The red curves represent the group of patients with (A) $\dot{\text{V}}$o_2peak ⩽ 39.4% predicted or (B) W_peak ⩽ 49.2% predicted. One patient had a valid W_peak test, but gas exchange data including oxygen uptake values were not valid (number of patients at risk at start of observation: n = 173 for $\dot{\text{V}}$o_2peak, n = 174 for W_peak).

Figure 3.

Conditional inference tree. The original cutoff values for W_peak were ⩽49.15% and >49.15% predicted, respectively. For ease of reading, we rounded the cutoff values to one decimal place. W_peak = peak work rate.