CFTR Modulator Therapy and Aerobic Fitness Changes in Aerobic Fitness Following Initiation of CFTR Modulator Therapy: A Systematic Review and Meta‐Analysis

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ABSTRACT Introduction Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to relevant clinical advances in people with cystic fibrosis (pwCF). However, its effects on aerobic fitness are unclear. Objective To evaluate the effects of CFTR modulator therapy on aerobic fitness in pwCF through a systematic review and meta‐analysis. Methods This systematic review (CRD420251066602) was conducted by searching major databases without date or language restrictions. Analytical studies evaluating cardiopulmonary exercise testing outcomes before and after CFTR modulator therapy were included. The primary outcome was peak oxygen uptake (peak VO 2 ). Secondary outcomes included peak VO 2 (% predicted), VO 2 at the first ventilatory threshold (VT 1 ), breathing reserve, workload, forced expiratory volume in one second (FEV 1 ), and body mass index. Meta‐analyses were performed using a random‐effects model with heterogeneity assessed by the I 2 statistic, and sensitivity analyses conducted. Results Thirteen studies ( n = 578 participants) were included, of which 11 were eligible for meta‐analysis. The meta‐analysis did not identify a significant improvement in peak VO 2 (mL·kg −1 ·min −1 ) after CFTR modulator use (MD = −0.22; 95% CI: −2.10 to 1.65; p = 0.82). For submaximal outcomes, after sensitivity analysis, VO 2 at VT 1 was significantly lower in the post‐intervention period (MD = −1.85; 95% CI: −2.61 to −1.10; p < 0.00001). Breathing reserve increased significantly (MD = 7.94; 95% CI: 2.15 to 13.73; p = 0.007), and workload also increased significantly (MD = 15.39; 95% CI: 2.20 to 28.58; p = 0.02). Conclusion CFTR modulator therapy is not consistently associated with improvements in aerobic fitness, as assessed by peak VO 2 , although it appears to variably influence outcomes related to ventilatory response and exercise performance.