de Almeida IS; Centro Infant, Rio Grande do Sul, Brazil
Vendrusculo FM; da Costa MS; Donadio MVF

Pediatric Pulmonology. 61(9):e71826, 2026 Sep.

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 VO2). Secondary outcomes included peak VO2 (%
predicted), VO2 at the first ventilatory threshold (VT1), breathing
reserve, workload, forced expiratory volume in one second (FEV1), and body
mass index. Meta-analyses were performed using a random-effects model with
heterogeneity assessed by the I2 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 VO2 (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, VO2 at VT1 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 VO2, although it
appears to variably influence outcomes related to ventilatory response and
exercise performance.