Effects of cystic fibrosis transmembrane conductance regulator potentiators on clinical outcomes of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Introduction: Excessive mucus secretion is pivotal in chronic obstructive pulmonary disease (COPD) pathophysiology, particularly in chronic bronchitis phenotypes. Cystic fibrosis transmembrane conductance regulator (CFTR) has been implicated in COPD-related hypersecretion with acquired dysfunction, and emerged as a therapeutic target. However, the clinical efficacy of CFTR-potentiators in COPD remains controversial.

Methods: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal (CSTJ), and Wanfang Database to retrieve eligible studies published before 28 May 2024.

Results: A total of 1172 COPD patients were included, meta-analysis showed that CFTR-potentiators significantly increased forced expiratory volume in 1 s (FEV₁) and decreased sweat chloride and fibrinogen levels, with moderate-to-high quality evidence. However, no significant effects were observed on the percentage of detected FEV₁ to predicted FEV₁ (FEV₁% predicted), forced vital capacity (FVC), COPD assessment test (CAT) score, St. George's Respiratory Questionnaire (SGRQ) score, or acute exacerbation times, with low-to-moderate quality evidence.

Conclusion: Our meta-analysis demonstrated CFTR-potentiators' potential efficacy in increasing FEV₁, decreasing sweat chloride and fibrinogen levels, despite limited impacts on FEV₁% predicted, FVC, CAT score, SGRQ score, and acute exacerbations, underscoring the necessity for future research to evaluate its effects on mucus hypersecretion, acute exacerbations, hospitalizations, and mortality in COPD management. Review registration PROSPERO Identifier: CRD42024538708.