Edith T Zemanick, Bonnie Ramsey, Dorota Sands, Edward F McKone, Isabelle Fajac, Jennifer L Taylor-Cousar, Marcus A Mall, Michael W Konstan, Nitin Nair, Jiaqiang Zhu, Emilio Arteaga-Solis, Fredrick Van Goor, Lisa McGarry, Valentin Prieto-Centurion, Patrick R Sosnay, Carmen Bozic, David Waltz, Nicole Mayer-Hamblett
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引用次数: 0
Abstract
Background: Highly effective CFTR modulators improve CFTR function and lead to dramatic improvements in health outcomes in many people with cystic fibrosis (pwCF). The relationship between measures of CFTR function, such as sweat chloride concentration, and clinical outcomes in pwCF treated with CFTR modulators is poorly defined. We conducted analyses to better understand the relationships between sweat chloride and CFTR function in vitro, and between sweat chloride and clinical outcomes following CFTR modulator treatment.
Methods: Mean sweat chloride values in healthy people, CF carriers, and pwCF treated with CFTR modulators at different doses were compared to chloride transport in corresponding human bronchial epithelial (HBE) cells. A pooled analysis of phase 3 CFTR modulator studies was performed to evaluate the relationship between attained values of sweat chloride and improvements in lung function, body mass index (BMI), patient reported outcomes, pulmonary exacerbations, and lung function change over time.
Results: Sweat chloride concentrations in vivo correlated strongly with CFTR-dependent chloride current in HBE cells in vitro. Sweat chloride values of <30 mmol/L and ≥30 to <60 mmol/L in pwCF following CFTR modulator treatment were associated with better clinical outcomes than sweat chloride ≥60 to <80 mmol/L and ≥80 mmol/L.
Conclusions: In pwCF treated with CFTR modulators, lower sweat chloride levels (reflecting greater CFTR function) are associated with better clinical outcomes. These results support the therapeutic strategy of further restoring CFTR function towards normal, as reflected in lowering sweat chloride to below the diagnostic threshold for CF (<60 mmol/L) and to normal (<30 mmol/L), with CFTR modulators.
期刊介绍:
The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.