Effect of lumacaftor-ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis: Results from the PROSPECT MCC sub-study

J Cyst Fibros. 2022 Jan;21(1):143-145. doi: 10.1016/j.jcf.2021.05.004. Epub 2021 May 31.

Abstract

CFTR function is required for normal mucociliary clearance (MCC) and cough-assisted clearance (CC). Lumacaftor-ivacaftor is approved for use in people with cystic fibrosis (CF) carrying two copies of F508del-CFTR. In this observational study performed at four study sites, we characterized the effect of lumacaftor-ivacaftor on mucociliary and cough clearance and related this to other clinical and research endpoints after one month of treatment. Twenty-five adolescents and adults were enrolled. No effect on whole lung MCC was observed, but CC was significantly increased. Sweat chloride improved by 18 mEq/L in this group, indicating a modest restoration of CFTR activity, but no demonstrable change in FEV1 or lung clearance index was observed. We speculate that the modest effect of lumacaftor-ivacaftor on CFTR function was insufficient to yield an improvement in MCC.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aminophenols / therapeutic use*
  • Aminopyridines / therapeutic use*
  • Benzodioxoles / therapeutic use*
  • Child
  • Chloride Channel Agonists / therapeutic use
  • Cohort Studies
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis Transmembrane Conductance Regulator / therapeutic use
  • Drug Combinations
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mucociliary Clearance / drug effects*
  • Prospective Studies
  • Quinolones / therapeutic use*
  • Young Adult

Substances

  • Aminophenols
  • Aminopyridines
  • Benzodioxoles
  • Chloride Channel Agonists
  • Drug Combinations
  • Quinolones
  • lumacaftor, ivacaftor drug combination
  • Cystic Fibrosis Transmembrane Conductance Regulator