Effect of elexacaftor/tezacaftor/ivacaftor on mucus and mucociliary clearance in cystic fibrosis.
Cystic fibrosis
Elexacaftor
Modulator
Mucociliary clearance
Rheology
mucus
Journal
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
received:
19
05
2023
revised:
15
09
2023
accepted:
12
10
2023
pubmed:
17
10
2023
medline:
17
10
2023
entrez:
16
10
2023
Statut:
ppublish
Résumé
The cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (E/T/I) is highly effective clinically for those with at least one F508del-CFTR allele. The effects of E/T/I on mucociliary clearance (MCC) and sputum properties are unknown. We, therefore, sought to characterize the effects of E/T/I on in vivo MCC and sputum characteristics hypothesized to impact mucus transport. Forty-four participants ≥12 years of age were enrolled into this prospective, observational trial prior to initiation of E/T/I and had baseline measurement of MCC and characterization of induced sputum and exhaled breath condensate (EBC) samples. Study procedures were repeated after 1 month of E/T/I treatment. Average age was 27.7 years with baseline forced expiratory volume in 1 second (FEV E/T/I improved the hydration of respiratory secretions (% solids) and markedly accelerated MCC. These data confirm the link between CFTR function, mucus solid content, and MCC and help to define the utility of MCC and mucus-related bioassays in future efforts to restore CFTR function in all people with CF.
Sections du résumé
BACKGROUND
BACKGROUND
The cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (E/T/I) is highly effective clinically for those with at least one F508del-CFTR allele. The effects of E/T/I on mucociliary clearance (MCC) and sputum properties are unknown. We, therefore, sought to characterize the effects of E/T/I on in vivo MCC and sputum characteristics hypothesized to impact mucus transport.
METHODS
METHODS
Forty-four participants ≥12 years of age were enrolled into this prospective, observational trial prior to initiation of E/T/I and had baseline measurement of MCC and characterization of induced sputum and exhaled breath condensate (EBC) samples. Study procedures were repeated after 1 month of E/T/I treatment.
RESULTS
RESULTS
Average age was 27.7 years with baseline forced expiratory volume in 1 second (FEV
CONCLUSIONS
CONCLUSIONS
E/T/I improved the hydration of respiratory secretions (% solids) and markedly accelerated MCC. These data confirm the link between CFTR function, mucus solid content, and MCC and help to define the utility of MCC and mucus-related bioassays in future efforts to restore CFTR function in all people with CF.
Identifiants
pubmed: 37845149
pii: S1569-1993(23)00931-1
doi: 10.1016/j.jcf.2023.10.010
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
155-160Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK065988
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK072482
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003098
Pays : United States
Informations de copyright
Copyright © 2023. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All authors received research support from the Cystic Fibrosis Foundation for the conduct of this study. In addition, SHD declares research funding from Vertex Pharmaceuticals, Astra Zeneca, Calithera Biosciences, Chiesi, and 4D Molecular Therapeutics, as well as consulting or advisory fees from Boehringer Ingleheim, Abbvie Pharmaceuticals, and Enterprise Therapeutics; PM reports research support from Eloxx Pharmaceuticals, Vertex Pharmaceuticals; CRE declares research funding Tavanta Therapeutics and the NIDDK; DPN reports consulting fees from Vertex Pharmaceuticals, Respirion, and Kither Biotechnology; WDB reports research funding from Vertex Pharmaceuticals; and SMR reports research funding and non-financial support from Vertex Pharmaceuticals. TEC, JMP, BLL, ERB, ESH, AC, LJE, KZ and JW declare no other relevant conflicts of interest.