TY - JOUR
T1 - Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on sputum viscoelastic properties, airway infection and inflammation in patients with cystic fibrosis
AU - Schaupp, Laura
AU - Addante, Annalisa
AU - Völler, Mirjam
AU - Fentker, Kerstin
AU - Kuppe, Aditi
AU - Bardua, Markus
AU - Duerr, Julia
AU - Piehler, Linus
AU - Röhmel, Jobst
AU - Thee, Stephanie
AU - Kirchner, Marieluise
AU - Ziehm, Matthias
AU - Lauster, Daniel
AU - Haag, Rainer
AU - Gradzielski, Michael
AU - Stahl, Mirjam
AU - Mertins, Philipp
AU - Boutin, Sébastien
AU - Graeber, Simon Y
AU - Mall, Marcus A
N1 - Publisher Copyright:
Copyright ©The authors 2023. For reproduction rights and permissions contact [email protected].
Publisher Copyright:
© 2023 European Respiratory Society. All rights reserved.
PY - 2023/8
Y1 - 2023/8
N2 - BACKGROUND: Recent studies demonstrated that the triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) improves lung function and reduces pulmonary exacerbations in cystic fibrosis (CF) patients with at least one
F508del allele. However, effects of ETI on downstream consequences of CFTR dysfunction,
i.e. abnormal viscoelastic properties of airway mucus, chronic airway infection and inflammation have not been studied. The aim of this study was to determine the longitudinal effects of ETI on airway mucus rheology, microbiome and inflammation in CF patients with one or two
F508del alleles aged ≥12 years throughout the first 12 months of therapy.
METHODS: In this prospective observational study, we assessed sputum rheology, the microbiome, inflammation markers and proteome before and 1, 3 and 12 months after initiation of ETI.RESULTS: In total, 79 patients with CF and at least one
F508del allele and 10 healthy controls were enrolled in this study. ETI improved the elastic modulus and viscous modulus of CF sputum at 3 and 12 months after initiation (all p<0.01). Furthermore, ETI decreased the relative abundance of
Pseudomonas aeruginosa in CF sputum at 3 months and increased the microbiome α-diversity at all time points
. In addition, ETI reduced interleukin-8 at 3 months (p<0.05) and free neutrophil elastase activity at all time points (all p<0.001), and shifted the CF sputum proteome towards healthy.
CONCLUSIONS: Our data demonstrate that restoration of CFTR function by ETI improves sputum viscoelastic properties, chronic airway infection and inflammation in CF patients with at least one
F508del allele over the first 12 months of therapy; however, levels close to healthy were not reached.
AB - BACKGROUND: Recent studies demonstrated that the triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) improves lung function and reduces pulmonary exacerbations in cystic fibrosis (CF) patients with at least one
F508del allele. However, effects of ETI on downstream consequences of CFTR dysfunction,
i.e. abnormal viscoelastic properties of airway mucus, chronic airway infection and inflammation have not been studied. The aim of this study was to determine the longitudinal effects of ETI on airway mucus rheology, microbiome and inflammation in CF patients with one or two
F508del alleles aged ≥12 years throughout the first 12 months of therapy.
METHODS: In this prospective observational study, we assessed sputum rheology, the microbiome, inflammation markers and proteome before and 1, 3 and 12 months after initiation of ETI.RESULTS: In total, 79 patients with CF and at least one
F508del allele and 10 healthy controls were enrolled in this study. ETI improved the elastic modulus and viscous modulus of CF sputum at 3 and 12 months after initiation (all p<0.01). Furthermore, ETI decreased the relative abundance of
Pseudomonas aeruginosa in CF sputum at 3 months and increased the microbiome α-diversity at all time points
. In addition, ETI reduced interleukin-8 at 3 months (p<0.05) and free neutrophil elastase activity at all time points (all p<0.001), and shifted the CF sputum proteome towards healthy.
CONCLUSIONS: Our data demonstrate that restoration of CFTR function by ETI improves sputum viscoelastic properties, chronic airway infection and inflammation in CF patients with at least one
F508del allele over the first 12 months of therapy; however, levels close to healthy were not reached.
UR - http://www.scopus.com/inward/record.url?scp=85166475244&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/f14178e9-bfe9-3f8c-abcc-7212de3c61b3/
U2 - 10.1183/13993003.02153-2022
DO - 10.1183/13993003.02153-2022
M3 - Journal articles
C2 - 37414422
SN - 0903-1936
VL - 62
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 2
M1 - 2202153
ER -