Impact of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Children with Cystic Fibrosis and One or Two

Journal

The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460

Informations de publication

Date de publication:
20 Jun 2024
Historique:
received: 01 01 2024
accepted: 27 05 2024
medline: 21 6 2024
pubmed: 21 6 2024
entrez: 20 6 2024
Statut: aheadofprint

Résumé

We recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children with CF and one or two This prospective, observational, multicenter, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and three months after initiation of ETI. A total of 107 children with CF including 40 heterozygous for F508del and a minimal function mutation (F/MF) and 67 homozygous for F508del (F/F) were enrolled in this study. Treatment with ETI improved the LCI in F/MF children (-1.0; IQR, -2.0 to -0.1; p<0.01) and F/F children (-0.8; IQR, -1.9 to -0.2; p<0.001) from 3 months onwards. Further, ETI improved the MRI global score in F/MF (-4.0; IQR, -9.0 to 0.0; p<0.01) and F/F children (-3.5; IQR, -7.3 to -0.8; p<0.001). ETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least one

Sections du résumé

BACKGROUND BACKGROUND
We recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children with CF and one or two
METHODS METHODS
This prospective, observational, multicenter, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and three months after initiation of ETI.
RESULTS RESULTS
A total of 107 children with CF including 40 heterozygous for F508del and a minimal function mutation (F/MF) and 67 homozygous for F508del (F/F) were enrolled in this study. Treatment with ETI improved the LCI in F/MF children (-1.0; IQR, -2.0 to -0.1; p<0.01) and F/F children (-0.8; IQR, -1.9 to -0.2; p<0.001) from 3 months onwards. Further, ETI improved the MRI global score in F/MF (-4.0; IQR, -9.0 to 0.0; p<0.01) and F/F children (-3.5; IQR, -7.3 to -0.8; p<0.001).
CONCLUSIONS CONCLUSIONS
ETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least one

Identifiants

DOI: 10.1183/13993003.00004-2024 PMID: 38901883
pubmed: 38901883
pii: 13993003.00004-2024
doi: 10.1183/13993003.00004-2024
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.

Auteurs

Mirjam Stahl (M)

Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany mirjam.stahl@charite.de.
Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.
German Center for Lung Research (DZL), associated partner site, Berlin, Germany.
Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany.
ORCID: 0000-0001-6941-8315

Martha Dohna (M)

Department for Radiology, Hannover Medical School, Hannover, Germany.
Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany.

Simon Y Graeber (SY)

Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.
German Center for Lung Research (DZL), associated partner site, Berlin, Germany.
Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany.
ORCID: 0000-0002-1666-8924

Olaf Sommerburg (O)

Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.
Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany.

Diane M Renz (DM)

Department for Radiology, Hannover Medical School, Hannover, Germany.

Sophia T Pallenberg (ST)

Department for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
German Center for Lung Research, Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Hannover Medical School, Hannover, Germany.

Andreas Voskrebenzev (A)

Department for Radiology, Hannover Medical School, Hannover, Germany.

Katharina Schütz (K)

Department for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
German Center for Lung Research, Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Hannover Medical School, Hannover, Germany.
ORCID: 0000-0003-2680-3541

Gesine Hansen (G)

Department for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
German Center for Lung Research, Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Hannover Medical School, Hannover, Germany.
Cluster of Excellence RESIST (EXC 2155), German Research Foundation (DFG), Hannover Medical School, Hannover, Germany.

Felix Doellinger (F)

Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Eva Steinke (E)

Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.
German Center for Lung Research (DZL), associated partner site, Berlin, Germany.

Stephanie Thee (S)

Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.
German Center for Lung Research (DZL), associated partner site, Berlin, Germany.
ORCID: 0000-0001-9090-7869

Jobst Röhmel (J)

Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.
German Center for Lung Research (DZL), associated partner site, Berlin, Germany.
ORCID: 0000-0002-1535-8852

Sandra Barth (S)

Department of Pediatrics, Justus-Liebig-University Giessen, Giessen, Germany.
Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Giessen, Germany.

Claudia Rückes-Nilges (C)

Department of Pediatrics, Justus-Liebig-University Giessen, Giessen, Germany.
Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Giessen, Germany.

Julian Berges (J)

Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.
Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.

Susanne Hämmerling (S)

Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.

Mark O Wielpütz (MO)

Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany.
ORCID: 0000-0001-6962-037X

Lutz Naehrlich (L)

Department of Pediatrics, Justus-Liebig-University Giessen, Giessen, Germany.
Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Giessen, Germany.
M.S., M.D., S.Y.G., O.S. contributed equally as first authors.

Jens Vogel-Claussen (J)

Department for Radiology, Hannover Medical School, Hannover, Germany.
German Center for Lung Research, Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Hannover Medical School, Hannover, Germany.
M.S., M.D., S.Y.G., O.S. contributed equally as first authors.

Burkhard Tümmler (B)

Department for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
German Center for Lung Research, Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Hannover Medical School, Hannover, Germany.
M.S., M.D., S.Y.G., O.S. contributed equally as first authors.
ORCID: 0000-0002-2566-8758

Marcus A Mall (MA)

Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.
German Center for Lung Research (DZL), associated partner site, Berlin, Germany.
M.S., M.D., S.Y.G., O.S. contributed equally as first authors.
ORCID: 0000-0002-4057-2199

Anna-Maria Dittrich (AM)

Department for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
German Center for Lung Research, Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Hannover Medical School, Hannover, Germany.
M.S., M.D., S.Y.G., O.S. contributed equally as first authors.
ORCID: 0000-0002-9582-1025

Classifications MeSH