Persistence of lung hyperinflation and small airway dysfunction in school-aged children with cystic fibrosis treated with elexacaftor–tezacaftor–ivacaftor: results from the real-world MODUL-CF study
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background Trapped gas (TG) and ventilation inhomogeneity (VI) are early markers of altered small airway function (SAF) in cystic fibrosis (CF) lung disease. The evolution of these markers in children with CF (chCF) treated with elexacaftor–tezacaftor–ivacaftor (ETI) remains poorly understood. Using data from multiple breath washout (MBW) and body plethysmography (pleth) from a national, real-world cohort of school-aged chCF, we tested the hypothesis that VI and TG do not consistently return to normal levels following ETI therapy. Methods Data from MBW and pleth tests were collected from seven centres prior to ETI initiation (month 0 (M0)), after a year of treatment (M12) and at M6 (when available). Analyses were conducted to assess the evolution of per cent predicted (pp) residual volume (ppRV), total lung capacity (ppTLC) and the ppRV/TLC ratio, as well as the difference between pp functional residual capacity (ppFRC) pleth and ppFRC MBW as markers of TG. Global and regional VI indices were compared to those of age- and sex-matched healthy controls. Results A total of 192 chCF aged from 6 to 18 years at ETI initiation underwent MBW at M0 and M12. Significant reductions were observed in ppRV, ppTLC, ppRV/TLC and TG. However, 28% of the chCF cohort had ppRV/TLC values >120% at M12. MBW-derived outcomes improved significantly, but 51.9% of the cohort had lung clearance index (LCI 2.5 ) values at M12 that had not returned to healthy control levels. Conclusion ETI significantly improved SAF. However, not all outcome measures returned to normal, indicating residual lung disease in some chCF.
Source: ERJ Open Research
Authors: Lucie Colin, Véronique Delaup, Muriel Le Bourgeois, Véronique Neve, Nathalie Wizla-Derambure, Iulia-Cristina Ioan, Aurélie Tatopoulos, Sebastien Kieffer, Aurore Blonde, Plamen Bokov, Véronique Houdoin, Laurence Le Clainche, Audrey Barzic, Camille Ohlmann, Tom Toin, Thomas Perrin, Laurianne Coutier, Rola Abou Taam, Anne-Sophie Bonnel, Anthony Rignani, Hala Feghali, Stephanie Bui, Michael Fayon, Alexia Letierce, Isabelle Sermet-Gaudelus, Philippe Reix
Institutions: Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Hôpital Necker-Enfants Malades, Assistance Publique – Hôpitaux de Paris, Inserm, Centre Hospitalier Universitaire de Lille, Hôpital Jeanne de Flandre, Centre Hospitalier Régional et Universitaire de Nancy, Hôpital Robert-Debré, Université de Bretagne Occidentale, Centre Hospitalier Régional Universitaire de Brest, Centre Hospitalier Universitaire de Bordeaux, Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Centre d'Investigation Clinique Plurithématique de Bordeaux, Université Paris Cité, Institut Necker Enfants Malades, ERN LUNG, Lyon 1 Université, Centre National de la Recherche Scientifique, Laboratoire de Biométrie et Biologie Evolutive
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $808
Award: G5562384665
OpenAlex ID: W4417467831