Structural changes in lung morphology detected by MRI after modulating therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with cystic fibrosis

Valentina Fainardi; Kaltra Skenderaj; Andrea Ciuni; Gianluca Milanese; Michela Deolmi; Francesco Longo; Cinzia Spaggiari; Nicola Sverzellati; Susanna Esposito; Giovanna Pisi

doi:10.1016/j.rmed.2023.107328

Structural changes in lung morphology detected by MRI after modulating therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with cystic fibrosis

Respir Med. 2023 Sep:216:107328. doi: 10.1016/j.rmed.2023.107328. Epub 2023 Jun 13.

Authors

Affiliations

¹ Cystic Fibrosis Unit, Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126, Parma, Italy. Electronic address: valentina.fainardi@unipr.it.
² Cystic Fibrosis Unit, Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126, Parma, Italy. Electronic address: kaltra.skenderaj@gmail.com.
³ Section of Radiology, Unit of Surgical Sciences, Department of Medicine and Surgery, University of Parma, 43126, Parma, Italy. Electronic address: aciuni@ao.pr.it.
⁴ Section of Radiology, Unit of Surgical Sciences, Department of Medicine and Surgery, University of Parma, 43126, Parma, Italy. Electronic address: gianluca.milanese@unipr.it.
⁵ Cystic Fibrosis Unit, Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126, Parma, Italy. Electronic address: michela.deolmi@studenti.unipr.it.
⁶ Respiratory Disease and Lung Function Unit, Azienda Ospedaliero-Universitaria, 43126, Parma, Italy. Electronic address: flongo@ao.pr.it.
⁷ Cystic Fibrosis Unit, Pediatric Clinic, Azienda Ospedaliero-Universitaria, 43126, Parma, Italy. Electronic address: spaggiaric@ao.pr.it.
⁸ Section of Radiology, Unit of Surgical Sciences, Department of Medicine and Surgery, University of Parma, 43126, Parma, Italy. Electronic address: nicola.sverzellati@unipr.it.
⁹ Cystic Fibrosis Unit, Pediatric Clinic, Department of Medicine and Surgery, University Hospital of Parma, 43126, Parma, Italy. Electronic address: susannamariaroberta.esposito@unipr.it.
¹⁰ Cystic Fibrosis Unit, Pediatric Clinic, Azienda Ospedaliero-Universitaria, 43126, Parma, Italy. Electronic address: gpisi@ao.pr.it.

PMID: 37321310
DOI: 10.1016/j.rmed.2023.107328

Abstract

Introduction: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in cystic fibrosis (CF) patients homozygous or heterozygous for F508del mutation. The aim of the study was to evaluate the response to ELX/TEZ/IVA treatment both clinically and morphologically in terms of bronchiectasis, bronchial wall thickening, mucus plugging, abscess and consolidations.

Methods: We retrospectively collected data from CF patients followed at Parma CF Centre (Italy) treated by ELX/TEZ/IVA between March and November 2021. Post-treatment changes in respiratory function, quality of life, sweat chloride concentration, body mass index, pulmonary exacerbations and lung structure by chest magnetic resonance imaging (MRI) were assessed. T2-and T1-weighted sequences were acquired with a 20 min-long scanning protocol on a 1.5T MRI scanner (Philips Ingenia) without administration of intravenous contrast media.

Results: 19 patients (32.5 ± 10.2 years) were included in the study. After 6 months of treatment with ELX/TEZ/IVA, MRI showed significant improvements in the morphological score (p < 0.001), with a reduction in bronchial wall thickening (p < 0.001) and mucus plugging (p 0.01). Respiratory function showed significant improvement in predicted FEV₁% (58.5 ± 17.5 vs 71.4 ± 20.1, p < 0.001), FVC% (79.0 ± 11.1 vs 88.3 ± 14.4, p < 0.001), FEV₁/FVC (0.61 ± 0.16 vs 0.67 ± 0.15, <0.001) and LCI_2.5% (17.8 ± 4.3 vs 15.8 ± 4.1 p < 0.005). Significant improvement was found in body mass index (20.6 ± 2.7 vs 21.9 ± 2.4, p < 0.001), pulmonary exacerbations (2.3 ± 1.3 vs 1.4 ± 1.3 p 0.018) and sweat chloride concentration (96.5 ± 36.6 vs 41.1 ± 16.9, p < 0.001).

Conclusions: Our study confirms the efficacy of ELX/TEZ/IVA in CF patients not only from a clinical point of view but also in terms of morphological changes of the lungs.

Keywords: Cystic fibrosis; ELX/TEZ/IVA; Lung structure; MRI; Modulators; Mucus plugging.

MeSH terms

Adolescent
Adult
Chlorides
Cystic Fibrosis* / diagnostic imaging
Cystic Fibrosis* / drug therapy
Cystic Fibrosis* / genetics
Humans
Lung / diagnostic imaging
Mutation
Quality of Life
Retrospective Studies

Substances

elexacaftor
ivacaftor
tezacaftor
Chlorides