Effects of elexacaf tor/tezacaf tor/ivacaf tor therapy in children with cystic fibrosis - a comprehensive assessment using lung clearance index, spirometry, and functional and structural lung MRI

被引：31

作者：

Streibel, Carmen ^{[1
]}

Willers, Corin C. ^{[1
,5
]}

Pusterla, Orso ^{[1
,2
,3
]}

Bauman, Grzegorz ^{[2
,3
]}

Stranzinger, Enno ^{[4
]}

Brabandt, Ben ^{[4
]}

Bieri, Oliver ^{[2
,3
]}

Curdy, Marion ^{[1
]}

Bullo, Marina ^{[1
]}

Frauchiger, Bettina Sarah ^{[1
]}

Korten, Insa ^{[1
]}

Krueger, Linn ^{[1
]}

Casaulta, Carmen ^{[1
]}

Ratjen, Felix ^{[6
,7
]}

Latzin, Philipp ^{[1
]}

Kieninger, Elisabeth ^{[1
,6
,7
,8
]}

机构：

[1] Univ Bern, Dept Paediat, Inselspital, Div Paediat Resp Med & Allergol,Bern Univ Hosp, Bern, Switzerland

[2] Univ Basel Hosp, Dept Radiol, Div Radiol Phys, Basel, Switzerland

[3] Univ Basel, Dept Biomed Engn, Allschwil, Switzerland

[4] Univ Bern, Bern Univ Hosp, Dept Intervent & Pediat Radiol, Inselspital, Bern, Switzerland

[5] Kantonsspital Aarau, Dept Paediat, Aarau, Switzerland

[6] Hosp Sick Children, Dept Paediat, Div Resp Med, Toronto, ON, Canada

[7] Univ Toronto, Toronto, ON, Canada

[8] Univ Bern, Univ Childrens Hosp Bern, Pediat Resp Med, Bern, Switzerland

来源：

JOURNAL OF CYSTIC FIBROSIS | 2023年 / 22卷 / 04期

基金：

瑞士国家科学基金会;

关键词：

Cystic fibrosis; Lung disease; Children; CFTR modulator therapy; Elexacaftor/tezacaftor/ivacaftor therapy; Lung function; Multiple breath washout; Lung clearance index; Functional lung MRI; IVACAFTOR;

D O I：

10.1016/j.jcf.2022.12.012

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

Background: With improvement in supportive therapies and the introduction of cystic fibrosis transmem-brane conductance regulator (CFTR)-modulator treatment in patients with cystic fibrosis (CF), milder disease courses are expected. Therefore, sensitive parameters are needed to monitor disease course and effects of CFTR-modulators. Functional lung MRI using matrix-pencil decomposition (MP-MRI) is a promising tool for assessing ventilation and perfusion quantitatively. This study aimed to assess the treatment effect of elexacaftor/tezacaftor/ivacaftor combination regimen (ELX/TEZ/IVA) on measures of structural and functional lung abnormalities.Methods: 24 children with CF underwent lung function tests (multiple breath washout, spirometry), functional and structural MRI twice (one year apart) before and once after at least two weeks (mean 4.7 & PLUSMN; 2.6 months) on ELX/TEZ/IVA. Main outcomes were changes ( A) upon ELX/TEZ/IVA in lung function, defect percentage of ventilation (VDP) and perfusion (QDP), defect distribution index of ventilation and perfusion (DDIV, DDIQ), and Eichinger score. Statistical analyses were performed using paired t-tests and multilevel regression models with bootstrapping.Results: We observed a significant improvement in lung function, structural and functional MRI param-eters upon ELX/TEZ/IVA treatment (mean; 95%-CI): ALCI2.5 (TO)-0.84 (-1.62 to-0.06); AFEV1 (z-score) 1.05 (0.56 to 1.55); AVDP (% of impairment)-6.00 (-8.44 to-3.55); AQDP (% of impairment)-3.90 (-5.90 to-1.90); ADDIV-1.38 (-2.22 to-0.53); ADDIQ-0.31 (-0.73 to 0.12); AEichinger score-3.89 (-5.05 to-2.72).Conclusions: Besides lung function tests, functional and structural MRI is a suitable tool to monitor treat-ment response of ELX/TEZ/IVA therapy, and seems promising as outcome marker in the future.& COPY; 2022 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.

引用

页码：615 / 622

页数：8

共 33 条

[1] Use of hyperpolarized helium-3 MRI to assess response to ivacaftor treatment in patients with cystic fibrosis [J].