Highlights
- •Structural and functional MP-MRI, LCI and FEV1 were compared after ETI treatment.
- •Ventilation and perfusion impairment assessed by MP-MRI improved upon ETI therapy.
- •MP-MRI adds information on ETI treatment effects complementary to FEV1 and LCI.
- •MP-MRI is a suitable and sensitive tool to monitor CFTR-modulator treatment effects.
ABSTRACT
Background
With improvement in supportive therapies and the introduction of cystic fibrosis transmembrane
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 ± 2.6 months) on ELX/TEZ/IVA. Main outcomes were changes (Δ) 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 parameters upon ELX/TEZ/IVA treatment (mean; 95%-CI): ΔLCI2.5 (TO) -0.84 (-1.62 to -0.06); ΔFEV1 (z-score) 1.05 (0.56 to 1.55); ΔVDP (% of impairment) -6.00 (-8.44 to -3.55); ΔQDP
(% of impairment) -3.90 (-5.90 to -1.90); ΔDDIV -1.38 (-2.22 to -0.53); ΔDDIQ -0.31 (-0.73 to 0.12); ΔEichinger score -3.89 (-5.05 to -2.72).
Conclusions
Besides lung function tests, functional and structural MRI is a suitable tool to monitor
treatment response of ELX/TEZ/IVA therapy, and seems promising as outcome marker in
the future.
Keywords
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Article info
Publication history
Published online: January 10, 2023
Accepted:
December 20,
2022
Received in revised form:
December 7,
2022
Received:
August 3,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.
