Lung T1-MRI and Multi-Breath Washout Detect Longitudinal Changes in Children 6-11 Years Old After Beginning Elexacaftor/Tezacaftor/Ivacaftor (ETI) Therapy.
Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy was approved in 2021 for clinical use in children with CF (cwCF) age 6-11 years, depending on their genetic variants. Our prior multi-center study showed that lung T1-MRI and multi-breath washout (MBW) provided complementary pathobiological information on CF lung disease in cwCF 6-11 years of age. In this study, we hypothesized that lung T1-MRI and MBW will sensitively detect lung improvements in cwCF after starting ETI therapy. To test this hypothesis, we obtained longitudinal lung T1-MRI, MBW, and spirometry assessments in a cohort of cwCF 6-11 years of age before and after starting ETI therapy.
CwCF (n = 48, mean age = 8.6 years) were recruited from 3 cystic fibrosis (CF) centers (Riley Hospital for Children (Indianapolis, IN), University of Michigan, Michigan Medicine (Ann Arbor, MI), and Rainbow Babies and Children's Hospital (Cleveland, OH) for longitudinal lung T1-MRI, MBW, and spirometry assessments before initiating ETI (baseline) as well as at 3-months and 6-months after initiating ETI. MBW and spirometry were performed according to published guidelines to obtain measurements of the lung clearance index (LCI) and percent predicted forced expiratory volume at 1 s (ppFEV1), and percent predicted forced expiratory flow at 25%-75% (FEF25 %-75%), respectively. Lung T1-MRI was used to obtain assessments of % normal lung perfusion (%NLP). An ANOVA analysis and descriptive statistics were used to compare the longitudinal changes in the lung T1-MRI, MBW, and spirometry findings.
Across all subjects, significant improvements in both spirometry (ppFEV1, FEF25 %-75%) and MBW (LCI 2.5) were observed at 3-months, and 6-months post treatment (p < 0.001). As a group, the lung T1-MRI findings showed no significant changes despite a trend for improved lung perfusion. However, lung T1-MRI did show a significant improvement in both 3-months and 6-months after starting ETI therapy (p < 0.03) when evaluating only those subjects with mild-moderate lung disease (ppFEV1 ≤ 90 % ) $\le 90 \% )$ at baseline.
MBW, spirometry, and lung T1-MRI are all capable of detecting lung airway and perfusion changes in cwCF 6-11 years of age following the start of ETI therapy. MBW and spirometry assessments were able to detect a sustained improvement in pulmonary function testing regardless of baseline lung status, while lung T1-MRI was able to detect significant improvements in lung perfusion in patients with more advanced lung disease. These findings, in combination with our prior cross-sectional findings, suggest that MBW and lung T1-MRI may provide complementary alternatives to chest CT and can be used to assess disease progression and/or response to therapy.
CwCF (n = 48, mean age = 8.6 years) were recruited from 3 cystic fibrosis (CF) centers (Riley Hospital for Children (Indianapolis, IN), University of Michigan, Michigan Medicine (Ann Arbor, MI), and Rainbow Babies and Children's Hospital (Cleveland, OH) for longitudinal lung T1-MRI, MBW, and spirometry assessments before initiating ETI (baseline) as well as at 3-months and 6-months after initiating ETI. MBW and spirometry were performed according to published guidelines to obtain measurements of the lung clearance index (LCI) and percent predicted forced expiratory volume at 1 s (ppFEV1), and percent predicted forced expiratory flow at 25%-75% (FEF25 %-75%), respectively. Lung T1-MRI was used to obtain assessments of % normal lung perfusion (%NLP). An ANOVA analysis and descriptive statistics were used to compare the longitudinal changes in the lung T1-MRI, MBW, and spirometry findings.
Across all subjects, significant improvements in both spirometry (ppFEV1, FEF25 %-75%) and MBW (LCI 2.5) were observed at 3-months, and 6-months post treatment (p < 0.001). As a group, the lung T1-MRI findings showed no significant changes despite a trend for improved lung perfusion. However, lung T1-MRI did show a significant improvement in both 3-months and 6-months after starting ETI therapy (p < 0.03) when evaluating only those subjects with mild-moderate lung disease (ppFEV1
MBW, spirometry, and lung T1-MRI are all capable of detecting lung airway and perfusion changes in cwCF 6-11 years of age following the start of ETI therapy. MBW and spirometry assessments were able to detect a sustained improvement in pulmonary function testing regardless of baseline lung status, while lung T1-MRI was able to detect significant improvements in lung perfusion in patients with more advanced lung disease. These findings, in combination with our prior cross-sectional findings, suggest that MBW and lung T1-MRI may provide complementary alternatives to chest CT and can be used to assess disease progression and/or response to therapy.
Authors
Nasr Nasr, Flask Flask, Kretzler Kretzler, Slaven Slaven, Joshi Joshi, Mahani Mahani, Clem Clem, Cooper Cooper, Farr Farr, MacAskill MacAskill, Gupta Gupta, Ferrebee Ferrebee, McBennett McBennett, Ren Ren
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