Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two F508del Alleles

Dynamic Perfluorinated Gas MRI Shows Improved Lung Ventilation in People with Cystic Fibrosis after Elexacaftor/Tezacaftor/Ivacaftor: An Observational Study

“…While perhaps not surprising, this helps to validate that observed ventilation abnormalities are truly a function of structural airways disease and not likely reflecting transient bronchoconstriction or other imaging artifacts. Our findings are also consistent with recent publications [ 14 , 18 ] that showed lung structural improvements after treatment with elexacaftor/tezacaftor/ivacaftor are driven by changes in bronchiectasis/airway wall thickening and mucus plugging. Our study adds to the growing body of literature that structural improvements are detectable within 4 weeks of starting highly effective CFTR modulator therapy and correspond to improvements in ventilation defects detected by 19 F MRI.…”

“…We also found a reduction in median LCI score and LCI z-score, which indicates improvement in ventilation homogeneity and reflects reduced obstruction of small airways. Despite participants having relatively mild structural abnormalities at baseline compared to prior studies [ 14 , 15 ], we were able to detect significant improvements in airway wall abnormalities and mucus plugging with treatment.…”

“…It is uncertain, therefore, whether our findings will translate to pediatric populations, or those with more significant lung disease. Of note, participants in our study generally had milder structural disease scores than those in other published studies [ 14 , 15 ] although we should also consider whether differences in scoring systems contributed to a milder overall score. The most robust magnetic resonance imaging scoring systems use a combination of morphologic score and perfusion score, requiring administration of intravenous contrast [ 13 , 19 , 20 ].…”

Regulatory T cell enhancement in adults with cystic fibrosis receiving Elexacaftor/Tezacaftor/Ivacaftor therapy

“…There was a positive correlation between the percentage change in six-minute walk test and Tregs at 3 months, suggesting that Treg enhancement may contribute to the clinical improvement in response to ELX/TEZ/IVA. Weak correlations between outcome parameters have been reported by other groups analyzing various clinical parameters in PwCF receiving ELX/TEZ/IVA ( 37 , 38 ). Possible explanations are a heterogenous study population in terms of pre-existing structural lung damage, infection status and established therapy with mono or dual combination CFTR modulators, different time intervals until full therapeutic effects are achieved and/or complementary, non-correlating effects being captured by a parameter.…”

How Should the Effects of CFTR Modulator Therapy on Cystic Fibrosis Lung Disease Be Monitored?

“…In this issue of the Journal , Graeber and colleagues (pp. 311–320 ) present their findings on the effects of ELX/TEZ/IVA on LCI and MRI scores in adolescent and adult patients with CF after 8–16 weeks of therapy ( 11 ). A total of 91 patients heterozygous for CFTR F508del and a minimal function mutation (F508del/MF) or homozygous for F508del (F508del/F508del) were included in this prospective observational postapproval multicenter trial.…”