In Phe508del homozygous patients with CF, previous studies indicated that lumacaftor–ivacaftor therapy results in partial recovery of CFTR (cystic fibrosis [CF] transmembrane conductance regulator) function and a moderate improvement in spirometry. The effects of lumacaftor–ivacaftor on the lung clearance index (LCI), lung shape, and perfusion assessed by chest magnetic resonance imaging (MRI), as well as the airway microbiota and inflammation, are unknown. A study was to see how lumacaftor–ivacaftor affected LCI, lung MRI scores, airway microbiota, and inflammation. In this prospective observational study, researchers looked at clinical outcomes such spirometry and BMI, LCI, lung MRI scores, sputum microbiota, and proinflammatory cytokines in 30 Phe508del homozygous CF patients aged 12 and up before and after starting lumacaftor–ivacaftor medication. 

In the study cohort, lumacaftor–ivacaftor had no effect on forced expiratory volume in 1 second (FEV1 % predicted) (1.7%; 95% confidence interval [CI], 1.0% to 4.3%; P=0.211), but improved LCI (1.6; 95% CI, 2.6 to 0.5; P<0.01), MRI morphology (1.3; 95% CI, 2.3 to 0.3; P<0.05), and perfusion score (1.2; Furthermore, lumacaftor–ivacaftor reduced total bacterial load (1.8; 95% CI, 3.3 to 0.34; P<0.05), increased Shannon diversity of the airway microbiome (0.4; 95% CI, 0.1 to 0.8; P<0.05), and reduced IL-1 (interleukin-1) concentration in sputum of Phe508del homozygous patients (median change, 324.2 pg/ml; 95%. In Phe508del homozygous individuals, lumacaftor–ivacaftor had positive effects on lung airflow, shape, and perfusion, as well as the airway microbiome and inflammation. The findings imply that LCI and MRI may be more sensitive than FEV1 % predicted in detecting response to CFTR modulator therapy in chronic CF lung disease patients.

 

Reference:www.atsjournals.org/doi/full/10.1513/AnnalsATS.202008-1054OC