Journal
ANNALS OF THE AMERICAN THORACIC SOCIETY
Volume 18, Issue 6, Pages 971-980Publisher
AMER THORACIC SOC
DOI: 10.1513/AnnalsATS.202008-1054OC
Keywords
cystic fibrosis; lumacaftor-ivacaftor; LCI; MRI; airway microbiome
Categories
Funding
- German Federal Ministry of Education and Research [82DZLE12A1, 82DZL004A1]
- Einstein Foundation Berlin [EP-2017-393]
- Berlin Institute of Health-Charite Clinician Scientist Program - Charite-University of Medicine Berlin
- Berlin Institute of Health
Ask authors/readers for more resources
This study found that lumacaftor-ivacaftor has beneficial effects on lung ventilation, morphology, perfusion, airway microbiome, and inflammation in CF patients. LCI and MRI may be more sensitive indicators than FEV1% predicted in assessing response to CFTR modulator therapy in patients with chronic CF lung disease.
Rationale: Previous studies showed that lumacaftor-ivacaftor therapy results in partial rescue of CFTR (cystic fibrosis [CF] transmembrane conductance regulator) activity and a moderate improvement of spirometry in Phe508del homozygous patients with CF. However, the effects of lumacaftor-ivacaftor on lung clearance index (LCI), lung morphology and perfusion detected by chest magnetic resonance imaging (MRI), and effects on the airway microbiome and inflammation remain unknown. Objectives: To investigate the effects of lumacaftor-ivacaftor on LCI, lung MRI scores, and airway microbiome and inflammation. Methods: In this prospective observational study we assessed clinical outcomes including spirometry and body mass index, LCI, lung MRI scores, sputum microbiome, and proinflammatory cytokines in 30 Phe508del homozygous patients with CF 12 years and older before and 8-16 weeks after initiation of lumacaftor-ivacaftor therapy. Results: Lumacaftor-ivacaftor had no effects 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) and MRI morphology (-1.3; 95% CI, -2.3 to -0.3; P < 0.05) and perfusion score (-1.2; 95% CI, -2.3 to -0.2; P < 0.05) in our study cohort. Furthermore, lumacaftor-ivacaftor decreased the total bacterial load (-1.8; 95% CI, -3.3 to -0.34; P < 0.05) and increased the Shannon diversity of the airway microbiome (0.4; 95% CI, 0.1 to 0.8; P < 0.05), and reduced IL-1 beta (interleukin-1 beta) concentration (median change, -324.2 pg/ml; 95% CI, -938.7 to 290.4 pg/ml; P < 0.05) in sputum of Phe508del homozygous patients. Conclusions: This study shows that lumacaftor-ivacaftor has beneficial effects on lung ventilation, morphology, and perfusion, as well as on the airway microbiome and inflammation in Phe508del homozygous patients. Our results suggest that LCI and MRI may be more sensitive than FEV1% predicted to detect response to CFTR modulator therapy in patients with chronic CF lung disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available