Introduction: It has previously been established that there is an increased incidence of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene amongst patients with non-cystic fibrosis bronchiectasis (NCFB). With the advent of new highly effective CFTR modulators, specifically elexacaftor-tezacaftor-ivacaftor (ETI), we asked whether NCFB patients with a single ETI amenable mutation who do not meet the criteria for a diagnosis of cystic fibrosis (CF) would benefit from this therapy.
Methods: We assembled a retrospective cohort of patients (n=12) with a single CFTR mutation amenable to ETI treatment. Patients included in this cohort did not meet the diagnostic criteria for CF but presented with similar pulmonary symptoms and frequent exacerbations. Medical records were reviewed to determine the effects of ETI on clinical outcomes. Paired sample t-test for univariate analysis and multivariate linear mixed effect modeling for continuous and categorical variables were used to examine the impact of ETI therapy.
Results: Improvements in pulmonary symptoms were observed in all 12 patients (100%), and 11 patients (91.6%) expressed improvement in quality of life. Mean % predicted forced expiratory volume in 1 s improved significantly from 69.3% to 75.0% (p=0.007). Mean reported pulmonary symptoms decreased to 2.17 (p=0.007) and mean reported pulmonary exacerbations decreased to 1.08 per year (p=0.0006). When controlling for sweat chloride and Poly T insertions, post-ETI improvement remained significant.
Conclusion: Amongst patients presenting with NCFB and an amenable CFTR mutation, treatment with ETI improved lung function, symptoms and quality of life and led to a significant reduction in annual pulmonary exacerbations. Larger clinical studies are needed to further validate these findings.
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