Association of the CFTR Gene With Asthma and Airway Mucus Hypersecretion

Abstract IntroductionAirway mucus hypersecretion is an undercharacterized phenotype of asthma. Objectives(1) To determine the presence of genetic variants of the CFTR gene in patients with asthma with and without airway mucus hypersecretion. (2) To identify the characteristics of the asthma phenotype with airway mucus hypersecretion.MethodComparative cross-sectional multicentre study including 39 hypersecretors and 61 non-hypersecretors asthma patients. Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least three months in two successive years. Spirometry, fractional exhaled nitric oxide, induced sputum cell count, blood test and questionnaires were performed. Blood DNA samples were sequenced using a MiSeq sequencer and the Illumina platform was used for the CFTR gene analysis.ResultsGenetic differences were observed in the c.1680-870T>A genetic variant of the CFTR gene, significantly more evident in hypersecretors than in non-hypersecretors: 78.94% vs. 59.32% in the majority allele and 21.05% vs. 40.67% in the minority allele (p=0.036). Asthma hypersecretors were older (57.4 years vs. 49.4 years; p=0.004) and had greater asthma severity (58.9% vs. 23.7%; p=0.005), greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p=0.041), poorer asthma control (60% vs. 29%; p=0.021), and lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p=0.003).ConclusionPatients with asthma and with mucus hypersecretion may have a different disease mechanism produced by an intronic genetic variant in the CFTR gene (NM_000492.3:c.1680-870T>A). They present a more severe disease, poorer asthma control and a non-allergic inflammatory phenotype.