In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 6 ( 2021-6-4), p. e0251881-
Abstract:
Asthma with airway mucus hypersecretion is an inadequately characterized variant of asthma. While several studies have reported that hypersecreting patients may carry genetic variants in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene, many of those studies have been questioned for their numerous limitations and contradictory results. 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 clinical, inflammatory and functional characteristics of the asthma phenotype with airway mucus hypersecretion. Method Comparative multicentre cross-sectional descriptive study that included 100 patients with asthma (39 hypersecretors and 61 non-hypersecretors). Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least 3 months in 2 successive years. The patients were tested for fractional exhaled nitric oxide, spirometry, induced sputum cell count, total immunoglobulin E (IgE), peripheral blood eosinophil count, C-reactive protein, blood fibrinogen and blood albumin and underwent a skin prick test. Asthma control and quality of life were assessed by the Asthma Control Test and Mini Asthma Quality of Life questionnaires, respectively. Blood DNA samples were collected from the patients and next-generation sequencing using a MiSeq sequencer and the Illumina platform was used for the CFTR gene analysis. Results Genetic differences were observed in the c.1680-870T 〉 A polymorphism 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). Clinically, asthma hypersecretors compared to non-hypersecretors were older (57.4 years vs. 49.4 years; p = 0.004); had greater asthma severity (58.9% vs. 23.7%; p = 0.005); experienced greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p = 0.041); had poorer asthma control (60% vs. 29%; p = 0.021); had lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p = 0.003); and were less likely to have a positive prick test (37.5% vs. 68.85%; p = 0.011). Conclusion The results suggest that patients with asthma and with mucus hypersecretion (1) may have a different phenotype and disease mechanism produced by an intronic polymorphism in the CFTR gene (NM_000492.3:c.1680-870T 〉 A), and (2) may have a poorer clinical outcome characterized by severe disease and poorer asthma control with a non-allergic inflammatory phenotype.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0251881
DOI:
10.1371/journal.pone.0251881.t001
DOI:
10.1371/journal.pone.0251881.t002
DOI:
10.1371/journal.pone.0251881.t003
DOI:
10.1371/journal.pone.0251881.t004
DOI:
10.1371/journal.pone.0251881.s001
DOI:
10.1371/journal.pone.0251881.s002
DOI:
10.1371/journal.pone.0251881.s003
DOI:
10.1371/journal.pone.0251881.s004
DOI:
10.1371/journal.pone.0251881.s005
DOI:
10.1371/journal.pone.0251881.r001
DOI:
10.1371/journal.pone.0251881.r002
DOI:
10.1371/journal.pone.0251881.r003
DOI:
10.1371/journal.pone.0251881.r004
DOI:
10.1371/journal.pone.0251881.r005
DOI:
10.1371/journal.pone.0251881.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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