Association of the CFTR gene with asthma and airway mucus hypersecretion
Crespo Lessmann, Astrid (Institut d'Investigació Biomèdica Sant Pau)
Bernal, Sara (Institut d'Investigació Biomèdica Sant Pau)
del Río, Elisabeth (Institut d'Investigació Biomèdica Sant Pau)
Rojas, Ester (Institut d'Investigació Biomèdica Sant Pau)
Martínez Rivera, Carlos (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Marina Malanda, Nuria (Hospital Universitario de Cruces (Barakaldo, País Basc))
Pallarés-Sanmartín, Abel (Hospital Álvaro Cunqueiro (Vigo))
Pascual, Silvia (Hospital de Galdakao (Usansolo, Biscaia))
García-Rivero, Juan Luis (Hospital Comarcal Laredo)
Padilla, Alicia (Hospital Costa del Sol (Marbella))
Curto Sánchez, Elena (Institut d'Investigació Biomèdica Sant Pau)
Cisneros, Carolina (Hospital Universitario de la Princesa (Madrid))
Serrano, José (Hospital Comarcal d'Inca)
Baiget Bastús, Montserrat (Institut d'Investigació Biomèdica Sant Pau)
Plaza, Vicente (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	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. (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. 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. 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). 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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 16 (june 2021) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0251881
PMID: 34086689

13 p, 537.0 KB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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