PMID- 34086689
OWN - NLM
STAT- MEDLINE
DCOM- 20211022
LR  - 20231111
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 6
DP  - 2021
TI  - Association of the CFTR gene with asthma and airway mucus hypersecretion.
PG  - e0251881
LID - 10.1371/journal.pone.0251881 [doi]
LID - e0251881
AB  - INTRODUCTION: 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.
FAU - Crespo-Lessmann, Astrid
AU  - Crespo-Lessmann A
AUID- ORCID: 0000-0002-2238-6851
AD  - Department of Respiratory Medicine, Hospital de la Santa Creu i Sant Pau, 
      Institute of Sant Pau Biomedical Research (IBB Sant Pau), Centro de Investigacion 
      Biomedica en Red de Enfermedades Respiratorias (CIBERES), Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
FAU - Bernal, Sara
AU  - Bernal S
AD  - Department of Genetics, Hospital de la Santa Creu i Sant Pau, Institute of Sant 
      Pau Biomedical Research (IBB Sant Pau), Centro de Investigacion Biomedica en Red 
      de Enfermedades Raras (CIBERER, U705), Barcelona, Spain.
FAU - Del Rio, Elisabeth
AU  - Del Rio E
AD  - Department of Genetics, Hospital de la Santa Creu i Sant Pau, Institute of Sant 
      Pau Biomedical Research (IBB Sant Pau), Centro de Investigacion Biomedica en Red 
      de Enfermedades Raras (CIBERER, U705), Barcelona, Spain.
FAU - Rojas, Ester
AU  - Rojas E
AD  - Department of Genetics, Hospital de la Santa Creu i Sant Pau, Institute of Sant 
      Pau Biomedical Research (IBB Sant Pau), Centro de Investigacion Biomedica en Red 
      de Enfermedades Raras (CIBERER, U705), Barcelona, Spain.
FAU - Martinez-Rivera, Carlos
AU  - Martinez-Rivera C
AD  - Department of Respiratory Medicine, H. German Trias i Pujol, CIBERES, Badalona, 
      Spain.
FAU - Marina, Nuria
AU  - Marina N
AD  - Department of Respiratory Medicine, H. de Cruces, Barakaldo, Vizcaya, Spain.
FAU - Pallares-Sanmartin, Abel
AU  - Pallares-Sanmartin A
AD  - Department of Respiratory Medicine, H. Alvaro Cunqueiro, Vigo, Spain.
FAU - Pascual, Silvia
AU  - Pascual S
AD  - Department of Respiratory Medicine, H. de Galdakao, Vizcaya, Spain.
FAU - Garcia-Rivero, Juan Luis
AU  - Garcia-Rivero JL
AD  - Department of Respiratory Medicine, H. Laredo, Cantabria, Spain.
FAU - Padilla-Galo, Alicia
AU  - Padilla-Galo A
AD  - Department of Respiratory Medicine, H. Costa del Sol de Marbella, Malaga, Spain.
FAU - Curto, Elena
AU  - Curto E
AD  - Department of Respiratory Medicine, Hospital de la Santa Creu i Sant Pau, 
      Institute of Sant Pau Biomedical Research (IBB Sant Pau), Centro de Investigacion 
      Biomedica en Red de Enfermedades Respiratorias (CIBERES), Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
FAU - Cisneros, Carolina
AU  - Cisneros C
AD  - Department of Respiratory Medicine, H. U. de La Princesa, Madrid, Spain.
FAU - Serrano, Jose
AU  - Serrano J
AD  - Department of Respiratory Medicine, Hospital Comarcal de Inca, Baleares, Spain.
FAU - Baiget, Montserrat
AU  - Baiget M
AD  - Department of Genetics, Hospital de la Santa Creu i Sant Pau, Institute of Sant 
      Pau Biomedical Research (IBB Sant Pau), Centro de Investigacion Biomedica en Red 
      de Enfermedades Raras (CIBERER, U705), Barcelona, Spain.
FAU - Plaza, Vicente
AU  - Plaza V
AD  - Department of Respiratory Medicine, Hospital de la Santa Creu i Sant Pau, 
      Institute of Sant Pau Biomedical Research (IBB Sant Pau), Centro de Investigacion 
      Biomedica en Red de Enfermedades Respiratorias (CIBERES), Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
CN  - Emerging Asthma Group
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210604
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CFTR protein, human)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Asthma/*genetics/metabolism
MH  - Cough/genetics
MH  - Cross-Sectional Studies
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/*genetics
MH  - Eosinophils/metabolism
MH  - Exhalation/genetics
MH  - Female
MH  - Genetic Variation/genetics
MH  - Humans
MH  - Immunoglobulin E/genetics
MH  - Male
MH  - Middle Aged
MH  - Mucus/metabolism
MH  - Nitric Oxide/metabolism
MH  - Respiratory Function Tests
MH  - Respiratory System/*metabolism
MH  - Sputum/*metabolism
PMC - PMC8177500
COIS- I have read the journal's policy and the authors of this manuscript have the 
      following competing interests: AC has received fees in the last three years for 
      talks at meetings sponsored by Chiesi, Esteve Laboratories, GlaxoSmithKline, 
      Novartis, Ferrer, Zambon and Boehringer Ingelheim, has received travel and 
      attendance expenses for conferences from Novartis, Bial, Teva and FAES Farma and 
      has received funds/grants for research projects from several state agencies and 
      non-profit foundations and from AstraZeneca. EC reports non-financial support 
      from Astrazeneca, personal fees from Boehringer-Ingleheim, personal fees and 
      non-financial support from Chiesi, non-financial support from Novartis, 
      non-financial support from Menarini, non-financial support from ALK, outside the 
      submitted work. SB, EdR, ER, CM, NM, AP, SP, JG, AP, CC, JS and MB have no 
      conflicts of interest to declare. VP has received fees in the last three years 
      for talks at meetings sponsored by AstraZeneca, Boehringer-Ingelheim, MSD and 
      Chiesi, has received travel and attendance expenses for conferences from 
      AstraZeneca, Chiesi and Novartis, has acted as a consultant for ALK, AstraZeneca, 
      Boehringer, MSD, MundiPharma and Sanofi, and has received funds/grants for 
      research projects from several state agencies and non-profit foundations and from 
      AstraZeneca, Chiesi and Menarini. This does not alter our adherence to PLOS ONE 
      policies on sharing data and materials.
EDAT- 2021/06/05 06:00
MHDA- 2023/02/25 06:00
PMCR- 2021/06/04
CRDT- 2021/06/04 17:24
PHST- 2020/12/02 00:00 [received]
PHST- 2021/05/05 00:00 [accepted]
PHST- 2021/06/04 17:24 [entrez]
PHST- 2021/06/05 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2021/06/04 00:00 [pmc-release]
AID - PONE-D-20-37886 [pii]
AID - 10.1371/journal.pone.0251881 [doi]
PST - epublish
SO  - PLoS One. 2021 Jun 4;16(6):e0251881. doi: 10.1371/journal.pone.0251881. 
      eCollection 2021.