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Войти в исследования BMC pulmonary medicine · 2018
IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Egli Adrian, Mandal Jyotshna, Schumann Desiree M, Roth Michael, Thomas Brad, Lorne Tyrrell D, Blasi Francesco, Kostikas Kostantinos, Boersma Wim, Milenkovic Branislava, Lacoma Alicia, Rentsch Katharina, Rohde Gernot G U, Louis Renaud, Aerts Joachim G, Welte Tobias, Torres Antoni, Tamm Michael, Stolz Daiana
Аннотация
BACKGROUND: Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations?
METHODS: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months.
RESULTS: The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV1%predicted and the tissue maturation biomarker Pro-collagen 3.
CONCLUSION: IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD.
TRIAL REGISTRATION: Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.
METHODS: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months.
RESULTS: The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV1%predicted and the tissue maturation biomarker Pro-collagen 3.
CONCLUSION: IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD.
TRIAL REGISTRATION: Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.
Предметные рубрики MeSH
AdrenomedullinAgedAtrial Natriuretic FactorCase-Control StudiesCohort StudiesDisease ProgressionDyspneaFemaleForced Expiratory VolumeGlycopeptidesHumansInterferonsInterleukinsMaleMiddle AgedPolymorphism, GeneticPolymorphism, Single NucleotideProcalcitoninPrognosisProportional Hazards ModelsProspective StudiesProtein PrecursorsPulmonary Disease, Chronic ObstructiveSeverity of Illness IndexInterferon Lambda