Egli, AdrianMandal, JyotshnaSchumann, Desiree M.Roth, MichaelThomas, BradTyrrell, D. LorneBlasi, FrancescoKostikas, KostantinosBoersma, WimMilenkovic, BranislavaLacoma, AliciaRentsch, KatharinaRohde, Gernot G. U.Louis, RenaudAerts, Joachim G.Welte, TobiasTorres Martí, AntoniTamm, MichaelStolz, Daiana2021-05-052021-05-052018-03-211471-2466https://hdl.handle.net/2445/177028Background: 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 2008.9 p.application/pdfengcc-by (c) Egli, Adrian et al., 2018http://creativecommons.org/licenses/by/3.0/esMortalitatMarcadors bioquímicsPolimorfisme genèticMortalityBiochemical markersGenetic polymorphismsinfo:eu-repo/semantics/article6973142021-05-05info:eu-repo/semantics/openAccess