IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes

• Published in: BMC pulmonary medicine Vol. 18; no. 1; p. 51
• Main Authors: 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
• Format: Journal Article Web Resource
• Language: English
• Published: England BioMed Central Ltd 21.03.2018; BioMed Central; BMC
• Subjects: Adrenomedullin - blood; Aged; Atrial Natriuretic Factor - blood; Biomarker; Cardiovascular & respiratory systems; Case-Control Studies; Cohort; Cohort Studies; Disease Progression; Dyspnea; Female; Forced Expiratory Volume; Glycopeptides - blood; Human health sciences; Humans; Interferons; Interleukin 28B; Interleukins - blood; Interleukins - genetics; Male; Middle Aged; Mortality; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Procalcitonin - blood; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors - blood; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - physiopathology; Sciences de la santé humaine; Severity of Illness Index; Single nucleotide polymorphisms; Systèmes cardiovasculaire & respiratoire; Interleukin 28B; Biomarker; Single nucleotide polymorphisms; Cohort; Mortality
• ISSN: 1471-2466; 1471-2466
• DOI: 10.1186/s12890-018-0616-6

Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations? 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. 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 FEV %predicted and the tissue maturation biomarker Pro-collagen 3. IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD. Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.