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

Egli, A.; Mandal, J.; Schumann, D.M.; Roth, M.; Thomas, B.; Lorne Tyrrell, D.; Blasi, F.; Kostikas, K.; Boersma, W.; Milenkovic, B.; Lacoma, A.; Rentsch, K.; Rohde, G.G.U.; Louis, R.; Aerts, J.G.; Welte, T.; Torres, A.; Tamm, M.; Stolz, D.

doi:10.1186/s12890-018-0616-6

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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.

Titolo:	IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes
Autori:	A. Egli J. Mandal D. M. Schumann M. Roth B. Thomas D. Lorne Tyrrell BLASI, FRANCESCO BRUNO ARTURO K. Kostikas W. Boersma B. Milenkovic A. Lacoma K. Rentsch G. G. U. Rohde R. Louis J. G. Aerts T. Welte A. Torres M. Tamm D. Stolz mostra contributor esterni nascondi contributor esterni
Parole Chiave:	Biomarker; Cohort; Interleukin 28B; Mortality; Single nucleotide polymorphisms
Settore Scientifico Disciplinare:	Settore MED/10 - Malattie dell'Apparato Respiratorio
Data di pubblicazione:	21-mar-2018
Rivista:	BMC PULMONARY MEDICINE
Tipologia:	Article (author)
Digital Object Identifier (DOI):	10.1186/s12890-018-0616-6
Appare nelle tipologie:	01 - Articolo su periodico

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