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Open Access 01-12-2018 | Research article

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

Authors: Adrian Egli, Jyotshna Mandal, Desiree M. Schumann, Michael Roth, Brad Thomas, D. Lorne Tyrrell, Francesco Blasi, Kostantinos Kostikas, Wim Boersma, Branislava Milenkovic, Alicia Lacoma, Katharina Rentsch, Gernot G. U. Rohde, Renaud Louis, Joachim G. Aerts, Tobias Welte, Antoni Torres, Michael Tamm, Daiana Stolz

Published in: BMC Pulmonary Medicine | Issue 1/2018

Abstract

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.

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Title: IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes
Authors: Adrian Egli
Jyotshna Mandal
Desiree M. Schumann
Michael Roth
Brad Thomas
D. Lorne Tyrrell
Francesco Blasi
Kostantinos Kostikas
Wim Boersma
Branislava Milenkovic
Alicia Lacoma
Katharina Rentsch
Gernot G. U. Rohde
Renaud Louis
Joachim G. Aerts
Tobias Welte
Antoni Torres
Michael Tamm
Daiana Stolz
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Pulmonary Medicine / Issue 1/2018
Electronic ISSN: 1471-2466
DOI: https://doi.org/10.1186/s12890-018-0616-6

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Abstract

Background

Methods

Results

Conclusion

Trial registration

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