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
- 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.
Keywords
- Biomarker
- Cohort
- Interleukin 28B
- Mortality
- Single nucleotide polymorphisms
