Interferon-lambda-genotype GG and IgG2 are predictors for frequent COPD exacerbations in a Swiss multicenter COPD cohort study (TOPDOCS)

Abstract

Background: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with disease progression, worsening health status, more hospitalizations and COPD-related mortality. During stable COPD, the identification of patients at high risk for exacerbations has a high impact for clinical management. Several biomarkers hold promise to predict exacerbation episodes, however, the assessment of the individual risk of exacerbation is challenging. Objective: The goal of this study was to investigate the impact of different biomarkers and genetic single nucleotide polymorphisms (SNPs) as predictors of frequent exacerbations (=/> 2/y). Methods: In 270 patients (mean age 63 years; 67% male) with COPD enrolled in The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland (TOPDOCS) biomarkers such as concentrations of serum mannose-binding lectin (MBL), immunoglobulins and IgG subclasses were quantified, IFN-lambda-genotypes (rs8099917) were determined and associated in COPD patients with frequent (≥2/year) and less frequent (0-1/year) exacerbations. Results: Conclusions: We observed that IgG, in particular IgG2 subclass concentrations but not serum MBL levels are associated with an increased risk of COPD exacerbations. Genotyping of the IFN-lambda-gen showed that GG-genotype may be linked to higher exacerbation risk as well. Therefore, measuring IgG2 and determining the IFN-lambda-genotype may be helpful to predict the risk of exacerbation in patients with COPD and thus to prevent complications and disease progression in these patients.