Respiratory Research | 2021
Association of mannose-binding lectin, ficolin-2 and immunoglobulin concentrations with future exacerbations in patients with chronic obstructive pulmonary disease: secondary analysis of the randomized controlled REDUCE trial
Abstract
Background The innate and adaptive immune system is involved in the airway inflammation associated with acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). We evaluated the association of mannose-binding lectin (MBL), immunoglobulin (Ig) and ficolin-2 concentrations with COPD exacerbations and according to the glucocorticoid treatment duration for an index exacerbation. Methods Post-hoc analysis of the randomized, double-blind, placebo-controlled REDUCE trial of 5 vs. 14\xa0days of glucocorticoid treatment for an index exacerbation. MBL, ficolin-2 and total IgG/IgA and subclass concentrations were determined in stored samples drawn (n\u2009=\u2009178) 30\xa0days after the index exacerbation and associated with the risk of re-exacerbation during a 180-day follow-up period. Results IgG and subclass concentrations were significantly lower after 14\xa0days vs. 5\xa0days of glucocorticoid treatment. Patients with higher MBL concentrations were more likely to suffer from a future exacerbation (multivariable hazard ratio 1.03 per 200\xa0ng/ml increase (95% confidence interval (CI) 1.00–1.06), p\u2009=\u20090.048), whereas ficolin-2 and IgG deficiency were not associated. The risk was most pronounced in patients with high MBL concentrations, IgG deficiency and 14\xa0days of glucocorticoid treatment pointing towards an interactive effect of MBL and IgG deficiency in the presence of prolonged glucocorticoid treatment duration [Relative excess risk due to interaction 2.13 (95% CI −\u20090.41–4.66, p\u2009=\u20090.10)]. IgG concentrations were significantly lower in patients with frequent re-exacerbations (IgG, 7.81\xa0g/L vs. 9.53\xa0g/L, p\u2009=\u20090.03). Conclusions MBL modified the short-term exacerbation risk after a recent acute exacerbation of COPD, particularly in the setting of concurrent IgG deficiency and recent prolonged systemic glucocorticoid treatment. Ficolin-2 did not emerge as a predictor of a future exacerbation risk.