Mannose binding lectin (MBL) levels predict lung function decline in severe asthma

Abstract

There is increasing evidence that activation of the complement system in asthma contributes to ongoing inflammation, tissue damage and airway remodeling. Mannose binding lectin (MBL) is a pattern recognition molecule that serves as the key mediator of the lectin pathway of complement activation. MBL levels are genetically determined and vary widely amongst individuals. In the present study we hypothesized that high MBL levels in asthma are associated with increased loss of lung function over time, as a consequence of inflammatory tissue damage. We measured serum MBL levels by ELISA in 68 patients with severe asthma and prospectively determined the change in post-bronchodilator (pb) FEV1 over a mean period of 5.7 years. The relationship between MBL and change in pbFEV1 (ΔFEV1) was analysed using (multiple) regression analysis and corrected for possible confounders (age, sex, age of onset, asthma duration, and pbFEV1). The median (range) MBL level was 332 (10.8-3587) ng·ml⁻¹. MBL was significantly associated with ΔFEV1 (p<0.04). Patients with a high MBL level (≥332 ng·ml⁻¹) had an increased risk of lung function decline compared to those with low MBL levels (OR (CI): 3.16 (1.14-8.79), p = 0.027); the excess decline being 42 ml·yr⁻¹ (p = 0.01). We conclude that a high MBL level is associated with an increased decline in lung function in patients with severe asthma. MBL might provide a clue towards better understanding of the pathophysiology of ongoing inflammation and subsequent decline in lung function of patients with severe asthma.