Serum lysozyme - a surrogate marker of pulmonary microvascular injury in smokers?

Progression rate of disease processes in smoke-induced lung injuries varies greatly. Diverse pathophysiological mechanisms may trigger these divergences. The aim of this study was to evaluate whether circulating markers of monocytes/macrophages and/or neutrophil [i.e. lysozyme (LZM) or myeloperoxidase (MPO)] were associated with reduced values of diffusion capacity (DL,CO), which is considered to serve as a mirror of pulmonary microvascular derangement and an early sign of tissue remodelling in smokers. Data obtained from 134 smokers (GOLD stage ≤1) and 24 matched healthy non-smoking volunteers were evaluated in a cross-sectional study design. Lung function tests as well as single breath test of DL,CO were assessed according to ATS/ERS guidelines. Biomarkers were measured in serum by means of sensitive immunoassays. A subgroup of smokers with normal lung function was created to minimize confounding, by excluding datasets showing significant airflow limitation and abnormally high values of carboxy haemoglobin (COHb), the latter indicating recent smoking. The capacity of serum lysozyme to correctly identify abnormally low values of DL,CO (i.e. <1·9SD units), tended to be higher than that of Myeloperoxidase as assessed by analyses of receiver operated curves (ROC; AUC 0·81, 95%CI: 0·69-0·89 versus AUC 0·67, 95%CI: 0·60-0·81). It is concluded that serum levels of lysozyme, reflecting mainly activated monocytes/macrophages but also neutrophils, were significantly associated with isolated decrements of DL,CO in smokers with normal lung function tests. This suggests monocytes/macrophages to have a significant mechanistic role in early phases of the disease process and/or pulmonary microvascular damage.