Neutrophil-associated activation markers in healthy smokers relates to a fall in DLCO and to emphysematous changes on high resolution CT

Smoking is a risk factor for developing chronic obstructive pulmonary disea se (COPD). but there are no good indicators for early identification of sub jects who will develop symptomatic COPD. The aim of this study was to inves tigate inflammatory mechanisms related to changes in lung function and emph ysematous changes on high resolution computed tomography (HRCT) in 'healthy ' smokers. Subjects were 60-year-old men From a population study. Bronchosc opy was performed in 30 smokers and 18 who had never smoked. Blood tests. l ung function measurements and HRCT were carried out in 58 and 34 subjects r espectively. In comparison with never-smokers, smokers had higher levels of myeloperoxid ase (MPO), human neutrophil lipocalin (HNL). eosinophil cationic protein (E CP) and lysozyme in blood, higher levels of MPO. interleukin-8 (IL-8) and H NL in bronchial lavage (BL). and of IL-8, HNL and interleukin-1 beta (lL-1 beta) in bronchoalveolar lavage (BAL). Smokers also had lower levels of Cla ra cell protein 16 (CC-16) in blood. HNL in BL and BAL showed strong correl ations to other inflammatory markers (MPO. IL-8, IL-1 beta). The variations in MPO in BL were explained by variations in HNL (R-2=0(.)69). while these variations in BAL were explained by variations in HNL and IL-1 beta (R-2=0 (.)76). DLCO was the lung function variable most closely related to MPO and IL-8 in BL and BAL and to IL-1 beta in BAL. In a multiple regression analy sis. MPO, IL-1 beta. IL-8 and CC-16 in BL and MPO in BAL contributed to the explanation of variations in DLCO to 41% and 22%, respectively, independen t of smoking habits. In smokers with emphysematous lesions on HRCT. HNL in BAL correlated to emphysema score (r(S)= 0(.)71). We conclude that 'healthy ' smoking men with a near normal FEV1 show signs of inflammation in the low er airways that are related to a decrease in DLCO acid to emphysematous les ions on HRCT. This inflammation seems to be the result of both monocyte,mac rophage and neutrophil activation.