The aim of the present study was to characterize the inflammatory pattern in "healthy"smokers and relate it to lung function, high resolution computed tomography (HRCT) findings and respiratory symptoms in order to identify smokers at risk to develop COPD. Subjects were recruited from a population study "Men born 1933 in Göteborg". Only smokers who considered themselves as healthy (n=58) were investigated. From the same population a random sample of healthy never-smokers (n=34) were recruited. All subjects underwent lung function tests, HRCT, and answered a questionnaire. Thirty smokers (30/58) and 18 never-smokers (18/34) accepted to undergo a bronchoscopy with bronchial lavage, bronchoalveolar lavage (BAL) and bronchial biopsies. The levels of neutrophil-associated soluble inflammatory markers e.g. human neutrophil lipocalin (HNL), were higher in smokers in both blood, bronchial lavage and BAL, as compared with never-smokers. Inflammatory markers in bronchial lavage and BAL were related to carbon monoxide transfer (DLCO) but not to forced expiratory volume in one second (FEV1). HRCT showed emphysematous changes in 25/57 smokers while only 1/32 never-smokers showed this. Such emphysematous changes in smokers were related to a decrease in transfer factor (DLCO/ VA) as well as to an increase in HNL in BAL. Smokers with emphysematous changes also had more alveolar macrophages in BAL as compared with smokers without changes. Bronchial biopsies were analysed according to some T cell subpopulations, in different compartments in never-smokers. In healthy never-smokers, an increased number of cytotoxic T cells (CD 8+) were found in the bronchial epithelium as compared with lamina propria. Also in smokers, the same gradient in bronchial biopsies was seen. Even if the number of CD8+ cells in lamina propria were not increased in smokers as compared with never-smokers, a relation between CD8+ cells and an impairment in FEV1 was demonstrated in smokers. In BAL in never-smokers, the proportion of different T cell activation markers were higher in BAL than in blood (e.g. HLA-DR, CD54+, CD69+). In BAL in smokers as compared with never-smokers, an increased proportion of CD8+ and decreased proportion of CD4+ T cells was seen. The CD4+/CD8+ ratio was also low. The occurrence of different respiratory symptoms in smokers who considered themselves as "healthy" were high. Smokers with symptoms had lower FEV1, FEV% and specific airway conductance (sGaw) as well as increased number of CD8+ cells in the bronchial biopsies as compared with smokers without symptoms. However, no relation between reported symptoms and soluble inflammatory markers in blood/BAL, emphysematous changes or lung function tests mainly reflecting the small airways, could be seen. In summary, smokers without any diagnosed pulmonary or bronchial disease, frequently report respiratory symptoms, have decreased lung function, emphysematous changes on HRCT and these findings are related to inflammatory markers in bronchial tissue and bronchial lavage, BAL and blood. Thus, "healthy" smokers have an inflammation in the bronchial mucosa suggesting early chronic obstructive pulmonary disease (COPD) or preclinical COPD
