Airways inflammation in subjects with chronic bronchitis who have never smoked

Abstract

Background - Smoking is the single most common cause of chronic bronchitis but the disease can also occur in non-smokers. Alterations in the lung responsible for the disease, such as oxidant/antioxidant and protease/antiprotease imbalance, have been investigated in smokers. The aim of our study was to evaluate local cellular and soluble factors (albumin, immunoglobulins, proteases, a,-antitrypsin, and transferrin) that may be involved in the development of chronic bronchitis in subjects who have never smoked. Methods - Sixteen clinically stable patients with chronic bronchitis who had never been smokers were studied and 17 healthy non-smokers served as controls. All subjects underwent bronchoalveolar lavage (BAL). Total and differential cell counts and concentrations of the main proteins (albumin, immunoglobulins, complement fractions, a,-antitrypsin, and transferrin) were measured. Elastase-like activity was assessed in cells and supernatants. To estimate the oxidant burden the release of superoxide anion (02-) from native cell populations was evaluated. Results - Recovery of BAL fluid was reduced in older individuals in both the chronic bronchitis and control groups. There was no difference in total cell count, but neutrophil percentage count was higher in those with chronic bronchitis (median (range) 3.5 (16.14.2)) than in controls (1.3 (0O5-3.7)). These differences were most pronounced in the first recovery, representative ofthe bronchial lavage. There was no difference in bronchial epithelial cells. Total proteins and albumin levels were comparable and IgG, IgA, IgM, C3, C4, transferrin and a,-antitrypsin values standardised to albumin did not show any significant differences. No differences in elastase-like levels in supernatants were detected. In cell lysates elastase-like activity x 107 cells (macrophages + neutrophils) was increased in patients with chronic bronchitis (0.25 (0.06-4.3) compared with controls 0-08 (0.03-0.9) pg PPEeq). The release of 02- both at baseline and after opsonised zymosan phagocytosis did not show any differences. Correlation analysis between FEV, and BAL fluid data showed a negative correlation only with neutrophils/ml. Conclusions - Clinically stable nonsmokers with chronic bronchitis show no alterations of local immune components, oxidant burden, and free elastase-like activity in BAL fluids, while the content of elastase-like activity in phagocytic cells is increased. As in smokers, bronchial neutrophilia is the most significant cellular modification which correlates with the degree of airflow obstruction.