Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis

Background: Lower airway secretions from patients with bronchiectasis show inflammatory cell infiltration and increased proinflammatory mediators. The aim of this study was to investigate the effects of antibiotic treatment for exacerbations on neutrophil apoptosis and necrosis. Methods: Sputum was induced from 15 subjects with idiopathic bronchiectasis at the beginning of an acute exacerbation and after intravenous antibiotic treatment. Neutrophil apoptosis and necrosis were assessed using flow cytometry and morphology and the supernatant was analysed for concentrations of inflammatory mediators. Results: Neutrophil numbers (x10(6) cells/g sputum) in sputum were significantly greater on day 0 than on day 14 (median difference (95% confidence interval (CI)) 5.14 (1.27 to 8.46), p=0.02). Controls had a significantly higher percentage of sputum macrophages than patients with bronchiectasis (day 0, 1.35 (95% CI 0.48 to 2.89), p=0.004; day 14, 1.09 (95% CI 0.26 to 2.86), p=0.02). The concentrations of tumour necrosis factor alpha (pg/ml), interleukin 8 (ng/ml), and neutrophil elastase (ng/ml) in sputum supernatant were significantly reduced on day 14 compared with day 0 ( median difference 294 ( 95% CI -158 to -27), p=0.005; -106 (95% CI -189 to -50), p=0.0006; and -73451 (95% CI -135495 to -12303), p=0.02 respectively). Patients with bronchiectasis had a significantly lower percentage of cells which were neither apoptotic nor necrotic than healthy controls (both days, -38.8 (95% CI -49.6 to -8.5), p=0.002; -45.0 (95% CI -58.0 to -34.1), p=0.0003, respectively), and on day 14 they had a significantly higher percentage of secondary necrotic cells than healthy controls (40 (95% CI 11.6 to 57.5), p=0.004). Conclusions: This study shows that antibiotic treatment affects concentrations of proinflammatory mediators and cell death and clearance may be altered in bronchiectasis.