Watt A P, Brown V, Courtney J, Kelly M, Garske L, Elborn J S, Ennis M
Respiratory Research Group, Centre for Infection, Inflammation and Repair, The Queen's University of Belfast, Belfast, UK.
Thorax. 2004 Mar;59(3):231-6. doi: 10.1136/thx.2003.008037.
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.
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.
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 -94 (95% CI -158 to -27), p = 0.005; -106 (95% CI -189 to -50), p = 0.0006; and -73 451 (95% CI -135 495 to -12 303), 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).
This study shows that antibiotic treatment affects concentrations of proinflammatory mediators and cell death and clearance may be altered in bronchiectasis.
支气管扩张症患者的下呼吸道分泌物显示有炎症细胞浸润且促炎介质增加。本研究的目的是调查抗生素治疗加重期对中性粒细胞凋亡和坏死的影响。
在急性加重期开始时及静脉给予抗生素治疗后,对15例特发性支气管扩张症患者进行痰液诱导。使用流式细胞术和形态学评估中性粒细胞凋亡和坏死情况,并分析上清液中炎症介质的浓度。
痰液中的中性粒细胞数量(×10⁶细胞/克痰液)在第0天显著高于第14天(中位数差异(95%置信区间)5.14(1.27至8.46),p = 0.02)。对照组痰液巨噬细胞的百分比显著高于支气管扩张症患者(第0天,1.35(95%置信区间0.48至2.89),p = 0.004;第14天,1.09(95%置信区间0.26至2.86),p = 0.02)。与第0天相比,痰液上清液中肿瘤坏死因子α(pg/ml)、白细胞介素8(ng/ml)和中性粒细胞弹性蛋白酶(ng/ml)的浓度在第14天显著降低(中位数差异 -94(95%置信区间 -158至 -27),p = 0.005;-106(95%置信区间 -189至 -50),p = 0.0006;以及 -73451(95%置信区间 -135495至 -12303),p = 0.02)。支气管扩张症患者既不凋亡也不坏死的细胞百分比显著低于健康对照组(两天均为,-38.8(95%置信区间 -49.6至 -8.5),p = 0.002;-45.0(95%置信区间 -58.0至 -34.1),p = 0.0003),并且在第14天,他们继发性坏死细胞的百分比显著高于健康对照组(40(95%置信区间11.6至57.5),p = 0.004)。
本研究表明抗生素治疗会影响促炎介质的浓度,并且支气管扩张症中细胞死亡和清除可能会发生改变。