Borrill Zoë L, Roy Kay, Vessey Rupert S, Woodcock Ashley A, Singh Dave
Medicines Evaluation Unit, University of Manchester, Wythenshawe Hospital, Southmoor Rd, Manchester, UK.
Int J Chron Obstruct Pulmon Dis. 2008;3(1):171-83. doi: 10.2147/copd.s1850.
Limited information exists regarding measurement, reproducibility and interrelationships of non-invasive biomarkers in smokers. We compared exhaled breath condensate (EBC) leukotriene B4 (LTB4) and 8-isoprostane, exhaled nitric oxide, induced sputum, spirometry, plethysmography, impulse oscillometry and methacholine reactivity in 18 smokers and 10 non-smokers. We assessed the relationships between these measurements and within-subject reproducibility of EBC biomarkers in smokers. Compared to non-smokers, smokers had significantly lower MMEF % predicted (mean 64.1 vs 77.7, p = 0.003), FEV1/FVC (mean 76.2 vs 79.8 p = 0.05), specific conductance (geometric mean 1.2 vs 1.6, p = 0.02), higher resonant frequency (mean 15.5 vs 9.9, p = 0.01) and higher EBC 8-isoprostane (geometric mean 49.9 vs 8.9 pg/ml p = 0.001). Median EBC pH values were similar, but a subgroup of smokers had airway acidification (pH < 7.2) not observed in non-smokers. Smokers had predominant sputum neutrophilia (mean 68.5%). Repeated EBC measurements showed no significant differences between group means, but Bland Altman analysis showed large individual variability. EBC 8-isoprostane correlated with EBC LTB4 (r = 0.78, p = 0.0001). Sputum supernatant IL-8 correlated with total neutrophil count per gram of sputum (r = 0.52, p = 0.04) and with EBC pH (r = -0.59, p = 0.02). In conclusion, smokers had evidence of small airway dysfunction, increased airway resistance, reduced lung compliance, airway neutrophilia and oxidative stress.
关于吸烟者中非侵入性生物标志物的测量、重复性及相互关系的信息有限。我们比较了18名吸烟者和10名非吸烟者的呼出气冷凝物（EBC）白三烯B4（LTB4）和8-异前列腺素、呼出一氧化氮、诱导痰、肺量计、体积描记法、脉冲振荡法及乙酰甲胆碱反应性。我们评估了这些测量值之间的关系以及吸烟者中EBC生物标志物的受试者内重复性。与非吸烟者相比，吸烟者的预计MMEF%显著降低（均值64.1对77.7，p = 0.003），FEV1/FVC降低（均值76.2对79.8，p = 0.05），比电导降低（几何均值1.2对1.6，p = 0.02），共振频率升高（均值15.5对9.9，p = 0.01），EBC 8-异前列腺素升高（几何均值49.9对8.9 pg/ml，p = 0.001）。EBC pH值中位数相似，但有一小部分吸烟者存在气道酸化（pH < 7.2），非吸烟者未观察到这种情况。吸烟者痰液中性粒细胞占优势（均值68.5%）。重复的EBC测量显示组均值之间无显著差异，但Bland Altman分析显示个体差异较大。EBC 8-异前列腺素与EBC LTB4相关（r = 0.78，p = 0.0001）。痰液上清液IL-8与每克痰液中的总中性粒细胞计数相关（r = 0.52，p = 0.04），与EBC pH相关（r = -0.59，p = 0.02）。总之，吸烟者存在小气道功能障碍、气道阻力增加、肺顺应性降低、气道中性粒细胞增多及氧化应激的证据。
