Sethi Sanjay, Maloney Jane, Grove Lori, Wrona Catherine, Berenson Charles S
Division of Pulmonary/Critical Care and Sleep Medicine, and Division of Infectious Diseases, Department of Medicine, University at Buffalo, Buffalo, NY, USA.
Am J Respir Crit Care Med. 2006 May 1;173(9):991-8. doi: 10.1164/rccm.200509-1525OC. Epub 2006 Feb 10.
Inflammation is now recognized as an integral part of the pathogenesis of chronic obstructive pulmonary disease (COPD). In contrast to the sterile airways of normal lungs, bacterial pathogens are often isolated from the airways in stable COPD. This "colonization" of the tracheobronchial tree, currently believed to be innocuous, could serve as an inflammatory stimulus, independent of current tobacco smoke exposure.
To test the hypothesis that bacterial colonization is associated with airway inflammation in stable COPD.
Bronchoscopy with bronchoalveolar lavage (BAL) was performed in three groups of subjects: 26 ex-smokers with stable COPD (COPD), 20 ex-smokers without COPD (ex-smokers), and 15 healthy nonsmokers (nonsmokers). Quantitative bacterial cultures, cell counts, chemokine, cytokine, proteinase/antiproteinase, and endotoxin levels in the BAL fluid were compared.
Potentially pathogenic bacteria were recovered at > or = 100 cfu/ml in 34.6% of COPD, 0% of ex-smokers, and in 6.7% of nonsmokers (p = 0.003). All values are expressed as median (interquartile range). Subjects with colonized COPD had significantly greater relative (12.0 [28.4] vs. 3.0 [7.8]%, p = 0.03) and absolute (4.98 [5.26] x 10(4)/ml vs. 3.04 [2.82] x 10(4)/ml, p = 0.02) neutrophil counts, interleukin 8 (33.8 [189.8] vs. 16.9 [20.1] pg/ml, p = 0.005), active matrix metalloproteinase-9 (2.16 [4.30] vs. 0.84 [0.99] U/ml, p = 0.03), and endotoxin (36.0 [72.6] vs. 3.55 [7.17] mEU/ml, p = 0.004) levels in the BAL than the subjects with noncolonized COPD. These inflammatory constituents of BAL were also significantly elevated in subjects with colonized COPD when compared with ex-smokers and nonsmokers.
Bacterial colonization is associated with neutrophilic airway lumen inflammation in ex-smokers with COPD and could contribute to progression of airway disease in COPD.
炎症现已被认为是慢性阻塞性肺疾病（COPD）发病机制中不可或缺的一部分。与正常肺脏无菌的气道不同，在稳定期COPD患者的气道中常可分离出细菌病原体。目前认为无害的气管支气管树的这种“定植”可能作为一种炎症刺激因素，与当前是否接触烟草烟雾无关。
验证细菌定植与稳定期COPD患者气道炎症相关这一假说。
对三组受试者进行支气管镜检查及支气管肺泡灌洗（BAL）：26例稳定期COPD的戒烟者（COPD组）、20例无COPD的戒烟者（戒烟者组）和15例健康非吸烟者（非吸烟者组）。比较BAL液中的细菌定量培养、细胞计数、趋化因子、细胞因子、蛋白酶/抗蛋白酶及内毒素水平。
COPD组中34.6%的患者BAL液中分离出的潜在致病菌≥100 cfu/ml，戒烟者组为0%，非吸烟者组为6.7%（p = 0.003）。所有数值均以中位数（四分位间距）表示。COPD定植组患者BAL液中的中性粒细胞相对计数（12.0 [28.4]% 对3.0 [7.8]%，p = 0.03）和绝对计数（4.98 [5.26]×10⁴/ml对3.04 [2.82]×10⁴/ml，p = 0.02）、白细胞介素8（33.8 [189.8] pg/ml对16.9 [20.1] pg/ml，p = 0.005）、活性基质金属蛋白酶-9（2.16 [4.30] U/ml对0.84 [0.99] U/ml，p = 0.03）及内毒素（36.0 [72.6] mEU/ml对3.55 [7.17] mEU/ml，p = 0.004）水平均显著高于COPD非定植组患者。与戒烟者组和非吸烟者组相比，COPD定植组患者BAL液中的这些炎症成分也显著升高。
细菌定植与COPD戒烟者的中性粒细胞性气道腔内炎症相关，并可能促使COPD气道疾病进展。
