Small airways dysfunction and neutrophilic inflammation in bronchial biopsies and BAL in COPD
Small airways dysfunction and neutrophilic inflammation in bronchial biopsies and BAL in COPD
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DOI：
10.1378/chest.06-0796
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发表时间：
2007-01-01
期刊：
影响因子：
9.6
通讯作者：
Sterk, Peter J.
中科院分区：
文献类型：
--
作者：
Lapperre, Therese S.;Willems, Luuk N. A.;Sterk, Peter J.
背景：单呼吸N-2试验（sbN(2)-试验）与吸烟者肺切除标本的小气道病理密切相关。我们研究了不均匀通气和气道关闭是否与明显慢性阻塞性肺病患者的支气管活检、BAIL和诱导痰获得的气道炎症特异性标志物相关。方法：在一项横断面研究中，对51例未接受皮质类固醇治疗的稳定期COPD患者进行了检查（43例男性，平均[SD]年龄63±8岁，戒烟者和吸烟者，中位包年41年[四分位数范围31 ~ 51包年]）。进行支气管扩张剂后肺活量测定（FEV1，预测值的63±8%）和sbN(2)试验（III期斜率[δ N-2]，闭合容量[CC]/总肺活量[TLC]预测值的百分比）。在支气管活检、BAL（仅在前一半患者中）和诱导痰中评估炎症细胞计数。测定BAL液中中性粒细胞弹性酶（NE）、分泌酶（secretoij）、白细胞蛋白酶抑制剂（SLPI）和白细胞介素-8水平。结果：δ N-2随支气管活检中上皮下中性粒细胞数量（rs = 0.337, p = 0.017）和BAL中NE水平（rs = 0.443, p = 0.039）、NE/中性粒细胞比值（rs = 0.575, p = 0.005）和SLPI水平（rs = 0.484, p = 0.022）升高而升高。CC/TLC与BAL中性粒细胞数目相关（rs = 0.448, p = 0.048）。sbN(2)-试验与am、BAL或活检中的其他炎症细胞类型无关，也与痰中的炎症细胞计数无关。重要的是，当调整FEV1预测百分比时，Delta N-2与BAL NE/中性粒细胞比率之间以及CC/TLC与BAL中性粒细胞数量之间的相关性仍然显着。结论：sbN(2)-试验结果与COPD患者支气管活检中的中性粒细胞炎症和BAL相关。我们的研究结果支持嗜中性粒细胞炎症在COPD小气道功能障碍发病机制中的作用。
Background: The single-breath N-2 test (sbN(2)-test) is closely related to small airways pathology in resected lung specimens of smokers. We investigated whether uneven ventilation and airway closure are associated with specific markers of airway inflammation as obtained by bronchial biopsies, BAIL, and induced sputum in patients with manifest COPD.Methods: Fifty-one patients with stable COPD not receiving corticosteroids were examined in a cross-sectional study (43 men; mean [SD] age, 63 +/- 8 years; exsmokers and smokers; median pack-years, 41 [interquartile range, 31 to 51 pack-years]). Postbronchodilator spirometry (FEV1, 63 +/- 8% of predicted) and sbN(2)-test (slope of phase III [Delta N-2], closing capacity [CC]/total lung capacity [TLC] percentage of predicted) were performed. Inflammatory cell counts were assessed in bronchial biopsies, BAL (only in the first half of patients), and induced sputum. Neutrophil elastase (NE), secretoij, leukocyte proteinase inhibitor (SLPI), and interleukin-8 levels were determined in BAL fluid.Results: Delta N-2 increased with subepithelial neutrophil numbers in bronchial biopsies (rs = 0.337, p = 0.017) and with NE levels (rs = 0.443, p = 0.039), NE/neutrophil ratio (rs = 0.575, p = 0.005) and SLPI levels (rs = 0.484, p = 0.022) in BAL. CC/TLC was associated with BAL neutrophil numbers (rs = 0.448, p = 0.048). The sbN(2)-test was not associated with am, other inflammatory cell type in BAL or biopsies, nor with inflammatory cell counts in sputum. Of importance, the correlations between Delta N-2 and BAL NE/neutrophil ratio, and between CC/TLC and BAL neutrophil numbers remained significant when adjusting for FEV1 percentage of predicted.Conclusions: The results of the sbN(2)-test are associated with neutrophilic inflammation in bronchial biopsies and BAL in patients with COPD. Our findings support a role of neutrophilic inflammation in the pathogenesis of small airways dysfunction in COPD.