Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY; VA Western New York Healthcare System, Buffalo, NY.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY; VA Western New York Healthcare System, Buffalo, NY.
Chest. 2011 Sep;140(3):611-617. doi: 10.1378/chest.10-2760. Epub 2011 Feb 24.
Pathogenic bacteria colonize the airways of 30% to 40% of patients with COPD and cause approximately 50% of exacerbations. New strains of nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis are associated with exacerbations. Antimicrobial protein/peptides (AMPs) play important roles in innate lung defense against pathogens. To our knowledge, the changes in AMP baseline levels in respiratory secretions during bacterial colonization and exacerbation have not been described. The objective of this study was to elucidate the effects of the acquisition of a new strain of pathogenic bacteria on the airway levels of AMPs in patients with COPD.
One hundred fifty-three samples from 11 patients were selected from COPD sputum samples collected prospectively over 6 years. Samples were grouped as culture-negative (no pathogenic bacteria), colonization, and exacerbation due to new strains of NTHI and M catarrhalis. Levels of lysozyme, lactoferrin, LL-37, and secretory leukocyte protease inhibitor (SLPI) were measured by enzyme-linked immunosorbent assay and compared among groups by paired analysis.
Compared with baseline, sputum lysozyme levels were significantly lower during colonization and exacerbation by NTHI (P = .001 and P = .013, respectively) and M catarrhalis (P = .007 and P = .018, respectively); SLPI levels were lower with exacerbation due to NTHI and M catarrhalis (P = .002 and P = .004, respectively), and during colonization by M catarrhalis (P = 032). Lactoferrin levels did not change significantly; LL-37 levels were higher during exacerbation by NTHI and M catarrhalis (P = .001 and P = .018, respectively).
Acquisition of NTHI and M catarrhalis is associated with significant changes in airway levels of AMPs, with larger changes in exacerbation. Airway AMP levels are likely to be important in pathogen clearance and clinical outcomes of infection in COPD.
30%至 40%的 COPD 患者的气道中定植有病原菌,这些病原菌约导致 50%的恶化。新的非定型流感嗜血杆菌(NTHI)和卡他莫拉菌株与恶化有关。抗菌蛋白/肽(AMPs)在先天肺防御病原体中发挥重要作用。据我们所知,在细菌定植和恶化期间,呼吸道分泌物中 AMP 基线水平的变化尚未描述。本研究的目的是阐明获得新的病原菌株对 COPD 患者气道中 AMP 水平的影响。
从前瞻性收集的 6 年 COPD 痰样本中选择了 11 名患者的 153 个样本。将样本分为培养阴性(无病原菌)、定植和因新的 NTHI 和 M 卡他莫拉菌株而恶化。通过酶联免疫吸附测定法测量溶菌酶、乳铁蛋白、LL-37 和分泌型白细胞蛋白酶抑制剂(SLPI)的水平,并通过配对分析比较各组之间的水平。
与基线相比,NTHI 和 M 卡他莫拉菌定植和恶化时痰溶菌酶水平显著降低(分别为 P =.001 和 P =.013,P =.007 和 P =.018);NTHI 和 M 卡他莫拉菌恶化时 SLPI 水平降低(分别为 P =.002 和 P =.004),M 卡他莫拉菌定植时 SLPI 水平降低(P =.032)。乳铁蛋白水平无显著变化;NTHI 和 M 卡他莫拉菌恶化时 LL-37 水平升高(分别为 P =.001 和 P =.018)。
NTHI 和 M 卡他莫拉菌的获得与气道 AMP 水平的显著变化有关,恶化时变化更大。气道 AMP 水平可能在 COPD 患者的病原体清除和感染临床结局中起重要作用。