Division of Infectious Diseases, University at Buffalo, State University of New York, 701 Ellicott Street, Buffalo, NY 14203, USA.
BMC Infect Dis. 2009 Nov 15;9:178. doi: 10.1186/1471-2334-9-178.
Moraxella catarrhalis causes approximately 10% of exacerbations in chronic obstructive pulmonary disease (COPD) and also colonizes the lower airway in stable patients. Little is known about the effects of colonization by M. catarrhalis on airway inflammation and protease-antiprotease balance, and how these changes compare to those seen during exacerbations. Since COPD is a progressive inflammatory disease, elucidating the effects of bacterial colonization and exacerbation on airway inflammation is relevant to understanding disease progression in COPD. Our aims were (1) Analyze changes in airway inflammation in colonization and exacerbation of COPD due to M. catarrhalis; (2) Explore protease-antiprotease balance in colonization and exacerbation due to M. catarrhalis. Our hypothesis were (1) Acquisition of a new strain of M. catarrhalis in COPD increases airway inflammation from baseline and alters the protease-antiprotease balance towards a more proteolytic environment; (2) These changes are greater during exacerbations associated with M. catarrhalis as compared to colonization.
Thirty-nine consecutive COPD patients with 76 acquisitions of a new strain of M. catarrhalis over a 6-year period were identified in a prospective study. Seventy-six pre-acquisition sputum supernatant samples, obtained just before acquisition of M catarrhalis, and 76 acquisition samples (34 were associated with exacerbation, 42 with colonization) were analyzed for IL-8, TNF-alpha, Neutrophil Elastase (NE) and Secretory leukocyte protease inhibitor (SLPI). Changes were compared in paired samples from each patient.
IL-8, TNF-alpha and NE were significantly elevated after acquisition of M. catarrhalis, compared to pre-acquisition samples (p =< 0.001 for all three). These changes were present in colonization (p = 0.015 for IL-8; p =< 0.001 for TNF-alpha and NE) as well as in exacerbation (p =< 0.001 for all three), compared to pre-acquisition levels. SLPI was significantly lower after acquisition (p =< 0.001), in colonization (p =< 0.001) as well as in exacerbation (p = 0.004), compared to pre-acquisition levels. SLPI levels correlated negatively with NE levels (R2 = 0.07; p = 0.001).
Acquisition of M. catarrhalis in COPD causes increased airway inflammation and worsening protease-antiprotease imbalance during exacerbations and also in colonization, even in the absence of increased symptoms. These effects could contribute to progression of airway disease in COPD.
莫拉氏菌（Moraxella catarrhalis）约占慢性阻塞性肺疾病（COPD）恶化的 10%，也定植于稳定期患者的下呼吸道。关于莫拉氏菌定植对气道炎症和蛋白酶-抗蛋白酶平衡的影响，以及这些变化与恶化期间的变化如何比较，知之甚少。由于 COPD 是一种进行性炎症性疾病，因此阐明细菌定植和恶化对气道炎症的影响与了解 COPD 中的疾病进展有关。我们的目的是：（1）分析 COPD 患者由于莫拉氏菌定植和恶化导致的气道炎症变化；（2）探讨由于莫拉氏菌定植和恶化导致的蛋白酶-抗蛋白酶平衡。我们的假设是：（1）COPD 中新的莫拉氏菌菌株的获得增加了从基线开始的气道炎症，并改变了蛋白酶-抗蛋白酶平衡，向更具蛋白水解作用的环境发展；（2）与莫拉氏菌定植相比，这些变化在与莫拉氏菌相关的恶化期间更为明显。
在一项前瞻性研究中，鉴定了 39 名连续 COPD 患者在 6 年期间有 76 次新的莫拉氏菌获得。在获得莫拉氏菌之前，获得了 76 个痰上清液样本（76 个预采集样本），并分析了这些样本中的白细胞介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）、中性粒细胞弹性蛋白酶（NE）和分泌型白细胞蛋白酶抑制剂（SLPI）。对每位患者的配对样本进行比较。
与预采集样本相比，莫拉氏菌获得后，IL-8、TNF-α 和 NE 显著升高（所有三个结果的 p <0.001）。这些变化在定植（IL-8 的 p = 0.015；TNF-α 和 NE 的 p <0.001）和恶化（所有三个结果的 p <0.001）中均存在，与预采集水平相比。获得后 SLPI 显著降低（p <0.001），在定植（p <0.001）和恶化（p = 0.004）中均低于预采集水平。SLPI 水平与 NE 水平呈负相关（R2 = 0.07；p = 0.001）。
在 COPD 中获得莫拉氏菌会导致气道炎症增加和蛋白酶-抗蛋白酶失衡恶化，在恶化期间以及在没有增加症状的情况下也会发生这种情况。这些影响可能会导致 COPD 中的气道疾病进展。
