Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine Denver, CO, USA.
Front Physiol. 2013 May 15;4:91. doi: 10.3389/fphys.2013.00091. eCollection 2013.
Chronic Obstructive Pulmonary Disease (COPD) is one of the foremost causes of death worldwide. It is primarily caused by tobacco smoke, making it an easily preventable disease, but facilitated by genetic α-1 antitrypsin deficiency. In addition to active smokers, health problems also occur in people involuntarily exposed to second hand smoke (SHS). Currently, the relationship between SHS and COPD is not well established. Knowledge of pathogenic mechanisms is limited, thereby halting the advancement of new treatments for this socially and economically detrimental disease. Here, we attempt to summarize tobacco smoke studies undertaken in animal models, applying both mainstream (direct, nose only) and side stream (indirect, whole body) smoke exposures. This overview of 155 studies compares cellular and molecular mechanisms as well as proteolytic, inflammatory, and vasoreactive responses underlying COPD development. This is a difficult task, as listing of exposure parameters is limited for most experiments. We show that both mainstream and SHS studies largely present similar inflammatory cell populations dominated by macrophages as well as elevated chemokine/cytokine levels, such as TNF-α. Additionally, SHS, like mainstream smoke, has been shown to cause vascular remodeling and neutrophil elastase-mediated proteolytic matrix breakdown with failure to repair. Disease mechanisms and therapeutic interventions appear to coincide in both exposure scenarios. One of the more widely applied interventions, the anti-oxidant therapy, is successful for both mainstream and SHS. The comparison of direct with indirect smoke exposure studies in this review emphasizes that, even though there are many overlapping pathways, it is not conclusive that SHS is using exactly the same mechanisms as direct smoke in COPD pathogenesis, but should be considered a preventable health risk. Some characteristics and therapeutic alternatives uniquely exist in SHS-related COPD.
慢性阻塞性肺疾病（COPD）是全球首要致死原因之一。它主要由烟草烟雾引起，是一种容易预防的疾病，但由于遗传α-1 抗胰蛋白酶缺乏而变得更容易发生。除了主动吸烟者，被动接触二手烟（SHS）的人群也会出现健康问题。目前，SHS 与 COPD 之间的关系尚未得到充分证实。对发病机制的了解有限，从而阻碍了针对这种对社会和经济造成严重损害的疾病的新治疗方法的进展。在这里，我们尝试总结了在动物模型中进行的关于烟草烟雾的研究，同时应用主流（直接，仅鼻）和侧流（间接，全身）烟雾暴露。这篇综述对 155 项研究进行了比较，比较了细胞和分子机制以及蛋白酶、炎症和血管反应性反应，这些反应是 COPD 发展的基础。这是一项艰巨的任务，因为大多数实验中对暴露参数的列表有限。我们发现，主流和 SHS 研究都主要呈现出相似的炎症细胞群，主要由巨噬细胞组成，以及升高的趋化因子/细胞因子水平，如 TNF-α。此外，与主流烟雾一样，SHS 已被证明会引起血管重塑和中性粒细胞弹性蛋白酶介导的蛋白酶解基质破坏，而无法修复。两种暴露情况的疾病机制和治疗干预似乎都一致。抗氧化治疗是一种广泛应用的干预措施，对主流和 SHS 都有效。本综述中直接与间接烟雾暴露研究的比较强调，即使存在许多重叠的途径，也不能得出结论认为 SHS 在 COPD 发病机制中使用的正是与直接烟雾相同的机制，但应被视为可预防的健康风险。SHS 相关的 COPD 存在一些独特的特征和治疗选择。
