FISIB, CIBER Enfermedades Respiratorias (CIBERES), Mallorca, Spain.
Expert Rev Clin Immunol. 2013 Sep;9(9):821-33. doi: 10.1586/1744666X.2013.828875.
Chronic obstructive pulmonary disease (COPD) is a major public health problem because of its high prevalence, rising incidence and associated socio-economic cost. The inhalation of toxic particles and gases, mostly tobacco smoke, is the main risk factor for COPD. Yet, not all smokers are equally susceptible to these toxic effects and only a percentage of them develop the disease (so-called 'susceptible smokers'). This, in combination with the observation that COPD shows familial aggregation, suggests that the genetic background of the smoker is a key element in the pathogenesis of the disease. On the other hand, it is well established that 'susceptible' smokers exhibit an enhanced inflammatory response of the lung parenchyma as compared with 'resistant' smokers (i.e., those who manage to maintain lung function within the normal age range despite their habit). Importantly, in COPD patients this inflammatory response does not resolve after quitting smoking, again at variance with resistant smokers. All in all, these observations suggest that the pathogenesis of COPD may involve, in some patients, an autoimmune component which contributes to the enhanced and persistent inflammatory response that characterizes the disease. Here we: i) review briefly the pathobiology of COPD; ii) present the available scientific evidence supporting a potential role for autoimmunity in COPD; iii) propose a three-step pathogenic hypothesis in the transition from smoking to COPD; and iv) discuss potential implications for the diagnosis and treatment of this frequent, growing, devastating and costly disease.
慢性阻塞性肺疾病（COPD）是一个主要的公共卫生问题，因为它的高患病率、发病率上升和相关的社会经济成本。吸入有毒颗粒和气体，主要是烟草烟雾，是 COPD 的主要危险因素。然而，并非所有吸烟者都同样容易受到这些有毒影响，只有一部分人会患上这种疾病（所谓的“易感吸烟者”）。这一点，再加上 COPD 表现出家族聚集的观察结果，表明吸烟者的遗传背景是疾病发病机制的关键因素。另一方面，已经确定“易感”吸烟者与“耐受”吸烟者（即尽管有吸烟习惯但仍能将肺功能维持在正常年龄范围内的人）相比，其肺实质的炎症反应增强。重要的是，在 COPD 患者中，这种炎症反应在戒烟后不会消退，这再次与耐受吸烟者不同。总而言之，这些观察结果表明，COPD 的发病机制在某些患者中可能涉及自身免疫成分，这有助于增强和持续的炎症反应，这是该疾病的特征。在这里，我们：i）简要回顾 COPD 的发病机制；ii）提出支持自身免疫在 COPD 中可能起作用的现有科学证据；iii）提出从吸烟到 COPD 的过渡过程中的三步骤发病假说；iv）讨论对这种常见、不断增长、具有破坏性和昂贵疾病的诊断和治疗的潜在影响。
