Department of Medicine, Monash University, The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria, Australia.
J Heart Lung Transplant. 2012 Jun;31(6):557-64. doi: 10.1016/j.healun.2012.02.029. Epub 2012 Apr 12.
Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide and is often complicated by the development of pulmonary hypertension (PHT). The presence of PHT in COPD subjects is associated with increased mortality, morbidity and use of health-care resources. Thus, there has been significant effort to treat PHT in COPD patients to achieve improved clinical outcomes, but with only minimal success. There is renewed interest in understanding the mechanisms contributing to PHT in COPD as the basis for exploring new therapeutic strategies. In this study we review the evidence supporting the postulated mechanisms contributing to PHT in COPD. Hypoxia plays a pivotal role in the development of COPD-associated PHT. However, other mechanisms are also likely involved in the pathogenesis of increased pulmonary vascular resistance in this cohort, including acidemia, dynamic pulmonary hyperinflation, parenchymal destruction, pulmonary vascular remodeling, endothelial dysfunction and inflammation. These mechanisms are interdependent, modulated by genetic factors, and may be confounded by comorbidities such as sleep-disordered breathing, left heart failure and pulmonary thromboembolism. Despite significant research in recent decades, there is surprisingly little evidence of a causal relationship between many of these factors and the development of COPD-associated PHT. The pathogenesis of PHT in COPD is complex and multifaceted. Ultimately, as we obtain better information on COPD phenotypes, we may be able to more precisely account for the varied pathologic mechanisms of PHT occurring in various COPD patients. This may ultimately enable targeted PHT therapy for each COPD phenotype.
慢性阻塞性肺疾病（COPD）是全球范围内主要的死亡和发病原因之一，并且常常伴有肺动脉高压（PHT）的发展。COPD 患者中存在 PHT 与死亡率、发病率和医疗资源的使用增加有关。因此，为了实现改善的临床结果，已经做出了很大的努力来治疗 COPD 患者的 PHT，但只有最小的成功。由于了解导致 COPD 中 PHT 的机制是探索新的治疗策略的基础，因此对理解导致 COPD 中 PHT 的机制重新产生了兴趣。
在这项研究中，我们回顾了支持导致 COPD 中 PHT 的假设机制的证据。缺氧在 COPD 相关 PHT 的发展中起着关键作用。然而，其他机制也可能参与这一人群中肺血管阻力增加的发病机制，包括酸中毒、动态性肺过度充气、实质破坏、肺血管重构、内皮功能障碍和炎症。这些机制是相互依存的，受遗传因素调节，并且可能与睡眠呼吸障碍、左心衰竭和肺血栓栓塞等合并症混淆。
尽管近几十年来进行了大量研究，但令人惊讶的是，这些因素与 COPD 相关 PHT 的发展之间的因果关系的证据很少。COPD 中 PHT 的发病机制复杂且多方面。最终，随着我们获得关于 COPD 表型的更好信息，我们可能能够更准确地解释发生在各种 COPD 患者中的不同的 PHT 病理机制。这可能最终使每个 COPD 表型的 PHT 治疗成为可能。
