Chest
Volume 134, Issue 4, October 2008, Pages 808-814
Journal home page for Chest

Translating Basic Research Into Clinical Practice
Pulmonary Vascular Involvement in COPD

https://doi.org/10.1378/chest.08-0820Get rights and content

Alterations in pulmonary vessel structure and function are highly prevalent in patients with COPD. Vascular abnormalities impair gas exchange and may result in pulmonary hypertension, which is one of the principal factors associated with reduced survival in COPD patients. Changes in pulmonary circulation have been identified at initial disease stages, providing new insight into their pathogenesis. Endothelial cell damage and dysfunction produced by the effects of cigarette smoke products or inflammatory elements is now considered to be the primary alteration that initiates the sequence of events resulting in pulmonary hypertension. Cellular and molecular mechanisms involved in this process are being extensively investigated. Progress in the understanding of the pathobiology of pulmonary hypertension associated with COPD may provide the basis for a new therapeutic approach addressed to correct the imbalance between endothelium-derived vasoactive agents. The safety and efficacy of endothelium-targeted therapy in COPD-associated pulmonary hypertension warrants further investigation in randomized clinical trials.

Section snippets

Pulmonary Vascular Remodeling in COPD

Remodeling is a process that causes thickening of the arterial wall and is thought to increase resistance by causing the vessel wall to encroach into the lumen and reduce its diameter. In COPD patients, pulmonary vascular remodeling affects small and precapillary arteries, and has been identified at different degrees of disease severity. Intimal enlargement is the most prominent feature of pulmonary vascular remodeling. It is apparent in arteries of different sizes, although it is more

Inflammatory Changes

COPD is an inflammatory disease, hence, inflammatory cells might contribute to the alterations of pulmonary vessels. Indeed, the extent of pulmonary vascular remodeling correlates with the severity of inflammatory cell infiltrate in small airways.2, 11 Patients with COPD have an increased number of inflammatory cells infiltrating the adventitia of pulmonary muscular arteries, compared with nonsmokers.12 This inflammatory infiltrate is largely constituted by activated T lymphocytes with a

Endothelial Dysfunction

Endothelial cells play a crucial role in the regulation of vascular homeostasis.14 In pulmonary vessels, endothelial cells contribute to the reduced vascular tone,15 regulate vessel adaptation to increased flow,16 and modulate hypoxic vasoconstriction.17, 18 Endothelial dysfunction of the pulmonary arteries has been shown with different degrees of COPD severity, as follows: patients with end-stage COPD who had undergone lung transplantation19; and patients with mild-to-moderate COPD.3 The

Stem Cells and Vascular Remodeling in COPD

The idea of a maintenance program in the adult lung has emerged in the past few years.25 The lung copes with external challenges by inhaled particles, toxic gases, and invading microorganisms. The defense against this external injury depends on immune mechanisms and an efficient system for removing and replacing apoptotic cells. Stem cells may play a critical role in lung homeostasis since they retain their ability to replicate and differentiate into structural cells. Both resident and bone

Pathobiology of Pulmonary Vascular Changes in COPD

Hypoxia has been classically considered to be the major pathogenic mechanism of pulmonary hypertension in COPD. However, its role is currently being reconsidered because pulmonary vascular remodeling and endothelial dysfunction can be observed in patients with mild COPD who do not have hypoxemia and in smokers with normal lung function,2, 4, 12 and because long-term oxygen therapy does not reverse pulmonary hypertension.31

Observations1 point out that cigarette smoke products might be at the

Clinical Implications

The results of basic research into the vascular biology of the pulmonary circulation in COPD patients have identified the following several issues having potential clinical relevance: (1) structural and functional changes in pulmonary vessels are highly prevalent in all disease stages; (2) in patients with mild-to-moderate disease, these changes may not cause pulmonary hypertension at rest but might produce it during exercise and, eventually, may contribute to exercise limitation; (3) the

Endothelium-Targeted Treatment

The treatment options for COPD-associated pulmonary vascular abnormalities are limited. To date, long-term oxygen therapy for the treatment of hypoxemia is the only treatment that has demonstrated efficacy in slowing down or reversing the progression of pulmonary hypertension.31 Nevertheless, pulmonary arterial pressure rarely returns to normal values, and the structural abnormalities of pulmonary vessels remain unaltered.9 Treatment with conventional vasodilators, such as calcium channel

Conclusions

Structural and functional impairment of pulmonary vessels are early phenomena in the natural history of COPD. Cigarette smoke products are now identified as the most likely causative agents of the initial changes in pulmonary circulation through either a direct effect on endothelial cells or an inflammatory mechanism. The combination of endothelial dysfunction, vessel remodeling and inflammatory cell infiltrate conform the basis for the development of pulmonary hypertension in COPD. Treatment

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    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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