title: Mechanisms of pulmonary hypertension in chronic obstructive pulmonary disease: a pathophysiologic review.
abstract: 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.
authors.affiliation: Department of Medicine, Monash University, The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria, Australia.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Wrobel
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Thompson
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Williams
mesh_terms: D015897:Comorbidity; D004730:Endothelium, Vascular / Q000503:physiopathology; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology*; D011655:Pulmonary Embolism / Q000453:epidemiology; D014655:Vascular Resistance / Q000502:physiology