beraprost and Pulmonary-Disease--Chronic-Obstructive

Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and meta-analysis to assess whether PH-specific therapies have an effect for stable COPD. Data sources were Medline, EMBASE, Cochrane Central Register of Controlled Trials, Korea med and references from relevant publications. Randomized prospective trials that compared PH specific therapy in COPD for more than 6 weeks with placebo were included. The outcomes were the exercise capacity and adverse events. Four randomized controlled trials involving 109 subjects were included in the analysis. Two trials involved bosentan, one sildenafil and one beraprost. The studies varied in duration of treatment from 3 to 18 months. In a pooled analysis of four trials, exercise-capacity was not significantly improved with PH-specific treatment for COPD (risk ratio, -5.1; 95% CI, -13.0 to 2.8). COPD with overt PH significantly improved the exercise capacity (mean difference, 111.6; 95% CI, 63.3 to 159.9) but COPD with PH unknown did not (mean difference, 26.6; 95% CI, -24.3 to 77.5). There was no significant difference in hypoxemia (mean difference, 2.6; 95% CI, -3.7 to 8.8). PH specific treatments have a significant effect in improving exercise capacity in COPD with overt PH.

Topics: Antihypertensive Agents; Bosentan; Clinical Trials as Topic; Databases, Factual; Epoprostenol; Humans; Hypertension, Pulmonary; Hypoxia; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Risk Factors; Sildenafil Citrate; Sulfonamides; Sulfones; Surveys and Questionnaires

Apoptosis is now widely recognized as an important part of chronic obstructive pulmonary disease (COPD) pathogenesis. Our previous study demonstrated that a prostacyclin (PGI(2)) analogue (beraprost sodium, BPS) prevented cigarette smoke extract (CSE) induced apoptosis of the pulmonary endothelium in rats. So we determined to clarify the apoptosis of vascular endothelial cells in COPD patient and the role of prostacyclin in the protection against apoptosis in vascular endothelial cells induced by CSE. Surgical specimens were obtained from 12 patients with COPD and 10 controls, and the level of apoptosis, prostacyclin synthase (PGI(2)S) expression and 6-keto-PGF1α (a stable metabolite of PGI(2)) were detected. The apoptotic index (AI), caspase-3 activity, expression of caspase-3 and 6-keto-PGF1α were examined in human umbilical vein endothelial cells (HUVECs) under exposure to varied concentrations of CSE for 24 h as well as under exposure to 2.5 % CSE for varied durations. Then, HUVECs under 2.5 % CSE were exposed to varied concentrations of BPS for 24 h and observed the alteration and the level of cAMP. Increased AI, decreased expression of PGI(2)S and 6-keto-PGF1α, were found in the lungs of patients with COPD compared with controls. Moreover, CSE induced apoptosis in means of both dose-dependent and time-dependent manners, and reduced the level of 6-keto-PGF1α in HUVECs. And with the treatment of BPS, an enhanced level of cAMP and decreased apoptosis were detected. The deficiency of PGI(2) critically contributes to the COPD-associated endothelial dysfunction and apoptosis. And BPS protects against the apoptosis in the vascular endothelial cells induced by CSE.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Apoptosis; Case-Control Studies; Caspase 3; Cyclic AMP; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Endothelial Cells; Epoprostenol; Female; Human Umbilical Vein Endothelial Cells; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Intramolecular Oxidoreductases; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Rats; Smoking; Time Factors