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Background Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition. Research Question Which factors determine the outcome of PH in COPD? Study Design and Methods We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH). Results The population included incident patients with moderate PH in COPD (n = 68), with severe PH in COPD (n = 307), and with IPAH (n = 489). Patients with PH in COPD were older, predominantly male, and treated mainly with phosphodiesterase-5 inhibitors. Despite similar hemodynamic impairment, patients with PH in COPD achieved a worse 6-min walking distance (6MWD) and showed a more advanced World Health Organization functional class (WHO FC). Transplant-free survival rates at 1, 3, and 5 years were higher in the IPAH group than in the PH in COPD group (IPAH: 94%, 75%, and 55% vs PH in COPD: 86%, 55%, and 38%; P = .004). Risk factors for poor outcomes in PH in COPD were male sex, low 6MWD, and high pulmonary vascular resistance (PVR). In patients with severe PH in COPD, improvements in 6MWD by ≥ 30 m or improvements in WHO FC after initiation of medical therapy were associated with better outcomes. Interpretation Patients with PH in COPD were functionally more impaired and had a poorer outcome than patients with IPAH. Predictors of death in the PH in COPD group were sex, 6MWD, and PVR. Our data raise the hypothesis that some patients with severe PH in COPD may benefit from PH treatment. Randomized controlled studies are necessary to explore this hypothesis further. Trial Registry ClinicalTrials.gov; No.: NCT01347216 ; URL: www.clinicaltrials.gov

Measures of ventilatory efficiency during cardiopulmonary exercise testing (CPX) are increasingly being used as prognostic markers in heart failure and pulmonary hypertension (PH). Little is known about whether these measures can be applied to all forms of PH, in particular chronic thromboembolic pulmonary hypertension (CTEPH), wherein thrombotic vascular occlusion has an impact on gas exchange.One hundred twenty-seven patients, 50 with CTEPH and 77 with pulmonary arterial hypertension (PAH), underwent incremental CPX.Physiologic ventilatory dead space fraction (Vd/Vtphys) measured at peak exercise with arterial blood gas analysis was higher in CTEPH than PAH (52.9% vs 41.8%, P.001). The V(E)/V(CO(2)) slope was higher in patients with CTEPH than in patients with PAH (50.7 L/min/L/min vs 44.4 L/min/L/min, P = .024) and was mirrored by similar changes in the ventilatory equivalent for CO(2) at anaerobic threshold (Eqco(2)_AT) (47.7 L/min/L/min vs 42.0 L/min/L/min, P = .008). In a multivariate linear regression analysis, disease subtype was found to be an independent predictor of Vd/Vtphys (P.001), V(E)/V(CO(2)) slope (P = .003), and Eqco(2)_AT (P.001). These three measures could distinguish between World Health Organization functional classes I/II and III/IV in PAH but not CTEPH.Significant differences in gas exchange exist between CTEPH and PAH, due to differences in Vd/Vtphys likely as a result of vascular occlusion due to thromboembolic disease. This dissociates measures of ventilatory efficiency from disease severity and also contributes to our understanding of the differences in exercise limitation and breathlessness in PAH and CTEPH. Common prognostic end points from CPX cannot be applied to all forms of PH.

More clinical trials in pulmonary hypertension (PH) are being conducted in developing countries now compared with the past. This is a welcome development, considering the rarity of the disease, with its limited treatment options and poor prognosis. Conducting clinical trials in the developing world potentially decreases the time and costs of drug development and provides access to new drugs to an underserved population. However, the range of PH presentations, standards of care, and socioeconomic environments among developing countries is different from that of developed countries. Eagerness to complete clinical trials universally should not compromise accepted ethical practices. Patients from developing countries may be particularly vulnerable because of illiteracy and poverty and may not truly understand the informed consent process and clinical trials. Investigators, ethics committees, and regulators must ensure that potential participants are not exploited. Drug trials should be done only in those communities in which the drug would be made accessible if proven effective. Studies have to be designed taking safety, accessibility, and generalizability into consideration. Selecting appropriate investigators and institutions, supporting them with proper training, and providing infrastructure and facilities would promote uniform standards of clinical research across the globe. Coordination and cooperation among regulatory bodies of different countries is an urgent necessity that would facilitate the globalization of clinical research. If done appropriately, the potential benefit for the worldwide population of patients with PH would be substantial.

Study objective To examine whether increased urinary cysteinyl-leukotriene E 4 (LTE 4 ) excretion, which has been found to be elevated in patients presenting with high-altitude pulmonary edema (HAPE), precedes edema formation. Design Prospective studies in a total of 12 subjects with susceptibility to HAPE. Setting In a chamber study, seven subjects susceptible to HAPE and five nonsusceptible control subjects were exposed for 24 h to an altitude of 450 m (control day), and exposed for 20 h to 4,000 m after slow decompression over 4 h. In a field study, prospective measurements at low and high altitude were performed in five subjects developing HAPE at 4,559 m. Participants Mountaineers with a radiographically documented history of HAPE and control subjects who did not develop HAPE with identical high-altitude exposure. Interventions 24-h urine collections. Measurements and results In the hypobaric chamber, none of the subjects developed HAPE. The 24-h urinary LTE 4 did not differ between HAPE susceptible and control subjects, nor between hypoxia and normoxic control day. In the field study, urinary LTE 4 was not increased in subjects with HAPE compared to values obtained prior to HAPE at high altitude and during 2 control days at low altitude. Conclusions These data do not provide evidence that cysteinyl–leukotriene-mediated inflammatory response is associated with HAPE susceptibility or the development of HAPE within the context of our studies.

More clinical trials in pulmonary hypertension (PH) are being conducted in developing countries now compared with the past. This is a welcome development, considering the rarity of the disease, with its limited treatment options and poor prognosis. Conducting clinical trials in the developing world potentially decreases the time and costs of drug development and provides access to new drugs to an underserved population. However, the range of PH presentations, standards of care, and socioeconomic environments among developing countries is different from that of developed countries. Eagerness to complete clinical trials universally should not compromise accepted ethical practices. Patients from developing countries may be particularly vulnerable because of illiteracy and poverty and may not truly understand the informed consent process and clinical trials. Investigators, ethics committees, and regulators must ensure that potential participants are not exploited. Drug trials should be done only in those communities in which the drug would be made accessible if proven effective. Studies have to be designed taking safety, accessibility, and generalizability into consideration. Selecting appropriate investigators and institutions, supporting them with proper training, and providing infrastructure and facilities would promote uniform standards of clinical research across the globe. Coordination and cooperation among regulatory bodies of different countries is an urgent necessity that would facilitate the globalization of clinical research. If done appropriately, the potential benefit for the worldwide population of patients with PH would be substantial.