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      International Journal of COPD (submit here)

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      Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension

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          Abstract

          Studies have shown that vasodilators such as iloprost can be useful for treating pulmonary hypertension (PH). However, in patients with COPD, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange. The efficacy and safety of iloprost inhalation was assessed in 67 patients with PH associated with COPD (COPD-PH), diagnosed by right heart catheterization. Of these, 37 patients had severe PH (mean pulmonary arterial pressure [mPAP] >35 mmHg or mPAP 25–35 mmHg with low cardiac index [<2.0 L⋅min −1⋅m −2]). All patients received a single 20 µg dose of iloprost via a nebulizer (4.4 µg delivered at the mouthpiece). No serious adverse events were reported. Hemodynamic and gas exchange parameters (arterial blood gas and shunt fraction [Qs/Qt]) were measured or calculated at baseline and 10 min after iloprost inhalation. mPAP decreased by 2.1 mmHg (95% CI, −3.3 to −1.0), pulmonary vascular resistance (PVR) decreased by 62.4 dyn⋅s⋅cm −5 (95% CI, −92.9 to −31.8), and cardiac output increased by 0.4 L⋅min −1 (95% CI, 0.2–0.5). There was a more significant decline in PVR in patients with severe COPD-PH than in those with nonsevere COPD-PH. Hypoxemia and intrapulmonary shunt were more extreme in patients with severe COPD-PH. However, there were no significant differences in arterial blood gas and Qs/Qt between patients with nonsevere and severe forms of COPD-PH. In conclusion, iloprost improved pulmonary hemodynamics without detrimental effects on arterial oxygenation in patients with COPD-PH, even in those with severe PH. These findings suggest that the short-term use of iloprost in patients with COPD-PH is effective and well tolerated.

          Most cited references27

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          Pulmonary hypertension in chronic lung diseases.

          Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP] <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ≥25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index [CI <2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group, and for the time being, these patients should be transferred to expert centers for individualized patient care.
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            A meta-analysis of randomized controlled trials in pulmonary arterial hypertension

            Aims There is no cure for pulmonary arterial hypertension, but current approved treatment options include prostanoids, endothelin-receptor antagonists, and phosphodiesterase type-5 inhibitors. The effect on survival of these compounds has not been appropriately assessed in individual trials because of small sample size and short duration. We performed a meta-analysis of all randomized controlled trials with drugs published in this condition. Methods and results Trials were searched in the Medline database from January 1990 to October 2008. The primary analysis included only studies with a placebo comparator arm, the sensitivity analysis also included studies comparing two active treatment arms. The main outcome measure was all-cause mortality. Twenty-one trials were included in the primary analysis (3140 patients) and two additional studies (59 patients) were included in the sensitivity analysis. Average duration of the trials was 14.3 weeks. All-cause mortality rate in the control group was 3.8%. Active treatments were associated with a reduction in mortality of 43% (RR 0.57; 95% CI 0.35–0.92; P = 0.023); the sensitivity analysis confirmed a reduction in mortality of 38% (RR 0.62; 95% CI 0.39–1.00; P = 0.048). Conclusion The results of this meta-analysis suggest an improvement of survival in the patients treated with the targeted therapies approved for pulmonary arterial hypertension.
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              Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation.

              To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). Retrospective study. One center in France. Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2017
                22 November 2017
                : 12
                : 3353-3360
                Affiliations
                [1 ]Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
                [2 ]Department of Cardiology, The Fourth Affiliated Hospital of China Medical University, Liaoning, China
                [3 ]Thrombosis and Vascular Medicine Center, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
                Author notes
                Correspondence: Zhi-Cheng Jing, Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China, Tel +86 021 6511 5006, Fax +86 021 5566 2767, Email jingzhicheng@ 123456vip.163.com
                [*]

                These authors contributed equally to this work

                Article
                copd-12-3353
                10.2147/COPD.S141798
                5702173
                29200842
                ef4872e8-7f02-462b-93ef-850b55a1ab84
                © 2017 Wang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Respiratory medicine
                iloprost,pulmonary hypertension,copd pulmonary gas exchange
                Respiratory medicine
                iloprost, pulmonary hypertension, copd pulmonary gas exchange

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