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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

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      Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on the risk of pneumonia and severe exacerbations in patients with COPD

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          Abstract

          Objectives

          This study aimed to compare the effects of angiotensin-converting-enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) on the risk of pneumonia and severe exacerbations in patients with COPD.

          Patients and methods

          All patients with COPD who used ACEis and ARBs for >90 days between 2000 and 2005 were recruited. Pairwise matching (1:1) of the ACEi and ARB groups resulted in two similar subgroups, with 6,226 patients in each. The primary outcomes were pneumonia and COPD exacerbations, and the secondary outcome was death.

          Results

          During the follow-up period, the incidence of pneumonia was 7.20 per 100 person-years in the ACEi group and 5.89 per 100 person-years in the ARB group. The ACEi group had a higher risk of pneumonia (adjusted hazard ratio [aHR], 1.22; 95% CI, 1.15–1.29) than the ARB group. The incidence of severe exacerbations was 0.65 per person-year for the patients receiving ACEis and 0.52 per person-year for those receiving ARBs. The patients receiving ACEis had a higher risk of severe exacerbations (aHR, 1.19; 95% CI, 1.16–1.21) than those receiving ARBs. Similar trends were noted in terms of severe exacerbations requiring hospitalization (aHR, 1.24; 95% CI, 1.21–1.28) or emergency department visits (aHR, 1.16; 95% CI, 1.13–1.18), pneumonia requiring mechanical ventilation (aHR, 1.35; 95% CI, 1.24–1.47), and mortality (aHR, 1.33; 95% CI, 1.26–1.42).

          Conclusion

          ARBs were associated with lower rates of pneumonia, severe pneumonia, and mortality than ACEis in patients with COPD.

          Most cited references14

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          Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease.

          The purpose of this study was to determine if statins (hydroxymethylglutaryl CoA reductase inhibitors [HMG-CoA]), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) reduce cardiovascular (CV) events and pulmonary morbidity in chronic obstructive pulmonary disease (COPD) patients. Few current COPD therapies alter prognosis. Although statins, ACE inhibitors, and ARBs improve outcomes in CV populations, their benefits in COPD patients both with and without concomitant heart disease has not previously been studied. A time-matched nested case-control study of two population-based retrospective cohorts was undertaken: 1) COPD patients having undergone coronary revascularization (high CV risk cohort); and 2) COPD patients without previous myocardial infarction (MI) and newly treated with nonsteroidal anti-inflammatory drugs (low CV risk cohort). Prespecified outcomes were COPD hospitalization, MI, and total mortality. These drugs reduced both CV and pulmonary outcomes, with the largest benefits occurring with the combination of statins and either ACE inhibitors or ARBs. This combination was associated with a reduction in COPD hospitalization (risk ratio [RR] 0.66, 95% confidence interval [CI] 0.51 to 0.85) and total mortality (RR 0.42, 95% CI 0.33 to 0.52) not only in the high CV risk cohort but also in the low CV risk cohort (RR 0.77, 95% CI 0.67 to 0.87, and RR 0.36, 95% CI 0.28 to 0.45, respectively). The combination also reduced MI in the high CV risk cohort (RR 0.39, 95% CI 0.31 to 0.49). Benefits were similar when steroid users were included. These agents may have dual cardiopulmonary protective properties, thereby substantially altering prognosis of patients with COPD. These findings need confirmation in randomized clinical trials.
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            Angiotensin receptor subtype AT(1) mediates alveolar epithelial cell apoptosis in response to ANG II.

            Previous work from this laboratory demonstrated induction of apoptosis in lung alveolar epithelial cells (AEC) by purified angiotensin II (ANG II) and expression of mRNAs for both ANG II receptor subtypes AT(1) and AT(2) (Wang R, Zagariya A, Ibarra-Sunga O, Gidea C, Ang E, Deshmukh S, Chaudhary G, Baraboutis J, Filippatos G, and Uhal BD. Am J Physiol Lung Cell Mol Physiol 276: L885-L889, 1999.). The present study was designed to determine the ANG II receptor subtype mediating AEC apoptosis in response to ANG II. Apoptosis was induced with purified ANG II applied to the human lung AEC-derived carcinoma cell line A549 or to primary AEC isolated from Wistar rats. In both cell types, the AT(1)-selective receptor antagonists L-158809 or losartan inhibited ANG II-induced apoptosis by 90% at concentrations of 10(-8) M and 10(-7) M, respectively. The inhibition was concentration dependent with IC(50) of 10(-12) M and 10(-11) M on the primary rat AEC. In contrast, the AT(2)-selective antagonists PD-123319 or PD-126055 could not block ANG II-induced apoptosis in either cell type. In primary rat AEC, apoptosis in response to ANG II was blunted in a dose-dependent manner by the protein kinase C inhibitor chelerythrine but not by the tyrosine phosphatase inhibitor sodium orthovanadate. Together, these data indicate that AEC apoptosis in response to ANG II is mediated by receptor subtype AT(1), despite the expression of mRNAs for both AT(1) and AT(2).
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              Antihypertensive agents acting on the renin-angiotensin system and the risk of sepsis.

              In response to safety concerns from two large randomized controlled trials, we investigated whether the use of telmisartan, an angiotensin receptor blocker (ARB), ARBs as a class and angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of sepsis, sepsis-associated mortality and renal failure in hypertensive patients.
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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
                2018
                08 March 2018
                : 13
                : 867-874
                Affiliations
                [1 ]Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan
                [2 ]Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
                [3 ]Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
                [4 ]Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
                [5 ]Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
                Author notes
                Correspondence: Cheng-Yi Wang, Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, Number 362, Zhongzheng Road, Xindian District, New Taipei City 23148, Taiwan, Tel +886 22 219 3391 ext 15433, Fax +886 222 219 0651, Email cywang@ 123456mospital.com
                Article
                copd-13-867
                10.2147/COPD.S158634
                5846309
                29563786
                4a0b889a-58be-4188-8f8e-2b90c08dd22c
                © 2018 Lai 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
                angiotensin-converting enzyme inhibitor,angiotensin receptor blocker,copd,severe exacerbation,pneumonia,mortality

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