The association of renin-angiotensin system blockades and pneumonia requiring admission in patients with COPD.
BACKGROUND
The hallmark of COPD is chronic airway inflammation, which may be mediated by renin-angiotensin system. The renin-angiotensin system blockers such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) have exhibited anti-inflammatory and immunomodulatory effects in patients with various diseases. We explored the effects of ACEi and ARBs on the risk of pneumonia in patients with COPD.


METHODS
A nested case-control study was performed on COPD patients recruited from January 2010 to August 2013 in two referral hospitals in Korea. A total of 130 COPD patients admitted with pneumonia were included, and 245 COPD patients without pneumonia were selected as controls from a total of 1,646 such patients. Controls were matched with test patients by age, sex, and severity of airflow limitation. The effects of ACEi/ARBs use on the odds ratio (OR) for the development of pneumonia were tested through conditional logistic regression.


RESULTS
Elderly patients (over 70 years of age) constituted ~30% of each group; most of the patients were male (85%). Of the COPD patients with pneumonia, 21.5% had taken ACEi/ARBs for a mean of 9.8 months (standard deviation ±3.5 months). The proportions of ACEi/ARBs users and the mean duration of such use did not differ when compared to those of the control patients (26.9%,P=0.25; 9.6±3.6 months,P=0.83). Univariate analyses indicated that the use of ACEi/ARBs was not associated with a decreased risk of pneumonia (OR =0.70, 95% confidence interval 0.41-1.23,P=0.21), whereas both a history of pulmonary tuberculosis (OR =1.85, 95% confidence interval 1.12-3.06,P=0.02) and exposure to systemic steroids (OR =2.33, 95% confidence interval 1.28-4.23,P=0.005) did show an association. After adjustment for a history of tuberculosis, comorbid chronic renal disease, and exposure to corticosteroids, ACEi/ARBs reduced the risk of pneumonia in COPD patients (OR =0.51, 95% confidence interval 0.27-0.98,P=0.04).


CONCLUSIONS
This study revealed that the use of ACEi/ARBs was associated with reducing the risk of pneumonia in patients with COPD. Further prospective studies are necessary to confirm the protective effect of ACEi/ARBs and elucidate the underlying mechanisms in COPD patients.
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University Hospital.
Junghyun
J
Kim
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
Jung-Kyu
JK
Lee
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
Eun Young
EY
Heo
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
Hee Soon
HS
Chung
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
Deog Kyeom
DK
Kim
COPD; angiotensin receptor antagonist; angiotensin-converting enzyme inhibitors; pneumonia
Adv Ther. 2012 Oct;29(10):900-12
22983755
Eur Respir J. 2006 Jul;28(1):219-42
16816350
J Infect Dis. 2012 Jan 1;205(1):13-9
22170954
J Epidemiol. 2013 Sep 5;23(5):344-50
23912052
J Hypertens. 2012 Nov;30(11):2223-9
22929610
CMAJ. 1999 Nov 30;161(11 Suppl):S1-61
10906907
Respir Res. 2009 Jun 03;10:45
19493329
Pharmacoeconomics. 2001;19 Suppl 2:1-6
11700783
CMAJ. 2012 Apr 17;184(7):E367-72
22431901
Respir Med. 2011 Dec;105(12):1872-84
21852081
Curr Pharm Des. 2003;9(9):715-22
12570789
Lancet. 1998 Sep 26;352(9133):1069-70
9759785
Lancet. 2007 Sep 1;370(9589):741-50
17765523
BMC Med. 2013 Aug 14;11:181
23945277
Chest. 2013 Apr;143(4):1009-17
23187314
Free Radic Biol Med. 2010 Jul 1;49(1):88-95
20353822
J Clin Invest. 2012 Jan;122(1):229-40
22182843
Pulm Pharmacol Ther. 2013 Apr;26(2):212-7
23142156
Int J Chron Obstruct Pulmon Dis. 2009;4:203-23
19554195
Eur Respir J. 2006 Jan;27(1):188-207
16387952
BMJ. 2012 Jul 11;345:e4260
22786934
J Manag Care Spec Pharm. 2014 Oct;20(10):1018-26
25278324
Thorax. 2013 Nov;68(11):1029-36
24130228
Tohoku J Exp Med. 1991 Jun;164(2):103-9
1721246
Eur Respir J. 2008 Mar;31(3):611-7
17959631
Hypertens Res. 2010 Jan;33(1):11-21
19911001
Lancet. 1998 Sep 26;352(9133):1069
9759784
Mov Disord. 2015 Apr;30(4):593-6
25641619
J Pharmacol Exp Ther. 2002 Oct;303(1):45-51
12235231
Lancet. 2009 Aug 29;374(9691):733-43
19716966
Curr Opin Pharmacol. 2006 Jun;6(3):271-6
16581295
Clin Infect Dis. 2012 Dec;55(11):1466-73
22918991
Expert Rev Respir Med. 2013 Oct;7(5):533-44
24138695
Pediatr Res. 2015 May;77(5):656-62
25665060
Curr Med Chem. 2011;18(23):3506-15
21756232
Eur Respir J. 2008 Jun;31(6):1334-56
18515558
Am J Respir Cell Mol Biol. 2011 Jul;45(1):53-61
20813992
EMBO Mol Med. 2010 Jul;2(7):247-57
20597104
Int J Chron Obstruct Pulmon Dis. 2013;8:295-304
23836970
Am J Manag Care. 2011 Sep;17(9):609-16
21902446
PLoS One. 2014 Oct 29;9(10):e110165
25353172
Clin Sci (Lond). 2012 Oct;123(8):487-98
22757959
Respir Med. 2012 Aug;106(8):1124-33
22621820