Effects of Low-dose Erythromycin on Patients with Stable COPD: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 FENGJing ¹ , TANGXiao-ju ² , CHENYi-fan ¹ , LIANGYa-sha ³ , YUANLi ³ ,  LUOFeng-ming ¹

1. Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China;
2. Regenerative Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China;
3. School of Clinical Medicine, Sichuan University, Chengdu 610041, China;

Corresponding?author：

LUOFeng-ming, Email: luofengming@hotmail.com

Keywords：

Chronic obstructive pulmonary disease; Low-dose erythromycin; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20140034

Video：

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Objective To systematically review the clinical efficacy of low-dose erythromycin in patients with stable chronic obstructive pulmonary disease (COPD). Methods Randomized controlled trials (RCTs) about low-dose erythromycin plus routine treatment versus routine treatment/placebo plus routine treatment in treating stable COPD was electronically searched in PubMed, EMbase, CBM, The Cochrane Library (Issue 4, 2013), CNKI, VIP and WanFang Data from the their establishment dates to May 2013. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. The results of meta-analysis was performed using RevMan 5.2 software. Results A total of eight RCTs involving 526 patients were finally included. The results of metaanalysis showed that:a) compared with the control group, low-dose erythromycin significantly improved six-minute walk distance (SMD=0.30, 95%CI 0.05 to 0.55, P=0.02), reduced the frequency of acute exacerbation (RR=0.44, 95%CI 0.25 to 0.78, P=0.005), and decreased the concentrations of IL-8 (SMD=-1.63, 95%CI-2.17 to-1.09, P < 0.000 01), TNF-α (SMD=-1.49, 95%CI-2.36 to-0.62, P=0.000 8), and neutrophil elastase (NE) (SMD=-0.94, 95%CI-1.36 to-0.51, P < 0.000 1) in sputum. b) the erythromycin therapy could improve forced expiratory volume in one second (FEV1) (SMD=0.19, 95%CI-0.19 to 0.58, P=0.32) but without significant differences compared with the control group. Conclusion Low-dose erythromycin could improve exercise tolerance, reduce the frequency of acute exacerbation, and help relieve airway inflammation, but in the improvement of FEV1, low-dose erythromycin is not better than routine treatment. Due to limited quantity and quality of the included studies, larger scale, multicenter, high quality RCTs are needed to verify the aforementioned conclusion.

Citation： FENGJing, TANGXiao-ju, CHENYi-fan, LIANGYa-sha, YUANLi, LUOFeng-ming. Effects of Low-dose Erythromycin on Patients with Stable COPD: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2014, 14(2): 191-196. doi: 10.7507/1672-2531.20140034 Copy

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2.	Swords WE, Rubin BK. Macrolide antibiotics, bacterial populations and inflammatory airway disease. Neth J Med, 2003, 61(7):242-248.
3.	Jaffe A, Bush A. Anti-inflammatory effects of macrolides in lung disease. Pediatr Pulmonol, 2001, 31(6):464-473.
4.	唐勇, 張淑玉, 陳珍旭, 等.紅霉素治療穩定期慢性阻塞性肺病患者的遠期療效觀察.實用醫學雜志, 2011, 27(5):863-865.
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8.	黃惠娟, 鐘小寧, 歐莉梅, 等.小劑量紅霉素對穩定期慢性阻塞性肺疾病患者Th1/Tc1介導氣道炎癥和運動耐力的影響.中華臨床醫師雜志, 2010, 4(10):1893-1900.
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16.	Nakamura H, Yoshimura K, McElvaney NG, et al. Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. J Clin Invest, 1992, 89(5):1478-1484.
17.	Chung KF. Cytokines in chronic obstructive pulmonary disease. Eur Respir J Suppl, 2001, 34:50s-59s.
18.	王勝, 徐鳳珍, 陳余清.慢性阻塞性肺疾病患者痰液白介素-8、6和腫瘤壞死因子測定及其意義.中華結核和呼吸雜志, 2000, 23(8):465.
19.	李雪華, 張洪玉, 龐寶森.慢性阻塞性肺疾病患者痰中性粒細胞彈性蛋白酶和基質金屬蛋白酶9的表達及其與氣流受限的關系.中華結核和呼吸雜志, 2007, 30(7):553-554.
20.	李梅華, 鐘小寧.紅霉素在慢性阻塞性肺疾病中的應用進展.國外醫學呼吸系統分冊, 2005, 25(11):816-817.
21.	Inamura K, Ohta N, Fukase S, et al. The effects of erythromycin on human peripheral neutrophil apoptosis. Rhinology, 2000, 38(3):124-129.
22.	Desaki M, Takizawa H, Ohtoshi T, et al. Erythromycin suppresses nuclear factor-kappaB and activator protein-1 activation in human bronchial epithelial cells. Biochem Biophys Res Commun, 2000, 267(1):124-128.
23.	Noma T, Sugawara Y, Fujiwara S, et al. Effect of roxithromycin on induction of apoptosis in peripheral blood lymphocytes from patients with bronchial asthma. Jpn J Antibiot, 2001, 54(Suppl A):148-152.
24.	Gotfried MH. Macrolides for the treatment of chronic sinusitis, asthma, and COPD. Chest, 2004, 125(Suppl 2):52-60.
25.	Kadota J, Mukae H, Mizunoe S, et al. Long-term macrolide antibiotic therapy in the treatment of chronic small airway disease clinically mimicking diffuse panbronchiolitis. Intern Med, 2005, 44(3):200-206.
26.	Gordon HG, Andrew DO, Victor M, et al. Grade指南證據質量評價——發表偏倚.中國循證醫學雜志, 2011, 11(12):1430-1434.

1. Soriano JB, Lamprecht B. Chronic obstructive pulmonary disease:a worldwide problem. Med Clin North Am, 2012, 96(4):671-680.
2. Swords WE, Rubin BK. Macrolide antibiotics, bacterial populations and inflammatory airway disease. Neth J Med, 2003, 61(7):242-248.
3. Jaffe A, Bush A. Anti-inflammatory effects of macrolides in lung disease. Pediatr Pulmonol, 2001, 31(6):464-473.
4. 唐勇, 張淑玉, 陳珍旭, 等.紅霉素治療穩定期慢性阻塞性肺病患者的遠期療效觀察.實用醫學雜志, 2011, 27(5):863-865.
5. 潘寶璇, 曾蘊湘, 陳友榮, 等.小劑量紅霉素長期治療穩定期慢性阻塞性肺疾病患者的臨床研究.中國老年醫學雜志, 2010, 30(2):167-169.
6. 徐永芳, 黃玲玲, 孫維羅.長期小劑量紅霉素對中重度COPD的影響.海峽藥學, 2010, 22(7):121-122.
7. 歐莉梅, 鐘小寧, 何志義, 等.小劑量紅霉素治療穩定期慢性阻塞性肺疾病臨床效果的研究.中國實用內科雜志, 2010, 30(12):1097-1100.
8. 黃惠娟, 鐘小寧, 歐莉梅, 等.小劑量紅霉素對穩定期慢性阻塞性肺疾病患者Th1/Tc1介導氣道炎癥和運動耐力的影響.中華臨床醫師雜志, 2010, 4(10):1893-1900.
9. He ZY, Ou LM, Zhang JQ, et al. Effect of 6 months of erythromycin treatment on inflammatory cells in induced sputum and exacerbations in chronic obstructive pulmonary disease. Respiration, 2010, 80(6):445-452.
10. Seemungal TA, Wilkinson TM, Hurst JR, et al. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med, 2008, 178(11):1139-1147.
11. Suzuki T, Yanai M, Yamaya M, et al. Erythromycin and common cold in COPD. Chest, 2001, 120(3):730-733.
12. Celli BR, MacNee W; ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD:a summary of the ATS/ERS position paper. Eru Respir J, 2004, 23:932-946.
13. 中華醫學會呼吸病學分會慢性阻塞性肺疾病學組.慢性阻塞性肺疾病診治指南.中華結核和呼吸雜志, 2002, 25(8):453-460.
14. 中華醫學會呼吸病學分會慢性阻塞性肺疾病學組.慢性阻塞性肺疾病診治指南(2007年修訂版).中華結核和呼吸雜志, 2007, 30(1):8-17.
15. Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions(Version 5.1.0).[cited 2012 Jan 5]. Available at: http://www.cochrane-handbook.org.
16. Nakamura H, Yoshimura K, McElvaney NG, et al. Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. J Clin Invest, 1992, 89(5):1478-1484.
17. Chung KF. Cytokines in chronic obstructive pulmonary disease. Eur Respir J Suppl, 2001, 34:50s-59s.
18. 王勝, 徐鳳珍, 陳余清.慢性阻塞性肺疾病患者痰液白介素-8、6和腫瘤壞死因子測定及其意義.中華結核和呼吸雜志, 2000, 23(8):465.
19. 李雪華, 張洪玉, 龐寶森.慢性阻塞性肺疾病患者痰中性粒細胞彈性蛋白酶和基質金屬蛋白酶9的表達及其與氣流受限的關系.中華結核和呼吸雜志, 2007, 30(7):553-554.
20. 李梅華, 鐘小寧.紅霉素在慢性阻塞性肺疾病中的應用進展.國外醫學呼吸系統分冊, 2005, 25(11):816-817.
21. Inamura K, Ohta N, Fukase S, et al. The effects of erythromycin on human peripheral neutrophil apoptosis. Rhinology, 2000, 38(3):124-129.
22. Desaki M, Takizawa H, Ohtoshi T, et al. Erythromycin suppresses nuclear factor-kappaB and activator protein-1 activation in human bronchial epithelial cells. Biochem Biophys Res Commun, 2000, 267(1):124-128.
23. Noma T, Sugawara Y, Fujiwara S, et al. Effect of roxithromycin on induction of apoptosis in peripheral blood lymphocytes from patients with bronchial asthma. Jpn J Antibiot, 2001, 54(Suppl A):148-152.
24. Gotfried MH. Macrolides for the treatment of chronic sinusitis, asthma, and COPD. Chest, 2004, 125(Suppl 2):52-60.
25. Kadota J, Mukae H, Mizunoe S, et al. Long-term macrolide antibiotic therapy in the treatment of chronic small airway disease clinically mimicking diffuse panbronchiolitis. Intern Med, 2005, 44(3):200-206.
26. Gordon HG, Andrew DO, Victor M, et al. Grade指南證據質量評價——發表偏倚.中國循證醫學雜志, 2011, 11(12):1430-1434.

Chinese Journal of Evidence-Based Medicine

Effects of Low-dose Erythromycin on Patients with Stable COPD: A Meta-Analysis

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