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

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, 张淑玉, 陈珍旭, 等.红霉素治疗稳定期慢性阻塞性肺病患者的远期疗效观察.实用医学杂志, 2011, 27(5):863-865.
5.	潘宝璇, 曾蕴湘, 陈友荣, 等.小剂量红霉素长期治疗稳定期慢性阻塞性肺疾病患者的临床研究.中国老年医学杂志, 2010, 30(2):167-169.
6.	徐永芳, 黄玲玲, 孙维罗.长期小剂量红霉素对中重度COPD的影响.海峡药学, 2010, 22(7):121-122.
7.	欧莉梅, 钟小宁, 何志义, 等.小剂量红霉素治疗稳定期慢性阻塞性肺疾病临床效果的研究.中国实用内科杂志, 2010, 30(12):1097-1100.
8.	黄惠娟, 钟小宁, 欧莉梅, 等.小剂量红霉素对稳定期慢性阻塞性肺疾病患者Th1/Tc1介导气道炎症和运动耐力的影响.中华临床医师杂志, 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.	中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南.中华结核和呼吸杂志, 2002, 25(8):453-460.
14.	中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2007年修订版).中华结核和呼吸杂志, 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.	王胜, 徐凤珍, 陈余清.慢性阻塞性肺疾病患者痰液白介素-8、6和肿瘤坏死因子测定及其意义.中华结核和呼吸杂志, 2000, 23(8):465.
19.	李雪华, 张洪玉, 庞宝森.慢性阻塞性肺疾病患者痰中性粒细胞弹性蛋白酶和基质金属蛋白酶9的表达及其与气流受限的关系.中华结核和呼吸杂志, 2007, 30(7):553-554.
20.	李梅华, 钟小宁.红霉素在慢性阻塞性肺疾病中的应用进展.国外医学呼吸系统分册, 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指南证据质量评价——发表偏倚.中国循证医学杂志, 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, 张淑玉, 陈珍旭, 等.红霉素治疗稳定期慢性阻塞性肺病患者的远期疗效观察.实用医学杂志, 2011, 27(5):863-865.
5. 潘宝璇, 曾蕴湘, 陈友荣, 等.小剂量红霉素长期治疗稳定期慢性阻塞性肺疾病患者的临床研究.中国老年医学杂志, 2010, 30(2):167-169.
6. 徐永芳, 黄玲玲, 孙维罗.长期小剂量红霉素对中重度COPD的影响.海峡药学, 2010, 22(7):121-122.
7. 欧莉梅, 钟小宁, 何志义, 等.小剂量红霉素治疗稳定期慢性阻塞性肺疾病临床效果的研究.中国实用内科杂志, 2010, 30(12):1097-1100.
8. 黄惠娟, 钟小宁, 欧莉梅, 等.小剂量红霉素对稳定期慢性阻塞性肺疾病患者Th1/Tc1介导气道炎症和运动耐力的影响.中华临床医师杂志, 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. 中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南.中华结核和呼吸杂志, 2002, 25(8):453-460.
14. 中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2007年修订版).中华结核和呼吸杂志, 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. 王胜, 徐凤珍, 陈余清.慢性阻塞性肺疾病患者痰液白介素-8、6和肿瘤坏死因子测定及其意义.中华结核和呼吸杂志, 2000, 23(8):465.
19. 李雪华, 张洪玉, 庞宝森.慢性阻塞性肺疾病患者痰中性粒细胞弹性蛋白酶和基质金属蛋白酶9的表达及其与气流受限的关系.中华结核和呼吸杂志, 2007, 30(7):553-554.
20. 李梅华, 钟小宁.红霉素在慢性阻塞性肺疾病中的应用进展.国外医学呼吸系统分册, 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指南证据质量评价——发表偏倚.中国循证医学杂志, 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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