提示: 手机请竖屏浏览!

阿奇霉素用于预防COPD的加重研究
Azithromycin for Prevention of Exacerbations of COPD


Richard K. Albert ... 呼吸系统疾病 • 2011.08.25
相关阅读
• 美泊利单抗治疗嗜酸性粒细胞性慢性阻塞性肺疾病 • 单次呼吸量测定是否能准确诊断慢性阻塞性肺疾病 • 长期大环内酯疗法治疗未控制的哮喘 • 长期吸氧治疗伴中度减饱和的COPD的随机试验 • 临床实践中糠酸氟替卡松-维兰特罗对COPD治疗的有效性

摘要


背景

急性加重会对慢性阻塞性肺疾病(以下简称COPD)患者造成不良反应。大环内酯类抗生素对于多种炎症性气道疾病的患者都有益。

 

方法

我们开展了一项随机试验,目的是确定阿奇霉素能否减少某类高风险COPD患者病情加重的频率,这些患者出现COPD加重的风险较高,但不伴有听力障碍、静息心动过速,也没有出现校正后QT间期延长的明显风险。

 

结果

我们一共筛查了1,577例受试者,其中的1,142例(72%)被纳入这项为期1年的试验。纳入试验的受试者被随机分配入在常规治疗的同时接受剂量为每日250 mg的阿奇霉素治疗(570例)组或在平常的治疗同时服用安慰剂(572例)组。阿奇霉素组的1年随访完成率为89%,安慰剂组的随访完成率为90%。阿奇霉素组受试者出现首次加重的时间中位数为266天(95% CI,227~313天),而安慰剂组出现首次加重的时间中位数为174天(95% CI,143~215天;P0.001)。阿奇霉素组出现加重的频率为1.48次/患者年,而安慰剂组出现加重的频率为1.83次/患者年(P=0.01),阿奇霉素组每患者年中出现一次COPD急性加重的风险比为0.73(95% CI,0.63~0.84;P<0.001)。与安慰剂组圣乔治呼吸问卷(按0~100分计分,较低的分数表明较好的功能状态)分数的降低(平均值±SD,0.6±11.4)相比,阿奇霉素组的分数改善(平均值±SD,2.8±12.1)较多(P=0.006);阿奇霉素组中分数改变超出具有临床意义的最小变化值(-4单位)的受试者比例为43%,而安慰剂组中的这一比例为36%(P=0.03)。阿奇霉素组中的听力下降比安慰剂组的听力下降常见(25%对20%;P=0.04)。

 

结论

在纳入试验的COPD患者中,连续1年在通常治疗的基础上每日服用阿奇霉素降低了加重的发生率并改善了生活质量,但导致一小部分的受试者出现听力下降。尽管这种干预措施可能会改变微生物的耐药模式,但尚不知晓这种变化的影响(该研究由美国国立卫生研究院资助;在ClinicalTrials.gov注册号为NCT00325897)。





作者信息

Richard K. Albert, M.D., John Connett, Ph.D., William C. Bailey, M.D., Richard Casaburi, M.D., Ph.D., J. Allen D. Cooper, Jr., M.D., Gerard J. Criner, M.D., Jeffrey L. Curtis, M.D., Mark T. Dransfield, M.D., MeiLan K. Han, M.D., Stephen C. Lazarus, M.D., Barry Make, M.D., Nathaniel Marchetti, M.D., Fernando J. Martinez, M.D., Nancy E. Madinger, M.D., Charlene McEvoy, M.D., M.P.H., Dennis E. Niewoehner, M.D., Janos Porsasz, M.D., Ph.D., Connie S. Price, M.D., John Reilly, M.D., Paul D. Scanlon, M.D., Frank C. Sciurba, M.D., Steven M. Scharf, M.D., Ph.D., George R. Washko, M.D., Prescott G. Woodruff, M.D., M.P.H., and Nicholas R. Anthonisen, M.D., for the COPD Clinical Research Network
The affiliations of the authors are listed in the Appendix.Address reprint requests to Dr. Albert at Denver Health, 777 Bannock St., MC 4000, Denver, CO 80204-4507, or at ralbert@dhha.org.

 

参考文献

1.Strassels SA, Smith DH, Sullivan SD, Mahajan PS. The costs of treating COPD in the United States. Chest 2001;119:344-352

2.Andersson F, Borg S, Jansson SA, et al. The costs of exacerbations in chronic obstructive pulmonary disease (COPD). Respir Med 2002;96:700-708

3.Druss BG, Marcus SC, Olfson M, Pincus HA. The most expensive medical conditions in America. Health Aff (Millwood) 2002;21:105-111

4.Miller JD, Foster T, Boulanger L, et al. Direct costs of COPD in the U.S.: an analysis of Medical Expenditure Panel Survey (MEPS) data. COPD 2005;2:311-318

5.Lindenauer PK, Pekow P, Gao S, Crawford AS, Gutierrez B, Benjamin EM. Quality of care for patients hospitalized for acute exacerbations of chronic obstructive;144:894-903.

6.Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418-1422

7.Kanner RE, Anthonisen NR, Connet JE. Lower respiratory illnesses promote FEV1 decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study. Am J Respir Crit Care Med 2001;164:358-364

8.Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronic obstructive pulmonary disease surveillance -- United States, 1971-2000. MMWR Surveill Summ 2002;51:1-16

9.Tsai CL, Sobrino JA, Carmago CA Jr. National study of emergency department visits for acute exacerbation of chronic obstructive pulmonary disease, 1993-2005. Acad Emerg Med 2008;15:1275-1283

10.Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002;57:847-852[Erratum, Thorax 2008;63:753.]

11.Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925-931

12.Burge PS, Calverley PMA, Jones PW, Spencer S, Anderson JA, Maslen TK. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 2000;320:1297-1303

13.Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003;361:449-456[Erratum, Lancet 2003;361:1660.]

14.Calverley PMA, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-789

15.Mahler DA, Donohue JF, Barbee RA, et al. Efficacy of salmeterol xinafoate in the treatment of COPD. Chest 1999;115:957-965

16.Vincken W, van Noord JA, Greefhorst APM, et al. Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium. Eur Respir J 2002;19:209-216

17.Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J 2002;19:217-224

18.Brusasco V, Hodder R, Miravitlles M, Korducki L, Towse L, Kesten S. Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. Thorax 2003;58:399-404[Erratum, Thorax 2005;60:105.]

19.Niewoehner DE, Rice K, Cote C, et al. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med 2005;143:317-326

20.Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008;359:1543-1554

21.Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease. Eur Respir J 2003;21:74-81[Erratum, Eur Respir J 2004;21:912.]

22.Welte T, Miravitlles M, Hernandez P, et al. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009;180:741-750

23.Aaron SD, Vandemheen KL, Fergusson D, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007;146:545-555

24.Sin DD, McAlister FA, Man SFP, Anthonisen NR. Contemporary management of chronic obstructive pulmonary disease: scientific review. JAMA 2003;290:2301-2312

25.Martinez FJ, Curtis JL, Albert R. Role of macrolide therapy in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2008;3:331-350

26.Banerjee D, Khair OA, Honeybourne D. The effect of oral clarithromycin on health status and sputum bacteriology in stable COPD. Respir Med 2005;99:208-215

27.Suzuki T, Yanai M, Yamaya M, et al. Erythromycin and common cold in COPD. Chest 2001;120:730-733

28.Seemungal TAR, Wilkinson TMA, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med 2008;178:1139-1147

29.Yamaya M, Azuma A, Tanaka H, et al. Inhibitory effects of macrolide antibiotics on exacerbations and hospitalization in chronic obstructive pulmonary disease in Japan: a retrospective multicenter analysis. J Am Geriatr Soc 2008;56:1358-1360

30.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 September 28 (Epub ahead of print).

31.Blasi F, Bonardi D, Aliberti S, et al. Long-term azithromycin use in patients with chronic obstructive pulmonary disease and tracheostomy. Pulm Pharmacol Ther 2010;3:200-207

32.Gomez J, Banos V, Simarro E, et al. Prospective, comparative study (1994-1998) of the influence of short-term prophylactic treatment with azithromycin on patients with advanced COPD. Rev Esp Quimioter 2000;13:379-383

33.Arizona Center for Education and Research on Therapeutics. QT drug lists by risk groups. (http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm.)

34.Jones PW, Quirk FH, Baveystock CM. The St. George's Respiratory Questionnaire. Respir Med 1991;85:Suppl B:25-31

35.Efron B, Tibshirani RJ. An introduction to the bootstrap. New York: Chapman & Hall, 1993.

36.Kim K, DeMets DL. Design and analysis of group sequential tests based on the type I error spending rate function. Biometrika 1987;74:149-154

37.Phaff SJ, Tiddens HA, Verbrugh HA, Ott A. Macrolide resistance of Staphylococcus aureus and Haemophilus species associated with long-term azithromycin use in cystic fibrosis. J Antimicrob Chemother 2006;57:741-746

38.Saiman L, Anstead M, Mayer-Hamblett N, et al. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 2010;303:1707-1715

39.Patel IS, Seemungal TAR, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 2002;57:759-764

服务条款 | 隐私政策 | 联系我们