山东大学学报 (医学版) ›› 2024, Vol. 62 ›› Issue (5): 21-27.doi: 10.6040/j.issn.1671-7554.0.2024.0131
• 慢性气道疾病的精准个体化诊疗——专家综述 • 上一篇
丁伊人,刘婉莹,姚蕾,姚欣
DING Yiren, LIU Wanying, YAO Lei, YAO Xin
摘要： 哮喘是一种慢性气道炎症性疾病,吸入性糖皮质激素是其主要治疗药物。然而,少部分患者无法得到有效控制,对于此类患者亟需新的治疗方法。近年来,除了生物制剂的研究外,对于大环内酯类抗生素在哮喘治疗中的潜力也备受关注。本文就大环内酯类抗生素治疗哮喘的疗效、可能机制和不良反应进行系统综述。
中图分类号:
| [1] Stern J, Pier J, Litonjua AA. Asthma epidemiology and risk factors[J]. Semin Immunopathol, 2020, 42(1): 5-15. [2] Porsbjerg C, Melén E, Lehtimäki L, et al. Asthma[J]. Lancet, 2023, 401(10379): 858-873. [3] Levy ML, Bacharier LB, Bateman E, et al. Key recommendations for primary care from the 2022 Global Initiative for Asthma(GINA)update[J]. NPJ Prim Care Respir Med, 2023, 33(1): 7. doi:10.1038/s41533-023-00330-1. [4] Idanesimhe Sado A, Afzal MS, Kannekanti L, et al. A meta-analysis on predictors of mortality among patients hospitalized for acute exacerbation of asthma[J]. Cureus, 2023, 15(2): e35225. doi:10.7759/cureus.35225. [5] Lenz KD, Klosterman KE, Mukundan H, et al. Macrolides: from toxins to therapeutics[J]. Toxins, 2021, 13(5): 347. doi:10.3390/toxins13050347. [6] Zimmermann P, Ziesenitz VC, Curtis N, et al. The immunomodulatory effects of macrolides-a systematic review of the underlying mechanisms[J]. Front Immunol, 2018, 9: 302. doi:10.3389/fimmu.2018.00302. [7] Kudoh S, Uetake T, Hagiwara K, et al. Clinical effects of low-dose long-term erythromycin chemotherapy on diffuse panbronchiolitis[J]. Nihon Kyobu Shikkan Gakkai Zasshi, 1987, 25(6): 632-642. [8] Pollock J, Chalmers JD. The immunomodulatory effects of macrolide antibiotics in respiratory disease[J]. Pulm Pharmacol Ther, 2021, 71: 102095. doi:10.1016/j.pupt.2021.102095. [9] Ortega H, Nickle D, Carter L. Rhinovirus and asthma: challenges and opportunities[J]. Rev Med Virol, 2021, 31(4): e2193. doi:10.1002/rmv.2193. [10] Kelly JT, Busse WW. Host immune responses to rhinovirus: mechanisms in asthma[J]. J Allergy Clin Immunol, 2008, 122(4): 671-682. [11] Jackson DJ, Gern JE. Rhinovirus infections and their roles in asthma: etiology and exacerbations[J]. J Allergy Clin Immunol Pract, 2022, 10(3): 673-681. [12] Oliver ME, Hinks TSC. Azithromycin in viral infections[J]. Rev Med Virol, 2021, 31(2): e2163. doi:10.1002/rmv.2163. [13] Shukla SD, Taylor SL, Gibson PG, et al. Add-on azithromycin reduces sputum cytokines in non-eosinophilic asthma: an AMAZES substudy[J]. Thorax, 2021, 76(7): 733-736. [14] Peebles RS Jr, Aronica MA. Proinflammatory pathways in the pathogenesis of asthma[J]. Clin Chest Med, 2019, 40(1): 29-50. [15] Mitchell S, Vargas J, Hoffmann A. Signaling via the NFκB system[J]. Wiley Interdiscip Rev Syst Biol Med, 2016, 8(3): 227-241. [16] Vran ci c M, Banjanac M, Nuji c K, et al. Azithromycin distinctively modulates classical activation of human monocytes in vitro[J]. Br J Pharmacol, 2012, 165(5): 1348-1360. [17] Kandikattu HK, Venkateshaiah SU, Verma AK, et al. Tacrolimus(FK506)treatment protects allergen-, IL-5- and IL-13-induced mucosal eosinophilia[J]. Immunology, 2021, 163(2): 220-235. [18] Sato E, Nelson DK, Koyama S, et al. Erythromycin modulates eosinophil chemotactic cytokine production by human lung fibroblasts in vitro[J]. Antimicrob Agents Chemother, 2001, 45(2): 401-406. [19] Boberg E, Weidner J, Malmhäll C, et al. Rapamycin dampens inflammatory properties of bone marrow ILC2s in IL-33-induced eosinophilic airway inflammation[J]. Front Immunol, 2022, 13: 915906. doi:10.3389/fimmu.2022.915906. [20] Zhao X, Yu FQ, Huang XJ, et al. Azithromycin influences airway remodeling in asthma via the PI3K/Akt/MTOR/HIF-1α/VEGF pathway[J]. J Biol Regul Homeost Agents, 2018, 32(5): 1079-1088. [21] Hur GY, Broide DH. Genes and pathways regulating decline in lung function and airway remodeling in asthma[J]. Allergy Asthma Immunol Res, 2019, 11(5): 604-621. [22] Sadeghdoust M, Mirsadraee M, Aligolighasemabadi F, et al. Effect of azithromycin on bronchial wall thickness in severe persistent asthma: a double-blind placebo-controlled randomized clinical trial[J]. Respir Med, 2021, 185: 106494. doi:10.1016/j.rmed.2021.106494. [23] Tojima I, Shimizu S, Ogawa T, et al. Anti-inflammatory effects of a novel non-antibiotic macrolide, EM900, on mucus secretion of airway epithelium[J]. Auris Nasus Larynx, 2015, 42(4): 332-336. [24] Hara K, Kondo M, Tsuji M, et al. Clarithromycin suppresses IL-13-induced goblet cell metaplasia via the TMEM16A-dependent pathway in guinea pig airway epithelial cells[J]. Respir Investig, 2019, 57(1): 79-88. [25] Mann TS, Larcombe AN, Wang KCW, et al. Azithromycin inhibits mucin secretion, mucous metaplasia, airway inflammation, and airways hyperresponsiveness in mice exposed to house dust mite extract[J]. Am J Physiol Lung Cell Mol Physiol, 2022, 322(5): L683-L698. [26] Tagaya E, Tamaoki J, Kondo M, et al. Effect of a short course of clarithromycin therapy on sputum production in patients with chronic airway hypersecretion[J]. Chest, 2002, 122(1): 213-218. [27] Lu S, Liu H, Sr Farley JM. Macrolide antibiotics inhibit mucus secretion and calcium entry in Swine airway submucosal mucous gland cells[J]. J Pharmacol Exp Ther, 2011, 336(1): 178-187. [28] Park HK, Choi Y, Lee DH, et al. Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma[J]. J Allergy Clin Immunol, 2020, 145(5): 1466-1469.e8. [29] Roduit C, Frei R, Ferstl R, et al. High levels of butyrate and propionate in early life are associated with protection against atopy[J]. Allergy, 2019, 74(4): 799-809. [30] Theiler A, Bärnthaler T, Platzer W, et al. Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival[J]. J Allergy Clin Immunol, 2019, 144(3): 764-776. [31] Wang YY, Zijp TR, Bahar MA, et al. Effects of prophylactic antibiotics on patients with stable COPD: a systematic review and meta-analysis of randomized controlled trials[J]. J Antimicrob Chemother, 2018, 73(12): 3231-3243. [32] Vermeersch K, Gabrovska M, Aumann J, et al. Azithromycin during acute chronic obstructive pulmonary disease exacerbations requiring hospitalization(BACE). A multicenter, randomized, double-blind, placebo-controlled trial[J]. Am J Respir Crit Care Med, 2019, 200(7): 857-868. [33] Pomares X, Montón C, Bullich M, et al. Clinical and safety outcomes of long-term azithromycin therapy in severe COPD beyond the first year of treatment[J]. Chest, 2018, 153(5): 1125-1133. [34] Kew KM, Undela K, Kotortsi I, et al. Macrolides for chronic asthma[J]. Cochrane Database Syst Rev, 2015(9): CD002997. doi:10.1002/14651858.CD002997.pub4. [35] Johnston SL, Szigeti M, Cross M, et al. Azithromycin for acute exacerbations of asthma: the AZALEA randomized clinical trial[J]. JAMA Intern Med, 2016, 176(11): 1630-1637. [36] Murray CS, Lucas SJ, Blakey J, et al. A real-life comparative effectiveness study into the addition of antibiotics to the management of asthma exacerbations in primary care[J]. Eur Respir J, 2021, 58(1): 2003599. doi:10.1183/13993003.03599-2020. [37] Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma(AMAZES): a randomised, double-blind, placebo-controlled trial[J]. Lancet, 2017, 390(10095): 659-668. [38] Hiles SA, McDonald VM, Guilhermino M, et al. Does maintenance azithromycin reduce asthma exacerbations? An individual participant data meta-analysis[J]. Eur Respir J, 2019, 54(5): 1901381. doi:10.1183/13993003.01381-2019. [39] Undela K, Goldsmith L, Kew KM, et al. Macrolides versus placebo for chronic asthma[J]. Cochrane Database Syst Rev, 2021, 11(11): CD002997. doi:10.1002/14651858.CD002997.pub5. [40] Fukuda Y, Horita N, Aga M, et al. Efficacy and safety of macrolide therapy for adult asthma: a systematic review and meta-analysis[J]. Respir Investig, 2024, 62(2): 206-215. [41] ONeill C, Gibson PG, Heaney LG, et al. The cost-effectiveness of azithromycin in reducing exacerbations in uncontrolled asthma[J]. Eur Respir J, 2021, 57(2): 2002436. doi:10.1183/13993003.02436-2020. [42] Venkatesan P. 2023 GINA report for asthma[J]. Lancet Respir Med, 2023, 11(7): 589. doi:10.1016/S2213-2600(23)00230-8. [43] Lei WT, Lin HH, Tsai MC, et al. The effects of macrolides in children with reactive airway disease: a systematic review and meta-analysis of randomized controlled trials[J]. Drug Des Devel Ther, 2018, 12: 3825-3845. doi:10.2147/DDDT.S183527. [44] Ghimire JJ, Jat KR, Sankar J, et al. Azithromycin for poorly controlled asthma in children: a randomized controlled trial[J]. Chest, 2022, 161(6): 1456-1464. [45] Wan KS, Liu YC, Huang CS, et al. Effects of low-dose clarithromycin added to fluticasone on inflammatory markers and pulmonary function among children with asthma: a randomized clinical trial[J]. Allergy Rhinol, 2016, 7(3): 131-134. [46] Koutsoubari I, Papaevangelou V, Konstantinou GN, et al. Effect of clarithromycin on acute asthma exacerbations in children: an open randomized study[J]. Pediatr Allergy Immunol, 2012, 23(4): 385-390. [47] Maeda T, Khurana S. Heterogeneity of treatment response to asthma[J]. Adv Exp Med Biol, 2023, 1426: 143-161. doi:10.1007/978-3-031-32259-4_7. [48] Brusselle GG, Vanderstichele C, Jordens P, et al. Azithromycin for prevention of exacerbations in severe asthma(AZISAST): a multicentre randomised double-blind placebo-controlled trial[J]. Thorax, 2013, 68(4): 322-329. [49] Niessen NM, Gibson PG, Baines KJ, et al. Sputum TNF markers are increased in neutrophilic and severe asthma and are reduced by azithromycin treatment[J]. Allergy, 2021, 76(7): 2090-2101. [50] Simpson JL, Powell H, Boyle MJ, et al. Clarithromycin targets neutrophilic airway inflammation in refractory asthma[J]. Am J Respir Crit Care Med, 2008, 177(2): 148-155. [51] Carlsson CJ, Rasmussen MA, Pedersen SB, et al. Airway immune mediator levels during asthma-like symptoms in young children and their possible role in response to azithromycin[J]. Allergy, 2021, 76(6): 1754-1764. [52] Thorsen J, Stokholm J, Rasmussen MA, et al. The airway microbiota modulates effect of azithromycin treatment for episodes of recurrent asthma-like symptoms in preschool children: a randomized clinical trial[J]. Am J Respir Crit Care Med, 2021, 204(2): 149-158. [53] Taylor SL, Ivey KL, Gibson PG, et al. Airway abundance of Haemophilus influenzae predicts response to azithromycin in adults with persistent uncontrolled asthma[J]. Eur Respir J, 2020, 56(4): 2000194. doi:10.1183/13993003.00194-2020. [54] Hansen MP, Scott AM, McCullough A, et al. Adverse events in people taking macrolide antibiotics versus placebo for any indication[J]. Cochrane Database Syst Rev, 2019, 1(1): CD011825. doi:10.1002/14651858.CD011825.pub2. [55] Smith D, Du Rand IA, Addy C, et al. British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease[J]. BMJ Open Respir Res, 2020, 7(1): e000489. doi:10.1136/bmjresp-2019-000489. [56] Ray WA, Murray KT, Hall K, et al. Azithromycin and the risk of cardiovascular death[J]. N Engl J Med, 2012, 366(20): 1881-1890. [57] Yang ZJ, Prinsen JK, Bersell KR, et al. Azithromycin causes a novel proarrhythmic syndrome[J]. Circ Arrhythm Electrophysiol, 2017, 10(4): e003560. doi:10.1161/CIRCEP.115.003560. [58] Smith D, Du Rand I, Addy CL, et al. British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease[J]. Thorax, 2020, 75(5): 370-404. [59] Avedissian SN, Rhodes NJ, Ng TMH, et al. The potential for QT interval prolongation with chronic azithromycin therapy in adult cystic fibrosis patients[J]. Pharmacotherapy, 2019, 39(6): 718-723. [60] Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma(AMAZES): a randomised, double-blind, placebo-controlled trial[J]. Lancet, 2017, 390(10095): 659-668. [61] Ghimire JJ, Jat KR, Sankar J, et al. Azithromycin for poorly controlled asthma in children: a randomized controlled trial[J]. Chest, 2022, 161(6): 1456-1464. [62] Trac MH, McArthur E, Jandoc R, et al. Macrolide antibiotics and the risk of ventricular arrhythmia in older adults[J]. CMAJ, 2016, 188(7): E120-E129. [63] Assimon MM, Pun PH, Wang L, et al. Azithromycin use increases the risk of sudden cardiac death in patients with hemodialysis-dependent kidney failure[J]. Kidney Int, 2022, 102(4): 894-903. [64] Taylor SL, Leong LEX, Mobegi FM, et al. Long-term azithromycin reduces Haemophilus influenzae and increases antibiotic resistance in severe asthma[J]. Am J Respir Crit Care Med, 2019, 200(3): 309-317. [65] Heidary M, Ebrahimi Samangani A, Kargari A, et al. Mechanism of action, resistance, synergism, and clinical implications of azithromycin[J]. J Clin Lab Anal, 2022, 36(6): e24427. doi:10.1002/jcla.24427. [66] Carrera-Salinas A, González-Díaz A, Ehrlich RL, et al. Genetic adaptation and acquisition of macrolide resistance in Haemophilus spp. during persistent respiratory tract colonization in chronic obstructive pulmonary disease(COPD)patients receiving long-term azithromycin treatment[J]. Microbiol Spectr, 2023, 11(1): e0386022. doi:10.1128/spectrum.03860-22. [67] Segal LN, Clemente JC, Wu BG, et al. Randomised, double-blind, placebo-controlled trial with azithromycin selects for anti-inflammatory microbial metabolites in the emphysematous lung[J]. Thorax, 2017, 72(1): 13-22. [68] Burr LD, Taylor SL, Richard A, et al. Assessment of long-term macrolide exposure on the oropharyngeal microbiome and macrolide resistance in healthy adults and consequences for onward transmission of resistance[J]. Antimicrob Agents Chemother, 2022, 66(4): e0224621. doi:10.1128/aac.02246-21. [69] Lin YC, Chen YC, Kuo CH, et al. Antibiotic exposure and asthma development in children with allergic rhinitis[J]. J Microbiol Immunol Infect, 2020, 53(5): 803-811. |
| [1] | 王凤燕,梁振宇,李雪萍,陈荣昌. 慢性阻塞性肺疾病近年临床研究热点[J]. 山东大学学报 (医学版), 2024, 62(5): 7-15. |
| [2] | 申永春,文富强. 线粒体损伤相关分子模式作为慢性阻塞性肺疾病生物标志物的研究进展[J]. 山东大学学报 (医学版), 2024, 62(5): 16-20. |
| [3] | 王静,刘粉,曾荣,黄思源,许长娟,梁子婷,董亮. 以胸膜病变为特征的IgG4相关性肺疾病1例[J]. 山东大学学报 (医学版), 2022, 60(3): 114-116. |
| [4] | 杨丽萍,慕婷婷,杨玉娟,张宇,宋西成. 吸入性变应原对腺样体肥大合并支气管哮喘患儿肺功能影响[J]. 山东大学学报 (医学版), 2020, 58(3): 107-112. |
| [5] | 张宁,杨燕,李锐,殷运红,李昊,曲仪庆. 慢阻肺患者感染鲍曼不动杆菌危险因素及耐药性分析[J]. 山东大学学报 (医学版), 2019, 57(9): 88-96. |
| [6] | 于晓琳,张军,杨柳,周林,崔亮亮,张济. 济南市慢性阻塞性肺部疾病患者在流感季呼吸系统疾病的罹患特征[J]. 山东大学学报（医学版）, 2017, 55(3): 79-82. |
| [7] | 顾建华,马晓天,李吉庆,薛付忠,王家林. 健康管理队列慢性阻塞性肺疾病风险预测模型[J]. 山东大学学报 (医学版), 2017, 55(12): 62-65. |
| [8] | 柳晓涓,丁荔洁,康凤玲,周苗,薛付忠. 健康管理人群支气管哮喘风险预测模型[J]. 山东大学学报 (医学版), 2017, 55(12): 56-61. |
| [9] | 刘琳,刘春红,王得翔,吴金香,赵继萍,刘甜,张元元,王俊飞,柳亚慧,曹柳兆,董亮. 应用呼出气一氧化氮联合脉冲振荡肺功能评估哮喘患者的小气道功能[J]. 山东大学学报（医学版）, 2016, 54(8): 78-83. |
| [10] | 潘青,吕志芳. 慢性阻塞性肺疾病新指南对临床患者分类的应用价值[J]. 山东大学学报（医学版）, 2016, 54(3): 63-67. |
| [11] | 吴珍, 宋国栋, 王伟. 他汀类药物对稳定期慢性阻塞性肺病治疗效果的Meta分析[J]. 山东大学学报（医学版）, 2015, 53(2): 12-18. |
| [12] | 韦中盛. 纤维支气管镜胸腔内喷洒滑石粉治疗 慢性阻塞性肺疾病合并难治性气胸的临床观察[J]. 山东大学学报（医学版）, 2014, 52(S2): 78-79. |
| [13] | 霍兴兰. 无创呼吸机治疗呼吸衰竭84例的临床观察[J]. 山东大学学报（医学版）, 2014, 52(S2): 50-50. |
| [14] | 刘晓静. 固本养脏汤对慢性阻塞性肺病急性加重期患者血清CRP、TNF-α、IL-8和肺通气功能的影响[J]. 山东大学学报（医学版）, 2014, 52(S1): 61-62. |
| [15] | 丁启翠1，王伟1，王永彬1，陈旭东2，吴倩1. 辛伐他汀对COPD大鼠肺组织凋亡相关因子的影响[J]. 山东大学学报(医学版), 2012, 50(6): 65-. |
|
||
