静脉注射免疫球蛋白 (IVIG)
IVIG 作为皮质类固醇助减剂的作用未在儿童患者中得到复制。[209]Niggemann B, Leupold W, Schuster A, et al. Prospective, double-blind, placebo-controlled, multicentre study on the effect of high-dose, intravenous immunoglobulin in children and adolescents with severe bronchial asthma. Clin Exp Allergy. 1998;28:205-210.http://www.ncbi.nlm.nih.gov/pubmed/9515594?tool=bestpractice.com[210]Kishiyama JL, Valacer D, Cunningham-Rundles C, et al. A multicenter, randomized, double-blind, placebo-controlled trial of high-dose intravenous immunoglobulin for oral corticosteroid-dependent asthma. Clin Immunol. 1999;91:126-133.http://www.ncbi.nlm.nih.gov/pubmed/10227804?tool=bestpractice.com 其对哮喘的治疗效果还不清楚，并且被限制使用。使用该药存在安全隐患，例如引起无菌性脑膜炎。[210]Kishiyama JL, Valacer D, Cunningham-Rundles C, et al. A multicenter, randomized, double-blind, placebo-controlled trial of high-dose intravenous immunoglobulin for oral corticosteroid-dependent asthma. Clin Immunol. 1999;91:126-133.http://www.ncbi.nlm.nih.gov/pubmed/10227804?tool=bestpractice.com IVIG 对与特异性抗体缺陷有关的哮喘可能有疗效。还需要进行进一步的研究。[211]Schwartz HJ, Hostoffer RW, McFadden ER Jr., et al. The response to intravenous immunoglobulin replacement therapy in patients with asthma with specific antibody deficiency. Allergy Asthma Proc. 2006;27:53-58.http://www.ncbi.nlm.nih.gov/pubmed/16598993?tool=bestpractice.com
补充医学 (CAM)
在任一时间，大约有 50%-60% 的家长会采用传统医学的方法控制孩子的哮喘。医生只知道其中的一半病例。[212]Shenfield G, Lim E, Allen H. Survey of the use of complementary medicines and therapies in children with asthma. J Paediatr Child Health. 2002;38:252-257.http://www.ncbi.nlm.nih.gov/pubmed/12047692?tool=bestpractice.com 由于缺乏高质量的随机研究，评估 CAM 在慢性哮喘患者管理中作用的受到限制。没有足够证据或无证据支持针灸、顺势疗法、草药、维生素 C、补充大豆异黄酮、手法治疗或各种呼吸技术对慢性哮喘的作用。[213]McCarney RW, Brinkhaus B, Lasserson TJ, et al. Acupuncture for chronic asthma. Cochrane Database Syst Rev. 2003;(3):CD000008.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000008.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/14973944?tool=bestpractice.com[214]McCarney RW, Linde K, Lasserson TJ. Homeopathy for chronic asthma. Cochrane Database Syst Rev. 2004;(1):CD000353.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000353.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/14973954?tool=bestpractice.com[215]Hondras MA, Linde K, Jones AP. Manual therapy for asthma. Cochrane Database Syst Rev. 2005;(2):CD001002.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001002.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/15846609?tool=bestpractice.com[216]Dennis J. Alexander technique for chronic asthma. Cochrane Database Syst Rev. 2012;(9):CD000995.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000995.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22972048?tool=bestpractice.com[217]Arnold E, Clark CE, Lasserson TJ, et al. Herbal interventions for chronic asthma in adults and children. Cochrane Database Syst Rev. 2008;(1):CD005989.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005989.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/18254089?tool=bestpractice.com[218]Milan SJ, Hart A, Wilkinson M. Vitamin C for asthma and exercise-induced bronchoconstriction. Cochrane Database Syst Rev. 2013;(10):CD010391.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010391.pub2/abstracthttp://www.ncbi.nlm.nih.gov/pubmed/24154977?tool=bestpractice.com[219]Smith LJ, Kalhan R, Wise RA, et al; American Lung Association Asthma Clinical Research Centers. Effect of a soy isoflavone supplement on lung function and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial. JAMA. 2015;313:2033-2043.http://www.ncbi.nlm.nih.gov/pubmed/26010632?tool=bestpractice.com[220]Macêdo TM, Freitas DA, Chaves GS, et al. Breathing exercises for children with asthma. Cochrane Database Syst Rev. 2016 Apr 12;4:CD011017.http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD011017.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27070225?tool=bestpractice.com对哮喘患者而言，瑜伽是一种有吸引力的治疗方法，但目前缺乏足够的证据来支持使用该方法进行哮喘治疗。[221]Yang ZY, Zhong HB, Mao C, et al. Yoga for asthma. Cochrane Database Syst Rev. 2016;(4):CD010346.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010346.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27115477?tool=bestpractice.com 其他方法（例如呼吸肌锻炼方法）仅仅在一些研究人群中使用，尚不清楚其临床意义。[222]Silva IS, Fregonezi GA, Dias FA, et al. Inspiratory muscle training for asthma. Cochrane Database Syst Rev. 2013;(9):CD003792.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003792.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24014205?tool=bestpractice.com
细胞因子拮抗剂
研究表明在哮喘成人患者中，连续使用肿瘤坏死因子-α 拮抗剂 10 周后，患者气道高反应性降低，生活质量改善。当前没有足够的证据，无法作为指南的一部分推荐其使用。[223]Berry MA, Hargadon B, Shelley M, et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med. 2006;354:697-708.http://www.nejm.org/doi/full/10.1056/NEJMoa050580#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/16481637?tool=bestpractice.com
并存胃食管反流的管理
胃食管反流可能与哮喘共存，经常无症状。多项非随机对照试验表明，在儿童中治疗反流能够改善临床评分，但是临床意义不明。[224]Andze GO, Luks FI, Bensoussan AL, et al. Role of surgical treatment of gastro-esophageal reflux in children with severe asthma [in French]. Pediatrie. 1991;46:451-454.http://www.ncbi.nlm.nih.gov/pubmed/1663240?tool=bestpractice.com[225]Tucci F, Resti M, Fontana R, et al. Gastroesophageal reflux and bronchial asthma: prevalence and effect of cisapride therapy. J Pediatr Gastroenterol Nutr. 1993;17:265-270.http://www.ncbi.nlm.nih.gov/pubmed/8271125?tool=bestpractice.com 然而，在一项针对无胃食管反流病症状且哮喘控制差（使用吸入用糖皮质激素）儿童的随机对照试验中，与使用安慰剂相比，使用兰索拉唑患并未改善症状或肺功能，却与不良呼吸事件增加有关。[226]Holbrook JT, Wise RA, Gold BD, et al; Writing Committee for the American Lung Association Asthma Clinical Research Centers. Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA. 2012;307:373-380.http://jama.jamanetwork.com/article.aspx?articleid=1104902http://www.ncbi.nlm.nih.gov/pubmed/22274684?tool=bestpractice.com 随机对照试验研究显示，使用质子泵抑制剂治疗难控性哮喘成人患者没有益处。[227]Mastronarde JG, Anthonisen NR, Castro M, et al; American Lung Association Asthma Clinical Research Centers. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009;360:1487-1499.http://www.nejm.org/doi/full/10.1056/NEJMoa0806290#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/19357404?tool=bestpractice.com
针对多种诱发因素开展的以家庭为基础的综合性干预
多项研究对经过特殊培训的人员进行患者家庭随访的干预效果进行评估，家庭随访重点是通过环境评估、教育和整治，减少患者暴露于一系列哮喘诱发因素（过敏原和刺激物）。到目前为止，尽管有些作者认为已经有足够的证据表明一些个体化干预措施有效，但依据已有数据尚无明确结论，因此还不能推荐普遍使用家庭随访方法。[228]Crocker DD, Kinyota S, Dumitru GG, et al. Effectiveness of home-based, multi-trigger, multicomponent interventions with an environmental focus for reducing asthma morbidity: a community guide systematic review. Am J Preventive Med. 2011;41(suppl1):S5-S32.http://www.ncbi.nlm.nih.gov/pubmed/21767736?tool=bestpractice.com[229]Krieger J, Jacobs DE, Ashley PJ, et al. Housing interventions and control of asthma-related indoor biologic agents: a review of the evidence. J Public Health Manag Pract. 2010;16(suppl 5):S11-S20.http://www.ncbi.nlm.nih.gov/pubmed/20689369?tool=bestpractice.com
室内环境控制
对于哮喘控制不完全的患者，温度控制可能有作用。[230]Boyle RJ, Pedroletti C, Wickman M, et al; 4A Study Group. Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial. Thorax. 2012;67:215-221.http://thorax.bmj.com/content/67/3/215.longhttp://www.ncbi.nlm.nih.gov/pubmed/22131290?tool=bestpractice.com[231]Free S, Howden-Chapman P, Pierse N, et al; Housing, Heating and Health Study Research Team. More effective home heating reduces school absences for children with asthma. J Epidemiol Community Health. 2010;64:379-386.http://jech.bmj.com/content/64/5/379.longhttp://www.ncbi.nlm.nih.gov/pubmed/19776423?tool=bestpractice.com
支气管热整形术
在严重哮喘成人患者中开展了支气管热整形术，结果表明其在减少急性发作以及改善生活质量和峰流速这些方面有一定效果。[232]Wu Q, Xing Y, Zhou X, et al. Meta-analysis of the efficacy and safety of bronchial thermoplasty in patients with moderate-to-severe persistent asthma. J Int Med Res. 2011;39:10-22.http://www.ncbi.nlm.nih.gov/pubmed/21672303?tool=bestpractice.com 但是人们对该方法的副作用和住院治疗有很多担心。目前还没有在儿童患者中开展此方法的研究，因此不推荐在儿童患者中使用。
远程医疗和其他技术
远程医疗的定义为患者和医务人员远距离、利用电子设备开展个性化的信息交换，患者提供信息，医疗专业人员利用他们的技术和判断，为患者提供一种医疗服务。[233]McLean S, Chandler D, Nurmatov U, et al. Telehealthcare for asthma. Cochrane Database Syst Rev. 2010;(10):CD007717.http://www.ncbi.nlm.nih.gov/pubmed/20927763?tool=bestpractice.com 一项系统评价指出该方法对轻度哮喘没有作用，但是对成人和儿童重度哮喘患者可能有用。[233]McLean S, Chandler D, Nurmatov U, et al. Telehealthcare for asthma. Cochrane Database Syst Rev. 2010;(10):CD007717.http://www.ncbi.nlm.nih.gov/pubmed/20927763?tool=bestpractice.com [ 
]What are the benefits and harms of home telemonitoring and remote feedback between clinic visits in people with asthma?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2087/full显示答案然而，这些额外的干预措施成本较高。父母选择顾问进行指导可以提高父母的生活质量水平，但没有减少儿童患者需紧急治疗的急性发作次数。[234]Garbutt JM, Banister C, Highstein G, et al. Telephone coaching for parents of children with asthma: impact and lessons learned. Arch Pediatr Adolesc Med. 2010;164:625-630.http://www.ncbi.nlm.nih.gov/pubmed/20603462?tool=bestpractice.com 智能手机中应用程序越来越多地应用于健康相关问题。利用智能手机管理哮喘前景广泛，但没有足够的证据可以推荐将该技术作为常规管理工具。[235]Marcano Belisario JS, Huckvale K, Greenfield G, et al. Smartphone and tablet self management apps for asthma. Cochrane Database Syst Rev. 2013;(11):CD010013.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010013.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24282112?tool=bestpractice.com
免疫抑制剂
在专科三级医疗保健中，对于已使用口服皮质类固醇的严重持续性哮喘患儿，有时会加用免疫抑制剂（例如硫唑嘌呤、环孢素、氯喹和甲氨蝶呤）作为辅助治疗。使用这些药物进行治疗的效果是有限的，在专科医疗机构外，不推荐使用这些药物。[189]Dean T, Dewey A, Bara A, et al. Azathioprine as an oral corticosteroid sparing agent for asthma. Cochrane Database Syst Rev. 2003;(4):CD003270.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003270.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/14974011?tool=bestpractice.com[190]Dewey A, Dean T, Bara A, et al. Chloroquine as a steroid sparing agent for asthma. Cochrane Database Syst Rev. 2003;(4):CD003275.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003275/fullhttp://www.ncbi.nlm.nih.gov/pubmed/14583965?tool=bestpractice.com
遗传药理学
虽然这个领域很有前景，早在 10 年前就有 β2 受体激动剂受体基因多态性的报告，更加严谨的研究表明 β 受体变异对长效 β2 受体激动剂治疗反应不存在遗传药理学效应。[236]Bleecker ER, Nelson HS, Kraft M, et al. Beta2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate. Am J Respir Crit Care Med. 2010;181:676-687.http://www.ncbi.nlm.nih.gov/pubmed/19910613?tool=bestpractice.com 到目前为止，根据对患者的基因分析所制定的针对性哮喘药物方案还未起作用。
即将出现的新的药物
半衰期更长、每日使用一次的吸入用皮质类固醇 (ICS)（例如糠酸氟替卡松）与新型长效 β-2 受体激动剂（例如维兰特罗）的联合用药正处于研究中。[237]European Medicines Agency. Summary of opinion (initial authorisation). Relvar Ellipta: fluticasone furoate/vilanterol. September 2013. http://www.ema.europa.eu (last accessed 18 August 2016).http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/002673/WC500150090.pdf[238]Bateman ED, Bleecker ER, Lotvall J, et al. Dose effect of once-daily fluticasone furoate in persistent asthma: a randomized trial. Respir Med. 2012;106:642-650.http://www.ncbi.nlm.nih.gov/pubmed/22342538?tool=bestpractice.com[239]Busse WW, Bleecker ER, Bateman ED, et al. Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial. Thorax. 2012;67:35-41.http://www.ncbi.nlm.nih.gov/pubmed/21828231?tool=bestpractice.com 美国食品药品监督管理局仅批准这种 ICS/长效 β受体激动剂 (LABA) 联合用药用于治疗 18 岁及以上的患者，但在其他国家/地区（例如澳大利亚），这种联合用药已获准用于治疗 12 岁及以上的哮喘儿童患者。由于维兰特罗是新型 LABA，它的长期安全性尚不明确。已经在严重哮喘患者中尝试使用白介素 (IL)-4 受体拮抗剂，但迄今为止的数据表明，它们没有临床意义。[240]Corren J, Busse W, Meltzer EO, et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am J Respir Critical Care Med. 2010;181:788-796.http://www.ncbi.nlm.nih.gov/pubmed/20056900?tool=bestpractice.com 对于已在使用一种 ICS 联合长效 β-2 受体激动剂治疗的大龄青少年和成人中度至重度哮喘者而言，雾化吸入去氢表雄酮-3-硫酸酯 (dehydroepiandrosterone-3-sulfate, DHEAS) 可以改善哮喘控制。[241]Wenzel SE, Robinson CB, Leonard JM, et al. Nebulized dehydroepiandrosterone-3-sulfate improves asthma control in the moderate-to-severe asthma results of a 6-week, randomized, double-blind, placebo-controlled study. Allergy Asthma Proc. 2010;31:461-471.http://www.ncbi.nlm.nih.gov/pubmed/21708057?tool=bestpractice.com 在成人哮喘患者中已经对另一种可以每日服用一次的超长效 β2 受体激动剂（茚达特罗）的效果进行了评估。[242]Sugihara N, Kanada S, Haida M, et al. 24-h bronchodilator efficacy of single doses of indacaterol in Japanese patients with asthma: a comparison with placebo and salmeterol. Respir Med. 2010;104:1629-1637.http://www.ncbi.nlm.nih.gov/pubmed/20619623?tool=bestpractice.com 尚不清楚该药是否与其他长效 β2 激动剂存在同样的安全问题，还没有评估该药对儿童哮喘患者的效果。神经激肽受体拮抗剂也可改善肺功能，降低气道高反应性。该药也未在儿童哮喘患者中被评估。[243]Ramalho R, Soares R, Couto N, et al. Tachykinin receptors antagonism for asthma: a systematic review. BMC Pulm Med. 2011;11:41.http://www.biomedcentral.com/1471-2466/11/41http://www.ncbi.nlm.nih.gov/pubmed/21810226?tool=bestpractice.com Lebrikizumab 是一种与 IL-13 结合的人源化单克隆抗体，也是另一种可改善气流受限的生物制剂，特别是对于骨膜蛋白水平较高和高 Th2 表型的成人。[244]Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088-1098.http://www.nejm.org/doi/full/10.1056/NEJMoa1106469http://www.ncbi.nlm.nih.gov/pubmed/21812663?tool=bestpractice.com
吸入用灭活草分枝杆菌
基于改变哮喘中的 Th1/Th2 失衡，在一项小型 (n=22)、单中心、随机对照试验中，对吸入性灭活草分枝杆菌进行了研究。数据是初步的，但这可能成为中度至重度哮喘儿童的一种新治疗方法。[245]Ming M, Li C, Luo Z, et al. Effect of inhaled inactivated Mycobacterium phlei in children with moderate asthma. Immunotherapy. 2013;5:191-197.http://www.ncbi.nlm.nih.gov/pubmed/23413910?tool=bestpractice.com
大环内酯类
在非嗜酸性粒细胞性哮喘成人患者中，大环内酯类抗生素可能会有效改善与哮喘相关的生活质量和气道炎症，但不能改善肺功能。[246]Simpson JL, Powell H, Boyle MJ, et al. Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med. 2008;177:148-155.http://www.atsjournals.org/doi/full/10.1164/rccm.200707-1134OC#.U_cyu_ldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/17947611?tool=bestpractice.com[247]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. Thorax. 2013;68:322-329.http://thorax.bmj.com/content/68/4/322.longhttp://www.ncbi.nlm.nih.gov/pubmed/23291349?tool=bestpractice.com[248]Kew KM, Undela K, Kotortsi I, et al. Macrolides for chronic asthma. Cochrane Database Syst Rev. 2015;(9):CD002997.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002997.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26371536?tool=bestpractice.com 在儿童中的数据有限。一篇系统评价介绍了儿童前期与后期研究，这些联合研究的总样本量为 69。[249]Mikailov A, Kane I, Aronoff SC, et al. Utility of adjunctive macrolide therapy in treatment of children with asthma: a systematic review and meta-analysis. J Asthma Allergy. 2013;6:23-29.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549681/http://www.ncbi.nlm.nih.gov/pubmed/23345983?tool=bestpractice.com 辅助使用大环内酯类抗生素的有益作用仅见于口服皮质类固醇依赖性哮喘患儿，它可使患者每日皮质类固醇使用剂量减少，FEV1 得到改善。[249]Mikailov A, Kane I, Aronoff SC, et al. Utility of adjunctive macrolide therapy in treatment of children with asthma: a systematic review and meta-analysis. J Asthma Allergy. 2013;6:23-29.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549681/http://www.ncbi.nlm.nih.gov/pubmed/23345983?tool=bestpractice.com
