氦氧混合气
氦氧混合气是氦/氧气混合气体,其密度低于室内空气或氧气但粘度高;因此,它的使用可以减少气流阻力和提高气道渗透力。 作为独立的治疗儿童严重急性哮喘的方法,meta 分析(其中包括 3 个随机对照研究,尽管样本量很小)已经证实其对于严重的急剧恶化的哮喘有潜在的益处。[79]Rodrigo G, Pollack C, Rodrigo C, et al. Heliox for nonintubated acute asthma patients. Cochrane Database Syst Rev. 2006;(4):CD002884.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002884.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17054154?tool=bestpractice.com 最近在进行进一步的小样本随机对照试验,使用氦氧混合气作为气溶胶交换的装置,显著改善了2至4小时的临床评分和12小时内的出院率。[80]Kim IK, Phrampus E, Venkataraman S, et al. Helium/oxygen-driven albuterol nebulization in the treatment of children with moderate to severe asthma exacerbations: a randomized, controlled trial. Pediatrics. 2005;116:1127-1133.http://www.ncbi.nlm.nih.gov/pubmed/16263999?tool=bestpractice.com 确定其在哮喘管理中的地位还需要进一步的研究。
白三烯受体拮抗剂
白三烯是促炎介质,在对变应原刺激的早期和晚期哮喘相关气道反应方面均有重要作用。白三烯受体拮抗剂 (leukotriene receptor antagonist, LTRA) 抑制部分哮喘相关炎症反应(这些反应相对不受口服皮质类固醇的影响),[81]Dworski R, Fitzgerald GA, Oates JA, et al. Effect of oral prednisone on airway inflammatory mediators in atopic asthma. Am J Respir Crit Care Med. 1994;149:953-959.http://www.ncbi.nlm.nih.gov/pubmed/8143061?tool=bestpractice.com 并使支气管有一定程度的扩张。静脉给药 10 分钟后和口服 2 小时后可发现其有益作用。[82]Camargo CA Jr, Smithline HA, Malice MP, et al. A randomized controlled trial of intravenous montelukast in acute asthma. Am J Respir Crit Care Med. 2003;167:528-533.http://www.jacionline.org/article/S0091-6749%2809%2901732-1/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/12456380?tool=bestpractice.com 尽管有证据表明静脉白三烯受体拮抗剂的使用可能是有益的,可显著降低住院的风险,但在建议制定之前还需要更多的研究。[83]Watts K, Chavasse RJ. Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children. Cochrane Database Syst Rev. 2012;(5):CD006100.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006100.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22592708?tool=bestpractice.com 尽管成人可见FEV1的改善,[84]Adachi M, Taniguchi H, Tohda Y, et al. The efficacy and tolerability of intravenous montelukast in acute asthma exacerbations in Japanese patients. J Asthma. 2012;49:649-656.http://www.ncbi.nlm.nih.gov/pubmed/22742205?tool=bestpractice.com 但一项关于在儿童中使用标准方案联合静脉给予孟鲁司特进行治疗的随机对照试验显示,60 分钟后未见 FEV1 或症状评分改善。[85]Morris CR, Becker AB, Piñieiro A, et al. A randomized, placebo-controlled study of intravenous montelukast in children with acute asthma. Ann Allergy Asthma Immunol. 2010;104:161-171.http://www.ncbi.nlm.nih.gov/pubmed/20306820?tool=bestpractice.com 静脉途径目前还没有在临床实践中使用。 在急性发作期应用口服LTRA的研究效果不理想。[83]Watts K, Chavasse RJ. Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children. Cochrane Database Syst Rev. 2012;(5):CD006100.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006100.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22592708?tool=bestpractice.com[86]Todi VK, Lodha R, Kabra SK. Effect of addition of single dose of oral montelukast to standard treatment in acute moderate to severe asthma in children between 5 and 15 years of age: a randomised, double-blind, placebo controlled trial. Arch Dis Child. 2010;95:540-543.http://www.ncbi.nlm.nih.gov/pubmed/20522464?tool=bestpractice.com [
]In children with acute asthma, is there randomized controlled trial evidence to support the use of oral leukotriene receptor antagonists in addition to usual care ?https://cochranelibrary.com/cca/doi/10.1002/cca.61/full显示答案 虽然成人和儿童的研究可见FEV1的改善得益于LTRA,但入院率并没有改善。对于学龄前儿童,LTRAs与首剂短效β受体激动剂共同作用可改善4小时的呼吸频率和症状评分,与安慰剂相比可减少1小时口服糖皮质激素的应用(20.8% vs 38.5%)。[87]Harmanci K, Bakirtas A, Turktas I, et al. Oral montelukast treatment of preschool-aged children with acute asthma. Ann Allergy Asthma Immunol. 2006;96:731-735.http://www.ncbi.nlm.nih.gov/pubmed/16729788?tool=bestpractice.com 间断哮喘发作的患儿经过家长给予LTRA 7天或自发作开始至缓解后48小时,可降低医疗资源利用、减轻症状及工作或学习的请假时间。[88]Robertson CF, Price D, Henry R, et al. Short-course montelukast for intermittent asthma in children: a randomized controlled trial. Am J Respir Crit Care Med. 2007;175:323-329.http://www.atsjournals.org/doi/full/10.1164/rccm.200510-1546OC#.U_dKuvldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/17110643?tool=bestpractice.com 进一步研究表明,其仅对哮喘症状严重度评分改善有益。[89]Bacharier LB, Phillips BR, Zeiger RS, et al; CARE Network. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. 2008;122:1127-1135.e8.http://www.jacionline.org/article/S0091-6749%2808%2901724-7/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/18973936?tool=bestpractice.com 然而,一项研究表明,增加口服孟鲁司特对哮喘急性发作的治疗(吸入支气管舒张剂和糖皮质激素的标准治疗基础上)没有任何临床益处。[86]Todi VK, Lodha R, Kabra SK. Effect of addition of single dose of oral montelukast to standard treatment in acute moderate to severe asthma in children between 5 and 15 years of age: a randomised, double-blind, placebo controlled trial. Arch Dis Child. 2010;95:540-543.http://www.ncbi.nlm.nih.gov/pubmed/20522464?tool=bestpractice.com 虽然这些结果充满希望,但目前的证据不足以推荐其在哮喘急性发作期的常规应用。 2009年美国食品药品监督管理局因为监测到自杀率增高而对该药进行警告,但目前无强烈的证据支持自杀率增加与该药明确相关。[90]Schumock GT, Lee TA, Joo MJ, et al. Association between leukotriene-modifying agents and suicide: what is the evidence? Drug Saf. 2011;34:533-544.http://www.ncbi.nlm.nih.gov/pubmed/21663330?tool=bestpractice.com
单一的维持和缓解治疗
引入福莫特罗作为长效β{0}2受体激动剂(LABA),它的起效速度与短效β{1}2受体激动剂相当,它与布地奈德联合雾化吸入,挑战了传统的单独的预防和缓解药物吸入疗法。 尽管最初成人和儿科数据显示联合用药是有利的,[91]O'Byrne PM, Bisgaard H, Godard PP, et al. Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am J Respir Crit Care Med. 2005;171:129-136.http://www.atsjournals.org/doi/full/10.1164/rccm.200407-884OChttp://www.ncbi.nlm.nih.gov/pubmed/15502112?tool=bestpractice.com[92]Bisgaard H, Le Roux P, Bjamer D, et al. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Chest. 2006;130:1733-1743.http://www.ncbi.nlm.nih.gov/pubmed/17166990?tool=bestpractice.com 但目前没有足够的儿科的数据证实。[93]Cates CJ, Lasserson TJ. Combination formoterol and inhaled steroid versus beta2-agonist as relief medication for chronic asthma in adults and children. Cochrane Database Syst Rev. 2009;(1):CD007085.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007085.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19160317?tool=bestpractice.com[94]Cates CJ, Karner C. Combination formoterol and budesonide as maintenance and reliever therapy versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults and children. Cochrane Database Syst Rev. 2013;(4):CD007313.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007313.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23633340?tool=bestpractice.com 目前人们对该方案使成人哮喘达到良好控制的能力产生了担忧,[95]Chapman KR, Barnes NC, Greening AP, et al. Single maintenance and reliever therapy (SMART) of asthma: a critical appraisal. Thorax. 2010;65:747-752.http://thorax.bmj.com/content/65/8/747http://www.ncbi.nlm.nih.gov/pubmed/20581409?tool=bestpractice.com 因为有证据显示采用这种方法治疗的成人气道炎症水平增高。[96]Pavord ID, Jeffery PK, Qiu Y, et al. Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol. J Allergy Clin Immunol. 2009;123:1083-1089,1089.e1-1089.e7.http://www.ncbi.nlm.nih.gov/pubmed/19368965?tool=bestpractice.com 但对儿童应用LABA安全性的担忧还是存在的,[97]Rodrigo GJ, Moral VP, Marcos LG, et al. Safety of regular use of long-acting beta agonists as monotherapy or added to inhaled corticosteroids in asthma. A systematic review. Pulm Pharmacol Ther. 2009;22:9-19.http://www.ncbi.nlm.nih.gov/pubmed/19026757?tool=bestpractice.com[98]Cates CJ, Cates MJ. Regular treatment with salmeterol for chronic asthma: serious adverse events. Cochrane Database Syst Rev. 2008;(3):CD006363.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006363.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/18646149?tool=bestpractice.com 尽管最近的数据表明LABA(联合制剂应用)对儿童可能是安全的。[99]Price JF, Radner F, Lenney W, et al. Safety of formoterol in children and adolescents: experience from asthma clinical trials. Arch Dis Child. 2010;95:1047-1053.http://www.ncbi.nlm.nih.gov/pubmed/21030368?tool=bestpractice.com 因此联合吸入治疗被推荐用于儿童哮喘管理之前应作进一步研究。福莫特罗的疗效与其他短效β2-受体激动剂的比较似乎在成人和儿童都具有可比性。[100]Rodrigo GJ, Neffen H, Colodenco FD, et al. Formoterol for acute asthma in the emergency department: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2010;104:247-252.http://www.ncbi.nlm.nih.gov/pubmed/20377114?tool=bestpractice.com[101]Bussamra MH, Stelmach R, Rodrigues JC, et al. A randomized, comparative study of formoterol and terbutaline dry powder inhalers in the treatment of mild to moderate asthma exacerbations in the pediatric acute care setting. Ann Allergy Asthma Immunol. 2009;103:248-253.http://www.ncbi.nlm.nih.gov/pubmed/19788023?tool=bestpractice.com[102]Arun JJ, Lodha R, Kabra SK. Bronchodilatory effect of inhaled budesonide/formoterol and budesonide/salbutamol in acute asthma: a double-blind, randomized controlled trial. BMC Pediatr. 2012;12:21.https://bmcpediatr.biomedcentral.com/articles/10.1186/1471-2431-12-21http://www.ncbi.nlm.nih.gov/pubmed/22394648?tool=bestpractice.com 然而,需进一步研究福莫特罗是否被推荐用于急性发作期,目前,还没有纳入全国性或国际哮喘管理指南。