2019-07-23GINA不再推荐单用短效支气管扩张剂治疗成人/青少年哮喘。取而代之的是症状驱动的（对于轻度哮喘患者）或每日常规的使用含糖皮质激素的吸入制剂，以减少严重发作的风险。 1、滥用SABA：风险巨大 2019年4月，GINA发布的新哮喘诊治指南堪称近30年来哮喘管理最大的变革。该指南基于十多年来GINA的工作，特别提出了长期以来单用SABA治疗哮喘的风险和结局。 早在1980-1990年代就有国际流行病学研究聚焦于SABA的使用风险[1]，病例对照显示滥用SABA与哮喘死亡呈正相关[2,3]，同时，许多研究提示常规使用糖皮质激素吸入制剂（ICS），可显著降低哮喘相关的住院率和死亡率[6,7]。 然而，由于口服糖皮质激素的副作用使医生们多有顾虑，难以接受每日常规使用ICS[1]。当时的指南中，单用SABA作为轻症哮喘的初始治疗，其地位仍难以动摇，ICS仅被推荐用于症状经常发作的患者。 2007 年，GINA开始致力于探讨和回顾轻症哮喘的治疗选择，重点在于对比单用SABA治疗是否减少了哮喘相关发作和死亡的风险。多项研究显示，即便是短期单用SABA也会发生很多不良反应[10,11]。健康管理数据研究显示：使用ICS少于SABA的患者其住院和急诊就诊风险较高[12]，而增加ICS的使用与住院和死亡的减少相关[13,14]。 但在实际生活中，ICS使用依从性很差，其使用量仅为处方量的25-35%[15]，这导致许多患者仍处于单用SABA治疗的风险中[16]。依从性差的原因是多方面的，包括其感知差异（特别是症状很少的患者），副作用及费用等[17,18]。 2、布地奈德+福莫特罗：基于SYGMA研究的新方案 在2014年，GINA就建议单用SABA治疗应仅限于每月哮喘症状少于2次或者没有急性发作风险的患者。 但在实际中，很多症状不频繁的哮喘患者不愿意每日使用ICS，结果还是又回归了单用SABA治疗。 这一鸿沟直到2018年按需使用布地奈德+福莫特罗用于治疗轻症哮喘的研究即SYGMA研究发表后才得以填补[24,25]。 2019年，GINA回顾了一系列证据，均可证实单用SABA的不良结局，建议成人/青少年哮喘患者不应再推荐单用SABA治疗，取而代之的是症状驱动的（对于轻度哮喘患者）或每日常规的含ICS的治疗方案，以减少严重发作的风险。 相关的推荐选项参见下图表：
对step2（每月症状发作2次以上或有急性发作风险的患者），以往的推荐是每日低剂量ICS治疗。但基于SGYMA研究，GINA提出另一个治疗方案选择：按需低剂量ICS+福莫特罗的方案。 该方案的主要优势有： 1）比单用SABA可减少约2/3的哮喘严重急性发作[25]， 2）在减少严重发作方面，其疗效不劣于每日常规ICS维持治疗，且可以减少近1/4的总激素负荷。 其他获益还包括：改善FEV1，改善症状，增加无症状的天数等[24,25]。 3、全面推广，任重道远 尽管GINA 2019对轻度哮喘患者的药物推荐做了全面的变革，但按需ICS/福莫特罗的推广使用还面临一系列问题，包括在不同国家的落地和药物经济学的分析等。 对于轻度哮喘患者来说，哮喘发作并不频繁：SYGMA1研究中使用按需SABA治疗组的患者，仅12%在过去一年中经历过一次严重的急性发作[25]。 但哮喘不同于其他慢性疾病，许多患者被表面上轻微的哮喘症状所迷惑，但稍不注意，可能遭遇哮喘突然发作造成严重后果：30-37%成人有急性发作，16%的患者经历过致命的急性发作，15-20%死于哮喘的患者在发作前三个月内的仅有每周不到一次的症状频率[33]。GINA推荐的基础治疗原则与针对每个患者的个体化治疗并不矛盾。 GINA致力于为提高哮喘治疗提供循证依据，当然各国都需要根据本地情况做出最佳选择。GINA新指南落地道路曲折，但前途光明。布地奈德+福莫特罗已被WHO列为基本药物之一。虽然各国国情不同，实际推广应用依然任重道远，但是GINA 2019已为轻度哮喘患者治疗开启了全新的篇章！ 参考文献 1 Crompton G. A brief history of inhaled asthma therapy over the last fifty years. Prim Care Respir J 2006; 15:326–331. 2 Suissa S, Ernst P, Boivin JF, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med 1994; 149: 604–610. 3 Abramson MJ, Bailey MJ, Couper FJ, et al. Are asthma medications and management related to deaths from asthma? Am J Respir Crit Care Med 2001; 163: 12–18. 4 Drazen JM, Israel E, Boushey HA, et al. Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma Clinical Research Network. N Engl J Med 1996; 335: 841–847. 5 Dennis SM, Sharp SJ, Vickers MR, et al. Regular inhaled salbutamol and asthma control: the TRUST randomized trial. Therapy Working Group of the National Asthma Task Force and the MRC General Practice Research Framework. Lancet 2000; 355: 1675–1679. 6 Suissa S, Ernst P, Benayoun S, et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000; 343: 332–336. 7 Suissa S, Ernst P, Kezouh A. Regular use of inhaled corticosteroids and the long term prevention of hospitalization for asthma. Thorax 2002; 57: 880–884. 8 O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med 2001; 164: 1392–1397. 9 Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 2003; 361: 1071–1076. 10 Taylor DR, Sears MR, Cockcroft DW. The beta-agonist controversy. Med Clin North Am 1996; 80: 719–748. 11 Hancox RJ. Concluding remarks: can we explain the association of beta-agonists with asthma mortality? A hypothesis. Clin Rev Allergy Immunol 2006; 31: 279–288. 12 Anis AH, Lynd LD, Wang XH, et al. Double trouble: impact of inappropriate use of asthma medication on the use of health care resources. CMAJ 2001; 164: 625–631. 13 Haahtela T, Tuomisto LE, Pietinalho A, et al. A 10 year asthma programme in Finland: major change for the better. Thorax 2006; 61: 663–670. 14 Souza-Machado C, Souza-Machado A, Franco R, et al. Rapid reduction in hospitalisations after an intervention to manage severe asthma. Eur Respir J 2010; 35: 515–521. 15 Boulet L-P, Vervloet D, Magar Y, et al. Adherence: the goal to control asthma. Clin Chest Med 2012; 33: 405–417. 16 Williams LK, Peterson EL, Wells K, et al. Quantifying the proportion of severe asthma exacerbations attributable to inhaled corticosteroid nonadherence. J Allergy Clin Immunol 2011; 128: 1185–1191. 17 Horne R. Compliance, adherence, and concordance: implications for asthma treatment. Chest 2006; 130: 65S–72S. 18 Barnes CB, Ulrik CS. Asthma and adherence to inhaled corticosteroids: current status and future perspectives. Respir Care 2015; 60: 455–468. 19 O’Byrne PM, Jenkins C, Bateman ED. The paradoxes of asthma management: time for a new approach? Eur Respir J 2017; 50: 1701103. 20 Beasley R, Bird G, Harper J, et al. The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity. Eur Respir J 2018; 52: 1800694. 21 Cates CJ, Lasserson TJ. Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev 2009: CD007313. 22 Papi A, Canonica GW, Maestrelli P, et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N Engl J Med 2007; 356: 2040–2052. 23 Royal College of Physicians. Why Asthma Still Kills: The National Review of Asthma Deaths (NRAD) Confidential Enquiry Report. 2014. www.rcplondon.ac.uk/file/868/download?token=3wikiuFg Last accessed: May 2019. 24 Bateman ED, Reddel HK, O’Byrne PM, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med 2018; 378: 1877–1887. 25 O’Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med 2018; 378: 1865–1876 26 Reddel HK, Busse WW, Pedersen S, et al. Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency: a post-hoc efficacy analysis of the START study. Lancet 2017; 389: 157–166. 27 Lazarinis N, Jørgensen L, Ekström T, et al. Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction. Thorax 2014; 69: 130–136. 28 Papi A, Corradi M, Pigeon-Francisco C, et al. Beclometasone–formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial. Lancet Respir Med 2013; 1: 23–31. 29 Martinez FD, Chinchilli VM, Morgan WJ, et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet 2011; 377: 650–657. 30 Calhoun WJ, Ameredes BT, King TS, et al. Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial. JAMA 2012; 308: 987–997. 31 Chauhan BF, Ducharme FM. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev 2012; 5: CD002314. 32 Sobieraj DM, Weeda ER, Nguyen E, et al. Association of inhaled corticosteroids and long-acting beta-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: A systematic review and meta-analysis. JAMA 2018; 319: 1485–1496. 33 Dusser D, Montani D, Chanez P, et al. Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations. Allergy 2007; 62: 591–604. 34 Beasley R, Holliday M, Reddel HK, et al. Controlled trial of budesonide-formoterol as needed for mild asthma. N Engl J Med 2019; 380: 2020–2030. 35 Fingleton J, Hardy J, Baggott C, et al. Description of the protocol for the PRACTICAL study: a randomized controlled trial of the efficacy and safety of ICS/LABA reliever therapy in asthma. BMJ Open Respir Res 2017; 4:e000217. 本篇原文: Reddel HK, FitzGerald JM, Bateman ED, et al: GINA 2019: a fundamental change in asthma management. Eur Respir J 2019; 53: 1901046. 翻译稿来自: 阿斯利康呼吸医学部哮喘组 本文首发： 南山呼吸（ID：nanshanhuxi） |
|
|
