治疗的主要目标是缓解气流阻塞和预防未来复发。及早治疗是最佳选择。患者教育(包括哮喘行动计划的使用)、识别病情恶化的早期征象、适当强化治疗(即增加短效 β-2 受体激动剂的剂量或添加口服皮质类固醇)、消除任何可能导致病情加重的环境因素,以及严重恶化时迅速与医生沟通,这些都是可以在家庭环境中实施的重要策略。在家中开始治疗可以防止病情恶化加重,并可避免治疗延误。这是否可行取决于患者的能力和经验。
如果不适宜家庭治疗,应立即开始使用短效 β-2 受体激动剂。对于较为严重的加重,还可能需要进行短程全身皮质类固醇治疗和辅助供氧治疗。对支气管舒张剂无反应的患者,应考虑其他治疗。
用药
短效支气管舒张剂可通过定量吸入器 (MDI) 或雾化器给予。定量吸入器 (MDI) 具有便携性强的优点,并且可以快速给药。如果患者不能协调地使用 MDI,则雾化器会有帮助。两者同样有效。现在要求必须使用不破坏臭氧层的氢氟烷吸入器。
对沙丁胺醇间歇性和连续雾化给药的研究得出的结果相互矛盾。治疗加重的一种合理方法是,初始使用连续治疗,然后对住院患者进行间歇性按需治疗。[22]Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2017. [internet publication]http://ginasthma.org/2017-gina-report-global-strategy-for-asthma-management-and-prevention/
对于轻至中度哮喘患者,当前证据不支持将增加吸入性皮质类固醇 (ICS) 的剂量作为自行启动行为计划的一部分用于治疗哮喘发作。[39]Kew KM, Quinn M, Quon BS, Ducharme FM. Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children. Cochrane Database Syst Rev. 2016 Jun 7;(6):CD007524.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007524.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27272563?tool=bestpractice.com
口服皮质类固醇与胃肠外给药一样有效,除非致命性哮喘发作,否则口服给药是首选给药方式。[20]Havemann B, Henderson CA, El-Serag HB. The association between gastroesophageal reflux disease and asthma: a systematic review. Gut. 2007;56:1654-1664.http://gut.bmj.com/content/56/12/1654.longhttp://www.ncbi.nlm.nih.gov/pubmed/17682001?tool=bestpractice.com
启动长效 β 受体激动剂 (long-acting beta agonist, LABA) 与吸入性皮质类固醇联合治疗是安全的,可以显著减少哮喘的住院治疗,但这需要进一步的大规模临床试验支持。[40]Rodrigo GJ, Castro-Rodriguez JA. Safety of long-acting beta agonists for the treatment of asthma: clearing the air. Thorax. 2012;67:342-349.http://www.ncbi.nlm.nih.gov/pubmed/21515554?tool=bestpractice.com[41]Papi A, Mansur AH, Pertseva T, et al. Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations. J Aerosol Med Pulm Drug Deliv. 2016 Aug;29(4):346-61.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965704/http://www.ncbi.nlm.nih.gov/pubmed/27104231?tool=bestpractice.com
在急性哮喘加重的标准诊疗中添加白三烯受体拮抗剂对临床结局未产生有意义的影响,现有数据不支持将其常规用于此状况。[42]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://www.ncbi.nlm.nih.gov/pubmed/22592708?tool=bestpractice.com [
]Is there randomized controlled trial evidence to support the use of oral leukotriene receptor antagonists in addition to usual care in adults with acute asthma?https://cochranelibrary.com/cca/doi/10.1002/cca.66/full显示答案
虽然质子泵抑制剂 (PPI) 治疗可使晨间峰值呼气流速出现小幅但有统计学意义的改善,但这种改善不太可能具有临床意义,而且目前没有足够的证据推荐在哮喘管理中经验性地使用这种疗法。[43]Chan WW, Chiou E, Obstein KL, et al. The efficacy of proton pump inhibitors for the treatment of asthma in adults: a meta-analysis. Arch Intern Med. 2011;171:620-629.http://archinte.jamanetwork.com/article.aspx?articleid=227086http://www.ncbi.nlm.nih.gov/pubmed/21482834?tool=bestpractice.com
轻度发作
反复给予吸入性短效 β-2 受体激动剂是用来快速逆转气流受限的一线治疗。β-2 受体激动剂作用于气道平滑肌,产生支气管舒张作用。应立即开始治疗,并根据患者的反应调整剂量。
由于哮喘加重提示哮喘控制不佳,因此应考虑使用短程口服皮质类固醇治疗。这既可在医院内进行,也可在医院外进行。研究显示全身皮质类固醇治疗能够加速病情急性加重的缓解。[37]Greenberger PA. Clinical aspects of allergic bronchopulmonary aspergillosis. Front Biosci. 2003;8:s119-s127.http://www.ncbi.nlm.nih.gov/pubmed/12456338?tool=bestpractice.com 一项随机对照临床试验对 18 至 45 岁急性哮喘发作患者(峰值呼气流速<理想值的 80%)给予口服地塞米松 2 天和口服泼尼松龙 5 天的治疗效果进行了比较,结果表明,在将患者恢复到正常活动水平和预防复发方面,前者至少与后者同样有效。[44]Kravitz J, Dominici P, Ufberg J, et al. Two days of dexamethasone versus 5 days of prednisone in the treatment of acute asthma: a randomized controlled trial. Ann Emerg Med. 2011;58:200-204.http://www.ncbi.nlm.nih.gov/pubmed/21334098?tool=bestpractice.com
新的证据表明,吸入性皮质类固醇与短效 β-2 受体激动剂联合给药对轻度加重的治疗有益。在没有使用全身皮质类固醇治疗的情况下,可以看到这样的效果。以前未曾使用过吸入性皮质类固醇的患者获益可能性更高。吸入性皮质类固醇与全身皮质类固醇治疗联合使用的作用尚不明确。[45]Rodrigo GJ. Rapid effects of inhaled corticosteroids in acute asthma: an evidence-based evaluation. Chest. 2006;130:1301-1311.http://www.ncbi.nlm.nih.gov/pubmed/17099004?tool=bestpractice.com 对于曾使用吸入皮质类固醇的患者,调整剂量可能会使病情加重有所减轻。 [
]How does increased doses of inhaled corticosteroids compare with stable doses for treating exacerbations of chronic asthma?https://cochranelibrary.com/cca/doi/10.1002/cca.1461/full显示答案
中度至重度加重
首先采用的治疗为重复给予吸入用短效 β-2 受体激动剂,[46]Rodrigo GJ, Nannini LJ. Comparison between nebulized adrenaline and beta2 agonists for the treatment of acute asthma: a meta-analysis of randomized trials. Am J Emerg Med. 2006;24:217-222.http://www.ncbi.nlm.nih.gov/pubmed/16490653?tool=bestpractice.com 早期应用全身皮质类固醇治疗,然后通过鼻导管辅助氧疗以实现动脉血氧饱和度>90%。[38]National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program expert panel report 3: guidelines for the diagnosis and management of asthma. July 2007. http://www.nhlbi.nih.gov (last accessed 14 September 2016).http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm 至少每小时重新评估一次治疗反应。
如果初始治疗后没有改善,应加用二线治疗,例如吸入抗胆碱能药物或静脉使用镁剂。[47]Kirkland SW, Vandenberghe C, Voaklander B, et al. Combined inhaled beta-agonist and anticholinergic agents for emergency management in adults with asthma. Cochrane Database Syst Rev. 2017 Jan 11;1:CD001284.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001284.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28076656?tool=bestpractice.com[48]Kew KM, Kirtchuk L, Michell CI. Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department. Cochrane Database Syst Rev. 20052014 May 28;(25):CD001276CD010909.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010909.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24865567?tool=bestpractice.com[49]Knightly R, Milan SJ, Hughes R, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2017 Nov 28;11:CD003898.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003898.pub6/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29182799?tool=bestpractice.com [
]For people with acute asthma, how does adding inhaled magnesium sulfate to beta-agonists (with or without ipratropium) affect outcomes?https://cochranelibrary.com/cca/doi/10.1002/cca.1954/full显示答案
对于因急性哮喘加重(尤其是重度加重)而到急诊科就诊的成人患者,短效 β-2 受体激动剂加短效抗胆碱能药物的联合吸入治疗可减少住院治疗需要和改善肺功能。但是,联合治疗更可能导致发生不良事件。[47]Kirkland SW, Vandenberghe C, Voaklander B, et al. Combined inhaled beta-agonist and anticholinergic agents for emergency management in adults with asthma. Cochrane Database Syst Rev. 2017 Jan 11;1:CD001284.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001284.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28076656?tool=bestpractice.com
应谨慎仔细地对治疗反应进行监测。如果对治疗缺乏反应或症状加剧(表现为尽管呼吸急促,仍出现发绀、意识混乱或呼吸性酸中毒),则需要紧急收住重症监护病房 (ICU) 和进行机械通气。
将要发生的呼吸衰竭。
对短效支气管舒张剂、皮质类固醇、吸氧、吸入性抗胆碱能药物和镁剂治疗反应不佳的患者,或有致命性哮喘征象(即,尽管呼吸急促,但仍出现发绀和呼吸性酸中毒)的患者,应收入重症监护病房 (ICU),并考虑进行诸如插管和机械通气等治疗。
同时给予支气管舒张剂与氦氧混合气 (heliox) 存在争议,但对某些呼吸衰竭患者可能有帮助。[22]Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2017. [internet publication]http://ginasthma.org/2017-gina-report-global-strategy-for-asthma-management-and-prevention/[50]Colebourn CL, Barber V, Young JD. Use of helium-oxygen mixture in adult patients presenting with exacerbations of asthma and chronic obstructive pulmonary disease: a systematic review. Anaesthesia. 2007;62:34-42.http://www.ncbi.nlm.nih.gov/pubmed/17156225?tool=bestpractice.com[51]Rodrigo G, Pollack C, Rodrigo C, et al. Heliox for nonintubated acute asthma patients. Cochrane Database Syst Rev. 2006;(4):CD002884.http://www.ncbi.nlm.nih.gov/pubmed/17054154?tool=bestpractice.com
气管插管的动画演示
球囊面罩通气的动画演示
发热或浓稠脓性痰患者
细菌感染不常导致哮喘加重;因此,抗生素一般用于给发热和浓稠脓性痰患者以及疑似肺炎或细菌性鼻窦炎患者。[38]National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program expert panel report 3: guidelines for the diagnosis and management of asthma. July 2007. http://www.nhlbi.nih.gov (last accessed 14 September 2016).http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm 抗生素的选择和给药应符合当地医疗机构规程。
后续治疗
指南推荐哮喘严重程度和控制情况可被看作是一个阶梯。在这个阶梯中,基于疾病的严重程度和控制情况,可加强或减弱哮喘药物治疗。[22]Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2017. [internet publication]http://ginasthma.org/2017-gina-report-global-strategy-for-asthma-management-and-prevention/[55]Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343-373.http://www.thoracic.org/statements/resources/allergy-asthma/Severe-Asthma-CPG-ERJ.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/24337046?tool=bestpractice.com 阶梯性治疗方法旨在辅助,而不是代替需要满足患者个体化需求的临床决策。患者可从阶梯的任何一步开始进行治疗,如果需要的话可以增加(加强)药物。通常短效 β 激动剂 (SABA) 使用增加或一周内因缓解症状使用的天数>2 天(不是预防运动诱发的支气管痉挛)通常表示哮喘控制不佳,需要加强治疗。应定期评估患者的哮喘控制情况,目的是如果疾病已经得到至少 3 个月的较好控制,就可以进行降阶。
与临床症状、肺量测定/峰流量和哮喘指南相比,没有足够证据支持推荐普遍使用痰嗜酸性粒细胞或呼出气一氧化氮 (FeNO) 水平来调整哮喘治疗。不过,一些证据表明这种方法可能会减少哮喘发作的频率。[22]Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2017. [internet publication]http://ginasthma.org/2017-gina-report-global-strategy-for-asthma-management-and-prevention/[56]Petsky HL, Li A, Chang AB. Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults. Cochrane Database Syst Rev. 2017 Aug 24;8:CD005603.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005603.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28837221?tool=bestpractice.com[57]Petsky HL, Kew KM, Turner C, Chang AB. Exhaled nitric oxide levels to guide treatment for adults with asthma. Cochrane Database Syst Rev. 2016 Sep 1;9:CD011440.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011440.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27580628?tool=bestpractice.com