在儿童哮喘的诊断过程中,应考虑儿童所面临的全部危险因素,并谨慎仔细地考虑其他可能的疾病。一般来说,对存在多种危险因素的高风险儿童应给予经验性治疗。对于中等和低风险的儿童以及对治疗反应差的高危儿童需要进行进一步的检查。根据患儿有出现可逆性气道阻塞病史,并对支气管扩张剂有反应,并且吸入支气管扩张剂或皮质类固醇后症状改善,则可确诊哮喘。
没有可表示哮喘风险的绝对明确标志物。对于 3 岁以前频繁喘息发作的儿童,结合哮喘多种危险因素建立的综合指数一直被用来构建持续哮喘风险指数,该指数一直被逐步修订。[55]Castro-Rodríguez JA, Holberg CJ, Wright AL, et al. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med. 2000;162:1403-1406.http://www.atsjournals.org/doi/full/10.1164/ajrccm.162.4.9912111#.U_c9BfldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/11029352?tool=bestpractice.com[56]Guilbert TW, Morgan WJ, Zeiger RS, et al. Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. J Allergy Clin Immunol. 2004;114:1282-1287.http://www.ncbi.nlm.nih.gov/pubmed/15577824?tool=bestpractice.com 该指数的主要价值在于其较高的阴性预测值,但遭遇越来越多的质疑,有些作者指出,哮喘预测指数为阴性不一定代表未来哮喘的风险下降。[57]Chang TS, Lemanske RF Jr, Guilbert TW, et al. Evaluation of the modified asthma predictive index in high-risk preschool children. J Allergy Clin Immunol Pract. 2013 Mar;1(2):152-6.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811153/http://www.ncbi.nlm.nih.gov/pubmed/24187656?tool=bestpractice.com
反复喘息的症状,尤其是在晚上或清晨的干咳,由于温度变化,病毒感染,运动,情绪等诱发因素出现的呼吸短促均是哮喘的特征。父母可能会将儿童出现的各种呼吸道杂音误认为喘息音,因此应该评估父母对喘息音的认知水平。[58]Cane RS, Ranganathan SC, McKenzie SA. What do parents of wheezy children understand by "wheeze"? Arch Dis Child. 2000;82:327-332.http://adc.bmj.com/content/82/4/327.longhttp://www.ncbi.nlm.nih.gov/pubmed/10735844?tool=bestpractice.com 其它特应性疾病的特点,例如患儿或其一级亲属中患有湿疹、特应性皮炎和过敏性鼻炎等可以支持儿童哮喘的诊断。
体格检查
许多儿童在未发作时无症状。根据患儿症状模式,检查时出现的一些体征包括胸壁听诊可闻及广泛多音调的喘鸣音,出现呼吸急促,呼气受限或呼吸肌收缩,依靠辅助肌呼吸等呼吸窘迫体征。对难控持续性哮喘患者,可出现反应气体滞留的临床过度通气和胸壁畸形(哈里逊氏沟)。检查时特应性疾病的特征较为明显。
肺量测定法
对 β-2 受体激动剂支气管扩张剂有反应,定义为 FEV1 或 FVC 增高 12% 或以上,可为哮喘诊断提供支持。[43]Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. Oct 2014. http://www.sign.ac.uk (last accessed 18 August 2016).http://sign.ac.uk/pdf/SIGN141.pdf
无论采用直接(乙酰甲胆碱、组胺)或间接(运动、甘露醇、高渗盐水)激发方法,都可使患者出现气道或支气管高反应性,但很少进行激发实验。对可以重复进行肺量测定法和经初步肺功能测定后还不能明确诊断的儿童可以考虑采用该方法。获得可重复、可再现的肺量测定结果的儿童的能力取决于其年龄。不推荐使用峰流速的监测来替代肺量测定。对于少部分对哮喘症状认识不清的患儿,峰值呼气流速的监测在持续性哮喘管理中发挥了一定的作用。然而,以峰流速为基础的哮喘控制行动计划 (asthma action plans, AAPs) 并不优于以症状为基础的哮喘控制行动计划 (AAPs)。[59]Kessler KR. Relationship between the use of asthma action plans and asthma exacerbations in children with asthma: a systematic review. J Asthma Allergy Educators. 2011;2:11-21.
峰流量检测动画演示
实验室和其他检查
没有专门的实验室检查可以明确的诊断哮喘。然而一些检查有助于对哮喘和其他疾病进行鉴别诊断。哮喘患者中全血细胞计数可显示嗜酸粒细胞比例(4% 或更高)。在异物误吸,支气管或气管软化可能被疑诊为哮喘时,支气管镜检查意义重大。如果患者出现单侧喘息或吸入性喘鸣时,也可以怀疑患者是否患有这些疾病。支气管肺泡灌洗显示的气道嗜酸性粒细胞增多 (>1.2%) 或痰中嗜酸性粒细胞增多 (>3%) 可支持但不能确诊哮喘。[63]Zimmerman B, Silverman FS, Tarlo SM, et al. Induced sputum: comparison of postinfectious cough with allergic asthma in children. J Allergy Clin Immunol. 2000;105:495-499.http://www.ncbi.nlm.nih.gov/pubmed/10719299?tool=bestpractice.com[64]Lex C, Ferreira F, Zacharasiewicz A, et al. Airway eosinophilia in children with severe asthma: predictive values of noninvasive tests. Am J Respir Crit Care Med. 2006;174:1286-1291.http://www.ncbi.nlm.nih.gov/pubmed/16973985?tool=bestpractice.com 大多数内科医生会安排患者进行胸部 X 线检查,可以显示过度通气的证据以及支气管扩张或内脏转位等其他鉴别疾病。当鉴别心脏与肺部疾病鉴别时也可以进行胸部 X 线检查。当进行哮喘与囊性肺纤维化鉴别诊断时可以考虑汗液检查。当确认细菌感染时进行痰培养非常有效。评估患者是否患有 Kartagener 综合征时(伴随罕见的胃转位的内脏转位)应进行电子显微镜下纤毛检查。皮肤点刺试验可用于确诊特应性疾病的存在。选择何种测试在很大程度上取决于医生的判断。
药物反应
如果使用吸入 β-2 受体激动剂或皮质类固醇后,无论是短期口服皮质类固醇(1-2 mg/kg/日,持续 3 日)[65]Chang AB, Clark R, Sloots TP, et al. A 5- versus 3-day course of oral corticosteroids for children with asthma exacerbations who are not hospitalised: a randomised controlled trial. Med J Aust. 2008;189:306-310.http://www.ncbi.nlm.nih.gov/pubmed/8803532?tool=bestpractice.com[66]Aljebab F, Choonara I, Conroy S. Systematic review of the toxicity of short-course oral corticosteroids in children. Arch Dis Child. 2016;101:365-370.http://www.ncbi.nlm.nih.gov/pubmed/26768830?tool=bestpractice.com 还是较长时间的低剂量吸入皮质类固醇治疗试验(尽管无证据基础,但持续治疗 1 个月),患者症状得以改善,则支持哮喘诊断。随机对照实验显示通常在两周内规律性地给予患者吸入皮质类固醇,患者症状得到改善,由此延长治疗到一个月是合理的。[67]Chang AB, Glomb WB. Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(suppl 1):260S-283S.http://journal.publications.chestnet.org/article.aspx?articleid=1084264&issueno=1_supplhttp://www.ncbi.nlm.nih.gov/pubmed/16428719?tool=bestpractice.com 相反地,如果患者对此治疗没有反应,则证明患者患有其他疾病。进一步评价治疗效果的客观方法包括肺活量改善。
其他肺功能测试
已有多种其他肺功能测试(分段呼出一氧化氮、用力或脉冲振荡法)。虽然有一些人建议使用它们作为诊断测试,缺乏支持它们作为常规诊断的证据。[68]Prasad A, Langford B, Stradling JR, et al. Exhaled nitric oxide as a screening tool for asthma in school children. Respir Med. 2006;100:167-173.http://www.ncbi.nlm.nih.gov/pubmed/15885997?tool=bestpractice.com
FeNo 水平增高可以支持哮喘的诊断,但不能作为确诊指标。[69]Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184:602-615.http://www.atsjournals.org/doi/full/10.1164/rccm.9120-11ST#.U_c0XfldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/21885636?tool=bestpractice.com[70]British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. A national clinical guideline. September 2016 [internet publication].https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-2016/持续升高的 FeNO 增加发生喘鸣、医生诊断的哮喘和学龄期前开始应用吸入皮质类固醇的可能性。[71]Global Initiative for Asthma. Global strategy for asthma management and prevention (2018 update). March 2018 [internet publication].http://ginasthma.org/2018-gina-report-global-strategy-for-asthma-management-and-prevention/ 然而,在各指南之间,对于 FeNO 检测的作用有很大分歧。临床医生主导的指南[70]British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. A national clinical guideline. September 2016 [internet publication].https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-2016/[71]Global Initiative for Asthma. Global strategy for asthma management and prevention (2018 update). March 2018 [internet publication].http://ginasthma.org/2018-gina-report-global-strategy-for-asthma-management-and-prevention/[72]Lougheed MD, Lemiere C, Ducharme FM, et al. Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Can Respir J. 2012 Mar-Apr;19(2):127-64. Erratum in: Can Respir J. 2013 May-Jun;20(3):185.https://cts-sct.ca/wp-content/uploads/2018/01/ASTHMA-GUIDELINE-APRIL-2012.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/22536582?tool=bestpractice.com赞同美国指南, [69]Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184:602-615.http://www.atsjournals.org/doi/full/10.1164/rccm.9120-11ST#.U_c0XfldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/21885636?tool=bestpractice.com即,对于哮喘的诊断,FeNO 的检测水平是辅助性的,但不是诊断性的。这与随后的回顾研究相悖,后者支持使用 FeNO 诊断儿童哮喘。[73]National Institute for Health and Care Excellence. Asthma: diagnosis, monitoring and chronic asthma management (NICE guideline NG80). November 2017 [internet publication].https://www.nice.org.uk/guidance/ng80
激素治疗儿童气道嗜酸粒细胞聚集会使呼出气一氧化氮值增加。然而,FeNO水平受多种因素影响,例如种族、吸烟和特应性。 FeNO水平高,并不能确诊患者患有哮喘,特别是当患者有特异性疾病时;
FeNO 的正常值上限(尤其当并存特应性时)还未确定,不同指南对 12 岁以上儿童有不同的推荐诊断值。[73]National Institute for Health and Care Excellence. Asthma: diagnosis, monitoring and chronic asthma management (NICE guideline NG80). November 2017 [internet publication].https://www.nice.org.uk/guidance/ng80[74]Scott M, Raza A, Karmaus W, et al. Influence of atopy and asthma on exhaled nitric oxide in an unselected birth cohort study. Thorax. 2010;65:258-262.http://thorax.bmj.com/content/65/3/258.longhttp://www.ncbi.nlm.nih.gov/pubmed/20335297?tool=bestpractice.com[75]Jackson DJ, Virnig CM, Gangnon RE, et al. Fractional exhaled nitric oxide measurements are most closely associated with allergic sensitization in school-age children. J Allergy Clin Immunol. 2009;124:949-953.http://www.jacionline.org/article/S0091-6749%2809%2901094-X/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/19748661?tool=bestpractice.com 虽然一项立场声明[76]Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184:602-615.http://www.atsjournals.org/doi/full/10.1164/rccm.9120-11ST#.U_c0XfldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/21885636?tool=bestpractice.com 推荐在哮喘患者中使用 FeNO,但无高水平证据。当前数据表明,监测 FeNO 水平[77]Petsky HL, Cates CJ, Lasserson TJ, et al. A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils). Thorax. 2012;67:199-208.http://www.ncbi.nlm.nih.gov/pubmed/20937641?tool=bestpractice.com[78]Gomersal T, Harnan S, Essat M, et al. A systematic review of fractional exhaled nitric oxide in the routine management of childhood asthma. Pediatr Pulmonol. 2016;51:316-328.http://www.ncbi.nlm.nih.gov/pubmed/26829581?tool=bestpractice.com 或气道高反应性与参考临床症状进行监测相比,对于临床结局没有或仅有很少的额外获益。然而,后者可能与过敏性哮喘患儿使用支气管舒张剂前的 FEV1 改善有关,亦有证据支持其常规应用。[79]Nuijsink MH. Long-term asthma treatment guided by airway hyperresponsiveness in children: A randomised controlled trial. Eur Respir J. 2007;30:457-466.http://www.ncbi.nlm.nih.gov/pubmed/17537770?tool=bestpractice.com 尽管还有其他适用于学龄前儿童的肺功能检测(例如强迫振荡技术),[80]Galant SP, Komarow HD, Shin HW, et al. The case for impulse oscillometry in the management of asthma in children and adults. Ann Allergy Asthma Immunol. 2017 Jun;118(6):664-671.http://www.ncbi.nlm.nih.gov/pubmed/28583260?tool=bestpractice.com 但还未有一个检测表现出令人信服的效用,故目前的主要指南中还未提及这些检测。[70]British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. A national clinical guideline. September 2016 [internet publication].https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-2016/[71]Global Initiative for Asthma. Global strategy for asthma management and prevention (2018 update). March 2018 [internet publication].http://ginasthma.org/2018-gina-report-global-strategy-for-asthma-management-and-prevention/[72]Lougheed MD, Lemiere C, Ducharme FM, et al. Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Can Respir J. 2012 Mar-Apr;19(2):127-64. Erratum in: Can Respir J. 2013 May-Jun;20(3):185.https://cts-sct.ca/wp-content/uploads/2018/01/ASTHMA-GUIDELINE-APRIL-2012.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/22536582?tool=bestpractice.com