儿童哮喘

病毒感染所致哮喘急性发作依然是儿童哮喘的一个突出特点。控制不佳或暴露于已知的化学物质可能增加哮喘急性发作的可能性。在儿童慢性哮喘中，使用长效 β-2 受体激动剂作为单药治疗，会增加哮喘急性发作率。证据 A导致严重和致命的哮喘发作增加，使患者对短效β受体激动剂快速耐受：对于轻度至中度儿童哮喘患者，长效β受体激动剂单药治疗的效果不如吸入用皮质类固醇。有充分的证据表明，儿童使用长效 β 受体激动剂可增加急性发作。[257]Walters EH, Gibson PG, Lasserson TJ, et al. Long-acting beta2-agonists for chronic asthma in adults and children where background therapy contains varied or no inhaled corticosteroid. Cochrane Database Syst Rev. 2007;(1):CD001385.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001385.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17253458?tool=bestpractice.com[133]Verberne AA, Frost C, Duiverman EJ, et al; The Dutch Asthma Study Group. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med. 1998;158:213-219.http://www.atsjournals.org/doi/full/10.1164/ajrccm.158.1.9706048#.U_dH2_ldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/9655732?tool=bestpractice.com[258]Ducharme FM, Ni Chroinin M, Greenstone I, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst Rev. 2010;(5):CD005535.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005535.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20464739?tool=bestpractice.com[259]Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children. Cochrane Database Syst Rev. 2009;(4):CD005307.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005307.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19821344?tool=bestpractice.com[260]Verberne AA, Frost C, Roorda RJ, et al; The Dutch Paediatric Asthma Study Group. One year treatment with salmeterol compared with beclomethasone in children with asthma. Am J Respir Crit Care Med. 1997;156:688-695.http://www.atsjournals.org/doi/full/10.1164/ajrccm.156.3.9611067#.U_dC5vldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/9309980?tool=bestpractice.com[261]Bisgaard H. Effect of long-acting beta2 agonists on exacerbation rates of asthma in children. Pediatr Pulmonol. 2003;36:391-398.http://www.ncbi.nlm.nih.gov/pubmed/14520721?tool=bestpractice.com 在系统评价中已经报告严重和危及生命的哮喘急性发作和哮喘相关死亡的风险增加，但还未经证实，[262]Cates CJ, Jaeschke R, Schmidt S, et al. Regular treatment with salmeterol and inhaled steroids for chronic asthma: serious adverse events. Cochrane Database Syst Rev. 2013;(3):CD006922.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006922.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23543548?tool=bestpractice.com 黑人和皮质类固醇初用患者的风险尤其高。[263]Salpeter SR, Buckley NS, Ormiston TM, et al. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006;144:904-912.http://www.ncbi.nlm.nih.gov/pubmed/16754916?tool=bestpractice.com[264]US Food and Drug Administration (FDA). Division director memorandum: overview of the FDA background materials prepared for the meeting to discuss the implications of the available data related to the safety of long-acting beta-agonist bronchodilators. June 2005. http://www.fda.gov (last accessed 18 August 2016).http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4148b1_03_01-fda-div-dir-memo.pdf 目前对吸入用皮质类固醇剂量超过多少时开始使用长效 β 受体激动剂还不确定。[133]Verberne AA, Frost C, Duiverman EJ, et al; The Dutch Asthma Study Group. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med. 1998;158:213-219.http://www.atsjournals.org/doi/full/10.1164/ajrccm.158.1.9706048#.U_dH2_ldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/9655732?tool=bestpractice.com[258]Ducharme FM, Ni Chroinin M, Greenstone I, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst Rev. 2010;(5):CD005535.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005535.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20464739?tool=bestpractice.com 规律使用长效 β 受体激动剂治疗可能诱发患者对以后使用短效 β 受体激动剂快速耐受和不敏感。系统评价或者受试者＞200名的随机对照临床试验（RCT）。

Acute asthma exacerbation in children

慢性炎症可能会导致气道壁的结构性改变（亦气道重塑）和固定性气道阻塞。虽然在有症状的婴儿患者中未发现该并发症，但气道重塑这种改变可能在很早就发生了。[265]Saglani S, Malmstrom K, Pelkonen AS, et al. Airway remodeling and inflammation in symptomatic infants with reversible airflow obstruction. Am J Respir Crit Care Med. 2005;171:722-727.http://www.atsjournals.org/doi/full/10.1164/rccm.200410-1404OC#.U_dAifldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/15657459?tool=bestpractice.com 在反复喘息的学龄前儿童和 6 岁及以上的学龄哮喘儿童中，已经发现上皮网状基底膜加厚。[25]Payne DN, Rogers AV, Adelroth E, et al. Early thickening of the reticular basement membrane in children with difficult asthma. Am J Respir Crit Care Med. 2003;167:78-82.http://www.atsjournals.org/doi/full/10.1164/rccm.200205-414OC#.U_c9PvldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/12502479?tool=bestpractice.com[266]Saglani S, Payne DN, Zhu J, et al. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am J Respir Crit Care Med. 2007;176:858-864.http://www.atsjournals.org/doi/full/10.1164/rccm.200702-212OC#.U_dAp_ldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/17702968?tool=bestpractice.com

哮喘与乳牙和恒牙龋齿增加有关。然而目前仍未证实这种因果关系。[267]Alavaikko S, Jaakkola MS, Tjaderhane L, et al. Asthma and caries: a systematic review and meta-analysis. Am J Epidemiol. 2011;174:631-641.http://aje.oxfordjournals.org/content/174/6/631.longhttp://www.ncbi.nlm.nih.gov/pubmed/21828369?tool=bestpractice.com

严重的中叶支气管阻塞除了导致哮喘的病理生理改变外，还导致肺不张和实变（原因为肺门淋巴结增大）。细菌感染可能是一种导致其发生的因素。

吸入皮质类固醇的局部不良反应包括口腔念珠菌病、咽炎和声音嘶哑，但是这通常不会是主要问题，通过使用储雾瓶限制咽部药物沉积能最大程度降低这些风险。新型的吸入性皮质类固醇（例如莫米松和环索奈徳）具有较少的不良反应。

Oral candidiasis

皮质类固醇治疗（尤其是较高剂量使用时）所引起的全身性不良反应包括对丘脑-垂体-肾上腺轴的抑制和对线形生长的影响。证据 A线性生长影响和肾上腺抑制的效果：有高质量的证据表明，吸入性皮质类固醇抑制轻度至中度持续性哮喘和使用高剂量吸入性皮质类固醇的儿童的生长。[105]The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med. 2000;343:1054-1063.http://www.nejm.org/doi/full/10.1056/NEJM200010123431501#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/11027739?tool=bestpractice.com[106]Sharek PJ, Bergman DA, Ducharme FM. Beclomethasone for asthma in children: effects on linear growth. Cochrane Database Syst Rev. 1999;(3):CD001282.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001282/fullhttp://www.ncbi.nlm.nih.gov/pubmed/10796632?tool=bestpractice.com[107]Guilbert TW, Mauger DT, Allen DB, et al; Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Growth of preschool children at high risk for asthma 2 years after discontinuation of fluticasone. J Allergy Clin Immunol. 2011;128:956-963.e7.http://www.jacionline.org/article/S0091-6749%2811%2900999-7/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21820163?tool=bestpractice.com 停药后可能出现赶上生长现象，但不是所有儿童都出现此现象。[108]Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. 2000;343:1064-1069.http://www.nejm.org/doi/full/10.1056/NEJM200010123431502#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/11027740?tool=bestpractice.com[109]Kelly HW, Sternberg AL, Lescher R, et al; CAMP Research Group. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367:904-912.http://www.nejm.org/doi/full/10.1056/NEJMoa1203229#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/22938716?tool=bestpractice.com 年幼儿童和那些使用较高剂量吸入性皮质类固醇的儿童的风险更高。[107]Guilbert TW, Mauger DT, Allen DB, et al; Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Growth of preschool children at high risk for asthma 2 years after discontinuation of fluticasone. J Allergy Clin Immunol. 2011;128:956-963.e7.http://www.jacionline.org/article/S0091-6749%2811%2900999-7/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/21820163?tool=bestpractice.com 男孩患者（但不是女孩）会出现骨矿物质的沉积减少，但随骨质疏松的风险不会增加。[110]Kelly HW, Van Natta ML, Covar RA, et al. CAMP Research Group. The effect of long-term corticosteroid use on bone mineral density in children: a prospective longitudinal assessment in the childhood Asthma Management Program (CAMP) study. Pediatrics. 2008;122:e53-e61.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928657/http://www.ncbi.nlm.nih.gov/pubmed/18595975?tool=bestpractice.com[111]Adams N, Lasserson TJ, Cates CJ, et al. Fluticasone versus beclomethasone or budesonide for chronic asthma in adults and children. Cochrane Database Syst Rev. 2007;(4):CD002310.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002310.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17943772?tool=bestpractice.com 已经证明使用 800-3200 μg 的布地奈德患者会出现肾上腺抑制，在出现肾上腺危象病例中，经常与使用高剂量的氟替卡松有关。[112]Adams N, Bestall J, Jones PW. Budesonide at different doses for chronic asthma. Cochrane Database Syst Rev. 2001;(4):CD003271.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003271/fullhttp://www.ncbi.nlm.nih.gov/pubmed/11687182?tool=bestpractice.com[106]Sharek PJ, Bergman DA, Ducharme FM. Beclomethasone for asthma in children: effects on linear growth. Cochrane Database Syst Rev. 1999;(3):CD001282.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001282/fullhttp://www.ncbi.nlm.nih.gov/pubmed/10796632?tool=bestpractice.com[113]Todd GR, Acerini CL, Ross-Russell R, et al. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child. 2002 Dec;87(6):457-61.http://adc.bmj.com/content/87/6/457.longhttp://www.ncbi.nlm.nih.gov/pubmed/12456538?tool=bestpractice.com 环索奈德（与其他吸入用皮质类固醇相比）一直被认为不会对患者的身高和肾上腺功能产生有害影响，[114]Skoner DP, Maspero J, Banerji D, et al. Assessment of the long-term safety of inhaled ciclesonide on growth in children with asthma. Pediatrics. 2008 Jan;121(1):e1-14.http://www.ncbi.nlm.nih.gov/pubmed/18070931?tool=bestpractice.com 但一项 meta 分析显示结论相反。[115]Kramer S, Rottier BL, Scholten RJ, et al. Ciclesonide versus other inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2013;(2):CD010352.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010352/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23450613?tool=bestpractice.com 曾有患者出现后囊白内障的相关报道，但一直没有发现长期使用低至中等剂量吸入性皮质类固醇是患者罹患白内障的一个危险因素。[101]Raissy HH, Sternberg AL, Williams P, et al. Risk of cataracts in the Childhood Asthma Management Program Cohort. J Allergy Clin Immunol. 2010;126:389-392.e4.http://www.jacionline.org/article/S0091-6749%2810%2900741-4/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/20621348?tool=bestpractice.com系统评价或者受试者＞200名的随机对照临床试验（RCT）。 目前只批准将新型吸入性皮质类固醇（例如莫米松和环索奈徳）用于 12 岁及以上的儿童，此类药物被认为拥有较少的副作用。近期更多证据已经显示，与布地奈德和氟替卡松相比，环索奈徳的益处未被证实或被反驳。[115]Kramer S, Rottier BL, Scholten RJ, et al. Ciclesonide versus other inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2013;(2):CD010352.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010352/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23450613?tool=bestpractice.com [ ]How does ciclesonide compare with other inhaled corticosteroids in children and adolescents with chronic asthma?https://cochranelibrary.com/cca/doi/10.1002/cca.250/full显示答案

Adrenal suppression