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1、Review articleReview articleDiagnosis and treatment of asthma in childhood: a PRACTALL consensus reportAsthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limit

2、ed and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical prac

3、tice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative*, which is endorsed by both academies.评论文章童年哮喘的诊断和治疗：一个PRACTALL 共识报告在大多数工

4、业国家，哮喘是首要的儿童慢性病，然而，建立在儿童哮喘特殊方面的证据，包括治疗措施，是有限的，而且没有最近的国际方针仅仅重点在儿童哮喘。结果，欧洲过敏和免疫学院和美国过敏，哮喘和免疫学院提名专家组来找到一个共识作为欧洲和北美的一个临床实践指引。这个共识报告推荐策略包括药理治疗，过敏原和避免触发以及哮喘教育。这个报告是PRACTALL的一部分，得到两个学院的赞同。Abbreviations: ACT, Asthma Control Test; DPI, dry powder inhaler; eNO, exhaled nitricoxide; FEF, forced expiratory flow

5、; FEV1, forced expiratory volume; FVC, forced vital capacity; GP, general practitioners; HPA, hypothalamicpituitaryadrenal; ICS, inhaled corticosteroids; IgE, immunoglobulin E; IL, interleukin; LABA, long-acting b2 receptor agonist; LTRA, leukotriene receptor antagonist; MDI, metered dose inhaler; n

6、NO, nasal nitric oxide; PEF, peak expiratory flow; SLIT, sublingual immunotherapy Bacharier et al.缩写： ACT 哮喘控制试验， DPI 干粉吸入器， eNO 呼出的一氧化碳，FEF，用力呼气流量， FEV1 用力呼气容积， FVC 用力肺活量， GP 普通科医生， HPA 下丘脑-垂体-肾上腺， ICS 吸入皮质类固醇， IgE 免疫球蛋白E， IL 白细胞介素， LABA 长效2受体激动剂， LTRA 白三烯受体拮抗剂，MDI 计量吸入器， nNO鼻一氧化氮， PEF 呼气流速峰值， SLIT

7、 舌下含服免疫疗法Bacharier 等人Asthma is the most common chronic childhood disease in nearly all industrialized countries. It is more prevalent in children with a family history of atopy, and symptoms and exacerbations are frequently provoked by a wide range of triggers including viral infections, indoor and

8、outdoor allergens, exercise, tobacco smoke and poor air quality. Many infants and preschool children experience recurrent episodes of bronchial symptoms, especially wheezing and cough, beginning at a few months of age, mainly during a lower respiratory tract infection, and since a clinical diagnosis

9、 of asthma usually can be made with certainty by age 5, the early diagnosis, monitoring and treatment of respiratory symptoms are essential.哮喘在几乎所有的工业国家中是最常见的儿童时期慢性病。它盛行在有家族过敏体质的儿童中，而且症状和病情加重经常因广泛的触发器激动包括，室内和室外过敏原，运动，吸入尼古丁和差的空气质量。 许多婴儿和学龄前儿童经历支气管症状的反复发作，特别是喘息和咳嗽，开始于几个月的年龄，主要是在一个下呼吸道感染的过程中，而且自从哮喘通常是自

10、5岁后才被诊断，早期的诊断，监测和治疗呼吸道症状是必要的。 At the time of this report, there are few national (14) and no up-to-date international guidelines (5) that focus exclusively on pediatric asthma, even though children have a higher overall prevalence of asthma compared to adults. Pharmacotherapy for childhood asthma ha

11、s been described in general asthma guidelines, including the recently updated Global Initiative for Asthma (GINA) guidelines (6) and in some national guidelines. However, the information available on specific aspects of pediatric asthma, in particular in children under 5 years of age, is limited and

12、 does not include the opinion and contributions of the pediatric allergy and respiratory community (1, 7, 8). In contrast to adults, the evidence base for pharmacotherapy in children under 5 years of age is very sparse. The current British Thoracic Society Guideline (9) has been the most accessible

13、source of information for treatment of pediatric asthma, with recommendations based on the available literature and where evidence is lacking on expert opinion. 在本报告的时间，这里有少许全国性的（1-4）和没有到日期的国际性的方针（5）专注于儿科哮喘，和成人比儿童哮喘更盛行， 药物治疗儿童哮喘是在普通哮喘方针中描述，包括最近更新的全球哮喘防治（GINA）方针（6） 和在一些全国的方针。 然而， 能从儿科哮喘的特殊方面获得的信息，特别是

14、在5岁以下儿童，是有限的而且不包括儿科过敏和呼吸社区的意见和贡献（1,7,8）。 和对比成人，建立在5岁以下儿童药物治疗基础上的证据是很稀少的。现在英国胸椎社会方针（9）已经是在治疗儿科哮喘中最能够得到的信息资源，伴随着可用的文学推荐和缺少专家意见的证据。 In view of the limited data from randomized controlled trials in children and the difficulties in applying systematic review criteria to diagnosis, prognosis and nonpharma

15、cological management, this report employed a consensus approach based on available published literature (June 2007) and on best current clinical practice. The report reviews the natural history and pathophysiology of pediatric asthma and provides recommendations for diagnosis, practical management a

16、nd monitoring. The recommendations are aimed at both pediatricians and general practitioners (GPs) working in hospitals, office or primary care settings. 鉴于从儿童随机对照试验得到的有限的数据和应用系统的审查标准来诊断，预后和非药物管理的困难，这个报告根据可供公开发表的文献使用了协商一致的办法（到2007年6月为止） 在最好的现在临床实践。报告复习了儿科哮喘的自然史和病理生理学，提供诊断，实践管理和监视的建议。建议旨在工作在医院的儿科医生和从

17、业人员（GPs），办公室或基层医疗服务的设置。 Natural history Asthma in children can be described as _repeated attacks of airway obstruction and intermittent symptoms of increased airway responsiveness to triggering factors, such as exercise, allergen exposure and viral infections_ (10). However, the definition becomes m

18、ore difficult to apply confidently in infants and preschool age children who present with recurrent episodes of coughing and/or wheezing. Although these symptoms are common in the preschool years, they are frequently transient, and 60% of children with infantile wheeze will be healthy at school age

19、(11). Physicians should manage and exclude diagnoses other than asthma, and be aware of the variable natural history patterns of recurrent wheezing in early childhood. Three different patterns of recurrent wheeze in pediatric patients have been proposed (12), and a fourth was recently described (13)

20、. However, it should be noted that patterns 1 and 2 (listed below) can only be discriminated retrospectively and are not suitable for use when treating the child.儿童哮喘的自然史可以被描述为反复发作的气道阻塞和间歇性气道反应性增加的症状作为触发因子。比如运动，过敏原暴露和病毒感染（10），然而，在婴儿和学龄前儿童正在经历反复发作的咳嗽和或/喘息。虽然这些症状在学龄前是很常见的，它们常常是短暂的，而且60%的儿童在婴儿时期出现过喘息在学

21、龄期会变得健康（11）。 医生应该管理和排除哮喘的诊断，做到对儿童早期的反复发作的喘息心中有数。儿科病人的三个不同的反复发作喘息的模式已经被建议（12）， 第四个最近被描述（13）， 然而， 注意模式1 和2 （ 见下列）只能追溯歧视但不适合用于治疗儿童。1. Transient wheezing: Children who wheeze during the first 23 years of life, but do not wheeze after the age of 3 years2. Nonatopic wheezing: Mainly triggered by viral inf

22、ection and tends to remit later in childhood3. Persistent asthma: Wheezing associated with the following: Clinical manifestations of atopy (eczema, allergic rhinitis and conjunctivitis, food allergy), blood eosinophilia, and/or elevated total immunoglobulin E (IgE) Specific IgE-mediated sensitizatio

23、n to foods in infancy and early childhood, and subsequently to common inhaled allergens (1418) Inhalant allergen sensitization prior to 3 years of age, especially with sensitization and high levels of exposure to specific perennial allergens in the home (10) A parental history of asthma (15)4. Sever

24、e intermittent wheezing (13): Infrequent acute wheezing episodes associated with the following: Minimal morbidity outside of time of respiratory tract illness Atopic characteristics, including eczema, allergic sensitization and peripheral blood eosinophilia 1. 瞬态喘息：儿童在初生的23年喘息，但是在3岁以后不再喘息。2. 非过敏体质的喘

25、息：主要由病毒感染触发，在儿童时代的后期趋于缓和3. 持久性哮喘：喘息与以下有关：过敏体质的临床表现（湿疹，过敏性鼻炎和结膜炎，食物过敏）， 血液中嗜酸性粒细胞浸润，和/或升高的总免疫球蛋白E（IgE）婴儿和早期儿童特异的IgE介导的食物过敏，和随后的对常见的吸入过敏原过敏（14-18）3岁前吸入性过敏原过敏，特别是过敏和在家中高暴露于特殊长期过敏原（10）父母有哮喘史（15）4. 严重的间歇性喘息（13）：偶发的与下列相关的急性发作的喘息呼吸道疾病以外的时间最小的发病率过敏体质特征，包括湿疹，过敏性致敏和外周血嗜酸性粒细胞浸润The highest incidence of recurren

26、t wheezing is found in the first year of life. According to long-term population related prospective birth cohort studies, up to 50% of all infants and children below the age of 3 years will have at least one episode of wheezing (19). Infants with recurrent wheezing have a higher risk of developing

27、persistent asthma by the time they reach adolescence, and atopic children in particular are more likely to continue wheezing (Fig. 1) (10). In addition, the severity of asthma symptoms during the first two years of life is stronglyrelated to later prognosis (20). However, both the incidence and peri

28、od prevalence of wheezing decrease significantly with increasing age (12).经常性喘息的发病率最高是在生命的第一年。根据长远的人口相关的准出生队列研究，达到50%的所有婴儿和3岁以下的儿童将会有至少一集的喘息（19）。有反复发作喘息的婴儿在他们到达青春期时有发展持续性喘息的高危险，尤其是过敏体质儿童更有可能继续喘息（Fig.1）(10).此外，生后头两年的哮喘症状严重程度和后来预后非常有关（20）. 然而，喘息疾病的发病率和持续时间显著与增加的年龄有关（12）Figure 1. Prevalence of current

29、wheeze from birth to age 13 years in children with any wheezing episode at school age (57 years), stratified for atopy at school age (10).图1， 目前从出生到13岁儿童在任何学龄（5-7岁）喘息情况喘息的患病率，在上学的年龄为过敏体质Determinants 决定因素 Genetic factors. Studies on mono- and dizygotic twins along with the association of asthma pheno

30、type within first degree relatives suggest a genetic basis to asthma. More recently, genome wide screens followed by positional cloning and candidate gene association studies have identified genetic loci related to increased risk of asthma in certain populations (21). The effect of genetic variance

31、on asthma and asthma-related phenotypes shows a great deal of heterogeneity, and may be strongly influenced by environmental factors (2224). Accordingly, many children who develop asthma do not have parents with asthma, and many parents with asthma have children who do not develop asthma (10). Most

32、studies on the incidence and prevalence of asthma in childhood have indicated that the prevalence is higher in boys than in girls in the first decade of life (25, 26), although one serial cross-sectional study has suggested a recent narrowing of this gender gap (27). However, as children approach the teenage years, new-onset asthma becomes more common in girls than boys, especially in those with obesity and early-onset puberty (28). The reason for these gender differences is not well understood基因因素。 研究单和异卵双胞胎随着哮喘表型协会在一级亲属暗示对哮喘有基因基础。最近，全基因组屏幕跟随着定位克隆和候选基因研究确定基因位点和增加的哮喘危险在特定的人群中（21）。哮喘的