Lau Susanne, Nickel Renate, Niggemann Bodo, Grüber Christoph, Sommerfeld Christine, Illi Sabina, Kulig Michael, Forster Johannes, Wahn Ulrich, Groeger Marketa, Zepp Fred, Kamin Wolfgang, Bieber Imke, Tacke Uta, Wahn Volker, Bauer Carl-Peter, Bergmann Renate, von Mutius Erika
University Children's Hospital, Department of Pneumology and Immunology Berlin, Charité Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany.
Paediatr Respir Rev. 2002 Sep;3(3):265-72. doi: 10.1016/s1526-0542(02)00189-6.
Epidemiological surveys have indicated that there has been a notable increase in the prevalence of both asthma and other allergic symptoms in children and young adults. Since it seems unlikely that genetic factors would contribute to the rising trend, environmental factors might play a major part in the development of childhood asthma. In a prospective birth-cohort study, we assessed the relevance of different exposures such as mite and cat allergen exposure, environmental tobacco smoke (ETS) exposure, early infectious diseases and vaccinations for the development of childhood asthma up to the age of 10 years. Data up to 7 years of age have been evaluated. Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 7 years were available for 939 children (72%). Assessments included repeated measurements of specific IgE to food and inhalant allergens, measurement of indoor allergen exposure at 6 months, 18 months and 3 years of age and yearly interviews by a paediatrician. At age 7 years, pulmonary function was tested and bronchial responsiveness was determined in 645 children. At age 7, the prevalence of wheezing in the past 12 months was 10% (94 out of 938), and 6.1% (57 out of 939) parents reported a doctor's diagnosis of asthma in their children. Sensitisation to indoor allergens was associated with asthma, wheeze and increased bronchial responsiveness. However, no relationship between early indoor allergen exposure and the prevalence of asthma, wheeze and bronchial responsiveness was seen. During the first 3 years of life, intra-uterine tobacco and consistent ETS exposure have an adjuvant effect on allergic sensitisation that is transient and restricted to children with a genetic predisposition for allergy. Children sensitised to any allergen early in life and sensitised to inhalant allergens by the age of 7 years were at a significantly increased risk of being asthmatic at this age (odds ratio (OR) = 10.12; 95% confidence interval (CI) = 3.81-26.88). Children with repeated episodes (> or =2) of runny nose before the age of 1 year were less likely to develop asthma by the age of 7 years (OR = 0.52; 95% CI = 0.29-0.92). Our data do not support the hypothesis that exposure to environmental allergens directly causes asthma in childhood but that induction of specific IgE responses and the development of childhood asthma are determined by independent factors. Indoor allergen avoidance is recommended as first line treatment in secondary and tertiary prevention; however, conclusions should be drawn with caution about the possible effect of primary preventative measures. Since allergic asthma seems to be a Th2-disease, immunomodulating factors such as early childhood infections, LPS-exposure or other factors influencing gene-environment interaction and individual susceptibility seem to be relevant for the development of childhood asthma.
流行病学调查表明，儿童和青年中哮喘及其他过敏症状的患病率显著上升。由于遗传因素似乎不太可能导致这一上升趋势，环境因素可能在儿童哮喘的发病中起主要作用。在一项前瞻性出生队列研究中，我们评估了不同暴露因素，如接触螨和猫过敏原、接触环境烟草烟雾（ETS）、早期传染病和疫苗接种对10岁以下儿童哮喘发病的相关性。已对7岁以下的数据进行了评估。1990年在德国五个城市招募的1314名新生儿中，939名儿童（72%）有7岁时的随访数据。评估包括对食物和吸入性过敏原特异性IgE的重复测量、6个月、18个月和3岁时室内过敏原暴露的测量以及儿科医生的年度访谈。在7岁时，对645名儿童进行了肺功能测试和支气管反应性测定。7岁时，过去12个月内喘息的患病率为10%（938名儿童中的94名），6.1%（939名儿童中的57名）的家长报告其孩子被医生诊断为哮喘。对室内过敏原的致敏与哮喘、喘息和支气管反应性增加有关。然而，未发现早期室内过敏原暴露与哮喘、喘息和支气管反应性患病率之间的关系。在生命的前3年，宫内烟草暴露和持续的ETS暴露对过敏致敏有辅助作用，这种作用是短暂的，且仅限于有过敏遗传倾向的儿童。在生命早期对任何过敏原致敏且在7岁时对吸入性过敏原致敏的儿童，在这个年龄患哮喘的风险显著增加（优势比（OR）=10.12；95%置信区间（CI）=3.81-26.88）。1岁前有反复流涕发作（≥2次）的儿童在7岁时患哮喘的可能性较小（OR=0.52；95%CI=0.29-0.92）。我们的数据不支持环境过敏原暴露直接导致儿童哮喘的假说，而是支持特异性IgE反应的诱导和儿童哮喘的发病由独立因素决定的观点。建议在二级和三级预防中将避免接触室内过敏原作为一线治疗方法；然而，对于一级预防措施的可能效果应谨慎得出结论。由于过敏性哮喘似乎是一种Th2疾病，免疫调节因素，如儿童早期感染、接触LPS或其他影响基因-环境相互作用和个体易感性的因素，似乎与儿童哮喘的发病有关。
