Epidemiology of asthma: risk and prognosis in a cohort from birth to adolescence

描述(由申请者提供)：哮喘在全球范围内呈戏剧性增长。这种疾病在7%-15%的美国儿童中被诊断出来，在整个童年时期在男孩中更普遍；然而，在青春期发生了性别颠倒。我们不知道哮喘是在女孩中持续存在，在男孩中缓解，还是在女孩中有新的哮喘发作。此外，我们不了解推动哮喘发生的这些变化的因素，但它们似乎与青春期特定性别的发育有关。我们建议检验以下假设：(1)哮喘的性别逆转是由于女孩新发病和男孩临床缓解率较高所致。(2)危险因素包括青春期提前、肥胖、污染物和早年生活因素，如父母吸烟和缺乏母乳喂养。(3)确定预后因素将允许有针对性的干预措施，以防止成人哮喘的持续和复发。1989年，我们在距离英格兰南海岸一英里的鬼魂岛招募了一个人口出生队列(1,456名儿童)，该岛人口为130,000。这个队列在1岁、2岁、4岁和10岁时被广泛用于哮喘和其他过敏性疾病的表型。每个年龄段都达到了很高的随访率(80%-95%)。从先前对队列的检查中可以获得大量信息。参与者现在都是青少年。因此，这个队列特别适合于解决上述假设。我们建议在18岁时对这些儿童进行研究，预计将有1,200人参与。采用问卷调查、体格检查、肺活量测定、支气管刺激、呼出一氧化氮、诱导痰、皮肤点刺试验和总IgE等方法评估症状、肺功能、呼吸道炎症和特应性标志物。使用以临床指标为结果的回归模型，我们将确定青春期因素、肥胖相关因素(体重指数、血清瘦素水平、瘦素和瘦素受体基因型别)以及环境风险因素(包括母乳喂养、吸烟暴露、污染标志物和农业暴露)的影响。利用所有可用的信息，我们将确定一个预测模型，以确定哪些儿童在成年后处于持续或复发哮喘的高危状态。这些结果将有助于预防哮喘的持续和复发。我们的工作汇集了一个多学科的研究团队，他们在呼吸系统医学、过敏和免疫学、流行病学、遗传学和生物统计学方面拥有经过验证的合作和专业知识。

DESCRIPTION (provided by applicant): Asthma has shown dramatic increase worldwide. The disorder is diagnosed in 7-15 percent of U.S. children and is more prevalent in boys throughout childhood; however, during puberty a gender reversal occurs. We do not know if asthma persists in girls and remits in boys or there is new onset asthma in girls. In addition, we do not understand factors driving these changes in asthma occurrence, but they seem to be related to gender- specific developments during puberty. We propose to test the following hypotheses: (1) Gender reversal of asthma is due to new onset in girls and higher rates of clinical remission in boys. (2) Risk factors include early onset of puberty, obesity, pollutants, and early life factors such as parental smoking and lack of breastfeeding. (3) Identification of prognostic factors will allow for targeted interventions to prevent persistence and recurrence of asthma in adulthood. In 1989, we recruited a population birth cohort (1,456 children) on the Isle of Wight, an island one mile off the south coast of England with a population of 130,000. This cohort has been extensively phenotyped for asthma and other allergic diseases at 1, 2, 4 and 10 years of age. High follow up proportions (80-95 percent) have been achieved at each age. A wealth of information is available from prior examinations of the cohort. Participants are now adolescents. Therefore, this cohort is uniquely suited to address the above hypotheses. We propose to study these children at the age of 18 years and anticipate that 1,200 will participate. We will assess symptoms, lung function, airway inflammation, and atopic markers using questionnaire, physical examination, spirometry, bronchial provocation, exhaled nitric oxide, sputum induction, skin prick test, and total IgE. Using regression models with clinical markers as outcomes, we will determine the impact of pubertal factors, obesity-related factors (body mass index, serum leptin levels, genotypes for leptin and leptin receptor), and environmental risk factors (including, breastfeeding, tobacco smoke exposure, markers of pollution and agriculture exposure). Using all available information, we will determine a predictive model to identify children who are at high risk of persistent or recurrent asthma in adult life. These results will facilitate prevention of asthma persistence and recurrence. Our work brings together a multidisciplinary research team with a proven record of collaboration and expertise in respiratory medicine, allergy and immunology, epidemiology, genetics, and biostatistics.