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

描述（由申请人提供）：哮喘在世界范围内呈急剧增长趋势。7- 15%的美国儿童被诊断出患有这种疾病，在整个童年时期，男孩中更为普遍；然而，在青春期发生了性别逆转。我们不知道女孩是否会持续哮喘，男孩是否会缓解，或者女孩是否会出现新发哮喘。此外，我们不了解导致哮喘发生这些变化的因素，但它们似乎与青春期的性别特异性发展有关。我们建议验证以下假设：(1)哮喘的性别逆转是由于女孩的新发病和男孩更高的临床缓解率。(2)危险因素包括青春期早发、肥胖、污染物以及父母吸烟和缺乏母乳喂养等早期生活因素。(3)确定预后因素将允许有针对性的干预措施，以防止哮喘在成年期的持续和复发。1989年，我们在怀特岛招募了一个人口出生队列（1456名儿童），怀特岛距离英格兰南海岸一英里，人口13万。该队列在1岁、2岁、4岁和10岁时进行了广泛的哮喘和其他过敏性疾病表型分析。每个年龄段的随访比例都很高（80- 95%）。从先前的队列检查中可以获得丰富的信息。参与者现在都是青少年。因此，这个队列是唯一适合解决上述假设。我们建议对这些18岁的孩子进行研究，预计将有1200人参与。我们将通过问卷调查、体格检查、肺活量测定、支气管刺激、呼出一氧化氮、痰诱导、皮肤点刺试验和总IgE来评估症状、肺功能、气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）和环境危险因素（包括母乳喂养、烟草烟雾暴露、污染标志物和农业暴露）的影响。利用所有可获得的信息，我们将确定一个预测模型，以确定成人生活中持续性或复发性哮喘的高风险儿童。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支多学科研究团队，他们在呼吸医学、过敏和免疫学、流行病学、遗传学和生物统计学方面有着良好的合作记录和专业知识。

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.