Common and distinct early environmental influences on cardiometabolic and respiratory health: Mechanisms and methods

项目摘要/摘要 肥胖和哮喘是儿童最常见的两种慢性病。肥胖是一种危险因素 哮喘以及与气流阻塞无关的呼吸困难。反过来，哮喘症状和 一些哮喘药物可能会增加体重超标的风险。因为没有有效的治疗方法，而且 由于这两种情况通常都是在学龄期之前建立的，因此早期生命预防至关重要。然而，我们的能力 确定最有希望的环境或行为目标进行预防一直受到 许多曝光可能很难测量，经常重叠和相互作用，很少发生在一次 时间点。由于遗传或其他因素，个体对暴露的敏感性可能会有所不同。 此外，肥胖和哮喘本身并不是一成不变的--它们都可能首先出现在儿童早期，后来才出现 童年、青春期或成年期；一旦出现，它们可能会持续、缓解或恶化；以及两种结果 可能会相互作用。需要复杂的分析方法来处理纵向和纵向的复杂性质 出生队列数据以及问题本身。 为此，我们提出了这个项目，它植根于我们波士顿地区的大范围出生前项目万岁队列。 我们招募了怀孕早期的母亲，并对她们和她们的孩子进行了频繁的面对面访问 (分娩后和婴儿期、幼儿期、儿童期中期和即将完成的青少年早期探视) 以及通过年度问卷调查。以我们已经评估的结果为基础，从出生到 青春期早期，我们现在建议表征肥胖症和心脏代谢的健康措施以及 肺功能和呼吸道症状进入青春期中期。 使用最先进的统计方法，我们将解决早期生活环境暴露，单独 作为混合物，会影响肥胖、哮喘和相关功能障碍的单独和共同进化。我们会 改进暴露措施，确定结果轨迹，并理清混淆、调解和 适度的暴露与结果的关系。最后，我们将使用基于代理的仿真模型 这将借鉴但也超越我们自己队列的结果，以确定有效的最佳杠杆 干预，包括从生理学到政策的多个层面的行动。我们会 将我们在队列中改进的数据、测量和方法也贡献给更大的ECHO企业 作为在具有儿童多样性代表的大型合成队列中的后续研究结果 全国范围内。

Project Summary/Abstract Obesity and asthma are the two most common chronic conditions in children. Obesity is a risk factor for asthma as well as for dyspnea not associated with airflow obstruction. Reciprocally, asthma symptoms and some asthma medications may increase risk of excess weight gain. Because no effective cures exist, and because both conditions are often established before school age, early life prevention is critical. Yet our ability to identify the most promising environmental or behavioral targets for prevention has been hampered by the fact that many exposures may be difficult to measure, often overlap and interact, and rarely occur at a single point in time. Individuals may vary in their sensitivity to exposures because of genetic or other factors. Furthermore, obesity and asthma themselves are not static – each may first emerge in early childhood, later childhood, adolescence, or adulthood; once present they may persist, remit, or worsen; and the two outcomes may interact. Sophisticated analytic approaches are needed to handle the complex natures of both longitudinal birth cohort data as well as of the questions themselves. To this end, we propose this project, which is grounded in our large Boston-area Project Viva pre-birth cohort. We recruited mothers in early pregnancy, and have followed them and their children at frequent in-person visits (after delivery and at infancy, early childhood, mid-childhood, and the nearly completed early teen visits) as well as via annual questionnaires. Building on the outcomes we have already assessed from birth through early adolescence, we now propose to characterize adiposity and cardiometabolic health measures as well as lung function and respiratory symptoms into the mid-teen years. Using state of the art statistical methods, we will address the early life environmental exposures that, singly and as mixtures, influence the separate and co-evolution of obesity, asthma and related dysfunctions. We will refine exposure measures, characterize outcome trajectories, and disentangle confounding, mediation and moderation in associations of exposures with outcomes. Finally, we will use agent based simulation models that will draw from but also go beyond the results from our own cohort, to identify optimal levers for effective intervention, incorporating multiple levels of action from physiologogy all the way up to policy. We will contribute the data, measures, and methods we refine within our cohort to the larger ECHO enterprise, as well as findings to be followed up in the large synthetic cohort with its diversity representative of children nationwide.