PROJECT SUMMARY/ABSTRACT Individual birth cohort studies have identified risk factors for developing childhood asthma, including environmental exposures in early life such as allergens, pollutants, patterns of infection and colonization with viruses and bacteria, and psychosocial stress. Despite such advances, further progress in understanding the root causes of asthma have been hampered by at least two factors. First, procedures and scientific methods are not standardized across cohorts, making it difficult to compare and validate findings. Second, asthma definitions across cohorts vary considerably. In fact, asthma is a syndrome; there are different subtypes of asthma with distinct clinical features (“asthma phenotypes”) and likely different etiologies (“asthma endotypes”). We hypothesize that host factors (genetics, epigenetics) interact with environmental exposures during the prenatal period and early childhood to cause specific endotypes of childhood asthma. We further propose that identification of endotypes and associated molecular biomarkers in early life can provide a new paradigm for asthma prevention. Unfortunately, single cohorts have limited ability to identify asthma endotypes due to small sample size and unique population characteristics. To overcome shortcomings of individual cohorts, investigators leading 12 asthma birth cohorts across the U.S. now propose the establishment of the Children's Respiratory Research and Environment Workgroup (“CREW”) consortium. This consortium proposes to identify asthma endotypes and overcome shortcomings of individual cohorts by: 1) providing a large (nearly 9000 births and long-term follow-up of 6000-7000 children and young adults) and diverse national data set, 2) harmonizing data related to asthma clinical indicators and early life environmental exposures, 3) developing standardized measures for prospective data collection across CREW cohorts and other ECHO studies, and 4) conducting targeted enrollment of additional subjects into existing cohorts. This approach will enable collection of samples that are optimized for a systems approach to understanding how environmental and host factors in early life promote the development of specific asthma endotypes. Collectively, the results of this comprehensive research to identify the root causes of asthma vs. resilience and health will go far beyond what can be accomplished by individual cohorts, and thus provide a foundation for future efforts aimed at personalized prevention of chronic childhood asthma.

PROJECT NARRATIVE The environment during the prenatal period and in early life is a major contributor to the risk of developing childhood asthma. Birth cohort studies from single research centers have identified several factors that affect the risk for developing childhood asthma, including being exposed in early life to allergens, pollutants, viruses and bacteria, and psychosocial stress. Despite such advances, further progress in understanding the root causes of asthma have been hampered by the small size of previous studies, which makes it difficult to: 1) identify asthma risk factors with certainty, 2) to know how environmental factors affect asthma, and 3) whether there are critical ages when babies or pregnant mothers are particularly susceptible to these influences. Furthermore, different research groups tend to use different methods to study asthma, making it difficult to either compare or pool findings. One other challenge is that there are several types of childhood asthma, but these are poorly understood. To help overcome these challenges, investigators leading 12 asthma birth cohorts across the U.S. now propose the establishment of the Children's Respiratory Research and Environment Workgroup (“CREW”) consortium. This consortium proposes to identify specific types of childhood asthma, develop an understanding of what early life environmental influences cause these different types of asthma, and identify targets for future efforts aimed at preventing childhood asthma. To accomplish these goals, the scientific information and resources from the 12 birth cohorts will be combined, and investigators and biostatisticians will work collaboratively to analyze data that has already been collected along with new information to better understand the underlying causes of childhood asthma.