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.