ECHO Renewal for the INSPIRE Study Cohort

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ABSTRACT The overarching goals of this proposal are 1) to maintain retention of children in the INSPIRE birth cohort with emphasis on diversity, and implementation of the ECHO Cohort Protocol with high fidelity, and 2) tackle the major limitation in diagnosis and management of childhood asthma - addressing the need to identify asthma phenotypes and endotypes to develop targeted treatment and prevention strategies. The term asthma is an umbrella diagnosis for several disease states with distinct variable clinical presentations (phenotypes) and mechanistic pathways (endotypes). Central to understanding the causal role of environmental exposures in asthma development and to disease management is identifying distinct asthma phenotypes. The scientific aims of this proposal are: 1) Aim 1: to determine the incidence and prevalence of two highly relevant asthma phenotypes, atopic and non-atopic asthma, by age, sex, cohort decade and geographic location, using widely available and harmonized variables and those collected through the ECHO Cohort Protocol. We will also determine the contribution of established environmental risk and protective factors with these specific clinically relevant asthma phenotypes. Lastly, we will calculate comparative estimates of childhood asthma morbidity by asthma phenotypes; 2) Aim 2: to further characterize asthma phenotypes and endotypes into clinically useful entities within the ECHO consortium and expand the findings to clinical practice by utilizing available or to be collected samples to add biomarkers of asthma routinely available in clinical practice, and nasal samples to perform transcriptomic analyses to define asthma endotypes; 3) Aim 3: to facilitate and oversee longitudinal follow-up of the established INSPIRE cohort, and biosample collection to maximize retention of existing participants with emphasis on diversity, and implement the ECHO Cohort Protocol with high fidelity. The INSPIRE birth cohort is a population-based birth cohort study that originally enrolled over 1950 term healthy infants. INSPIRE is unique in including surveillance for infant respiratory viral infection through biweekly active and passive surveillance using PCR for viral detection and respiratory syncytial virus (RSV) serology at age one. The children will be ages 8-10 years when the current ECHO funding period ends, entering adolescence, and will be followed to age 15-17 years during this next funding period. The proposed research is an innovative, novel, multi-faceted and practical approach to move away from viewing “asthma” as a single umbrella disease, and identifying and understanding asthma phenotypes, endotypes, and the influence of risk and protective factors on specific asthma phenotypes. The approach we propose is also practical in moving toward solutions that utilize currently available technologies and laboratory testing to aide in development of diagnostic criteria for childhood asthma sub-types.