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Principal Investigator: Leonard B Bacharier
Organization: VANDERBILT UNIVERSITY MEDICAL CENTER
Fiscal Year: 2024
Award: $1,663,001
Funding agency: NIH Office of the Director
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.
Terms: <0-11 years old><12-20 years old><6-11 years old><Active Follow-up><Address><Adolescence><Age><Allergens><Allergic><Asthma><Asthma in Children><Biological><Biological Markers><Biological Response Modifier Therapy><Biological Response Modifiers><Biological Specimen Banks><Biological Substance Banks><Biological Therapy><Biology><Biomodulators><Birth><Blood Eosinophil><Blood Sample><Blood specimen><Bronchial Asthma><Child><Child Health><Child Youth><Childhood Asthma><Children (0-21)><Clinical><Cohort Studies><Collection><Concurrent Studies><DNA><Data><Data Collection><Data Element><Deoxyribonucleic Acid><Development><Diagnosis><Disease><Disease Management><Disorder><Disorder Management><Endogenous Nitrate Vasodilator><Endothelium-Derived Nitric Oxide><Enrollment><Ensure><Environmental Exposure><Environmental Factor><Environmental Risk Factor><Eosinophilic Granulocyte><Eosinophilic Leukocyte><Ethnic Origin><Ethnicity><Exhalation><Exhaling><Funding><Gene Transcription><Genes><Genetic Transcription><Genotype><Geographic Area><Geographic Locations><Geographic Region><Geographical Location><Geography><Goals><Hypersensitivity skin testing><IgE><Immune Mediators><Immune Mediators/Modulators><Immune Regulators><Immunoglobulin E><Impoverished><Incidence><Individual><Infant><Laboratories><Lung Function Tests><Marrow Eosinophil><Measures><Mentors><Methodology><Mononitrogen Monoxide><Morbidity><Morbidity - disease rate><Nasal><Nasal Passages Nose><Nitric Oxide><Nitrogen Monoxide><Nitrogen Protoxide><Nose><Outcome><Participant><Parturition><Pathway interactions><Pediatric asthma><Phenotype><Population><Population Heterogeneity><Poverty><Prevalence><Preventative strategy><Prevention strategy><Preventive strategy><Protocol><Protocols documentation><Publications><Pulmonary function tests><RNA Expression><Race><Races><Research><Respiratory Epithelium><Respiratory Expiration><Respiratory System, Nose, Nasal Passages><Respiratory syncytial virus><Risk Factors><Role><Rural Community><Sample Size><Sampling><Science><Scientific Publication><Serology><Skin Tests><Southeast U.S.><Southeast US><Southeastern United States><Structure of respiratory epithelium><Technology><Testing><Time><Transcription><Urban Community><Viral Respiratory Tract Infection><Visit><active followup><adolescence (12-20)><ages><airway epithelium><airway microbiome><asthma prevention><bio-markers><biologic><biologic marker><biological specimen repository><biological therapeutic><biological treatment><biologically based therapeutics><biomarker><biosample repository><biospecimen bank><biospecimen repository><biotherapeutics><biotherapy><clinical care><clinical practice><clinical relevance><clinically relevant><cohort><comparative><comparator group><comparison group><developmental><diagnostic criteria><diagnostic development><differential expression><differentially expressed><disease prevention><disorder prevention><diverse populations><early life exposure><endothelial cell derived relaxing factor><enroll><environmental risk><eosinophil><ethnic diversity><ethnically diverse><fecal microbiome><follow up><follow-up><followed up><followup><geographic site><heterogeneous population><high dimensional data><hypersensitivity test><immunologic skin test><immunomodulatory biologics><innovate><innovation><innovative><kids><middle childhood><multidimensional data><multidimensional datasets><novel><pathway><policy implication><population based><population diversity><protective factors><racial><racial background><racial diversity><racial origin><racially diverse><respiratory><respiratory microbiome><respiratory tract epithelium><respiratory tract microbiome><sex><social role><specimen bank><specimen repository><stool microbiome><stool-associated microbiome><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><transcriptional differences><transcriptomics><treatment strategy><viral detection><viral respiratory infection><virus detection><youngster>