Residential Greenness, Airway Microbiome,and Incident Childhood Asthma

The major challenges for developing primary prevention strategies for childhood asthma are the early identification of modifiable risk factors (e.g., environmental factors, microbiome) and the heterogeneity of asthma. Our group has applied integrated omics approaches to infancy data, and identified endotypes at high risk for asthma. No study has examined the integrated role of residential greenness, airway microbiome (both composition and functional capacity), and host response during infancy in the development of childhood asthma and its phenotypes. Our central hypothesis is that an interrelation between the residential, airway microbiome, and the host will shape earlylife immunity and contribute to the development of asthma and its phenotypes. We will leverage airway samples and comprehensive environmental, clinical, and omics data from three multicenter prospective cohorts. The 30th Multicenter Airway Research Collaboration Finland (MARC-30 Finland) is an ongoing multicenter cohort study of 408 infants with severe bronchiolitis. The MARC-35 (U01 AI087881) is an ongoing multicenter cohort study of 919 infants with severe bronchiolitis. The MARC-43 (UG3/UH3 OD023253) is an ongoing multicenter cohort study of 599 healthy infants. The present R01 project would extend these well-phenotyped cohorts by generating the residential greenness indices (Normalized Difference Vegetation Index and Green Chlorophyll Index), sequencing airway metagenome and then examining their relations to the development of asthma and its phenotypes by age 6-7 years. In Aim 1, we will identify the integrated role of residential greenness and airway metagenome on developing asthma (and its phenotypes) in severe bronchiolitis infants (MARC-30 Finland and MARC-35). In Aim 2, we will identify the integrated role of residential greenness, airway metagenome, and host genome, on developing asthma (and its phenotypes) in severe bronchiolitis infants (MARC-35 only). In Aim 3, to examine the reproducibility and generalizability of findings from Aims 1-2, we will identify the integrated role of residential greenness, airway metagenome, and host genome, on developing asthma (and its phenotypes) in healthy infants (MARC-43 only). The environmental (i.e., residential greenness and air pollution) and metagenome data generated by this R01 project—along with parallel multi-omics (e.g., genome, DNA methylome, transcriptome, metabolome) and immunological data available—offer an unprecedented opportunity to develop data-driven mechanistic models for childhood asthma and highlight preventive strategies based on the modifiable risk factors.