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Channing Asthma Research

Investigating the Epidemiological, Genetic and Biochemical Pathways Underlying Asthma Susceptibility and Development

Asthma is an inflammatory disease of the lung that affects 300 million people worldwide and incurs over $80 billion/year in healthcare costs in the United States. Asthma can occur at any age but overwhelmingly begins in very early childhood, where over 20% of children wheeze in the first year of life, and half of these are still wheezing at age 6.

The developmental origin of disease hypothesis suggests that factors such as the diet of pregnant women, as well as other environmental exposures, are important sources of environmental determinants of fetal programming of lung function and the development of asthma and lung disease in later life. Also contributing to asthma development are pregnancy conditions such as pre-eclampsia and pre-term birth.

Current Research

Investigators at the Channing Division of Network Medicine (CDNM) have developed a comprehensive research program to:

  • Study the epidemiology and natural history of asthma
  • Identify the genetic determinants of asthma
  • Define key biochemical pathways underlying asthma susceptibility and variability

CDNM investigators apply clinical trial designs and longitudinal pre-birth cohort studies to understand how asthma develops, its clinical course, and its underlying causes, both environmental and genetic.

Achievements


Early research at Channing demonstrated that in utero smoke exposure could cause childhood asthma. And the natural history of childhood asthma and its link to COPD was first described by Channing.

Additionally, we have identified numerous genes for asthma using genome-wide association studies (GWAS). And we have defined different subtypes of asthma and identified genes that determine responses to asthma therapies, such as inhaled corticosteroids and beta agonists.

Multi-omics approaches to understanding asthma

We have utilized a variety of different "omics" data types to understand asthma, including genome-wide association studies (GWAS) gene chips, whole genome sequencing, 850k methylation chip, mRNA-Seq, miRNA-Seq, single-cell mRNA-Seq, metabolomics, microbiomics, and others. Many of our populations have all or most of these "omics" data types collected on at least a subset of subjects.

Network approaches to understanding asthma

CDNM asthma investigators have utilized network approaches to understand genes that cause asthma, gene and miRNA expression to predict childhood wheeze, and genetic and metabolomic data to understand asthma origins.

Study populations

Study populations developed and analyzed by CDNM investigators to study asthma include:

  • Childhood Asthma Management Program (CAMP)
  • Genetics of Asthma in Costa Rica Study (GACRS)
  • Vitamin D Antenatal Asthma Reduction Trial (VDAART)
  • Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE)
  • GERA Asthma
  • Mass General Brigham Biobank with over 15,000 asthmatics
  • EVE
  • UK Biobank

National and international collaborations

Asthma investigators at CDNM have participated in a variety of national and international collaborations with organizations such as NHLBI, Trans-Omics in Precision Medicine (TOPMed), EVE, the American Thoracic Society, the European Respiratory Society, NHGRI, and eMERGE.