Both childhood asthma and obesity are major public health problems. There is strong evidence of an association between both diseases; obese children with asthma have increased asthma severity, poor control, and reduced medication response. Yet, to date, the underpinning mechanisms are not well understood. Our central hypothesis is that the obese asthma is driven by changes in the epigenetic regulation and transcriptomic activity within adipose tissue. To test this hypothesis, we will recruit a cohort of children with asthma, obesity, both, or controls, in whom we will perform extensive phenotyping, and obtain subcutaneous and intra-abdominal adipose tissue. In addition to BMI, we will assess other indices of adiposity and body composition measured by anthropometry and impedance analysis.
In Specific Aim 1, we will assess the transcriptomic and epigenetic changes in adipose tissue (using RNA-seq and genome-wide DNA methylation, respectively) associated with obesity and asthma in this cohort, after adjustment for relevant covariates. Secondary measures will include body composition and adiposity distribution, and atopy and inflammatory biomarkers. We will then integrate genome-wide genotyping, DNA methylation, and RNA-seq data via mQTL, eQTL, and eQTM analyses.
In Specific Aim 2, we will use the same approach to evaluate measures of asthma severity and control in children with obesity and asthma. We will focus on acute exacerbations, Asthma Control Test (ACT) scores, and lung function changes. And in Specific Aim 3, we will conduct an initial functional/causal validation by assessing differential gene expression in normal and asthmatic bronchial epithelial and airway smooth muscle cells, in response to treatment with the products of the top genes identified in Aims 1-2, as well as other candidate genes for obese asthma from the literature. This proposal innovates by focusing on the ?source? tissue of obese asthma, rather than using blood biomarkers or mediators, and by validating the effect of the top results on the ?target? tissues. Elucidating adipose tissue pathways associated with obese asthma will have critical implications for our understanding of this phenotype and may allow us to identify ways to improve the management of these patients.

Public Health Relevance

Elucidating adipose tissue pathways associated with obesity and asthma in children will improve our understanding of this important phenotype. Furthermore, it may allow us to identify potential therapeutic targets and other ways to improve the management of obese children with asthma.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Lachowicz-Scroggins, Marrah Elizabeth
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Schools of Medicine
United States
Zip Code