The specific mechanisms linking asthma and obesity remain hypothetical. The complex matrix of pro-and-anti-inflammatory markers that explain this relationship is poorly understood. Synergistically, the severity of asthmatic symptoms and rate of morbidity intensify as obesity level increases. Therefore, obesity state may increase the production of inflammatory markers, including cytokines, which increase inflammation. In turn, the production of inflammatory markers can be regulated at the DNA level by the presence of single nucleotide polymorphisms (SNP). Our primary hypothesis is that inflammatory SNPs may regulate the degree of the inflammatory response, with obesity modifying the severity of the disease. In this instance, asthma that develops in the context of obesity demonstrates the potential deleterious relationship between a specific pro-inflammatory state (obesity) and the genetic regulators of inflammation (SNPs). Secondly, weight reduction improves the severity of asthmatic symptoms, likely through reductions in inflammation. However, the precise mechanisms that drive these positive outcomes are unknown. This consistent temporal relationship is likely related to positive alterations in lung specific inflammatory mediators and airway inflammation, which may be independently altered by diet or exercise. Or, collectively diet and exercise may reduce body fat, which in turn improves the metabolic profile, reduces reactive oxygen species and decreases inflammation. Thus, our secondary hypothesis proposes that weight loss by diet alone, but not exercise alone, will significantly reduce lung specific inflammation and diminish the pro-inflammatory responses in obese African American female adolescents with asthma compared to controls. A third exploratory hypothesis proposes that the frequency of identified SNPs will be significantly related to the fat loss through diet and/or exercise and will be mediated by specific airway and, pro- and anti-inflammatory markers. This study would allow us to define a genetic profile in African American female adolescents, which could be used to modify in advance the therapeutic interventions for asthma and obesity management and likely produce a cost-effective and time-efficient solution in these high-risk youth.

Public Health Relevance

Asthma and obesity preferentially affect African American children and seriously worsens their health throughout their lives. The associated lung inflammation is conditioned in part by genetic factors and diet. By understanding the relationship between factors we can (diet and exercise) and cannot (genetic) change, we may determine how genetic regulators and weigh loss can be used to improve patient outcome.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Exploratory Grants (P20)
Project #
5P20MD004817-05
Application #
8632847
Study Section
Special Emphasis Panel (ZMD1-PA)
Project Start
2014-03-01
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2014
Total Cost
$336,720
Indirect Cost
$48,750
Name
Dillard University
Department
Type
DUNS #
062665468
City
New Orleans
State
LA
Country
United States
Zip Code
70122
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