Project 3

将哮喘和肥胖联系起来的具体机制仍然是假设的。支持和抗炎标志物的复杂基质解释了这种关系，但人们知之甚少。协同作用下，哮喘症状的严重程度和发病率随着肥胖水平的增加而加剧。因此，肥胖状态可能会增加炎症标志物的产生，包括增加炎症的细胞因子。反过来，炎症标志物的产生可以在DNA水平上通过

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.