Project 3

哮喘和肥胖之间的具体机制仍然是假设性的。解释这种关系的促炎和抗炎标记物的复杂基质知之甚少。协同地，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水平上由炎症因子调节。 单核苷酸多态性（SNP）。我们的主要假设是，炎症SNP可能调节炎症反应的程度，肥胖改变疾病的严重程度。在这种情况下，在肥胖症的背景下发展的哮喘证明了特定的促炎状态（肥胖症）和炎症的遗传调节因子（SNP）之间的潜在有害关系。其次，体重减轻改善了哮喘症状的严重程度，可能是通过减少炎症。然而，驱动这些积极成果的确切机制尚不清楚。这种一致的时间关系可能与肺部特异性炎症介质和气道炎症的阳性改变有关，这可能独立于饮食或运动。或者，饮食和运动可以减少身体脂肪，从而改善代谢状况，减少活性氧和减少炎症。因此，我们的次要假设提出，与对照组相比，仅通过饮食减肥而不是仅通过运动减肥将显著降低患有哮喘的肥胖非裔美国女性青少年的肺部特异性炎症并减少促炎反应。第三个探索性假设提出，所鉴定的SNP的频率将与通过饮食和/或运动的脂肪损失显著相关，并且将由特定的气道和促炎和抗炎标记物介导。这项研究将使我们能够确定非裔美国女性青少年的遗传特征，这可以用于提前修改哮喘和肥胖管理的治疗干预措施，并可能在这些高危青年中产生具有成本效益和时间效益的解决方案。

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.