Project 3

将哮喘和肥胖联系起来的具体机制仍然是假设的。对于解释这种关系的促炎和抗炎标志物的复杂矩阵，人们知之甚少。协同作用是，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，包括细胞因子，从而增加炎症。反过来，炎症标志物的产生可以在DNA水平上由 存在单核苷酸多态(SNP)。我们的主要假设是，炎症性SNPs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，在肥胖的背景下发展起来的哮喘表明了特定的促炎状态(肥胖)和炎症的遗传调节因子(SNPs)之间的潜在有害关系。其次，减肥可能通过减轻炎症来改善哮喘症状的严重程度。然而，推动这些积极结果的确切机制尚不清楚。这种持续的时间关系可能与肺部特异性炎症介质和呼吸道炎症的积极变化有关，这些变化可能是由饮食或运动独立改变的。或者，饮食和锻炼可能会减少身体脂肪，进而改善新陈代谢状况，减少活性氧物种，减少炎症。因此，我们的第二个假说提出，与对照组相比，仅通过饮食减肥，而不是仅通过运动减肥，将显著减少患有哮喘的肥胖非裔美国女性青少年的肺部特异性炎症和促炎反应。第三个探索性假说提出，SNPs的出现频率将与饮食和/或运动中的脂肪减少显著相关，并将由特定的呼吸道以及促炎和抗炎标记物介导。这项研究将使我们能够定义非裔美国女性青少年的基因图谱，可以用来提前修改哮喘和肥胖症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.