Novel role for adiponectin-enhancing drugs for asthma in the obese

脂联素增强药物治疗肥胖哮喘的新作用

• 批准号: 8726688
• 负责人: AKSHAY SOOD
• 金额: $ 39.51万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8726688
• 关键词: Novel; role; adiponectin; enhancing; drugs

DESCRIPTION (provided by applicant): Asthma is a chronic lung disease that affects 8.2% of all American adults, particularly obese individuals. Current treatment for asthma primarily involves inhaled corticosteroids but these drugs are less effective among obese individuals. There is therefore an unmet need to discover more efficacious asthma medications targeting obese individuals. Recent research has shown that low serum concentrations of adiponectin, a unique anti-inflammatory product of adipose tissue, predict both incident asthma and worse clinical severity of asthma in some populations. In addition, low adiponectin is similarly associated with depression and ischemic cardiovascular disease. Potent adiponectin-enhancing drugs include the antidiabetic drug class of thiazolidinediones (TZD) and antihypertensive drug class of angiotensin receptor blockers (ARB). Our overarching hypothesis is that use of adiponectin-enhancing drugs among obese adults can help prevent or treat asthma as well as depression and ischemic cardiovascular disease. Specific Aim 1: To determine the effect of adiponectin-enhancing drugs on incident asthma, depression or ischemic cardiovascular disease among obese subjects with concomitant diabetes and/or hypertension. Based upon our preliminary data, our working primary hypothesis is that TZD and/or ARB use is associated with a lower risk for developing incident asthma than use of other antidiabetic and/or antihypertensive drugs and this association is stronger among women than men. Our secondary hypotheses are that similar beneficial effects are seen with respect to incident depression and incident ischemic cardiovascular disease in this population. The proposed study examines a longitudinal cohort of veteran Americans over two decades, using the Veterans Administration (VA) National Data System. We will conduct parallel analyses for each disease in which we first exclude prevalent disease at 'baseline' visit and analyze incident disease at subsequent visits. Specific Aim 2: To determine the effect of adiponectin-enhancing drugs on risk for disease complications among subjects with that disease (i.e. asthma, depression or ischemic cardiovascular disease) plus obesity plus concomitant diabetes and/or hypertension. Based upon our preliminary data, our working primary hypothesis is that TZD and/or ARB use in our population subgroup with asthma is associated with a lower risk for asthma exacerbations than use of other antidiabetic and/or antihypertensive drugs and this association is stronger among women than men. Our secondary hypotheses are that similar beneficial effects are seen with respect to emergency room visits or hospitalizations from depression or ischemic cardiovascular disease. For Specific Aim 2, we will include only those with prevalent disease in each statistical model and analyze risk for complications related to that disease. Survival analysis will be used to study the events in Aims 1 and 2. If our research shows that adiponectin-enhancing drugs favorably affect the natural history of diseases related to hypoadiponectinemia, it will help develop novel strategies for preventing and treating asthma as well as depression and ischemic cardiovascular disease in the obese.

描述（由申请人提供）：哮喘是一种慢性肺部疾病，影响所有美国成年人，尤其是肥胖个体的8.2％。目前对哮喘的治疗主要涉及吸入的皮质类固醇，但这些药物在肥胖个体中的有效性较小。因此，尚无满足的需要发现针对肥胖个体的更有效的哮喘药物。最近的研究表明，脂肪组织的独特抗炎产物的脂联素的低血清浓度可以预测某些人群中哮喘的入口哮喘和临床严重程度较差。另外，低脂联素与抑郁症和缺血性心血管疾病类似。有效的脂联素增强药物包括噻唑烷二酮（TZD）的抗糖尿病药物类别和血管紧张素受体阻滞剂（ARB）的抗高杂技药物类别。我们的总体假设是，在肥胖成年人中使用脂联素增强药物可以帮助预防或治疗哮喘以及抑郁症和缺血性心血管疾病。具体目的1：确定脂联素增强药物对伴有糖尿病和/或高血压的肥胖受试者中哮喘，抑郁或缺血性心血管疾病的影响。基于我们的初步数据，我们有效的主要假设是，与使用其他抗糖尿病和/或抗高血压药物相比，使用TZD和/或ARB的使用与发生入口哮喘的风险较低，而女性中这种关联比男性更强。我们的次要假设是，在该人群中，在入射抑郁和缺血性心血管疾病方面也可以看到类似的有益作用。拟议的研究研究了使用退伍军人管理局（VA）国家数据系统，研究了二十年来的老将美国人的纵向队列。我们将对每种疾病进行平行分析，其中我们首先在“基线”访问中排除普遍的疾病，并在随后的就诊时分析事件疾病。具体目的2：确定脂联素增强药物对该疾病受试者（即哮喘，抑郁或缺血性心血管疾病）的疾病风险的影响，以及肥胖以及伴随的糖尿病和/或/或高血压。基于我们的初步数据，我们有效的主要假设是，与使用其他抗糖尿病和/或抗疾病的药物相比，与使用其他抗糖尿病和/或抗型药物相比，与哮喘患者的人群亚组中使用TZD和/或ARB相比，这种关联在女性中比男性更强。我们的次要假设是，对于急诊室就诊或抑郁症或缺血性心血管疾病的住院也可以看到类似的有益效果。对于特定目标2，我们将仅包括每个统计模型中患有普遍疾病的患者，并分析与该疾病有关的并发症的风险。生存分析将用于研究目标1和2中的事件。如果我们的研究表明，脂联素增强药物有利地影响与低肾上腺基质血症相关的疾病的自然史，它将有助于制定新的策略，以防止和治疗肥胖症以及肥胖症中的抑郁症和缺血性心血管疾病。