Obesity-related Host Susceptibility Factors for Asthma in Women

描述(由申请人提供)：应聘者是一名受过临床训练的肺科医生，最近开始在新墨西哥大学从事翻译研究。这位候选人的长期目标是建立一个资金充足的独立研究生涯，并在哮喘流行病学领域提供全国领先地位。他感兴趣的是研究肥胖相关宿主易感因素在女性哮喘中的作用。对这一领域的兴趣是在常规临床观察期间产生的，这促使应聘者重新强调他在研究员期间接受的流行病学培训。拟议的职业发展计划结合了一个多学科计划，旨在提供紧张的、密切指导的、以患者为导向的研究经验，并结合与候选人的项目和职业目标相关的特定能力的结构化教学课程。在高级研究人员玛丽安·本威克博士、马克·舒勒医学博士和克利福德·奎斯博士的指导下，候选人将调查中心性肥胖和血清脂肪因子的促炎平衡是否影响患有哮喘的绝经前妇女哮喘的特定生理和病理生理亚型。具体目标1将通过对200名患有乙酰胆碱激发确诊哮喘的绝经前妇女的横断面研究，检验中心性肥胖和主要结局指标之间的关联。气道结果测量包括乙酰甲胆碱、支气管刺激后的动态过度充气，以及诱导痰和呼出的呼吸冷凝物中的嗜酸性炎症和氧化应激的标志物。具体目标2涉及19名肥胖和19名正常体重的哮喘正常月经妇女的嵌套前瞻性队列。将研究与每日和月经时相有关的血清瘦素/脂联素比率的生理性变化对IAN/AY预后指标的影响。在2004年NHLBI关于肥胖和哮喘的研讨会上，这一研究领域被认为是一个高度优先的领域。这项研究可能有助于确定肥胖和哮喘之间关系的机制基础，这反过来可能使治疗和预防哮喘的新方法成为可能。相关性(见说明书)：这项研究可能有助于确定女性哮喘和肥胖相关宿主易感因素之间关系的机制基础，这反过来可能使治疗和预防哮喘的新方法成为可能。这项研究还将为临床医生提供以患者为导向的研究生涯的指导培训。(摘要结束)

DESCRIPTION (provided by applicant): The candidate is a clinically trained pulmonologist who has recently embarked on a career in translational research at the University of New Mexico. The candidate's long-term objective is to establish a fully funded, independent research career and provide national leadership in the field of asthma epidemiology. He is interested in investigating the role of obesity-related host susceptibility factors for asthma in women. Interest in this field developed during routine clinical observations that prompted the candidate to re-emphasize his past training in epidemiology during his fellowship. The proposed career development plan incorporates a multi-disciplinary program designed to provide an intense, closely mentored, patient-oriented research experience in association with a structured didactic curriculum in specific competencies related to the candidate's project and career goals. Under the mentorship of senior investigators, Marianne Benwick, Ph.D., Mark Schuyler, MD and Clifford Quails, Ph.D., the candidate will investigate whether central adiposity and the pro-inflammatory balance of serum adipokines affect specific physiologic and pathophysiologic sub- phenotypes of asthma in pre-menopausal women with asthma. Specific Aim 1 will examine the association between central adiposity and ainway outcome measures, using a cross-sectional study of 200 pre- menopausal women with methacholine challenge-confirmed asthma. Airway outcome measures include dynamic hyperinflation following methacholine bronchoprovocation and markers of eosinophilic inflammation and oxidant stress in induced sputum and exhaled breath condensate respectively. Specific Aim 2 involves a nested prospective cohort of 19 obese and 19 normal weight eumenorrheic women with asthma. The effect of diurnal and menstrual phase-related physiological variation in serum leptin to adiponectin ratio on ainn/ay outcome measures will be studied. This area of research is considered a high priority at the 2004 workshop on 'Obesity and Asthma' by the NHLBI. This study may help define the mechanistic basis forthe relationship between obesity and asthma, which in turn may make possible newer ways of treatment and prevention of asthma. RELEVANCE (See instructions): This study may help define the mechanistic basis for the relationship between asthma and obesity-related host susceptibility factors in women, which in turn may make possible newer ways of treatment and prevention of asthma. This study will also provide mentored training to a clinician for a patient-oriented research career. (End of Abstract)