Obesity-related Host Susceptibility Factors for Asthma in Women

描述（由申请人提供）：候选人是一名经过临床培训的肺病学家，最近在新墨西哥州大学从事转化研究。候选人的长期目标是建立一个完全资助的，独立的研究生涯，并在哮喘流行病学领域提供国家领导。他对研究肥胖相关的宿主易感因素在女性哮喘中的作用感兴趣。对这一领域的兴趣是在常规临床观察中发展起来的，这促使候选人在研究期间重新强调他过去在流行病学方面的培训。拟议的职业发展计划包括一个多学科的计划，旨在提供一个激烈的，密切指导，以病人为导向的研究经验，与结构化的教学课程，在相关的候选人的项目和职业目标的具体能力。在高级调查员玛丽安·本威克博士的指导下，Mark斯凯勒，医学博士和Clifford Quails，博士，候选人将研究中心性肥胖和血清脂肪因子的促炎平衡是否影响绝经前哮喘妇女的哮喘的特定生理和病理生理亚表型。具体目标1将使用对200名患有乙酰甲胆碱激发证实的哮喘的绝经前妇女的横断面研究来检查中枢性肥胖与气道结局指标之间的关联。气道结果指标包括乙酰甲胆碱支气管激发后的动态过度充气，诱导痰和呼出气冷凝液中的嗜酸性粒细胞炎症和氧化应激标志物。具体目标2涉及一个嵌套的前瞻性队列，包括19名肥胖和19名正常体重的女性哮喘患者。将研究昼夜和月经期相关的血清瘦素与脂联素比值的生理变化对ainn/ay结果测量的影响。在2004年NHLBI举办的“肥胖和哮喘”研讨会上，这一研究领域被视为高度优先事项。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（参见说明）：这项研究可能有助于确定女性哮喘与肥胖相关宿主易感因素之间关系的机制基础，这反过来可能会使哮喘的治疗和预防成为可能。这项研究还将提供指导培训，以临床医生为导向的研究生涯。 (End摘要）

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)