Obesity-related Host Susceptibility Factors for Asthma in Women

描述（由申请人提供）：候选人是一名临床训练有素的肺科医生，最近在新墨西哥大学开始了转化研究的职业生涯。候选人的长期目标是建立一个完全资助的独立研究生涯，并在哮喘流行病学领域发挥国家领导作用。他对研究肥胖相关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日常临床观察中发展起来的，这促使候选人再次强调他在研究期间接受的流行病学培训。拟议的职业发展计划包括一个多学科项目，旨在提供密集的、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。在资深研究员Marianne Benwick博士、Mark Schuyler博士和Clifford Quails博士的指导下，候选人将研究中枢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哮喘的特定生理和病理生理亚表型。特异性目的1将通过对200例经甲胆碱挑战证实的哮喘绝经前妇女的横断面研究，检验中枢性肥胖与预后指标之间的关系。气道结局测量包括甲胆碱支气管激发后的动态恶性膨胀，以及诱导痰和呼出冷凝水中嗜酸性粒细胞炎症和氧化应激标志物。特异性目标2涉及一个嵌套的前瞻性队列，包括19名肥胖和19名体重正常的哮喘女性痛经。将研究昼夜和经期相关的血清瘦素/脂联素比值生理变化对ainn/ay结局指标的影响。在2004年NHLBI举办的“肥胖与哮喘”研讨会上，这一研究领域被认为是一个高度优先事项。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，进而可能为治疗和预防哮喘提供新的方法。相关性（见说明）：本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，进而可能为治疗和预防哮喘提供新的方法。本研究亦将为临床医师提供指导训练，以发展以病人为导向的研究事业。（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)