In-Utero Smoke, Vitamin C and Newborn Lung Function

描述(由申请人提供)： 本申请提出了一项培训计划，旨在将医学博士辛西娅·麦克沃伊培养成一名独立的临床医生和科学家，专门从事新生儿和婴儿肺功能测试的研究。麦克埃沃伊博士是一名具有委员会认证的儿科医生，接受过新生儿学专科培训。指导职业发展计划包括三个层次的方法：获得临床研究硕士学位的教学教育，基础广泛的体验式学习计划，以及指导临床研究经验。麦克埃沃伊博士的主要目标将是在所有方面实现作为临床调查员的独立。麦克埃沃伊博士目前在俄勒冈健康与科学大学(OHSU)参加人类调查项目。这是一项为期两年的K30(NIH)项目，旨在培养以患者为中心的研究技能。指导研究将在指导委员会的指导下进行，指导委员会的成员包括OHSU医学信息学和结果研究教授辛西娅·莫里斯博士、OHSU公共卫生和预防医学教授索尼娅·比斯特博士、OHSU生物统计学家道恩·彼得斯博士和儿科肺病科主任迈克尔·沃尔博士。南加州大学的曼努埃尔·杜兰德博士将担任非现场导师和委员会成员。这项拟议的研究是一项前瞻性的盲法试验，旨在确定给吸烟孕妇补充维生素C是否可以阻止吸烟对胎儿肺发育的宫内影响。大约12%的女性在怀孕期间吸烟，每年至少有50万名婴儿出生时暴露在烟雾中。这些婴儿在出生时改变了肺功能，并增加了呼吸道疾病，包括儿童哮喘的增加。我们假设尼古丁与发育中的肺中的尼古丁受体相互作用，导致生长和肺功能改变。尼古丁受体介导的一些活动需要活性氧中间体，并可能被抗氧化剂维生素C阻断，这一点得到了灵长类动物数据的支持。主要目的是确定补充维生素C可以阻断吸烟对出生时测量的胎儿肺发育/肺功能的宫内影响。第二个目的是证明怀孕期间随机服用维生素C的吸烟母亲所生的婴儿与怀孕期间随机服用安慰剂的吸烟母亲所生的婴儿相比，12个月大时的肺功能有所改善。

DESCRIPTION (provided by applicant): This application proposes a training program to develop Cynthia McEvoy, MD, into an independent clinician-scientist specializing in investigations of pulmonary function testing in neonates and infants. Dr. McEvoy is a board certified Pediatrician with subspecialty training in neonatology. The mentored career development plan consists of a three-tiered approach: a didactic education resulting in a Master in Clinical Research degree, a broad-based experiential learning program, and a mentored clinical research experience. The primary goal will be for Dr. McEvoy to achieve independence as a clinical investigator in all respects. Dr. McEvoy is currently enrolled in the Humans Investigation Program at Oregon Health and Science University (OHSU). This is a two-year K30 (NIH) conducted program for the purposes of developing patient-oriented research skills. Mentored research will be conducted under the direction of a mentorship committee composed of Dr. Cynthia Morris, Professor of Medical Informatics and Outcomes Research, OHSU;Dr. Sonia Buist, Professor of Public Health and Preventive Medicine, OHSU; Dr. Dawn Peters, biostatistician, OHSU; and Dr. Michael Wall, Chief, Division of Pediatric Pulmonology. Dr. Manuel Durand from the University of Southern California will serve as an off-site mentor and committee member. The proposed research is a prospective blinded trial to determine if supplemental Vitamin C given to smoking pregnant women can block the in utero effects of smoking on fetal lung development. About 12% of women smoke during pregnancy with at least 500,000 smoke-exposed babies born per year. These infants have altered pulmonary function at birth with increased respiratory morbidities including increased childhood asthma. We hypothesize that nicotine interacts with nicotinic receptors in the developing lung, causing altered growth and pulmonary function. Some of nicotine's receptor mediated actions need reactive oxygen intermediates and may be blocked by the anti-oxidant Vitamin C. This is supported by data in primates. The primary aim is to establish that supplemental Vitamin C can block the in utero effects of smoking on fetal lung development/pulmonary function measured at birth. A secondary aim is to document that infants delivered to smoking mothers randomized to supplemental Vitamin C during gestation have improved pulmonary function at 12 months of age compared to infants delivered to smoking mothers randomize to placebo during gestation.