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Cynthia McEhrs（医学博士）培养为独立的临床医生-科学家，专门从事新生儿和婴儿肺功能测试的研究。McEhrman博士是一名经过委员会认证的儿科医生，接受过儿科学的亚专业培训。指导的职业发展计划包括三个层次的方法：教学教育导致临床研究硕士学位，基础广泛的体验式学习计划和指导的临床研究经验。主要目标是使McEhran博士在各方面都能独立地作为临床研究者。McEhran博士目前就读于俄勒冈州健康与科学大学（OHSU）的人类调查项目。这是一个为期两年的K30（NIH）进行的计划，目的是发展以患者为导向的研究技能。指导研究将在导师委员会的指导下进行，该委员会由OHSU医学信息学和成果研究教授Cynthia Morris博士、OHSU公共卫生和预防医学教授Sonia Buist博士、OHSU生物统计学家Dawn Peters博士和儿科肺病科主任Michael Wall博士组成。来自南加州大学的Manuel Durand博士将担任场外导师和委员会成员。这项研究是一项前瞻性盲法试验，旨在确定吸烟孕妇补充维生素C是否可以阻断吸烟对胎儿肺部发育的宫内影响。大约12%的妇女在怀孕期间吸烟，每年至少有50万名婴儿出生在吸烟环境中。这些婴儿出生时肺功能改变，呼吸道疾病发病率增加，包括儿童哮喘增加。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。 尼古丁的一些受体介导的作用需要活性氧中间体，并且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，与在妊娠期间随机接受安慰剂的吸烟母亲所生的婴儿相比，在妊娠期间随机接受补充维生素C的吸烟母亲所生的婴儿在12月龄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.