MALNUTRITION AND LUNG DISEASE IN CYSTIC FIBROSIS

描述(申请人提供)：囊性纤维化(CF)是最常见的威胁生命的遗传性疾病，在高加索人中的发病率约为1：3400。虽然慢性萎缩性胃炎在早期婴儿期就开始了，但延迟诊断是很常见的，而且常常会导致严重的、潜在不可逆转的营养不良。阻塞性肺病合并反复呼吸道感染也是不可避免的；大约80%的人死于心肺衰竭，三分之一的人在20岁之前死亡。这项应用的总体目标是通过利用流行病学研究来量化营养不良与慢性肺病之间的联系，以改进对慢性肺病的筛查和治疗。具体目标是：1)通过使用自1985年以来收集的两个持续的免费数据库，即CF基金会患者登记处和威斯康星州新生儿筛查随机对照试验(RCT)，建立营养不良和肺部疾病相关性的预测风险模型，以检验营养不良会恶化肺部疾病的假设；2)通过比较自1994年威斯康星州常规囊性纤维化新生儿筛查计划启动以来通过威斯康星州全州常规囊性纤维化新生儿筛查计划确诊的儿童的营养和肺状况，测试实施常规的全州新生儿筛查计划将提供先前在RCT中证实的类似医疗益处的假设。没有其他调查拥有类似的研究人员和工具来开展拟议的工作。在获得K01奖后，首席研究员已发展成为国家公认的CF流行病学家，在营养和肺部方面都具有特殊的专业知识。她与特定目标1相关的工作已经导致了CF临床实践的变化。鉴于疾控中心2004年的新报告建议在全国范围内实施CF新生儿筛查计划，并进行后续结果研究以评估计划的有效性，完成特定目标2的临床影响在不久的将来也是可以预见的。完成这笔赠款的具体目的将增进我们对营养不良对肺部疾病进展的影响的了解，改变CF的临床实践，改善CF患者的健康结局，并为公共卫生政策制定者解决关于实施常规CF新生儿筛查计划好处的争议。

DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is the most common life-threatening genetic disorder with an incidence of approximately 1:3400 in Caucasians. Although CF begins in early infancy, delayed diagnosis is common and often leads to severe, potentially irreversible malnutrition. Obstructive lung disease with recurrent respiratory infections is also inevitable; about 80 percent die from cardio respiratory failure and one-third die before age 20 years. The overall objective of this application is to quantify the associations between malnutrition and lung disease in CF by utilizing epidemiological studies in order to improve screening and treatment of CF. Specific aims are: 1) to test the hypothesis that malnutrition worsens lung disease, by developing risk models predictive of malnutrition and lung disease associations through the use of two ongoing, complimentary databases collected since 1985, namely, the CF Foundation Patient Registry and the Wisconsin Randomized Controlled Trial (RCT) of CF Neonatal Screening, and 2) to test the hypothesis that implementing a routine statewide neonatal screening program will provide similar medical benefits previously proven in RCT, by comparing the nutritional and pulmonary status of the cohort of children diagnosed through the Wisconsin Statewide Routine Cystic Fibrosis Newborn Screening Program since its inception in 1994 to the Wisconsin RCT cohort. No other investigation has comparable researchers and tools to conduct the proposed work. With a K01 award, the principal investigator has developed into a nationally recognized CF epidemiologist, with special expertise in both nutritional and pulmonary aspects. Her work related to Specifc Aim 1 has already led to changes in the clinical practices of CF. In view of the CDC's new 2004 report that recommends nationwide implementation of CF newborn screening programs with follow-up outcome studies to evaluate program effectiveness, the clinical impact as a result of completing Specific Aim 2 is also foreseeable in the near future. Accomplishing the specific aims of this grant will advance our understanding of the impact of malnutrition on lung disease progression iri CF, change the clinical practices of CF, improve the health outcomes of CF patients, and resolve the controversy on the benefits of implementing routine CF neonatal screening program for public health policy makers.