PULMONARY BENEFITS OF CYSTIC FIBROSIS NEONATAL SCREENING

囊性纤维化新生儿筛查对肺部的益处

• 批准号: 2391365
• 负责人: PHILIP M FARRELL
• 金额: $ 40.49万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2391365
• 关键词: Pseudomonas aeruginosa; cystic fibrosis; diagnosis procedure safety; diagnosis quality /standard; early diagnosis; enzyme linked immunosorbent assay; gender difference; genetic counseling; health care cost /financing; human subject; inborn metabolism disorder diagnosis; longitudinal human study; mass screening; medical complication; middle childhood (6-11); newborn human (0-6 weeks); preschool child (1-5); prognosis; pulsed field gel electrophoresis; radioimmunoassay; respiratory disorder epidemiology; respiratory infections; statistics /biometry; trypsinogen

Although cystic fibrosis (CF) is the most common, severe autosomal recessive genetic disorder of the white population, there are often delays in diagnosis and hence initiation of treatment. This problem has made CF neonatal screening seem attractive. It has not been established in a controlled study, however, that early treatment achieved by neonatal diagnoses will be medically beneficial for CF patients, nor have the risks been fully defined. Advances of the past decade have made CF screening feasible using routinely collected neonatal blood specimens and determining immunoreactive trypsinogen (IRT) levels and CF mutations by DNA analyses. Applying the IRT assay and more recently a two-tiered IRT/DNA method, we have successfully conducted a unique controlled study of both benefits and risks of CF neonatal screening. Using a randomized design, we screen half of the Wisconsin newborn population in the neonatal period to generate an early diagnosis/treatment group, whereas the other half (control or standard diagnosis group) has "blind" IRT or IRT/DNA testing performed, with the results not reported until the child is 4 years old; prior to that time, CF is diagnosed in the control group based on the standard approach requiring either symptoms or a positive family history. This experimental design, coupled to our comprehensive surveillance system, allows an unbiased, complete evaluation of the two groups. Randomized screening has been underway for almost nine years, and progress has been good, with results thus far indicating a number of potential advantages of CF screening. Continuous accrual of study patients from over 600,000 screening tests has generated sufficient enrolled subjects to meet our prespecified goal during 1994 and provide enough statistical power for conclusions. However, our annual statistical analyses have not yet demonstrated significant pulmonary or nutritional benefits in the screened group, although favorable trends are emerging. With continuation of funding, we should be able to accept or reject the following hypothesis: neonatal screening for cystic fibrosis will be medically beneficial without major risks. Answering the key question about pulmonary benefits will require three more years of follow-up evaluation. Extension of the evaluation phase would also make it possible to delineate fundamental epidemiologic characteristics of CF allow us to define the course of childhood cystic fibrosis in quantitative terms, and elucidate risk factors for colonization and infection with Pseudomonas aeruginosa in the respiratory tract. We believe that if the questions underlying this study are answered favorably, neonatal screening using a combination of IRT and DNA tests will become the routine method for identifying new cases of CF, and that diagnosis in early infancy will allow prevention of many clinically significant problems such as malnutrition. If CF neonatal screening is implemented nationally, however, several epidemiologic gaps must be closed, including more precise data on the incidence and course of this disease, and determination of risk factors for pulmonary infection; this project will generate that important information.

尽管囊性纤维化（CF）是最常见的，严重的常染色体 白人人口的隐性遗传疾病，通常会有延迟 在诊断中，因此开始治疗。这个问题使CF 新生儿筛查似乎很有吸引力。它尚未建立 但是，对照研究，新生儿实现的早期治疗 诊断对CF患者对医学有益，也没有风险 已完全定义。过去十年的进步进行了CF筛查 使用常规收集的新生儿血液标本和可行 通过确定免疫反应性胰蛋白酶原（IRT）水平和CF突变 DNA分析。应用IRT分析，最近是两层 IRT/DNA方法，我们成功地进行了一项独特的对照研究 CF新生儿筛查的好处和风险。使用随机 设计，我们筛选了新生儿中威斯康星州新生儿的一半 产生早期诊断/治疗组的时期，而另一个 一半（对照或标准诊断组）具有“盲”或IRT/DNA 进行的测试进行了，直到孩子4岁时才报告结果 年龄；在此之前，在基于对照组中诊断出CF 在需要症状或积极家庭的标准方法上 历史。这种实验设计，加上我们的综合 监视系统，允许对两者进行公正，完整的评估 组。随机筛查已经进行了将近九年，并且 进度一直很好，到目前为止的结果表明了许多 CF筛选的潜在优势。研究患者的连续应计 超过60万次筛选测试已经产生了足够的注册 受试者在1994年实现我们预先指定的目标并提供足够的目标 结论的统计能力。但是，我们的年度统计 分析尚未显示出明显的肺或营养 筛选小组的好处，尽管有利的趋势正在出现。 通过持续资金，我们应该能够接受或拒绝 以下假设：囊性纤维化的新生儿筛查将是 没有重大风险的医学有益。回答有关的关键问题 肺部益处将需要再进行三年的随访评估。 评估阶段的扩展也将使划定 CF的基本流行病学特征使我们能够定义 用定量术语和阐明儿童囊性纤维化的过程 在铜绿假单胞菌中定植和感染的危险因素 呼吸道。我们相信，如果提出问题的问题 研究得到有利的回答，新生儿筛查结合 IRT和DNA测试将成为识别新病例的常规方法 CF和婴儿早期诊断将允许预防许多 临床上的重要问题，例如营养不良。如果CF新生儿 但是，筛查是在全国范围内实施的，但是几个流行病学差距 必须关闭，包括有关发生率和过程的更精确的数据 这种疾病，并确定肺部感染的危险因素； 该项目将产生重要的信息。