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.

虽然囊性纤维化（CF）是最常见的，但严重的常染色体 白人隐性遗传病，经常出现延误 诊断并开始治疗。这个问题让CF 新生儿筛查似乎很有吸引力。它尚未建立在 然而，对照研究表明，新生儿的早期治疗 诊断对囊性纤维化患者有医学上的益处，也没有风险 已被完全定义。过去十年的进步使得CF筛查 使用常规采集的新生儿血液样本是可行的 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 分析和最近的两层分析 IRT/DNA方法，我们成功地进行了独特的对照研究 CF 新生儿筛查的益处和风险。使用随机 设计中，我们对威斯康星州一半的新生儿进行了筛查 产生早期诊断/治疗组的时期，而其他时期 一半（对照组或标准诊断组）进行“盲”IRT 或 IRT/DNA 进行测试，直到孩子 4 岁才报告结果 岁；在此之前，基于对照组的 CF 被诊断为 标准方法需要症状或阳性家庭 历史。这个实验设计，加上我们的综合 监控系统，可以对两者进行公正、完整的评估 组。随机筛查已经进行了近九年，并且 进展良好，迄今为止的结果表明一些 CF 筛查的潜在优势。研究患者的持续增加 超过 600,000 次筛选测试已产生足够的注册 科目以达到我们在 1994 年预定的目标并提供足够的 结论的统计功效。然而，我们每年的统计 分析尚未证明显着的肺部或营养 尽管正在出现有利的趋势，但筛选组仍受益匪浅。 随着资助的持续，我们应该能够接受或拒绝 以下假设：新生儿囊性纤维化筛查将 具有医疗益处且无重大风险。回答有关的关键问题 肺部益处将需要三年以上的随访评估。 评估阶段的延长也将有可能划定 CF 的基本流行病学特征使我们能够定义 定量地描述儿童囊性纤维化的过程，并阐明 铜绿假单胞菌定植和感染的危险因素 呼吸道。我们相信，如果这背后的问题 研究得到了积极的答复，新生儿筛查结合使用 IRT 和 DNA 检测将成为识别新病例的常规方法 CF 的发生，并且在婴儿早期进行诊断将有助于预防许多 临床上重大的问题，例如营养不良。如果 CF 新生儿 筛查在全国范围内实施，但存在一些流行病学差距 必须关闭，包括有关发病率和病程的更准确数据 这种疾病，并确定肺部感染的危险因素； 该项目将产生重要信息。