Pulmonary Benefits of Cystic Fibrosis Neonatal Screening

描述（由申请人提供）：尽管囊性纤维化（CF）是白人人群中最常见的、危及生命的常染色体隐性遗传疾病，但诊断经常会有延误，但这些可以通过使用DNA分析进行新生儿筛查来克服。该项目的总体目标是解决以下假设：通过新生儿筛查对CF进行早期诊断在医学上是有益的，而不会产生重大风险。“医学上有益”是指更好的长期营养和/或肺状态，有望导致更好的生活质量（QoL）。具体目标包括评估整个儿童时期的营养状况，包括相关结果，如社会心理和认知功能；肺部疾病的演变、进展和流行病学；以及新生儿筛查的成本效益。自1985年以来，一项以早期诊断为关键变量的全面随机临床试验已经开始进行，该试验纳入了筛查和对照的CF患者，这些患者参加了有史以来最长的儿童期慢性疾病队列随访研究。通过人体测量学和生化方法评估了营养状况，结果表明筛查组的幼儿有显著的益处。然而，需要更多数据才能得出结论的有趣观察结果包括早期营养不良导致永久性生长迟缓的证据，以及与延迟诊断相关的明显认知功能改变。在筛查组和对照组的肺预后方面也获得了令人振奋的数据，但结果仍不确定。关于慢性肺病决定因素的流行病学发现需要澄清，包括基因型-表型关系、营养不良的影响以及呼吸道感染在引起结构性肺损伤中的作用。因此，回答有关肺预后的关键问题将需要5年以上的随访评估。此外，需要扩展对生活质量和成本效益的研究，以完成这些独特的组成部分。在CF基金会资助的一项综合研究中获得的社会心理数据将用于我们对新生儿筛查相关的长期成本的分析和成本效益的计算。如果剩下的问题得到了很好的回答，新生儿筛查很可能会成为全国范围内识别CF新病例的常规方法，并且在婴儿早期进行诊断将可以预防许多临床重大问题。该项目的结果导致19个州目前正在对新生儿进行CF筛查，而其他州正在考虑进行胰蛋白酶原/DNA检测，但迫切需要更多关于营养、肺、社会心理和经济结果的数据，以支持新的卫生政策计划。该项目通过促进所有新生儿的分子遗传学筛查，有可能对医疗保健产生重大影响。

DESCRIPTION (provided by applicant): Although cystic fibrosis (CF) is the most common, life-threatening autosomal recessive genetic disorder of the white population, there are often delays in diagnosis, but these can be overcome with newborn screening using DNA analysis. The project's overall goal is to address the following hypothesis: Early diagnosis of CF through neonatal screening will be medically beneficial without major risks. "Medically beneficial" refers to better long term nutritional and/or pulmonary status, hopefully leading to better quality of life (QoL). Specific aims include assessment of nutritional status throughout childhood, including associated outcomes such as psychosocial and cognitive functioning; the evolution, progression and epidemiology of lung disease; and newborn screening cost effectiveness. A comprehensive, randomized clinical trial with early diagnosis as the key variable has been underway since 1985 and has involved screened and control CF patients enrolled in the longest cohort follow-up study ever for a chronic disease of childhood. Nutritional status has been assessed by anthropometric and biochemical methods and the results have demonstrated significant benefits in young children of the screened group. Intriguing observations requiring more data for conclusions, however, include evidence of permanent growth retardation from early malnutrition and apparently altered cognitive function associated with delayed diagnosis. Provocative data have also been obtained on pulmonary outcomes in the screened and control groups, but the results remain inconclusive. Epidemiologic findings on the determinants of chronic lung disease need to be clarified, including genotype-phenotype relationships, the impact of malnutrition, and the role of respiratory infections in causing structural lung damage. Thus, answering key questions about pulmonary outcomes will require five more years of follow-up evaluation. In addition, studies on QoL and cost effectiveness need to be extended to complete these unique components. Psychosocial data obtained in an integrated study funded by the CF Foundation will be used in our analyses of the long-term costs associated with newborn screening and calculation of cost-effectiveness. If the remaining questions are answered favorably, it is likely that newborn screening will become the routine method nationwide for identifying new cases of CF and that diagnosis in early infancy will allow prevention of many clinically significant problems. Results from this project have led to 19 states currently screening newborns for CF, while others are considering trypsinogen/DNA testing, but more data on nutritional, pulmonary, psychosocial and economic outcomes are sorely needed to support new health policy plans. This project has the potential to impact healthcare quite significantly by promoting molecular genetics screening of all newborn infants.