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: 7992500
• 负责人: PHILIP M FARRELL
• 金额: $ 9.98万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7992500
• 关键词: 14 year old; Acceleration; Accounting; Acute; Address; Adolescence; Adolescent; Advisory Committees; Age; Benefits and Risks; Biochemical; Caring; Centers for Disease Control and Prevention (U.S.); Chest; Child; Childhood; Chronic; Chronic Disease; Chronic lung disease; Control Groups; Costs and Benefits; Cystic Fibrosis; DNA analysis; Data; Data Analyses; Databases; Deterioration; Diagnosis; Disease; Disease Progression; Early Diagnosis; Early treatment; Economics; Enrollment; Epidemiologic Studies; Epidemiology; Equation; Evaluation; Evolution; Expert Opinion; Follow-Up Studies; Foundations; Funding; Gender; Gene Mutation; Genetic; Genetic Screening; Genotype; Goals; Growth; Health Policy; Health Services; Healthcare; Heart Diseases; Hereditary Disease; Hospitalization; Impaired cognition; Infection; Investigation; Knowledge; Learning; Life; Living Costs; Long-Term Effects; Lung; Lung diseases; Malnutrition; Marshal; Measures; Methodology; Methods; Modeling; Molecular Genetics; Morbidity - disease rate; Nature; Neonatal Screening; Newborn Infant; Nutritional; Nutritional status; Outcome; Patients; Pediatric Research; Pharmaceutical Preparations; Phase; Phenotype; Poliomyelitis; Population; Prevention; Pseudomonas aeruginosa; Puberty; Pulmonary Cystic Fibrosis; Quality of life; Randomized; Randomized Clinical Trials; Recommendation; Registries; Respiratory Tract Infections; Risk; Risk Factors; Role; Screening procedure; Secondary to; Subgroup; Testing; Time; Treatment Cost; Trypsinogen; United States National Institutes of Health; Vaccines; Wisconsin; adverse outcome; children with cystic fibrosis; clinically significant; cognitive function; cohort; cost; cost effectiveness; cystic fibrosis patients; design; diagnosis standard; dietary supplements; economic outcome; epidemiology study; experience; follow-up; improved; infancy; innovation; interest; meetings; mortality; mucoid; multidisciplinary; outcome forecast; patient population; prospective; psychosocial; research study

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.

描述（由申请人提供）：虽然囊性纤维化 (CF) 是白人中最常见、危及生命的常染色体隐性遗传病，但诊断常常会出现延误，但可以通过使用 DNA 分析进行新生儿筛查来克服这些问题。该项目的总体目标是解决以下假设：通过新生儿筛查早期诊断囊性纤维化将在医学上有益，且无重大风险。 “医学上有益”是指更好的长期营养和/或肺部状况，有望带来更好的生活质量（QoL）。具体目标包括评估整个童年时期的营养状况，包括心理社会和认知功能等相关结果；肺部疾病的演变、进展和流行病学；和新生儿筛查的成本效益。自 1985 年以来，一直在进行一项以早期诊断为关键变量的全面、随机临床试验，其中包括筛选和对照 CF 患者，这些患者参加了有史以来最长的儿童慢性病队列随访研究。通过人体测量和生化方法评估了营养状况，结果表明筛查组的幼儿有显着的益处。然而，需要更多数据才能得出结论的有趣观察包括早期营养不良导致的永久性生长迟缓以及与延迟诊断相关的明显认知功能改变的证据。筛选组和对照组的肺部结果也获得了令人兴奋的数据，但结果仍不确定。需要澄清关于慢性肺病决定因素的流行病学发现，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，回答有关肺部结果的关键问题将需要五年以上的随访评估。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。 CF 基金会资助的一项综合研究中获得的心理社会数据将用于我们分析与新生儿筛查相关的长期成本和计算成本效益。如果剩下的问题得到满意的回答，新生儿筛查很可能将成为全国范围内识别新发 CF 病例的常规方法，并且在婴儿早期进行诊断将有助于预防许多临床重大问题。该项目的结果导致 19 个州目前正在筛查新生儿 CF，而其他州则正在考虑胰蛋白酶原/DNA 检测，但迫切需要更多有关营养、肺、心理和经济结果的数据来支持新的卫生政策计划。该项目有可能通过促进所有新生儿的分子遗传学筛查对医疗保健产生相当大的影响。