PULMONARY BENEFITS OF CYSTIC FIBROSIS NEONATAL SCREENING

尽管囊性纤维化（CF）是白种人最常见的致命遗传性疾病，但诊断和转诊到提供全面护理的中心往往会延迟。 因此，在过去的三十年里，人们对建立一种可靠的早期检测这种疾病的方法非常感兴趣。 一个相对较新的进展，似乎有希望涉及测量免疫反应性胰蛋白酶原（IRT）的干新生儿血斑收集在大规模筛选其他先天性代谢缺陷的时间，它已被证明，这种测试可以与DNA分析检测CF突变。 虽然一般认为是有益的，新生儿筛查计划已经负担了三种不良影响：错误（假阳性和假阴性），误解/误解，和污名化。 此外，在对照研究中还没有确定早期诊断对于CF患者通常是成本效益和医学上有益的，特别是对于通常决定个体患者预后的慢性肺病。由于对症状前CF患者实施积极治疗的有效性存在争议，因此在美国开展大规模筛查之前，对获益和风险进行对照研究非常重要。 因此，我们正在研究CF新生儿筛查，以评估潜在的肺部和营养益处，以及医疗和心理社会风险。 我们的设计包括随机筛选一半的新生儿人口的威斯康星州使用胰蛋白酶原放射免疫测定干新生儿血斑耦合DNA分析。 我们正在比较婴儿早期确诊为CF的患者与通过传统医疗服务系统诊断的儿童。 特别注意对这两个群体的营养状况和肺病进行比较评价，并对接受筛查的人口的潜在心理社会问题进行评估。 本研究所验证的假设包括：（1）大多数CF患者可在新生儿时通过IRT/DNA两级筛查试验确诊;（2）CF的早期诊断过程（筛查和汗液测试）不会产生长期有害的心理社会影响;（3）在婴儿早期诊断将防止营养不良和生长迟缓;和（4）在未筛查人群中，那些在新生儿时被诊断患有CF的患者比年龄匹配的患者患肺部疾病的情况更少。

Despite the fact that cystic fibrosis (CF) is the most common lethal hereditary disorder of Caucasians, there are often delays in diagnosis and referral to centers that provide comprehensive care. Thus, over the past three decades, there has been a great deal of interest in establishing a reliable method for early detection of this disease. A relatively recent advance that appears promising involves measurement of immunoreactive trypsinogen (IRT) on dried neonatal blood spots collected at the time of mass screening for other inborn errors of metabolism; it has been shown that this test can be linked to DNA analysis for detecting CF mutations. Although generally considered beneficial, newborn screening programs have been burdened with three kinds of adverse effects: errors (false-positives and false-negatives), miscommunication/ misunderstanding, and stigmatization. Furthermore, it has not been established in a controlled study that early diagnosis will be generally cost-effective and medically beneficial for CF patients, particularly in regard to the chronic lung disease which usually determines an individual patient's prognosis. Because the efficacy of implementing aggressive treatment for presymptomatic CF patients is controversial, it is important to perform a controlled study of both benefits and risks before mass screening is instituted in the United States. Accordingly, we are investigating CF neonatal screening to evaluate both the potential pulmonary and nutritional benefits, as well as the medical and psychosocial risks. Our design involves randomly screening half the newborn population of Wisconsin using the radioimmunoassay for trypsinogen on dried neonatal blood spots coupled to DNA analysis. We are comparing patients identified as having CF during early infancy with children diagnosed through the conventional health care delivery system. Special attention is being given to comparative evaluation of nutritional status and pulmonary disease in the two groups and to assessment of potential psychosocial problems in the screened population. Hypotheses being tested include the following: (1) the majority of CF patients can be diagnosed as neonates by the IRT/DNA two-tiered screening test; (2) the process of early diagnosis (screening and sweat testing) will not have long-term harmful psychosocial impacts; (3) diagnosis in early infancy will prevent malnutrition and growth retardation; and (4) those diagnosed with CF as neonates will have less pulmonary disease than age-matched patients in the unscreened population.