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，但在诊断和转诊到提供综合护理的中心时往往会出现延误。因此，在过去三十年中，人们对建立一种早期发现这种疾病的可靠方法非常感兴趣。一项相对较新的进展似乎很有希望，包括在大规模筛查其他先天性代谢错误时收集的干燥新生儿血斑上测量免疫反应性胰蛋白酶原（IRT）；研究表明，该测试可以与检测CF突变的DNA分析联系起来。尽管通常认为新生儿筛查是有益的，但它也背负着三种不良影响：错误（假阳性和假阴性）、错误沟通/误解和污名化。此外，在对照研究中尚未确定早期诊断对CF患者通常具有成本效益和医学上有益，特别是对于通常决定个体患者预后的慢性肺部疾病。由于对症状前CF患者实施积极治疗的有效性存在争议，因此在美国进行大规模筛查之前，对获益和风险进行对照研究是很重要的。因此，我们正在研究CF新生儿筛查，以评估潜在的肺和营养益处，以及医疗和社会心理风险。我们的设计包括随机筛选威斯康星州一半的新生儿，使用放射免疫法在干燥的新生儿血斑上检测胰蛋白酶原，并结合DNA分析。我们将婴儿期早期确诊为CF的患者与通过传统医疗保健系统确诊的儿童进行比较。目前特别注意对两组患者的营养状况和肺部疾病进行比较评价，并对筛查人群中潜在的社会心理问题进行评估。被检验的假设包括：(1)大多数CF患者可以通过IRT/DNA两层筛选试验诊断为新生儿；(2)早期诊断过程（筛查和汗液检测）不会产生长期有害的心理社会影响；(3)婴儿期早期诊断可预防营养不良和生长迟缓；(4)与未筛查人群中年龄匹配的患者相比，新生儿诊断为CF的患者肺部疾病较少。

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.