BIOMARKERS OF DISEASE PROGRESSION IN CHILDREN W/CF IDENTIFIED BY NEWBORN SCREEN

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。囊性纤维化（CF）是一种多系统遗传性疾病，以胰腺损伤、生长不良、营养不良、慢性肺部疾病和潜在的肝脏疾病为特征。众所周知，这些特征都可能出现在婴儿身上。肺部疾病的进展决定生存；然而，其他异常与这种进展的关系尚不完全清楚。此外，考虑到在年轻时进行肺功能检查的困难，需要改进肺部疾病的标志物。早期识别肝脏受累可能会改善肝病患者的治疗方法。在这项研究中，我们的目标是开发一组CF疾病进展的生物标志物，可以预测儿童后期的预后。我们还测试了这组生物标志物在预测预后（最重要的是肺预后）方面的有效性。我们正在测试的生物标志物有：血清免疫反应性胰蛋白酶原和脂肪酶、粪便弹性酶、人体测量学、用于评估骨密度的DEXA、脂溶性维生素和胡萝卜素水平、推测的炎症标志物（c反应蛋白、弹性酶α 1抗蛋白酶复合物、IL-6、ECP髓过氧化物酶）、胸部CT扫描、肝脏疾病的全身标志物和鼻电位差测量。我们的长期目标是利用疾病进展的生物标志物作为早期干预的基础。CF的新生儿筛查可能会变得更加普遍，因此通过新生儿筛查确定的人群中疾病进展的生物标志物的开发是一个重要的目标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cystic fibrosis (CF) is a multi-system hereditary disease characterized by pancreatic injury, poor growth, under-nutrition, chronic pulmonary disease, and the potential for hepatic disease. It is known that each of these features can be present in infants. The progression of lung disease determines survival; however how the other abnormalities relate to this progression is incompletely understood. In addition, given the difficulty with performing pulmonary function tests at a young age improved markers for lung disease are needed. The early recognition of liver involvement may allow improved treatment approaches for those patients who have hepatic disease. Within this study we aim to develop a panel of biomarkers of disease progression in CF that can predict outcome in later childhood. We also test the usefulness of this panel of biomarkers in predicting outcome most importantly pulmonary outcome. The biomarkers that we are testing are: Serum immunoreactive trypsinogen and lipase, fecal elastase, anthropometrics, DEXA to assess bone density, fat soluble vitamin and carotene levels, putative markers of inflammation: (c-reactive protein, elastase alpha one antiprotease Complexes, IL-6, ECP Myeloperoxidase), CT scan of the chest, Systemic markers of hepatic disease, and Nasal Potential Difference Measurements. Our long term objective is to use biomarkers of disease progression as a basis for early intervention. Newborn screening for CF is likely to become more widespread and hence the development of biomarkers for disease progression in a population identified through newborn screening is an important goal.