NASAL ELECTRIC POTENTIAL DIFFERENCE IN NORMAL AND CYSTIC FIBROSIS PATIENTS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 囊性纤维化（CF）是白种人最常见的致死性遗传病。 CF是由编码囊性纤维化跨膜传导调节因子（CFTR）的基因突变引起的，CFTR在受影响的上皮细胞的顶膜中形成氯离子通道。 由于CFTR的功能缺陷，受影响的上皮细胞具有异常的跨上皮电解质转运。 在包括鼻上皮在内的气道上皮中，囊性纤维化缺陷被测量为异常增加的电压和对调节氯离子转运的试剂的异常反应。 缺乏氯离子转运是CF的诊断标准。 此外，基础Vt的增加和灌注阿米洛利后Vt的变化与CF的发病机制有关。 然而，先前的数据表明，这可能对疾病的发病机制没有意义。 因此，这些研究者提出了三个假设：a）鼻Vt测量可用作评价体内CFTR功能和CFTR基因转移至气道上皮的终点; B）没有CF但患有支气管扩张症的人将具有异常钠或氯转运，如通过鼻Vt方案所测量的;和c）增加VtAmil的干预不会导致囊性纤维化肺病。

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 the most common lethal genetic disease of Caucasians. CF is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) which forms a chloride channel in the apical membrane of affected epithelia. As a result of the defective function of the CFTR, affected epithelia have abnormal transepithelial electrolyte transport. In airway epithelia, including the nasal epithelium, the cystic fibrosis defect is measured as an abnormally increased voltage and an abnormal response to agents that modulate chloride transport. The lack of chloride transport is a diagnostic criteria for CF. In addition, an increase in basal Vt and the change in Vt after perfusion with amiloride have been implicated by others in the pathogenesis of CF. However, previous data suggest this may not be of significance for the pathogenesis of the disease. Thus, these investigators have developed three hypotheses: a) nasal Vt measurement can be used as an end point for evaluating CFTR function and CFTR gene transfer to airway epithelia in vivo; b) people wihout CF but with bronchiectasis will have an abnormal sodium or chloride transport as measured by the nasal Vt protocol; and c) interventions that increase the VtAmil will not result in cystic fibrosis lung disease.