Knowles M R, Olivier K N, Hohneker K W, Robinson J, Bennett W D, Boucher R C
Department of Medicine, University of North Carolina at Chapel Hill.
Chest. 1995 Feb;107(2 Suppl):71S-76S. doi: 10.1378/chest.107.2_supplement.71s.
Cystic fibrosis (CF) is a recessive genetic disease reflecting mutations in the gene coding for the CF transmembrane regulator (CFTR) protein, which normally functions as a cyclic adenosine monophosphate (cAMP)-regulated chloride (Cl-) channel. Functional abnormalities include thick airway secretions resulting from defective cAMP-mediated Cl- (liquid) secretion and a related defect, excessive sodium (Na+) (liquid) absorption. Novel pharmacologic agents are being tested as therapy for these ion transport defects. Aerosolized amiloride inhibits excessive Na+ absorption, and pilot studies in adult patients with CF show slowing of the disease-associated decline in lung function. Clinical trials of amiloride are currently underway in adults and adolescents, and short-term safety studies have been initiated in children. Aerosolized uridine triphosphate (UTP) induces Cl- (and liquid) secretion in CF airway epithelia via non-CFTR Cl- channels. Short-term aerosolized UTP is well tolerated by normal subjects and patients with CF, and pilot studies in normal subjects show that aerosolized UTP is an effective stimulator of mucociliary clearance. Pharmacotherapy that modifies airway epithelial ion transport may provide new opportunities for treatment of CF lung disease.
囊性纤维化（CF）是一种隐性遗传病，反映了编码CF跨膜调节因子（CFTR）蛋白的基因突变，该蛋白通常作为一种环磷酸腺苷（cAMP）调节的氯离子（Cl-）通道发挥作用。功能异常包括由于cAMP介导的Cl-（液体）分泌缺陷导致气道分泌物黏稠，以及相关缺陷，即过量的钠（Na+）（液体）吸收。新型药物正在作为这些离子转运缺陷的治疗方法进行测试。雾化阿米洛利可抑制过量的Na+吸收，对成年CF患者的初步研究表明，与疾病相关的肺功能下降有所减缓。阿米洛利的临床试验目前正在成人和青少年中进行，并且已经在儿童中启动了短期安全性研究。雾化尿苷三磷酸（UTP）通过非CFTR Cl-通道诱导CF气道上皮细胞分泌Cl-（和液体）。正常受试者和CF患者对短期雾化UTP耐受性良好，对正常受试者的初步研究表明，雾化UTP是黏液纤毛清除的有效刺激剂。改变气道上皮离子转运的药物治疗可能为CF肺部疾病的治疗提供新的机会。
