Knowles M R, Olivier K, Noone P, Boucher R C
Division of Pulmonary Diseases, University of North Carolina at Chapel Hill 27599-7020.
Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 2):S65-9. doi: 10.1164/ajrccm/151.3_Pt_2.S65.
Cystic fibrosis (CF) is a recessive genetic disease with thickened airway secretions that result from abnormal airway epithelial ion transport, including defective cyclic AMP-mediated Cl- (liquid) secretion and excessive Na+ (liquid) absorption. These abnormalities reflect mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which normally functions as a cyclic AMP-regulated Cl- channel. Aerosolized pharmacologic agents are being tested as novel treatment for these genetic ion transport defects. Amiloride aerosol inhibits excessive Na+ absorption, and pilot studies in adult patients with CF show improved biorheology and mucociliary clearance of airway secretions, as well as slowing of the decline in lung function. Phase III studies of amiloride in adults and adolescents are underway, and short-term safety studies in children are under way. Aerosolized uridine triphosphate (UTP) induces Cl- secretion in CF airway epithelia via non-CFTR Cl- channels. Initial safety studies suggest that acute aerosolized UTP is well tolerated, and acute studies of the effect on mucociliary clearance are underway. Pharmacotherapy that targets abnormal ion transport holds promise for the treatment of CF airway disease.
囊性纤维化（CF）是一种隐性遗传病，其气道分泌物增厚是由气道上皮离子转运异常所致，包括环磷酸腺苷（cAMP）介导的氯离子（Cl-，液体）分泌缺陷和钠离子（Na+，液体）过度吸收。这些异常反映了编码囊性纤维化跨膜传导调节因子（CFTR）蛋白的基因突变，该蛋白通常作为一种受cAMP调节的Cl-通道发挥作用。雾化药物正在作为这些遗传性离子转运缺陷的新型治疗方法进行测试。氨氯地平雾化剂可抑制过度的Na+吸收，对成年CF患者的初步研究表明，其可改善生物流变学和气道分泌物的黏液纤毛清除功能，并减缓肺功能下降。氨氯地平在成人和青少年中的III期研究正在进行，在儿童中的短期安全性研究也在进行中。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-。初步安全性研究表明，急性雾化UTP耐受性良好，对黏液纤毛清除功能影响的急性研究正在进行中。针对异常离子转运的药物治疗有望用于治疗CF气道疾病。
