RW Wilmott

Abstract

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which codes for a cyclic-AMP regulated chloride channel. Characteristic clinical features are recurrent pulmonary infections, exocrine pancreatic insufficiency and increased sweat electrolyte concentrations. CF was not clearly described in the medical literature until 1938. In this article the major discoveries and innovations that have been made since that time are reviewed and placed in historical context. They include the sweat test, comprehensive pulmonary and nutritional therapies, lung transplantation, discovery of the CFTR gene, and introduction of newborn screening. Therapies such as aerosolised mucolytic agents (dornase-a and hypertonic saline), aerosolised antibiotics (for example high-dose tobramycin and aztreonam) and CFTR modulator therapies such as ivacaftor have been developed in more recent years. These approaches have been associated with a significant increase in median life expectancy which reached 39.3 years in 2014.

囊性纖維病（CF）是一種由於囊性纖維跨膜轉運調節因數（CFTR）基因突變導致的常染色體隱性遺傳病，該基因編碼為環腺苷酸（cAMP）介導的氯離子通道。其特徵性的臨床表現為肺部感染，胰腺外分泌功能下降，以及汗液電解質濃度上升。這種疾病直到1938年才在醫學文獻上有明確的記錄。該疾病自有記錄以來的主要發現，以及突破在本文中都做了詳細的歷史回顧和整理，如汗液測試，綜合肺及營養療法，肺移植，CFTR基因的發現以及一些新生兒篩查的介紹。最近幾年中出現了一些如使用霧化黏液溶解劑（鏈道酶-α及高滲鹽水），霧化抗生素（如大劑量妥布黴素和氨曲南）和CFTR調節劑如伊伐卡托（ivacaftor）的治療方法。而2014年記錄顯示該病中位元預期壽命有顯著的延長，可達至39.3年。這一結果與這些新興治療方法的出現有著緊密的因果關係。