Non-CF bronchiectasis: a spectrum of CFTR (and ENaC) dysfunction?

Abstract

Disorders of the respiratory epithelium's ion conductance result in abnormal airway surface liquid hydration, defective mucociliary clearance and impaired host defense and may contribute to the pathogenesis of bronchiectasis. This may affect either the amiloride-sensitive epithelial sodium channel (ENaC) or the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR). The most prominent channelopathy associated with bronchiectasis is cystic fibrosis (CF), an autosomal recessive disease caused by mutations in the CFTR gene, which encodes the chloride CFTR channel. The diagnosis of a defective ion conductance is difficult and the most important diagnostic tool for subjects with bronchiectasis, the measurement of the nasal transepithelial potential difference (nPD), is not readily available in most centers. Nevertheless, the efficient and exact diagnosis of underlying CFTR or ENaC dysfunction is an issue of increasing relevance as targeted treatment options like specific modulators of CFTR or specific inhibitors of ENaC function have already become available or may enter clinical routine as a mucolytic approach in the near future.