Is there a secondary defect in CFTR in the nasal epithelium of patients with primary ciliary dyskinesia?

Abstract

Introduction Cystic fibrosis (CF) is caused by mutations in the epithelial ion channel cystic fibrosis transmembrane conductance regulator (CFTR) gene but there is evidence that inflammation may alter CFTR function. We hypothesized that CFTR function may be impaired in subjects with primary ciliary dyskinesia (PCD), an inherited disorder of motile cilia associated with chronic airway inflammation. Objectives: We measured CFTR function using nasal potential difference (NPD) in subjects with PCD, CF and healthy controls (HC) and correlated NPD with markers of inflammation. Methods: 23 subjects (7 PCD, 8 CF and 8 HC) underwent NPD, nasal nitric oxide (nNO), sweat chloride, spirometry and CFTR genotyping. Nasosoprtion was performed using a synthetic absorptive matrix to collect nasal epithelial lining fluid (NLF) for the measurement of 9 cytokines. Results Median basal NPD values in PCD patients were similar to HC (-17 vs -24 mV, p 0.05). Cytokines were increased in PCD patients (p Conclusion PCD patients had reduced chloride secretion on NPD but this was not accompanied by evidence of sodium hyperabsorption. Results did not correlate with the increased nasal inflammation, although the study was small. More work is planned to establish whether this reflects CFTR dysfunction secondary to inflammation or is due to impaired epithelial integrity.