Multiple documented underlying etiologies may lead to bronchiectasis, but the European Bronchiectasis Registry found that in 38% of patients the cause is unknown, referred to as idiopathic. We wanted to resolve the role of CFTR dysfunction in people with idiopathic bronchiectasis by nasal potential difference (NPD) measurements. NPD was examined in people with cystic fibrosis (CF), healthy controls, 40 people with idiopathic bronchiectasis recruited from the local outpatient clinic and in 60 people with idiopathic bronchiectasis with the suspected etiology of CF who had been referred from 2010 – 2022 to our electrophysiological laboratory to make a diagnosis by NPD. The unselected MHH cohort and the preselected diagnostic cohort of people with idiopathic bronchiectasis matched in their basal NPD potential with healthy controls. Conversely, after inhibition of the sodium conductance with amiloride, the distribution of the CFTR-mediated depolarization potential upon exposure to chloride-free solution and isoproterenol was in between those of healthy controls and CF patients with exocrine pancreatic insufficiency and overlapped with that of patients with exocrine pancreatic sufficiency. This intermediate phenotype was characteristic for the whole study population of 100 people with idiopathic bronchiectasis irrespectively of whether clinical features of CFTR dysfunction had been recognized before in an individual. Taking the Sermet Score that was developed to discriminate patients with CF from non-CF patients by NPD, the bronchiectasis population was significantly distinct from both healthy people and people with CF. A CFTR activity of the nasal surface epithelium in the lower quartile is typical for people with idiopathic bronchiectasis, but further CFTR-independent inherited susceptibilities and external insults are necessary to materialize the emergence of bronchiectasis. Clinical trial number: not applicable.
Tümmler et al. (Tue,) studied this question.