Research in the field of bronchiectasis has gained significant momentum over the past 15 years. Nevertheless, the underlying cause remains unclear in approximately 38 percent of cases despite extensive diagnostics, and the disease is therefore classified as idiopathic—as shown by data from the EMBARC registry. This persistent clinical challenge is the focus of a recent publication by BREATH researchers in the journal Respiratory Research. The team led by Prof. Dr. Dr. Burkhard Tümmler and Prof. Dr. Felix C. Ringshausen investigated whether a previously unrecognized partial CFTR dysfunction could contribute to the development of the disease.

To explore this hypothesis, the authors used nasal potential difference (nPD) as a functional measurement method. nPD enables direct assessment of CFTR channel activity in the respiratory epithelium under defined stimulation conditions, thereby revealing functional differences between patient groups. “With nasal potential difference, we can characterize CFTR-mediated permeability of the cell membrane to negatively charged chloride ions in vivo in a differentiated manner and, in particular, capture transitional ranges between normal and clearly impaired function,” explains first author Prof. Dr. Dr. Burkhard Tümmler, emeritus professor at the Department of Pediatric Pulmonology, Allergology and Neonatology at MHH and a long-standing expert in CFTR research.

In the study, patients with idiopathic bronchiectasis were compared both with healthy controls and with individuals with cystic fibrosis. Initially, a similar pattern was observed in baseline potential difference, suggesting that epithelial ion conductance is largely unremarkable under resting conditions. However, clear differences emerged under functional stimulation. CFTR-mediated chloride conductance was significantly lower in bronchiectasis patients than in healthy controls, but still markedly higher than in patients with classical cystic fibrosis.

This pattern was also reflected in the distribution of individual measurements. A substantial proportion of the bronchiectasis cohort fell within the lower normal range of CFTR activity without reaching the diagnostic thresholds for cystic fibrosis. In composite diagnostic indices such as the Sermet score, this group also occupied a clear intermediate position and could be distinguished from both healthy controls and CF patients.

Against this background, the authors interpret their findings as evidence of an intermediate CFTR phenotype. This fits into the concept of so-called CFTR-related disorders, in which classical cystic fibrosis is not present but a clinically relevant impairment of CFTR function still exists. The data suggest that bronchiectasis cases previously classified as idiopathic may fall within this spectrum.

At the same time, it becomes clear that reduced CFTR function alone is not sufficient to explain the disease. Rather, the findings point to a multifactorial process in which diminished CFTR function interacts with additional genetic predispositions, environmental factors, or recurrent infections. Notably, these functional alterations were detectable even in patients who had previously shown no specific clinical suspicion of a CFTR-associated disorder.

“For affected individuals, this means that idiopathic bronchiectasis may in the future be classified in a more differentiated way. Functional characterization such as nPD could help identify previously hidden disease mechanisms and, in the long term, open up new avenues for personalized diagnostics and therapy,” says senior author Prof. Dr. Felix C. Ringshausen, head of the cystic fibrosis and bronchiectasis outpatient clinic and senior physician at the Department of Pulmonology and Infectious Diseases at Hannover Medical School.

These findings contribute to a better understanding of the mechanisms underlying idiopathic bronchiectasis, which have so far remained poorly understood. At the same time, they underscore the importance of functional testing methods such as nPD measurements for uncovering hidden pathophysiological relationships and, prospectively, enabling more refined diagnostics within the spectrum of CFTR-associated diseases.

Original publication:
Tümmler, B., Schulz, A., Minso, R. et al. CFTR activity in nasal potential difference of adults with idiopathic bronchiectasis. Respir Res (2026). https://doi.org/10.1186/s12931-026-03599-1

Text: BREATH/AB
Foto: MHH/Figiel and MHH/Schweigler