Research in the field of bronchiectasis has gained considerable momentum over the past 15 years. Nevertheless, the underlying cause remains unknown in around 38 percent of cases despite comprehensive diagnostic work-ups, and these cases are therefore classified as idiopathic \u2013 as shown by data from the EMBARC registry. This persistent clinical challenge is the focus of a recent publication by DZL researchers at the BREATH site. The team led by DZL scientists Prof. Dr. Dr. Burkhard T\u00fcmmler and Prof. Dr. Felix C. Ringshausen investigated whether a previously unrecognized partial CFTR dysfunction may contribute to the development of the disease.<\/p>\n
To explore this hypothesis, the authors used nasal potential difference (nPD) as a functional measurement method. nPD allows the activity of the CFTR channel to be assessed directly at the respiratory epithelium under defined stimulation conditions, making it possible to detect functional differences between patient groups. \u201cUsing nasal potential difference, we can characterize CFTR-mediated chloride transport across the cell membrane in vivo in a differentiated manner and, in particular, identify transitional states between normal and clearly impaired function,\u201d explains first author Prof. Dr. Dr. Burkhard T\u00fcmmler, emeritus professor at the Department of Pediatric Pneumology, Allergology and Neonatology at Hannover Medical School (MHH) and a long-standing expert in CFTR research.<\/p>\n
In the study, patients with idiopathic bronchiectasis were compared both with healthy control subjects and with individuals with cystic fibrosis. Initially, basal potential differences were similar across groups, indicating largely normal epithelial ion conductance under resting conditions. However, clear differences emerged under functional stimulation. CFTR-mediated chloride conductance was significantly reduced in patients with bronchiectasis compared with healthy controls, yet markedly higher than in patients with classical cystic fibrosis.<\/p>\n
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 diagnostic thresholds for cystic fibrosis. Similarly, in composite diagnostic indices such as the Sermet score, this group occupied an intermediate position, clearly distinguishable from both healthy controls and cystic fibrosis patients.<\/p>\n
Against this background, the authors interpret their findings as evidence of an intermediate CFTR phenotype. This fits within the concept of so-called CFTR-related disorders, in which classical cystic fibrosis is absent but clinically relevant impairment of CFTR function is nevertheless present. The data suggest that bronchiectasis cases previously classified as idiopathic may fall within this spectrum.<\/p>\n
At the same time, it is evident that reduced CFTR function alone is not sufficient to explain the disease. Rather, the findings point to a multifactorial process in which diminished CFTR activity interacts with additional genetic predispositions, environmental factors, or recurrent infections. Notably, these functional alterations were also detected in patients for whom there had previously been no specific clinical suspicion of a CFTR-associated condition.<\/p>\n
\u201cFor affected patients, this means that we may in the future be able to classify idiopathic bronchiectasis more precisely. Functional characterization using methods such as nPD could help identify previously hidden disease mechanisms and, in the long term, open up new avenues for personalized diagnostics and therapy,\u201d says senior author Prof. Dr. Felix C. Ringshausen, head of the cystic fibrosis and bronchiectasis outpatient clinic and senior physician at the Department of Pneumology and Infectious Diseases at Hannover Medical School.<\/p>\n
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 highlight the importance of functional testing methods such as nPD in uncovering hidden pathophysiological processes and enabling more differentiated diagnostics within the spectrum of CFTR-related disorders.<\/p>\n
Original publication:<\/strong>
T\u00fcmmler, B., Schulz, A., Minso, R. et al. CFTR activity in nasal potential difference of adults with idiopathic bronchiectasis.<\/em> Respir Res (2026). https:\/\/doi.org\/10.1186\/s12931-026-03599-1<\/a><\/p>\n