Every CFTR variant counts - Target-capture based next-generation-sequencing for molecular diagnosis in the German CF Registry.

Background: In times of genotype guided therapy options, a total of 3.2 % of people with CF (pwCF) in the German CF Registry[1] only have one or no CFTR-variant detected after genetic analysis. Additionally, genetic data in the Registry can be documented as free text and can therefore be prone to error.

Qualitative and quantitative evaluation of computed tomography changes in adults with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor: a retrospective observational study.

The availability of highly effective triple () modulator combination therapy with elexacaftor-tezacaftor-ivacaftor (ETI) has improved pulmonary outcomes and quality of life of people with cystic fibrosis (pwCF). The aim of this study was to assess computed tomography (CT) changes under ETI visually with the Brody score and quantitatively with dedicated software, and to correlate CT measures with parameters of clinical response. Twenty two adult pwCF with two consecutive CT scans before and after ETI treatment initiation were retrospectively included.

Spirometric and anthropometric improvements in response to elexacaftor/tezacaftor/ivacaftor depending on age and lung disease severity.

Triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) was introduced in August 2020 in Germany for people with CF (pwCF) ≥12 years (yrs.) of age and in June 2021 for pwCF ≥6 yrs of age. In this single-center study, we analyzed longitudinal data on the percent-predicted forced expiratory volume (ppFEV1) and body-mass-index (BMI) for 12 months (mo.

Changes in cystic fibrosis transmembrane conductance regulator protein expression prior to and during elexacaftor-tezacaftor-ivacaftor therapy.

Defects in expression, maturation or function of the epithelial membrane glycoprotein CFTR are causative for the progressive disease cystic fibrosis. Recently, molecular therapeutics that improve CFTR maturation and functional defects have been approved. We aimed to verify whether we could detect an improvement of CFTR protein expression and maturation by triple therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA).

CFTR modulation with elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis assessed by the β-adrenergic sweat rate assay.

Background: The cystic fibrosis (CF) sweat gland is defective in β-adrenergically-stimulated sweat secretion in the coil and chloride reabsorption in the duct. Whereas chloride reabsorption is regularly assessed by quantitative pilocarpine iontophoresis (QPIT), the measurement of β-adrenergic sweat secretion is not yet established in clinical practice.

Methods: A novel sweat bubble imaging protocol was developed that determines sweat secretion rates by automatic recording, processing and quality control of the kinetics of sweat droplet formation.

Intestinal current measurement and nasal potential difference to make a diagnosis of cases with inconclusive genetics and sweat test.

Background: Nasal potential difference (NPD) and intestinal current measurements (ICM) are cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers recommended to make a diagnosis in individuals with inconclusive sweat test and genetics and a clinical suspicion for cystic fibrosis (CF) or CFTR-related disorder (CFTR-RD).

Methods: NPD and ICM were measured according to standard operating procedures of the European Cystic Fibrosis Society Diagnostic Network Working Group.

Results: We assessed 219 individuals by NPD or ICM who had been referred to our laboratory due to clinical symptoms suggestive of CF, but inconclusive sweat test and genetics (median age: 16.

Assessment of a Mobile App by Adolescents and Young Adults With Cystic Fibrosis: Pilot Evaluation.

Background: Cystic fibrosis (CF) continues to be the most common life-limiting chronic pulmonary disease in adolescents and young adults. Treatment of CF demands a high treatment time investment to slow the progression of lung function decline, the most important contributor to morbidity and mortality. Adherence is challenging in CF due to the high treatment burden and the lack of immediate health consequences in case of nonadherence.

Towards individualized diagnostics of biofilm-associated infections: a case study.

Organized within biofilm communities, bacteria exhibit resistance towards a broad spectrum of antibiotics. Thus, one might argue that bacteria isolated from biofilm-associated chronic infections should be subjected to resistance profiling under biofilm growth conditions. Various test systems have been developed to determine the biofilm-associated resistance; however, it is not clear to what extent the in vitro results reflect the situation in vivo, and whether the biofilm-resistance profile should guide clinicians in their treatment choice.

Cohort Study of Airway Mycobiome in Adult Cystic Fibrosis Patients: Differences in Community Structure between Fungi and Bacteria Reveal Predominance of Transient Fungal Elements.

The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult patients with cystic fibrosis (CF) during nonexacerbation periods and under continuous antibiotic treatment.

High individuality of respiratory bacterial communities in a large cohort of adult cystic fibrosis patients under continuous antibiotic treatment.

Background: Routine clinical diagnostics of CF patients focus only on a restricted set of well-known pathogenic species. Recent molecular studies suggest that infections could be polymicrobial with many bacteria not detected by culture-based diagnostics.

Methodology And Principal Findings: A large cohort of 56 adults with continuous antibiotic treatment was studied and different microbial diagnostic methods were compared, including culture-independent and culture-based bacterial diagnostics.

Effects of ivacaftor on severely ill patients with cystic fibrosis carrying a G551D mutation.

Background: Recently, ivacaftor, a CFTR-potentiator, has been shown to be effective and safe in patients with cystic fibrosis carrying a G551D mutation and moderately impaired lung function. The objective of this retrospective study was to assess efficacy and safety of ivacaftor in severely ill patients with at least one G551D mutation.

Methods: Data from 14 patients with a FEV1 <40% predicted who received ivacaftor on a "named patient program" base in Germany were analyzed.