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).

Comparison of Three Eradication Treatment Protocols for Pseudomonas Aeruginosa in Children and Adolescents with Cystic Fibrosis.

Background: Pseudomonas aeruginosa (Pa) continues to affect disease progression in cystic fibrosis (CF). However, the best eradication regimen remains unclear. This work compares three different antibiotic eradication regimens in pediatric CF: an administration according to a standard-operating procedure (SOP) order vs.

The First 4 Years - Outcome of Children Identified by Newborn Screening for CF in Germany.

Background: Newborn screening (NBS) has been shown to improve cystic fibrosis (CF) disease course and has been widely implemented worldwide. This monocentric study compared children diagnosed by NBS vs. a cohort preceding the implementation of NBS in Germany in 2016 to evaluate ascribed benefits of NBS.

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.

Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent Staphylococcus aureus.

Background: Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures.

Skeletal Muscle Function in Young Patients With Cystic Fibrosis.

Purpose: Defects in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) cause CF. Absence of the CFTR may result in skeletal muscle dysfunction. Here, we tested skeletal muscle function in male adolescent patients with CF.

High variability in oral glucose tolerance among 1,128 patients with cystic fibrosis: a multicenter screening study.

Background: In cystic fibrosis, highly variable glucose tolerance is suspected. However, no study provided within-patient coefficients of variation. The main objective of this short report was to evaluate within-patient variability of oral glucose tolerance.

Quality of life is associated with physical activity and fitness in cystic fibrosis.

Background: Health-related and disease-specific quality of life (HRQoL) has been increasingly valued as relevant clinical parameter in cystic fibrosis (CF) clinical care and clinical trials. HRQoL measures should assess - among other domains - daily functioning from a patient's perspective. However, validation studies for the most frequently used HRQoL questionnaire in CF, the Cystic Fibrosis Questionnaire (CFQ), have not included measures of physical activity or fitness.

Diabetes in cystic fibrosis: multicenter screening results based on current guidelines.

Background: Published estimates on age-dependent frequency of diabetes in cystic fibrosis (CF) vary widely, and are based mostly on older data. However, CF treatment and prevention of comorbidities changed over recent years. In many studies, definition of cystic fibrosis-related diabetes (CFRD) is not in line with current guideline recommendations.

Inhalation treatment with glutathione in patients with cystic fibrosis. A randomized clinical trial.

Rationale: Glutathione is the major antioxidant in the extracellular lining fluid of the lungs and depleted in patients with cystic fibrosis (CF).

Objectives: We aimed to assess glutathione delivered by inhalation as a potential treatment for CF lung disease.

Methods: This randomized, double-blind, placebo-controlled trial evaluated inhaled glutathione in subjects with CF 8 years of age and older and FEV1 of 40-90% of predicted.

Effect of supervised training on FEV1 in cystic fibrosis: a randomised controlled trial.

Background: Long-term exercise interventions have been shown to improve vital capacity in cystic fibrosis (CF). Yet, no data are available indicating positive effects of long-term exercise training on FEV1.

Methods: 39 Swiss patients with CF were randomly divided into strength training (ST, n=12), endurance training (AT, n=17) and controls (CON(CH), n=10), and also compared with age-matched Swiss (n=35) and German (n=701) CF registry data.

Calculation of the capnographic index based on expiratory molar mass-volume-curves--a suitable tool to screen for cystic fibrosis lung disease.

Background: Volumetric capnography reflecting the course of CO2-exhalation is used to assess ventilation inhomogeneity. Calculation of the slope of expiratory phase 3 and the capnographic index (KPIv) from expirograms allows quantification of extent and severity of small airway impairment. However, technical limitations have hampered more widespread use of this technique.

Functional analysis of F508del CFTR in native human colon.

The major cystic fibrosis mutation F508del has been classified by experiments in animal and cell culture models as a temperature-sensitive mutant defective in protein folding, processing and trafficking, but literature data on F508del CFTR maturation and function in human tissue are inconsistent. In the present study the molecular pathology of F508del CFTR was characterized in freshly excised rectal mucosa by bioelectric measurement of the basic defect and CFTR protein analysis by metabolic labelling or immunoblot. The majority of investigated F508del homozygous subjects expressed low amounts of complex-glycosylated mature F508del CFTR and low residual F508del CFTR-mediated chloride secretory activity in the rectal mucosa.