ABSTRACT
Cystic fibrosis (CF) is a genetic disease caused by a bi-allelic mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. When the diagnosis cannot be confirmed by a positive sweat test or/and the identification of two CF-causing variants, international guidelines recommend the use of CFTR functional assays. These tests assess whether CFTR activity is normal or diminished/absent through measurement of CFTR-mediated chloride secretion/absorption. CFTR functional assays are not only useful for diagnostic purposes but can also serve as a surrogate outcome for clinical trials of CFTR modulators, which are emerging therapeutic agents designed to correct the malfunctioning protein. In the near future they could also be used as precision-medicine techniques, to help guidance and optimisation of treatment. Until now, sweat testing has been the only CFTR functional assay available in Switzerland. Since 2020, the Centre Hospitalier Universitaire Vaudois (CHUV) at Lausanne and the Lucerne Children’s Hospital perform nasal potential difference measurement. Moreover, The Ecole Polytechnique Fédérale de Lausanne (EPFL) established a reliable procedure to generate adult intestinal organoids, i.e., stem cell-derived in-vitro grown mini tissues, extracted from rectal biopsies, which can be used to assess CFTR function in vitro. This narrative review describes the most popular CFTR functional assays, as well as their indications, limitations and availability in Switzerland.
Subject(s)
Cystic Fibrosis , Chlorides/analysis , Chlorides/metabolism , Cystic Fibrosis/diagnosis , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Humans , Mutation , Sweat/chemistry , Sweat/metabolism , SwitzerlandSubject(s)
Adenoma/diagnosis , Adrenal Gland Neoplasms/diagnosis , Cushing Syndrome/etiology , Acneiform Eruptions/etiology , Adenoma/complications , Adrenal Gland Neoplasms/complications , Adrenal Glands/diagnostic imaging , Cushing Syndrome/congenital , Cushing Syndrome/diagnosis , Humans , Hydrocortisone/blood , Infant , Male , Radiography , Weight GainSubject(s)
Hypertension/etiology , Obesity/etiology , Diagnosis , Exanthema/etiology , Humans , Infant , MaleABSTRACT
OBJECTIVE: To document current practices using continuous subcutaneous insulin infusion (CSII) by downloading electronically the 90-d pump data held within the pump memory and relating that to clinical data from children and adolescents in different pediatric diabetes centers from Europe and Israel. METHODS: Data of patients (1-18 yr) treated with CSII in 23 centers from nine European countries and Israel were recorded with the encapture software (PEC International, Frankfurt, Germany). The number of patients who participated was 377 (48% female; mean diabetes duration +/- SD: 6.8 +/- 3.7 yr; age: 12.9 +/- 3.8 yr, preschool n = 33; prepubertal n = 95; adolescent n = 249; CSII duration: 1.6 +/- 1.2 yr; local HbA1c: 8.1 +/- 1.2%). RESULTS: The total insulin dose was lower than previously reported for injection therapy (0.79 +/- 0.20 U/kg/d). Covariance coefficient of daily total insulin was high in all age groups (adolescents 19 +/- 9%, prepubertal 18 +/- 8 and preschool 17 +/- 8). The distribution of basal insulin infusion rates over 24 hr (48 +/- 12% of total dose) varied significantly between centers and age groups. The number of boluses per day (7 +/- 3) was not significantly different between the age groups (average daily bolus amount: 0.42 +/- 0.16 U/kg). The rate of severe hypoglycemia (coma/convulsions) was 12.4 episodes per 100 patient-years and the number of diabetes-related hospital days was 124 per 100 patient-years. DISCUSSION: Pediatric CSII patients show a high variability in their insulin therapy. This relates both to age-dependent differences in the distribution of basal insulin as to the age-independent day-to-day variation in prandial insulin.
