Proteomic profiling of sweat in patients with cystic fibrosis provides new insights into epidermal homoeostasis

International audienceBackground: A high proportion of patients with Cystic Fibrosis (CF) also present the rare skin disease aquagenic palmoplantar keratoderma. A possible link between this condition and absence of a functional CF Transmembrane conductance Regulator protein in the sweat acinus and collecting duct remains unknown. Methods: In-depth characterization of sweat proteome profiles was performed in 25 CF patients compared to 12 healthy controls. A 20 μL sweat sample was collected after pilocarpine iontophoresis and liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomic analysis was performed. Results: Sweat proteome profile of CF patients was significantly different from that of healthy subjects with 57 differentially expressed proteins. Cystic Fibrosis sweat proteome was characterized by an increase in 25 proteins including proteases (Kallikrein 7 and 13, Phospholipase B domain containing 1, Cathepsin A L2 and B, Lysosomal Pro-X carboxypeptidase); proinflammatory proteins (Annexin A2, Chitinase-3-like protein 1); cytochrome c and transglutaminases. Thirty-two proteins were downregulated in CF sweat including proteases (Elastase 2), antioxidative protein FAM129 B; membrane-bound transporter SLC6A14 and regulator protein Sodiumhydrogen antiporter 3 regulator 1. Conclusion:This study is the first toreportin depth characterization of endogenous peptides in CFsweat and could help under stand the complex physiology of the sweat gland.The proteome profile highlights the unbalanced proteolytic and proinflammatory activity of sweatin CF.These results also suggest a efectin pathways involved in skin barrier integrity in CF patients.Sweat proteome profile could prove to be a useful tool in the context of personalized medicine in CF.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Mucoviscidose et traitements inhalés : quoi de neuf en 2013 ?

Depuis quelques années, de nouvelles molécules administrées par voie inhalée et de nouveaux dispositifs d’inhalation sont apparus pour le traitement de la mucoviscidose. Les nébuliseurs synchronisés sur l’inspiration permettent un dépôt pulmonaire plus important, moins variable, et une durée de traitement raccourcie. Les nouvelles formulations de tobramycine, colistine ou mannitol en poudre sèche modifient la technique d’inhalation à travers l’inhalateur de poudre sèche qui doit maintenant être lente et profonde. Dans le domaine des fluidifiants inhalés, le sérum salé hypertonique et le mannitol semblent intéressants chez certains patients. En antibiothérapie, si la tobramycine et colistine en poudre peuvent être substituées à la même molécule délivrée en nébulisation, la place de l’aztréonam nébulisé reste à préciser. Ces traitements représentent une avancée certaine pour les patients et méritent donc d’être connus. Leur position dans l’arsenal thérapeutique reste donc à définir

Lumacaftor-ivacaftor effects on cystic fibrosis-related liver involvement in adolescents with homozygous F508 del-CFTR

International audienceAdvances in digital medicine now make it possible to use digital twin systems (DTS), which combine (1) extensive patient monitoring through the use of multiple sensors and (2) personalized adaptation of patient care through the use of software. After the artificial pancreas system already operational in children with type 1 diabetes, new DTS could be developed for real-time monitoring and management of children with chronic diseases. Just as providing care for children is a specific discipline—pediatrics—because of their particular characteristics and needs, providing digital care for children also presents particular challenges. This article reviews the technical challenges, mainly related to the problem of data collection in children; the ethical challenges, including the need to preserve the child's place in their care when using DTS; the legal challenges and the dual need to guarantee the safety of DTS for children and to ensure their access to DTS; and the societal challenges, including the needs to maintain human contact and trust between the child and the pediatrician and to limit DTS to specific uses to avoid contributing to a surveillance society and, at another level, to climate change

Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

International audienceRationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at 1 and 3 months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. Measurements and Main Results: Elexacaftor-tezacaftor- ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV1 = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV1 was +15.1 (+13.8 to +16.4; P < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; P < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P < 0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only 2 received a transplant, and 1 died. By September 2020, only five patients were still on the transplantation path. Compared with the previous 2 years, a twofold decrease in the number of lung transplantations in patients with CF was observed in 2020, whereas the number of deaths without transplantation remained stable. Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended