This is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy.
CFTR is a membrane protein that functions as an ion channel. Mutations that disrupt its biosynthesis, trafficking or function cause cystic fibrosis (CF). Here, we present a novel in vitro model system prepared using CRISPR/Cas9 genome editing with endogenously expressed WT-CFTR tagged with a HiBiT peptide. To enable the detection of CFTR in the plasma membrane of live cells, we inserted the HiBiT tag in the fourth extracellular loop of WT-CFTR. The 11-amino acid HiBiT tag binds with high affinity to a large inactive subunit (LgBiT), generating a reporter luciferase with bright luminescence. Nine homozygous clones with the HiBiT knock-in were identified from the 182 screened clones; two were genetically and functionally validated. In summary, this work describes the preparation and validation of a novel reporter cell line with the potential to be used as an ultimate building block for developing unique cellular CF models by CRISPR-mediated insertion of CF-causing mutations.
- MeSH
- buněčná membrána metabolismus MeSH
- buněčné linie MeSH
- CRISPR-Cas systémy genetika MeSH
- cystická fibróza * genetika metabolismus MeSH
- lidé MeSH
- protein CFTR * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Trimethoprim-sulfamethoxazole (SXT) is the preferable treatment option of the infections caused by Achromobacter spp. Our study aimed to analyze the SXT resistance of 98 Achromobacter spp. isolates from pediatric patients, among which 33 isolates were SXT-resistant. The presence of intI1 was screened by PCR and genome sequence analyses. The intI1 gene was detected in 10 of SXT-resistant isolates that had shorter intI1 PCR fragments named intI1S. Structural changes in intI1S were confirmed by genome sequencing and analyses which revealed 86 amino acids deletion in IntI1S protein compared to canonical IntI1 protein. All IntI1S isolates were of non-CF origin. Pan-genome analysis of intI1S bearing A. xylosoxidans isolates comprised 9052 genes, with the core genome consisting of 5455 protein-coding genes. Results in this study indicate that IntI1S isolates were derived from clinical settings and that cystic fibrosis (CF) patients were potential reservoirs for healthcare-associated infections that occurred in non-CF patients.
- MeSH
- Achromobacter denitrificans * genetika MeSH
- Achromobacter * MeSH
- antibakteriální látky terapeutické užití MeSH
- cystická fibróza * MeSH
- dítě MeSH
- genomika MeSH
- gramnegativní bakteriální infekce * MeSH
- integrasy terapeutické užití MeSH
- integrony genetika MeSH
- kombinace léků trimethoprim a sulfamethoxazol MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Srbsko MeSH
BACKGROUND: Achromobacter species are emerging pathogens isolated from respiratory samples of Patients with cystic fibrosis (pwCF) causing growing concerns in the CF community. The epidemiology and the clinical impact of Achromobacter in CF is unclear since data are restricted to small case control studies or selected populations. AIM: To characterize the effect of Achromobacter respiratory infection on CF lung disease. METHODS: European CF Society Patient Registry data was analysed for association between Achromobacter infection and demographic/clinical characteristics and outcomes of pwCF. RESULTS: Of eligible 38,795 patients, Achromobacter infection was reported in 2,093 (prevalence (95% CI) of 5.40% (5.17 - 5.62). The prevalence varied significantly between the countries and increased with age peaking at the age 20-30. Achromobacter infection was more prevalent in pwCF carrying class minimal function mutations, having worse nutrition or lower pulmonary function, and more patients inhaled antibiotics against P. aeruginosa. Patient infected with Achromobacter had similar pulmonary function and BMI to patients infected with P. aeruginosa at all age groups. Being infected with both bacteria was associated with significantly lower pulmonary function and BMI at all age groups. CONCLUSIONS: Achromobacter infection was associated with disease severity similar to infection with P. aeruginosa. Being infected with both bacteria is associated with even more severe disease. This suggests to study if eradication will improve the outcome of pwCF.
- MeSH
- Achromobacter * genetika MeSH
- cystická fibróza * komplikace epidemiologie mikrobiologie MeSH
- dospělí MeSH
- gramnegativní bakteriální infekce * diagnóza farmakoterapie epidemiologie MeSH
- infekce dýchací soustavy * mikrobiologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- plíce MeSH
- Pseudomonas aeruginosa MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- antibakteriální látky terapeutické užití MeSH
- aplikace inhalační MeSH
- bakteriální infekce etiologie komplikace MeSH
- cystická fibróza * diagnóza genetika terapie MeSH
- dechová cvičení metody MeSH
- dietoterapie metody MeSH
- genetické testování metody MeSH
- lidé MeSH
- malabsorpční syndromy etiologie terapie MeSH
- novorozenecký screening metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: The aim of this study was to record the current status of newborn bloodspot screening (NBS) for CF across Europe and assess performance. METHODS: Survey of representatives of NBS for CF programmes across Europe. Performance was assessed through a framework developed in a previous exercise. RESULTS: In 2022, we identified 22 national and 34 regional programmes in Europe. Barriers to establishing NBS included cost and political inertia. Performance was assessed from 2019 data reported by 21 national and 21 regional programmes. All programmes employed different protocols, with IRT-DNA the most common strategy. Six national and 11 regional programmes did not use DNA analysis. CONCLUSIONS: Integrating DNA analysis into the NBS protocol improves PPV, but at the expense of increased carrier and CFSPID recognition. Some programmes employ strategies to mitigate these outcomes. Programmes should constantly strive to improve performance but large datasets are needed to assess outcomes reliably.
- MeSH
- cystická fibróza * diagnóza genetika MeSH
- genetické testování * metody MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecký screening metody MeSH
- protein CFTR genetika MeSH
- trypsinogen MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
Pneumology ; září 2023 Evidence-based medicine ; 10 Pneumology
30 stran : ilustrace (některé barevné) ; 27 cm
- MeSH
- cystická fibróza MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- sborníky MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- pneumologie a ftizeologie
- gastroenterologie
Cystická fibróza (CF) je nejčastější život limitující dědičné onemocnění, které postihuje přibližně 100 000 pacientů po celém světě. Příčinou onemocnění je patogenní varianta v genu CFTR (cystic fibrosis conductance regulator), plnícím funkci iontového přenašeče na apikální membráně epitelových buněk. Léčba tohoto závažného onemocnění byla donedávna pouze symptomatická. Možnosti kauzální terapie mířící přímo na opravu molekulárního defektu CFTR proteinu se objevily v roce 2012, kdy byl registrován první lék ze třídy tzv. CFTR modulátorů. V současné době máme k dispozici čtyři CFTR modulátory, všechny dohromady mohou účinkovat až u 90 % všech pacientů s CF. Určujícím parametrem příslušné léčby je genotyp pacienta.
Cystic fibrosis (CF) is the most common life-shortening genetic disease. It affects approximately 100,000 people worlwide. The disease is caused by bi-allelic patogenic variants in the gene encoding the CFTR (Cystic Fibrosis Conductance Regulator) protein, which plays a major role in ion transport across the apical membrane of the epithelial cells. Until recently, treatment of this disease was solely symptomatic. Causal therapy targeting molecular defect of CFTR protein has been available since 2012, when first therapeutic agent was registered. Currently, there are four CFTR modulators available and all together they can work in up to 90 % of all patients with CF. Determining parameter of the respective treatment is the patient’s genotype.
