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.

• MeSH
• cystická fibróza * farmakoterapie   MeSH
• látky ovlivňující dýchací systém * terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• protein CFTR genetika   MeSH
• systémy dodávající nikotin elektronicky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

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

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

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.

• MeSH
• aktivátory chloridových kanálů terapeutické užití   MeSH
• aminofenoly terapeutické užití   MeSH
• cystická fibróza * farmakoterapie   klasifikace   MeSH
• lidé MeSH
• modulátory membránového transportu terapeutické užití   MeSH
• protein CFTR genetika   účinky léků   MeSH
• Check Tag
• lidé MeSH

There is considerable activity with respect to diagnosis in the field of cystic fibrosis (CF). This relates primarily to developments in newborn bloodspot screening (NBS), more extensive gene analysis and improved characterisation of CFTR-related disorder (CFTR-RD). This is particularly pertinent with respect to accessibility to variant-specific therapy (VST), a transformational intervention for people with CF with eligible CFTR gene variants. This advance reinforces the need for a timely and accurate diagnosis. In the future, there is potential for trials to assess effectiveness of variant-specific therapy for CFTR-RD. The guidance in this paper reaffirms previous standards, clarifies a number of issues, and integrates emerging evidence. Timely and accurate diagnosis has never been more important for people with CF.

• MeSH
• cystická fibróza * diagnóza   genetika   terapie   MeSH
• lidé MeSH
• novorozenec MeSH
• novorozenecký screening metody   MeSH
• protein CFTR genetika   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• CFTR modulátory,
• MeSH
• aktivátory chloridových kanálů farmakologie   terapeutické užití   MeSH
• cystická fibróza * diagnóza   farmakoterapie   MeSH
• fixní kombinace léků MeSH
• lidé MeSH
• modulátory membránového transportu farmakologie   terapeutické užití   MeSH
• protein CFTR farmakologie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• cystická fibróza * komplikace   terapie   MeSH
• infekce dýchací soustavy diagnóza   mikrobiologie   MeSH
• kongresy jako téma MeSH
• lidé MeSH
• mykózy diagnóza   farmakoterapie   mikrobiologie   MeSH
• protein CFTR genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• zprávy MeSH

• MeSH
• cystická fibróza * terapie   MeSH
• kongresy jako téma MeSH
• lidé MeSH
• modulátory membránového transportu terapeutické užití   MeSH
• protein CFTR genetika   účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• zprávy MeSH

BACKGROUND: We previously documented that elevated HE4 plasma concentration decreased in people with CF (pwCF) bearing the p.Gly551Asp-CFTR variant in response to CFTR modulator (CFTRm) ivacaftor (IVA), and this level was inversely correlated with the FEV1% predicted values (ppFEV1). Although the effectiveness of lumacaftor (LUM)/IVA in pwCF homozygous for the p.Phe508del-CFTR variant has been evaluated, plasma biomarkers were not used to monitor treatment efficacy thus far. METHODS: Plasma HE4 concentration was examined in 68 pwCF drawn from the PROSPECT study who were homozygous for the p.Phe508del-CFTR variant before treatment and at 1, 3, 6 and 12 months after administration of LUM/IVA therapy. Plasma HE4 was correlated with ppFEV1 using their absolute and delta values. The discriminatory power of delta HE4 was evaluated for the detection of lung function improvements based on ROC-AUC analysis and multiple regression test. RESULTS: HE4 plasma concentration was significantly reduced below baseline following LUM/IVA administration during the entire study period. The mean change of ppFEV1 was 2.6% (95% CI, 0.6 to 4.5) by 6 months of therapy in this sub-cohort. A significant inverse correlation between delta values of HE4 and ppFEV1 was observed especially in children with CF (r=-0.7053; p<0.0001). Delta HE4 predicted a 2.6% mean change in ppFEV1 (AUC: 0.7898 [95% CI 0.6823-0.8972]; P < 0.0001) at a cut-off value of -10.7 pmol/L. Moreover, delta HE4 independently represented the likelihood of being a responder with ≥ 5% delta ppFEV1 at 6 months (OR: 0.89, 95% CI: 0.82-0.95; P = 0.001). CONCLUSIONS: Plasma HE4 level negatively correlates with lung function improvement assessed by ppFEV1 in pwCF undergoing LUM/IVA CFTRm treatment.

• MeSH
• aktivátory chloridových kanálů terapeutické užití   MeSH
• aminofenoly terapeutické užití   MeSH
• aminopyridiny terapeutické užití   MeSH
• benzodioxoly terapeutické užití   MeSH
• cystická fibróza * diagnóza   farmakoterapie   genetika   MeSH
• dítě MeSH
• fixní kombinace léků MeSH
• homozygot MeSH
• lidé MeSH
• mutace MeSH
• protein CFTR genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cystic fibrosis (CF) is the most common genetic disease in the Caucasion population. Thanks to the CFTR modulators therapy, life expectancy will significantly improve. New therapeutic challenges can be expected, including diseases associated with ageing and higher incidence of cancer, as evidenced by recent epidemiological studies. The increasing incidence of tumors includes also breast cancer. The risk of breast cancer is higher in CF patients compared to the general population. Sex hormones, especially estrogens, also affect on the pathophysiology and immunology of the CF. Previous research, has demonstrated unequivocal survival rates for female CF patients compared to their male counterparts. Is demonstrated, that chemotherapy used for breast cancer affects the CFTR channel and CFTR modulator therapy has frequent side effects on breast tissue. In this review, we focus on the effects of female sex hormones on CF disease, pathophysiological relationships between CF and breast cancer, and the impact of antitumor treatment on both, malignant disease and CF. The potential for further investigation is also discussed.

• MeSH
• cystická fibróza * farmakoterapie   genetika   MeSH
• estrogeny terapeutické užití   MeSH
• incidence MeSH
• karcinogeneze MeSH
• lidé MeSH
• mutace MeSH
• nádory prsu * farmakoterapie   komplikace   MeSH
• pohlavní steroidní hormony terapeutické užití   MeSH
• prognóza MeSH
• protein CFTR genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH