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.
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.
- 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
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
- MeSH
- cystická fibróza * diagnóza farmakoterapie komplikace MeSH
- kongresy jako téma MeSH
- lidé MeSH
- protein CFTR účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- zprávy MeSH
- MeSH
- aminofenoly MeSH
- benzodioxoly MeSH
- chinoliny MeSH
- cystická fibróza * farmakoterapie MeSH
- dítě MeSH
- fixní kombinace léků MeSH
- indoly MeSH
- lidé MeSH
- náklady na léky MeSH
- přehodnocení terapeutických indikací léčivého přípravku MeSH
- pyrazoly MeSH
- pyridiny MeSH
- všeobecné zdravotní pojištění ekonomika normy MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
In this review, we summarize the main points that were raised and highlighted during the pre-conference meeting to the 17th European Cystic Fibrosis Society Basic Science Conference, held from 30 March to 2 April, 2022 in Albufeira, Portugal. Keynote lectures provided an update on the latest information regarding the phenomenon of antimicrobial resistance (AMR) in cystic fibrosis (CF). Traditional themes such as in vitro antibiotic susceptibility testing and its clinical value, AMR evolution in persistent Pseudomonas aeruginosa infection and the impact of biofilm on AMR were discussed. In addition, the report gives an overview on very recent AMR-related topics that include an ecological view of AMR in CF lung, referred to as resistome, and novel anti-infective approaches in preclinical or early clinical research such as antibiofilm drugs and bacteriophages.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- bakteriální léková rezistence MeSH
- cystická fibróza * komplikace farmakoterapie MeSH
- infekce dýchací soustavy * farmakoterapie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- pseudomonádové infekce * diagnóza farmakoterapie MeSH
- Pseudomonas aeruginosa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- cystická fibróza * farmakoterapie epidemiologie genetika MeSH
- lidé MeSH
- protein CFTR * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- Geografické názvy
- východní Evropa MeSH
Superior efficacy of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) over tezacaftor/ivacaftor (TEZ/IVA) in people with cystic fibrosis (CF) and Phe508del/Phe508del genotype was shown in clinical trials. We utilized intestinal organoid approach to compare in vitro responses to these 2 CFTR modulator drug combinations and to check potential inter-individual variability in therapeutic response to the triple combination. Organoids from 17 subjects with Phe508del/Phe508del were screened with forskolin induced swelling assay. Significantly larger swelling, when exposed to ELX/TEZ/IVA as compared to TEZ/IVA, was observed in 16 of them. However, 1 sample showed no additional effect of ELX. The finding of unique CFTR variants in this sample indicates that genetic traits other than CF-causing CFTR mutation are worth exploring as they may have an impact on the definitive modulator drug response.
- MeSH
- aktivátory chloridových kanálů farmakologie terapeutické užití MeSH
- aminofenoly farmakologie terapeutické užití MeSH
- benzodioxoly farmakologie terapeutické užití MeSH
- chinolony MeSH
- cystická fibróza * farmakoterapie genetika MeSH
- fixní kombinace léků MeSH
- indoly MeSH
- lidé MeSH
- mutace MeSH
- organoidy * MeSH
- protein CFTR genetika MeSH
- pyrazoly MeSH
- pyridiny MeSH
- pyrrolidiny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
