Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti-inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy-driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non-immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non-specific eosinophil-targeting therapies. Despite the overall favourable safety profile of the currently available anti-eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences.
- MeSH
- biologické markery MeSH
- eozinofily * MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
We collected a multi-centric retrospective dataset of patients (N = 213) who were admitted to ten hospitals in Czech Republic and tested positive for SARS-CoV-2 during the early phases of the pandemic in March-October 2020. The dataset contains baseline patient characteristics, breathing support required, pharmacological treatment received and multiple markers on daily resolution. Patients in the dataset were treated with hydroxychloroquine (N = 108), azithromycin (N = 72), favipiravir (N = 9), convalescent plasma (N = 7), dexamethasone (N = 4) and remdesivir (N = 3), often in combination. To explore association between treatments and patient outcomes we performed multiverse analysis, observing how the conclusions change between defensible choices of statistical model, predictors included in the model and other analytical degrees of freedom. Weak evidence to constrain the potential efficacy of azithromycin and favipiravir can be extracted from the data. Additionally, we performed external validation of several proposed prognostic models for Covid-19 severity showing that they mostly perform unsatisfactorily on our dataset.
- MeSH
- COVID-19 epidemiologie patologie terapie MeSH
- dospělí MeSH
- farmakoterapie COVID-19 MeSH
- hospitalizace * MeSH
- lidé středního věku MeSH
- lidé MeSH
- progrese nemoci * MeSH
- senioři MeSH
- statistické modely MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Vztahy mezi astmatem a obezitou jsou komplexní a jdou nad rámec prosté asociace mezi vzestupem hmotnosti a příznaky astmatu. Z klinického pohledu obezita může modifikovat astma – snižovat odpověď na léčbu kortikoidy, zvyšovat riziko exacerbací, vést k těžšímu průběhu onemocnění a měnit výpovědní hodnotu biomarkerů. U obézních pacientů může být kromě patofyziologických procesů ovlivněna také farmakokinetika a farmakodynamika (FK/FD) léčiv, včetně monoklonálních protilátek. Cílové procesy, které se snažíme biologickou léčbou ovlivnit, mohou být u obézních pacientů odlišné od pacientů neobézních. Článek komentuje některé současné poznatky o této komplexní a někdy kontra-intuitivní lékové problematice, podává přehled analýz klinických studií zaměřených na zhodnocení efektu biologické léčby u obézních astmatiků a diskutuje úskalí individualizace léčby v kontextu farmakologie a biologie onemocnění.
- MeSH
- COVID-19 diagnostické zobrazování MeSH
- farmakoterapie COVID-19 MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakt z konference MeSH
PURPOSE OF REVIEW: Severe asthma is a serious condition that requires an individualized approach combining several treatment agents administered simultaneously in order to reach adequate control. Glucocorticosteroid treatment, as the cornerstone of asthma pharmacotherapy, has great disease-controlling capability, although it may induce a vast amount of severe adverse effects. This review describes our current knowledge of the monitoring and managing options of these adverse effects and possibilities to prevent them, including new therapeutic options. RECENT FINDINGS: A large amount of new drugs is emerging, which may offer a better control of glucocorticosteroid-induced adverse effects. At the same time, major achievements in our understanding of the underlying mechanisms in severe asthma and in the field of biologic agents may help to substantially reduce the need of glucocorticosteroids in the first-line treatment. SUMMARY: We discuss new insights and approaches to treatment strategy of severe asthma allowing less oral glucocorticosteroid use and hence, substantial less severe adverse effects of the treatment.
- MeSH
- antiastmatika * klasifikace terapeutické užití MeSH
- bronchiální astma farmakoterapie MeSH
- glukokortikoidy * škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- management farmakoterapie trendy MeSH
- nežádoucí účinky léčiv etiologie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
