Asthma is a common, multifaceted respiratory disease with a major impact on quality of life. Despite increased insights into mechanisms underlying various asthma phenotypes and endotypes and the availability of targeted biologic treatment options, the disease remains uncontrolled in a substantial proportion of patients with risk of exacerbations, requiring systemic corticosteroids, and with progressive disease. Current international guidelines advocate for a personalized management approach to patients with uncontrolled severe asthma. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) asthma expert panel was convened to discuss strategies to optimize asthma care and to prevent systemic corticosteroid overuse and disease progression. In this meeting report, we summarize current concepts and recommendations and provide a rationale to implement personalized asthma management at earlier stages of the disease. The ultimate goal is to move away from the current one-size-fits-most concept, which focuses on a symptom-driven treatment strategy, and shift toward a phenotype- and endotype-targeted approach aimed at curbing the disease course by improving clinical outcomes and preserving health-related quality of life. Herein, we provide a consensus view on asthma care that advocates a holistic approach and highlight some unmet needs to be addressed in future clinical trials and population studies.
- MeSH
- antiastmatika * terapeutické užití MeSH
- bronchiální astma * prevence a kontrola terapie farmakoterapie MeSH
- individualizovaná medicína MeSH
- indukce remise MeSH
- konsensus MeSH
- kvalita života MeSH
- lidé MeSH
- management nemoci MeSH
- progrese nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
Úvod: Klonálne ochorenie mastocytov a/alebo zvýšená koncentrácia bazálnej sérovej tryptázy patria medzi rizikové faktory závažnejšieho až život ohrozujúceho priebehu anafylaktickej reakcie po bodnutí blanokrídlym hmyzom. Pre rizikovosť týchto pacientov by mala byť každému takémuto pacientovi navrhnutá realizácia jedinej kauzálnej terapie – venómovej imunoterapie (VIT). Materiál a metódy: Vytvorili sme prospektívnu štúdiu, ktorú tvorilo 93 pacientov (58 mužov, 35 žien), ktorí spĺňali indikačné kritériá na liečbu VIT. Pacientov sme do štúdie zaradzovali postupne a dáta boli zhromažďované od roku 2015 do roku 2023. Zadefinovali sme základnú charakteristiku súboru, zamerali sme sa na identifikáciu pacientov s elevovanou koncentráciou sérovej bazálnej tryptázy (> 8 ng/ml) a systémovou mastocytózou, špecifiká priebehu ich systémovej alergickej reakcie po bodnutí blanokrídlym hmyzom, toleranciu liečby a výskyt nežiaducich účinkov. Výsledky: Z celkovo 93 zaradených pacientov liečených VIT sme zaznamenali u 15 pacientov (16,7 %) trvalo elevované koncentrácie sérovej bazálnej tryptázy (sBT) > 8 ng/ml. U jedného pacienta sme diagnostikovali systémovú mastocytózu. U pacientov s elevovanými hodnotami sBT sme pri systémovej alergickej reakcii po bodnutí blanokrídlym hmyzom častejšie pozorovali poruchu vedomia a hypotenziu. Z hľadiska tolerancie liečby sme pozorovali približne porovnateľný výskyt nežiaducich účinkov u pacientov s eleváciou ako aj bez elevácie sBT počas podávania VIT a prevažná väčšina nežiaducich účinkov bola v zmysle lokálnych reakcií. Celkovo 53,3 % pacientov liečených VIT s elevovanou koncentráciou sBT prekonalo prirodzenú reexpozíciu blanokrídlym hmyzom, pričom ani u jedného pacienta nedošlo k rozvoju systémovej alergickej reakcie s nutnosťou podania adrenalínového autoinjektora. Záver: Alergia na jed blanokrídleho hmyzu patrí medzi život ohrozujúci stav, pričom jej výskyt je oveľa častejší a priebeh závažnejší u pacientov s elevovanými koncentráciami bazálnej sérovej tryptázy a/alebo klonálnym ochorením mastocytov. U každého pacienta s potvrdeným klonálnym ochorením mastocytov je potrebné anamnesticky pátrať po výskyte alergickej reakcie na jed blanokrídleho hmyzu a zvažovať indikáciu venómovej imunoterapie ako jedinej kauzálnej liečby.
Introduction: Clonal mast cell disease and/or increased basal serum tryptase concentration are among the risk factors for a more severe life-threatening anaphylactic reaction following a Hymenoptera insect sting. Because of the risk carried by these patients, the single available causal therapy – venom immunotherapy (VIT) should be recommended for each such patient. Material and methods: We designed a prospective study consisting of 93 patients (58 men, 35 women) who met the indication criteria for VIT treatment. Patients were enrolled and data was collected from 2015 to 2023. We defined the basic characteristics of the group, we focused on the identification of patients with an elevated concentration of serum basal tryptase (> 8 ng/mL) and systemic mastocytosis, the details of their systemic allergic reaction after a Hymenoptera insect sting, treatment tolerance, and occurrence of adverse effects. Results: From a total of 93 enrolled patients treated with VIT, we recorded persistently elevated concentrations of serum basal tryptase (sBT) > 8 ng/mL in 15 patients (16.7%). We diagnosed systemic mastocytosis in one patient. In patients with elevated sBT values, we observed loss of consciousness and hypotension more frequently during a systemic allergic reaction after a Hymenoptera sting. From the point of view of treatment tolerance, we observed a roughly comparable incidence of adverse effects and the predominant majority of adverse effects were in terms of local reactions. A total of 53.3% of patients treated with VIT with elevated concentration of sBT overcame natural re-exposure to Hymenoptera insects, while not a single patient developed a systemic allergic reaction requiring the administration of an adrenaline autoinjector. Conclusion: Hymenoptera venom allergy is a life-threatening condition, and its occurrence is much more frequent, and its course more severe in patients with elevated basal serum tryptase concentrations and/or clonal mast cell disease. In each patient with a confirmed clonal mast cell disorder, it is necessary to search for the occurrence of an allergic reaction to Hymenoptera insect venom in the patient’s history and to consider venom immunotherapy as the only causal treatment.
- MeSH
- alergie etiologie MeSH
- anafylaxe etiologie prevence a kontrola terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mastocytóza * imunologie MeSH
- přecitlivělost na hmyzí jed * etiologie prevence a kontrola MeSH
- prospektivní studie MeSH
- systémová mastocytóza imunologie MeSH
- tryptasy analýza krev MeSH
- včelí jedy MeSH
- vosí jedy MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
We present the results of an association study involving hospitalized coronavirus disease 2019 (COVID-19) patients with a clinical background during the 3rd pandemic wave of COVID-19 in Slovakia. Seventeen single nucleotide variants (SNVs) in the eleven most relevant genes, according to the COVID-19 Host Genetics Initiative, were investigated. Our study confirms the validity of the influence of LZTFL1 and 2'-5'-oligoadenylate synthetase (OAS)1/OAS3 genetic variants on the severity of COVID-19. For two LZTFL1 SNVs in complete linkage disequilibrium, rs17713054 and rs73064425, the odds ratios of baseline allelic associations and logistic regressions (LR) adjusted for age and sex ranged in the four tested designs from 2.04 to 2.41 and from 2.05 to 3.98, respectively. The OAS1/OAS3 haplotype 'gttg' carrying a functional allele G of splice-acceptor variant rs10774671 manifested its protective function in the Delta pandemic wave. Significant baseline allelic associations of two DPP9 variants in all tested designs and two IFNAR2 variants in the Omicron pandemic wave were not confirmed by adjusted LR. Nevertheless, adjusted LR showed significant associations of NOTCH4 rs3131294 and TYK2 rs2304256 variants with severity of COVID-19. Hospitalized patients' reported comorbidities were not correlated with genetic variants, except for obesity, smoking (IFNAR2), and hypertension (NOTCH4). The results of our study suggest that host genetic variations have an impact on the severity and duration of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the differences in allelic associations between pandemic waves, they support the hypothesis that every new SARS-CoV-2 variant may modify the host immune response by reconfiguring involved pathways.
- MeSH
- 2',5'-oligoadenylátsynthetasa genetika MeSH
- COVID-19 * genetika epidemiologie virologie MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus * MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- SARS-CoV-2 * genetika MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
- MeSH
- bronchiální astma * diagnóza terapie MeSH
- lidé MeSH
- pacienti MeSH
- praktičtí lékaři * MeSH
- stupeň vzdělání MeSH
- zdravotničtí záchranáři MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that spread around the world during the past 2 years, has infected more than 260 million people worldwide and has imposed an important burden on the healthcare system. Several risk factors associated with unfavorable outcome were identified, including elderly age, selected comorbidities, immune suppression as well as laboratory markers. The role of immune system in the pathophysiology of SARS-CoV-2 infection is indisputable: while an appropriate function of the immune system is important for a rapid clearance of the virus, progression to the severe and critical phases of the disease is related to an exaggerated immune response associated with a cytokine storm. We analyzed differences and longitudinal changes in selected immune parameters in 823 adult COVID-19 patients hospitalized in the Martin University Hospital, Martin, Slovakia. Examined parameters included the differential blood cell counts, various parameters of cellular and humoral immunity (serum concentration of immunoglobulins, C4 and C3), lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, NK cells, CD4+CD45RO+), expression of activation (HLA-DR, CD38) and inhibition markers (CD159/NKG2A). Besides already known changes in the differential blood cell counts and basic lymphocyte subsets, we found significantly higher proportion of CD8+CD38+ cells and significantly lower proportion of CD8+NKG2A+ and NK NKG2A+ cells on admission in non-survivors, compared to survivors; recovery in survivors was associated with a significant increase in the expression of HLA-DR and with a significant decrease of the proportion of CD8+CD38+cells. Furthermore, patients with fatal outcome had significantly lower concentrations of C3 and IgM on admission. However, none of the examined parameters had sufficient sensitivity or specificity to be considered a biomarker of fatal outcome. Understanding the dynamic changes in immune profile of COVID-19 patients may help us to better understand the pathophysiology of the disease, potentially improve management of hospitalized patients and enable proper timing and selection of immunomodulator drugs.
COVID-19 (Coronavirus Disease) is an infectious disease caused by the coronavirus SARS-CoV-2 (Severe acute respiratory syndrome Coronavirus 2), which belongs to the genus Betacoronavirus. It was first identified in patients with severe respiratory disease in December 2019 in Wuhan, China. It mainly affects the respiratory system, and in severe cases causes serious lung infection or pneumonia, which can lead to the death of the patient. Clinical studies show that SARS-CoV-2 infection in critical cases causes acute tissue damage due to a pathological immune response. The immune response to a new coronavirus is complex and involves many processes of specific and non-specific immunity. Analysis of available studies has shown various changes, especially in the area of specific cellular immunity, including lymphopenia, decreased T cells (CD3+, CD4+ and CD8+), changes in the T cell compartment associated with symptom progression, deterioration of the condition and development of lung damage. We provide a detailed review of the analyses of immune checkpoint molecules PD-1, TIM-3, LAG-3 CTLA-4, TIGIT, BTLA, CD223, IDO-1 and VISTA on exhausted T cells in patients with asymptomatic to symptomatic stages of COVID-19 infection. Furthermore, this review may help to better understand the pathological T cell immune response and improve the design of therapeutic strategies for patients with SARS-CoV-2 infection.
- MeSH
- COVID-19 imunologie metabolismus virologie MeSH
- fenotyp MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- proteiny kontrolních bodů imunitní reakce metabolismus MeSH
- SARS-CoV-2 imunologie patogenita MeSH
- signální transdukce MeSH
- T-lymfocyty imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
