BACKGROUND: A monoclonal antibody such as mepolizumab typically first appears as a parenteral lyophilized formulation (LYO), then as various parenteral solution forms, and finally as a self-administered form at homecare. While more studies compare mepolizumab safety and efficacy across dosage forms, no data exists on the impact of switching to more successive dosage forms in real-world settings. This study aims to assess clinical outcomes in patients from five national Czech asthma centers who were switched from the LYO to the liquid formulation and then to home self-administration. METHODS: Mepolizumab was administered in three phases: LYO for 6-9 months, followed by prefilled syringes (PFS) or autoinjectors (AI) in hospitals for 6-9 months, and finally, liquid forms at homecare for another 6-9 months. Data collected included age, BMI, nasal polyposis (NP), gastroesophageal reflux (GERD), and other comorbidities. The results were statistically evaluated using exacerbation rate (ER), asthma control test, forced expiratory volume, blood eosinophil count, and required systemic oral corticosteroid (OCS) daily dose. RESULTS: Three months after initiation of administration, all methods showed improvement compared to the values at the beginning of treatment, with ER decreasing from a median of 4 to 0. Similarly, the median OCS decreased from 5 mg to 0 mg across all methods throughout the treatment. A more significant OCS dose reduction was observed in patients with NP (87.5% vs. 50%) and GERD (70% vs. 50%), who typically require higher OCS doses to achieve asthma control. AI/PFS outperformed LYO in ER (97.5-100% vs. 50-100% after 6-9 months of treatment) and OCS reduction (50-100% vs. 31.2-100% after 6-9 months of treatment), which was influenced rather by the later usage of AI/PFS and thus longer overall treatment times than the administrating method. CONCLUSION: Mepolizumab improved real-life clinical outcomes in patients with severe asthma, regardless of the dosage forms or homecare settings.

• Klíčová slova
• autoinjector, homecare, lyophilized injection, mepolizumab, monoclonal antibody, parenteral dosage form, severe asthma, syringe,
• Publikační typ
• časopisecké články MeSH

The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma.

• Klíčová slova
• S. aureus biofilm, chronic rhinosinusitis with nasal polyps, eosinophils, late onset asthma, mast cells, non-allergic rhinitis, virulence genes,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIMS: Mepolizumab, a fully-humanized recombinant IgG1 kappa monoclonal antibody directed against IL-5, has shown improved asthma control and lung function in randomised controlled trials. The aim of this study was to evaluate real-world clinical experience in patients with severe eosinophilic asthma treated with mepolizumab in Slovakia. METHODS: A retrospective, non-interventional study based on medical records of all adult asthma patients initiating mepolizumab between November 1, 2017 and January 31, 2019, completing 12 months of treatment. At baseline, general and clinical profile data were recorded 12 months prior to treatment. Primary and secondary endpoints described the results of mepolizumab use at 2, 6, and 12 months after the initiation and compared to baseline. Statistical testing of individual change (in each patient) in selected parameters was performed. RESULTS: The cohort included 17 patients with particularly severe asthma at baseline, with frequent severe exacerbations (SE, median 5 [IQR 4-6]/patient/year), high blood eosinophil counts (median 0.6x109/L), frequent oral corticosteroid (OCS) dependence (82.35%), median dose 15 (IQR 7.5-20) mg/day, impaired lung function, and a spectrum of comorbidities. In a one-year follow-up, the data showed reductions in median SE (0 [IQR 0-1] patient/year, eosinophilia (median 0.175x109/L) and OCS maintenance dose (median 6.25 [IQR 2.5-20] mg/day), all statistically significant after 12 months on mepolizumab. Improved and stabilised lung functions throughout the cohort and a reduced incidence of nasal polyposis were observed. CONCLUSIONS: The results provide clinical evidence of mepolizumab efficacy in a real sample of patients with severe asthma when administered in routine care settings in Slovakia.

• Klíčová slova
• Slovakia, exacerbations, mepolizumab, real world evidence, severe eosinophilic asthma,
• MeSH
• antiastmatika * terapeutické užití   MeSH
• bronchiální astma * farmakoterapie   komplikace   MeSH
• dospělí MeSH
• eozinofilie * komplikace   farmakoterapie   MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH
• Názvy látek
• antiastmatika * MeSH
• hormony kůry nadledvin MeSH
• mepolizumab MeSH Prohlížeč

Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP) are chronic respiratory diseases. These two disorders often co-exist based on common anatomical, immunological, histopathological, and pathophysiological basis. Usually, asthma with comorbid CRSwNP is driven by type 2 (T2) inflammation which predisposes to more severe, often intractable, disease. In the past two decades, innovative technologies and detection techniques in combination with newly introduced targeted therapies helped shape our understanding of the immunological pathways underlying inflammatory airway diseases and to further identify several distinct clinical and inflammatory subsets to enhance the development of more effective personalized treatments. Presently, a number of targeted biologics has shown clinical efficacy in patients with refractory T2 airway inflammation, including anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab)/anti-IL5R (benralizumab), anti-IL-4R-α (anti-IL-4/IL-13, dupilumab), and anti-TSLP (tezepelumab). In non-type-2 endotypes, no targeted biologics have consistently shown clinical efficacy so far. Presently, multiple therapeutical targets are being explored including cytokines, membrane molecules and intracellular signalling pathways to further expand current treatment options for severe asthma with and without comorbid CRSwNP. In this review, we discuss existing biologics, those under development and share some views on new horizons.

• Klíčová slova
• airway remodelling, asthma, biologics, chronic rhinosinusitis, precision medicine, type 2 inflammation,
• MeSH
• biologické přípravky * terapeutické užití   MeSH
• bronchiální astma * komplikace   farmakoterapie   epidemiologie   MeSH
• chronická nemoc MeSH
• komorbidita MeSH
• lidé MeSH
• nosní polypy * komplikace   farmakoterapie   MeSH
• rýma * komplikace   farmakoterapie   MeSH
• sinusitida * komplikace   farmakoterapie   MeSH
• zánět farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické přípravky * MeSH

The existence of eosinophils was documented histopathologically in the first half of the 19th century. However, the term "eosinophils" was first used by Paul Ehrlich in 1878. Since their discovery and description, their existence has been associated with asthma, allergies, and antihelminthic immunity. Eosinophils may also be responsible for various possible tissue pathologies in many eosinophil-associated diseases. Since the beginning of the 21st century, the understanding of the nature of this cell population has undergone a fundamental reassessment, and in 2010, J. J. Lee proposed the concept of "LIAR" (Local Immunity And/or Remodeling/Repair), underlining the extensive immunoregulatory functions of eosinophils in the context of health and disease. It soon became apparent that mature eosinophils (in line with previous morphological studies) are not structurally, functionally, or immunologically homogeneous cell populations. On the contrary, these cells form subtypes characterized by their further development, immunophenotype, sensitivity to growth factors, localization, role and fate in tissues, and contribution to the pathogenesis of various diseases, including asthma. The eosinophil subsets were recently characterized as resident (rEos) and inflammatory (iEos) eosinophils. During the last 20 years, the biological therapy of eosinophil diseases, including asthma, has been significantly revolutionized. Treatment management has been improved through the enhancement of treatment effectiveness and a decrease in the adverse events associated with the formerly ultimately used systemic corticosteroids. However, as we observed from real-life data, the global treatment efficacy is still far from optimal. A fundamental condition, "sine qua non", for correct treatment management is a thorough evaluation of the inflammatory phenotype of the disease. We believe that a better understanding of eosinophils would lead to more precise diagnostics and classification of asthma subtypes, which could further improve treatment outcomes. The currently validated asthma biomarkers (eosinophil count, production of NO in exhaled breath, and IgE synthesis) are insufficient to unveil super-responders among all severe asthma patients and thus give only a blurred picture of the adepts for treatment. We propose an emerging approach consisting of a more precise characterization of pathogenic eosinophils in terms of the definition of their functional status or subset affiliation by flow cytometry. We believe that the effort to find new eosinophil-associated biomarkers and their rational use in treatment algorithms may ameliorate the response rate to biological therapy in patients with severe asthma.

• Klíčová slova
• asthma, biological therapy, biomarkers, eosinophils, immunophenotype,
• MeSH
• alergie * metabolismus   MeSH
• biologické markery metabolismus   MeSH
• bronchiální astma * farmakoterapie   MeSH
• eozinofily metabolismus   MeSH
• lidé MeSH
• počet leukocytů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH

INTRODUCTION: Treatment with biologics for severe asthma is informed by international and national guidelines and defined by national regulating bodies, but how these drugs are used in real-life is unknown. MATERIALS AND METHODS: The European Respiratory Society (ERS) SHARP Clinical Research Collaboration conducted a three-step survey collecting information on asthma biologics use in Europe. Five geographically distant countries defined the survey questions, focusing on seven end-points: biologics availability and financial issues, prescription and administration modalities, inclusion criteria, continuation criteria, switching biologics, combining biologics and evaluation of corticosteroid toxicity. The survey was then sent to SHARP National Leads of 28 European countries. Finally, selected questions were submitted to a broad group of 263 asthma experts identified by national societies. RESULTS: Availability of biologics varied between countries, with 17 out of 28 countries having all five existing biologics. Authorised prescribers (pulmonologists and other specialists) also differed. In-hospital administration was the preferred deliverance modality. While exacerbation rate was used as an inclusion criterion in all countries, forced expiratory volume in 1 s was used in 46%. Blood eosinophils were an inclusion criterion in all countries for interleukin-5 (IL-5)-targeted and IL-4/IL-13-targeted biologics, with varying thresholds. There were no formally established criteria for continuing biologics. Reduction in exacerbations represented the most important benchmark, followed by improvement in asthma control and quality of life. Only 73% (191 out of 263) of surveyed clinicians assessed their patients for corticosteroid-induced toxicity. CONCLUSION: Our study reveals important heterogeneity in the use of asthma biologics across Europe. To what extent this impacts on clinical outcomes relevant to patients and healthcare services needs further investigation.

• Publikační typ
• časopisecké články MeSH