[Modern approaches to rational combination pharmacotherapy of allergic rhinitis]. / Sovremennye podkhody k ratsional'noi kombinirovannoi farmakoterapii allergicheskogo rinita.

Allergic rhinitis (AR) can significantly reduce the quality of life of patients leading to increased fatigue, mood changes, cognitive impairment, and depression. In clinical practice, insufficient effectiveness of initial AR monotherapy is often noted, and a significant proportion of patients referring for medical care have moderate-severe AR. In this regard, the issues of optimization of combined pharmacological treatment of AR are becoming more and more urgent. This paper provides analysis of the opportunities of combined pharmacotherapy within the framework of current management strategy of AR. Based on the results of some studies and known pharmacological properties of medications it is being discussed the advantages of combined use of intranasal corticosteroids and leukotriene receptor antagonists, in particular mometasone furoate and montelukast, in the therapy of AR, including such comorbidities as bronchial asthma, chronic polyposis rhinosinusitis and pharyngeal tonsil hyperplasia. Some aspects of combination therapy with montelukast and second-generation systemic antihistamines as an alternative approach in case of inability to take intranasal corticosteroids, including the reasonability of using a fixed combination of montelukast and levocetirizine, are analyzed from the perspective of rational pharmacotherapy. The problem of interchangeability of brand-name and generic drugs for the treatment of AR is discussed, considering the almost complete absence of studies of their therapeutic equivalence.

Epidemiological and clinical characteristics of adult patients with chronic spontaneous urticaria in Latvia: insights from a two-centre study.

Chronic spontaneous urticaria (CSU) significantly impacts the quality of life of affected individuals. This study aimed to elucidate the epidemiological and clinical profiles of adult CSU patients in Latvia. Patient interviews and electronic medical records from two study centres in Riga, Latvia, were reviewed. PROMs, including UCT, UAS7, USS, and CU-Q2oL, were used to assess disease control, activity, severity, and quality of life. Statistical analysis was performed using Jamovi v. 2.3.28 and IBM SPSS v. 29.0.0.0. The cohort included 140 CSU patients (76.4% female; mean age 41.3 ± 14.9 years), mostly urban residents (87.1%) and non-smokers (53.6%). Urticaria with angioedema occurred in 52.1% and isolated urticaria in 47.9%, with 40% experiencing CSU for 1-5 years. Accompanying symptoms were reported by 63% and triggers by 72.9%. Allergy history and autoimmune disease diagnosis were noted in 49.3% and 29.3%. Treatment mainly involved second-generation antihistamines (85.7%) and omalizumab (17.9%). Mean scores for USS, UCT, and UAS7 were 28.8 (SD: 17.8), 8.2 (SD: 3.7), and 17.2 (SD: 14.1). UAS7 indicated severe CSU in 28.6%, and UCT suggested poorly controlled disease in 77.9%. CU-Q2oL total scores revealed mental status as the most affected domain (mean score: 51.7, SD: 28.7), with a significant association between accompanying symptoms and questionnaire scores. This study provides insights into the demographic and clinical aspects of CSU patients in Latvia, highlighting areas for potential improvement in patient care and emphasizing the need for further investigation into treatment outcomes and patient quality of life.

Anti-Allergic and Anti-Inflammatory Signaling Mechanisms of Natural Compounds/Extracts in In Vitro System of RBL-2H3 Cell: A Systematic Review.

Various extracts are tested for anti-allergic or anti-inflammatory properties on in vitro models. RBL-2H3 cells are widely used in allergic or immunological studies. FCεRI and its downstream signaling cascades, such as MAPK, NF-κB, and JAK/STAT signaling pathways, are important allergic or inflammatory signaling mechanisms in mast and basophil cells. This systematic review aims to study common signaling pathways of the anti-allergic or anti-inflammatory compounds on RBL-2H3 cells. We selected the relevant research articles published after 2015 from the PubMed, Scopus, Science Direct and Web of Science databases. The risk of bias of the studies was assessed based on the modified CONSORT checklist for in vitro studies. The cell lines, treatments, assay, primary findings, and signaling pathways on RBL-2H3 cells were extracted to synthesize the results. Thirty-eight articles were included, and FCεRI and its downstream pathways, such as Lyn, Sky, PLCγ, and MAPK, were commonly studied. Moreover, the JAK/STAT pathway was a potential signaling mechanism in RBL-2H3 cells. However, the findings based on RBL-2H3 cells needed to be tested along with human mast cells to confirm its relevance to human health. In conclusion, a single plant extract may act as an anti-inflammatory reagent in RBL-2H3 cells via multiple signaling pathways besides the MAPK signaling pathway.

Pearls and pitfalls of OTC medications for seasonal allergies.

ABSTRACT: Seasonal allergies have a negative impact on patients' quality of life. Nurses must be aware of the different treatment options and lifestyle modifications to help patients manage their symptoms. This article discusses the benefits and risks of over-the-counter medications for seasonal allergies and other implications for nurses.

Omalizumab for management of hypersensitivity reactions to anticancer drugs.

Hypersensitivity reactions to anticancer drugs include treatment-limiting toxicity. Standard drug desensitisation offers temporary tolerance and hence requires repetition. We used omalizumab, an anti-immunoglobulin E antibody, to overcome immediate and delayed hypersensitivity reactions to various anticancer drugs. Seven of the eight patients in the current study successfully resumed the desired anticancer drug regimen without standard desensitisation. No safety issues from omalizumab were observed.

New insights into chronic inducible urticaria.

PURPOSE OF REVIEW: Chronic inducible urticaria (CIndU) is a group of long-persisting and challenging to manage diseases, characterized by recurrent wheals and angioedema induced by definite triggers. In this review, we address recent findings on CIndU pathogenesis, diagnosis as well as its treatment, and we discuss novel potential targets that may lead to the development of more effective therapies for CIndU patients. RECENT ADVANCES: Meaningful advances in the understanding of its pathogenesis have been reported in the last decades. Novel CIndU-specific patient-reported outcome measures enable a closer and better evaluation of patients. CIndU is a hard-to-treat disease that highly impairs quality of life (QoL) of affected patients. Provocation tests allow to diagnose CIndU subtypes. The only licensed and recommended treatment for CIndU are second generation non-sedating H1-antihistamines, which lack efficacy in many cases. Omalizumab off-label use has been assessed in all types of CIndU with overall good outcomes. Promising emerging therapies currently assessed in chronic spontaneous urticaria are paving the path for novel treatments for CIndU.

Omalizumab in the treatment of bullous pemphigoid: A single-center series of 15 cases.

Bullous pemphigoid (BP) is a chronic autoimmune disease affecting the elderly population and characterized by the formation of subepidermal tense bullae. Treatment options include topical steroids, systemic steroids, immunosuppressants, and antimicrobials, and there is emerging evidence of the efficacy of omalizumab. In this study, we aimed to demonstrate omalizumab's efficacy for treating BP, and we also reported treatment-related adverse events. The retrospective cohort study included patients with BP who were followed up in our clinic's bullous diseases department between 2016 and 2023. Patients who received omalizumab were included in the study. Treatment responses of all patients were assessed by BP Disease Area Index activity and damage scores, treatment scale scoring, steroid dose reduction, and the presence/absence of pruritus. Also, total IgE levels of patients before the treatment onset and at the last visit were compared. There were 15 (male/female = 8/7) BP patients receiving omalizumab treatment. Omalizumab therapy allowed steroid dose reduction at a median of 1 month. Omalizumab (25.5 mg, 95% confidence interval 17.2-33.9, P < .001) provided a significant steroid dose reduction at the last visit compared to the beginning of treatment. Omalizumab resulted in a decrease in BP Disease Area Index activity score of 80.8 (95% confidence interval 71.8-89.8, P < .001). Also, omalizumab caused significant decline in IgE levels compared to baseline (1102.5 ±â€…834.5 vs 834.6 ±â€…613.6, P = .002). In this study, omalizumab treatment was an effective and safe option in BP patients with high baseline IgE levels who are refractory to or cannot tolerate other immunosuppressive therapies.

What can be learned from real-world data about chronic spontaneous urticaria?

Background: Chronic spontaneous urticaria (CSU) is a common disease with complex pathogenesis. Patients' clinical characteristics and responses to treatment vary. Objective: We aimed to investigate the role of data obtained from routinely recommended tests in predicting the response to omalizumab, the only biologic agent approved for treatment, and in defining the clinical characteristics of the patients. Methods: A retrospective study of patients who started omalizumab treatment for CSU between 2015 and 2022 at the Department of Dermatology, Pamukkale University, was conducted. Response criteria were based on the urticaria control test, and patients with a urticaria control test score <12 at 6 months were considered treatment non-responders. Eosinophil and basophil counts, neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and total immunoglobulin E (IgE) levels of the patients were evaluated before treatment and at the sixth month of treatment. Results: A total of 23.1% of the patients were unresponsive to omalizumab. The response rate to the omalizumab treatment of the patients with a total IgE level ≤ 30 IU/L (n = 4 [5.7%]) was significantly lower than patients with total IgE level > 30 IU/L (n = 66 [94.3%]) (p = 0.015). The mean ± standard deviation SIRI levels were significantly higher in non-responders versus responders (1.53 ± 1.03 versus 1.15 ± 7.76; p = 0.026). Eosinophil counts positively correlated with basophil counts (r = 587; p < 0.001) and IgE levels (r = 0.290; p = 0.005) but a negative correlation was found with levels of NLR (r = -0.475; p < 0.001), SIRI (r = -0.259; p = 0.013), and SII (r = -0.285; p = 0.006). NLR levels were lower in CSU patients with atopy, than in those without atopy (1.9 ± 0.9 vs 2.9 ± 2.1, p = 0.022). Conclusion: We suggest that eosinopenia and high NLR levels are linked to autoimmune CSU. Predicting a poor response to omalizumab seems possible with total IgE levels < 30 IU/L and high SIRI levels.

Treatment of patients with evidence of mast cell-mediated itch in the absence of hives with omalizumab.

PURPOSE: The presence of wheals or hives has been viewed as a hallmark symptom of urticaria, a highly debilitating disease. This study explores our experience with omalizumab in patients with apparent mast-cell mediated pruritus in the absence of hives. MATERIALS AND METHODS: This is a retrospective case series examining all patients with mast cell-mediated pruritus in the absence of hives from April 2022 to May 2024 at a tertiary referral clinic at Icahn School of Medicine at Mount Sinai in New York. Peak pruritus-numerical rating scale (PP-NRS) itch score changes over time were recorded and analyzed. RESULTS: Six patients (67% women; mean [SD] age, 47.67 [13.52] years) were included in the analysis. The median [IQR] pruritus PP-NRS itch score before omalizumab injection was 9 [6 - 10] and the final median [IQR] PP-NRS itch score was 2.5 [0 - 5]. The mean [SD] reduction in the PP-NRS itch score was 6 [3.16]. CONCLUSIONS: This study suggests that patients with evidence of mast cell-mediated pruritus can be identified based on clinical features and may benefit from omalizumab therapy.

Inhibition of pseudo-allergic reactions by vitamin K3 directly targeting GAB1 in mast cells.

BACKGROUND: Vitamin K3 (VK3), a fat-soluble synthetic analog of the vitamin K family, has coagulant, anti-inflammatory, antibacterial, and anticancer properties. Pseudo allergy is a IgE-independent immune response associated with mast cells. This study investigated the role of VK3 in IgE-independent mast cell activation. METHODS: Substance P (SP) was used to induce LAD2-cell activation in order to analyze the effects of VK3 in vitro. Cutaneous allergy and systemic allergy mouse models were used to analyze the anti-pseudo-allergic effects of VK3. Proteome microarray assays were used to analyze VK3-binding protein. Biolayer interferometry and immunoprecipitation were used to verify interaction between VK3 and its key targets. RNA interference was used to determine the role of GAB1 in LAD2cell activation. RESULTS: VK3 inhibited SP-induced LAD2-cell activation, and resulted in the release of ß-hexosaminidase, histamine and cytokines; VK3 inhibited SP-induced pseudo allergic reactions in mice, and serum histamine and TNF-α levels decreased. Degranulation of skin mast cells was reduced; GAB1 in mast cells was stably bound to VK3. GAB1 participated in SP-induced LAD2-cell activation. GAB1 knockdown in LAD2 cells prevented SP-induced ß-hexosaminidase release, calcium mobilization and cell skeletal remodeling. VK3 directly binds to GAB1 and reduces its expression to inhibited SP-induced LAD2 cell activation. CONCLUSION: The anti-pseudo-allergic activity of VK3 was confirmed in vitro and in vivo. VK3 can inhibit SP-induced mast cell activation by directly targeting GAB1. This study provides new insights on the activity of VK3 and the mechanism of pseudoallergic reaction.

Atopic dermatitis and IgE-mediated food allergy: Common biologic targets for therapy and prevention.

OBJECTIVE: To highlight common mechanistic targets for the treatment of atopic dermatitis (AD) and IgE-mediated food allergy (IgE-FA) with potential to be effective for both diseases and prevent atopic progression. DATA SOURCES: Data sources were PubMed searches or National Clinical Trials (NCT)-registered clinical trials related to AD, IgE-FA, and other atopic conditions, especially focused on the pediatric population. STUDY SELECTIONS: Human seminal studies and/or articles published in the past decade were emphasized with reference to preclinical models when relevant. NCT-registered clinical trials were filtered by inclusion of pediatric subjects younger than 18 years with special focus on children younger than 12 years as a critical period when AD and IgE-FA diseases may often be concurrent. RESULTS: AD and IgE-FA share several pathophysiologic features, including epithelial barrier dysfunction, innate and adaptive immune abnormalities, and microbial dysbiosis, which may be critical for the clinical progression between these diseases. Revolutionary advances in targeted biologic therapies have shown the benefit of inhibiting type 2 immune responses, using dupilumab (anti-interleukin-4Rα) or omalizumab (anti-IgE), to potentially reduce symptom burden for both diseases in pediatric populations. Although the potential for biologics to promote disease remission (AD) or sustained unresponsiveness (IgE-FA) remains unclear, the refinement of biomarkers to predict infants at risk for atopic disorders provides promise for prevention through timely intervention. CONCLUSION: AD and IgE-FA exhibit common features that may be leveraged to develop biologic therapeutic strategies to treat both conditions and even prevent atopic progression. Future studies should be designed with consistent age stratification in the pediatric population and standardized regimens of adjuvant oral immunotherapy or dose escalation (IgE-FA) to improve cross-study interpretation.

Ameliorative effects of Wikstroemia trichotoma 95% EtOH extract on a mouse model of DNCB-induced atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD). AIM OF THE STUDY: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA). MATERIALS AND METHODS: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured. RESULTS: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited ß-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-ß-apiofuranosyl (1 â†’ 6)-ß-glucopyranoside. CONCLUSIONS: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD.

Shiikuwasha leaf and peel extracts inhibit allergic reactions by suppressing degranulation in RBL-2H3 rat basophilic leukemia cells and immunoglobulin production in mouse spleen lymphocytes.

This study aims to investigate the antiallergic effects of Shiikuwasha (Citrus depressa Hayata) leaf and peel extracts by examining the regulation of degranulation and inflammatory cytokine production from rat basophilic leukemia (RBL-2H3) cells and antigen-specific antibody production in sensitized mouse spleen lymphocytes. In vivo antiallergic activity was evaluated using the passive cutaneous anaphylaxis (PCA) reaction model. Extracts of Shiikuwasha leaves and peel were prepared using 80% methanol and dissolved in dimethylsulfoxide. The dinitrophenyl-human serum albumin-induced ß-hexosaminidase levels in immunoglobulin (Ig) E-sensitized RBL-2H3 cells were assessed using enzymatic assays. Cytokine production was measured by enzyme-linked immunosorbent assay. Antibody production capacity was evaluated using lymphocytes isolated from spleens of type I allergy model mice. Lymphocytes were cultured for 72 h with Shiikuwasha extracts, and ovalbumin-specific IgE, IgG1, and IgG2a levels were measured. Shiikuwasha leaf and peel extract significantly reduced ß-hexosaminidase release and suppressed interleukin-4 and tumor necrosis factor-α production from RBL-2H3 cells. Ovalbumin-specific IgE and IgG1 production decreased in Shiikuwasha extract-treated lymphocytes. These extracts also significantly suppressed the PCA reaction. Shiikuwasha leaf and peel extract reduce degranulation in RBL-2H3 cells and antibody production in spleen-derived lymphocytes and therefore exhibit antiallergic effects.

Chronic Spontaneous Urticaria: An Update on the Evaluation and Management.

Chronic spontaneous urticaria (CSU) affects 0.5% to 1% of the general population and is often managed by allergy and immunology specialists. Guidelines have evolved over the past several decades with an emphasis on decreasing extensive screening laboratory testing as they are of low-yield and cost-ineffective. The utility of biomarkers remains under investigation but total immunoglobulin E may be helpful in determining specific endotypes and response to omalizumab. Antihistamines and omalizumab remain the primary therapeutic options for CSU, but an expanding body of evidence supports the use of immunosuppressants and anti-inflammatory medications in refractory cases.

Se-rich tea polysaccharide extracted by high hydrostatic pressure attenuated anaphylaxis by improving gut microbiota and metabolic regulation.

Selenium-rich tea polysaccharides (Se-TPS) were extracted via high hydrostatic pressure technology with a pressure of 400 MPa (200-500 MPa) for 10 min (3-20 min) at a material-to-solvent ratio of 1:40 (1:20-1:50). Subsequently, Se-TPS1-4 were isolated and purified, with Se-TPS3-4 as the main components. A spectral analysis proved that Se, which has antioxidant activity, existed. An in vitro study found that among Se-TPS, Se-TPS3-4 attenuated the release of ß-hexosaminidase, histamine, and interleukin (IL)-4. Furthermore, in vivo experiments revealed that treatment with Se-TPS downregulated IL-4 levels and upregulated TGF-ß and interferon-γ levels to improve imbalanced Th1/Th2 immunity in tropomyosin-sensitized mice. Moreover, Se-TPS promoted Lactobacillus and norank_f_Muribaculaceaek growth and upregulated metabolites such as genipin and coniferyl alcohol. Overall, these results showed the strong anti-allergy potential of Se-TPS by regulating mast cell-mediated allergic inflammatory responses and microbiota regulation, highlighting the potential of Se-TPS as a novel therapeutic agent to regulate allergy-associated metabolic disorders.

Stressful life events, psychiatric comorbidities and serum neuromediator levels in patients with chronic spontaneous urticaria treated with omalizumab.

INTRODUCTION: Many chronic spontaneous urticaria (CSU) patients have highly stressful life events and exhibit psychiatric comorbidities. Emotional stress can cause or exacerbate urticaria symptoms by causing mast cell degranulation via neuromediators. OBJECTIVES: To investigate the frequency of stressful life events and compare psychiatric comorbidities and serum neuromediator levels in patients with CSU who responded to omalizumab with healthy controls. METHODS: In this cross-sectional study, we included 42 patients with CSU who received at least 6 months of omalizumab treatment and a control group of 42 healthy controls. Stressful life events were evaluated with the Life Events Checklist for DSM-5 (LEC-5). The Depression Anxiety Stress Scale-42 (DASS-42) was used to evaluate depression, anxiety and stress levels. Serum nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and substance P (SP) levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Twenty-six (62%) patients reported at least one stressful life event a median of 3.5 months before the onset of CSU. There were no significant differences in all three variables in the DASS subscales between the patient and control groups. Serum NGF levels were found to be significantly lower in patients with CSU (p <0.001), whereas CGRP levels were found to be significantly higher (p <0.001). There was no significant difference for SP. CONCLUSIONS: The psychological status of patients with CSU who benefited from omalizumab was similar to that of healthy controls. Omalizumab may affect stress-related neuromediator levels.

Comparison of anti-allergic activities of different types of lotus seed resistant starch in OVA-induced mouse model.

Currently, evidence from observational studies suggests dietary fiber intake may be associated with decreased risk of food allergy. As a type of dietary fiber, resistant starch was also widely reported to possess anti-allergic properties. However, there is a relative paucity of studies assessing the influence of resistant starch types on their anti-allergic activity and its possible underlying mechanisms. In the current study, the anti-allergic effects of RS3-type (retrograded starch), RS4-type (chemically modified starch, cross-bonded), and RS5-type (starch-palmitic acid complex) of lotus seed resistant starch were evaluated in the OVA (100 mg/kg)-induced food allergic mice model. The results showed that oral administration of RS3 or RS4 lotus seed resistant starch (0.3 g/100 g b.w.) for 25 days significantly improved adverse symptoms of food allergy such as weight loss, increases in allergy symptom score and diarrhea rate; with significant reduction of serum specific antibody IgE, TNF-α, IL-4 levels and improved Th1/Th2 balance being observed. The mechanism may involve the regulation of lotus seed resistant starch on intestinal flora and the metabolites short-chain fatty acids and bile acids. Taken together, the findings may enhance understanding towards ameliorative effects of resistant starch on food allergy, and offer valuable insights for the exploration of novel anti-allergic bioactive compounds.