Allergic Asthma Research Articles

Developmental Origins of Non-Communicable Chronic Diseases: Role of Fetal Undernutrition and Gut Dysbiosis in Infancy

There is an increasing prevalence of non-communicable chronic diseases (NCCDs) like obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), hypertension, allergic asthma, and neuro-developmental/psychiatric problems in many parts of the world. A suboptimal lifestyle as an adult is often blamed for the occurrence of NCCDs. This review discusses the developmental origin of health and disease theory and how suboptimal nutrition in intrauterine life and the establishment of a suboptimal gut microbiome during infancy can influence the predisposition to NCCDs.

Depigmented, polymerized cat epithelium extract is safe and improves rhinitis and asthma symptoms in cat allergic patients: A real-world retrospective study.

Cat allergy is often difficult to avoid. Here, we evaluated the safety and effectiveness of a depigmented, polymerized cat epithelium extract (Dpg-pol-cat) for the treatment of allergic rhinoconjunctivitis and asthma. Real-world, retrospective study of patients ≥12 years with cat allergy and moderate to severe allergic rhinitis/rhinoconjunctivitis, with or without asthma, who started allergen immunotherapy (AIT) with Dpg-pol-cat extract during routine visits to the Allergy Department. Safety and effectiveness (improvement in FEV1) of AIT were evaluated. The use of rescue medication and patient perceptions were also assessed. A total of 62 patients were included, of which 34 (54.8%) received at least 12 months of AIT. There were 15 adverse reactions, 8 local and 7 systemic, of which 3 led to AIT discontinuation. Patients with moderate to severe rhinitis decreased from 88.2% at baseline to 29.4% at 12 months (p <0.0001), and patients with moderate asthma decreased from 76.5% to 38.2% (p = 0.0004). FEV1 improved from a mean (SD) of 3188.9 (771.4) ml to 3419.6 (878.4) ml (p = 0.0023). The use of rescue medications for rhinitis decreased from 94.1% to 23.5% (p <0.0001), all patients requiring rescue medications for conjunctivitis (20.6%) were medication free at 12 months, and 97.1% and 92.6% of patients reported improvement in rhinitis and asthma symptoms, respectively. AIT with Dpg-pol-cat extract shows a favorable safety and effectiveness profile in patients with allergic rhinitis/rhinoconjunctivitis, with or without allergic asthma, due to cat allergy, representing a valuable treatment option for these patients.

Genetically Predicted Immune Cell-Mediated Effect of Lipid Metabolism on Allergic Diseases: A Two-Step, Mediation Mendelian Randomization Study.

An increasing number of studies have demonstrated that dynamic changes in lipid species can affect allergic diseases; however, the causal relationship and mediating role of immune cells remain unclear. We conducted a bidirectional two-sample mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on 179 lipid species (n = 7,174) and three types of allergic diseases including allergic rhinitis (AR) (n = 370,158), allergic asthma (n = 219,753), and allergic conjunctivitis (n = 377,277). The principal model used was the inverse variance-weighted approach, and a series of sensitivity analyses were conducted to ensure the robustness of the results. We used a two-step MR approach to assess whether the causal effect was mediated by immune cells (n = 3,757). Sterol ester and sphingomyelin played pathogenic roles in allergic asthma, AR, and allergic conjunctivitis; however, the effective subtypes differed. Among them, CD45RA- CD4+ mature T cells and CCR2 on CD14+ CD16+ monocytes affected the promoting impact of sterol ester's metabolism on allergic asthma and AR with different mediating proportions, while the role of sphingomyelin may not involve the immune cells. Moreover, we observed that HLA-DR on CD33- HLA DR+ myeloid cells, CD11b on CD66b++ myeloid cells, and IgD+ CD38- B cells played the most mediating effect of phosphatidylethanolamine (O-18:2_20:4) in allergic asthma, phosphatidylinositol (16:0_18:1) in AR, and phosphatidylethanolamine (18:0_18:2) in allergic conjunctivitis. This MR study provides evidence for specific lipid species associated with the risk of allergic diseases, especially sterol esters, and identifies the immune cells that mediate this causal relationship.

Maternal asthma during pregnancy and the likelihood of neurodevelopmental disorders in offspring.

Asthma is the most common chronic disease during pregnancy. Maternal asthma has been associated with a multitude of unwanted pregnancy outcomes, in some studies also with neurodevelopmental disorders. Here we investigated associations between maternal asthma and neurodevelopmental disorders. We studied a retrospective population-based cohort of 1 271 439 mother-child pairs from singleton live births in Finland between the years 1996-2018. We used multiple high-cover registers for data collection. Adjusted unconditional Cox regression models were used to investigate associations between maternal asthma, asthma medication used during pregnancy, and offspring's neurodevelopmental disorder diagnoses. We identified 106 163 mother-child pairs affected by maternal asthma. We found that maternal asthma was associated with offspring neurodevelopmental disorders, but the differences in absolute prevalence between the control and exposure groups were small. Attention-deficit hyperactivity disorder (ADHD) was found in 4114 (3.9%) offspring with maternal asthma and in 32 122 (3.0%) controls (adjusted hazard ratio (HR): 1.49; 95% CI 1.44-1.54); autism in 1617 (1.5%) offspring versus 13 701 (1.3%) controls (HR: 1.33; 95% CI 1.26-1.40); motor-developmental disorder in 1569 (1.5%) offspring versus 12 147 (1.1%) controls (HR: 1.37; 95% CI 1.30-1.45); language disorder in 3057 (2.9%) offspring versus 28 421 (2.7%) controls (HR: 1.13; 95% CI 1.08-1.17), learning disabilities in 849 (0.8%) offspring versus 6534 (0.6%) controls (HR: 1.51; 95% CI 1.41-1.62); mixed developmental disorder in 1633 (1.5%) offspring versus 14 434 (1.3%) controls (HR 1.20; 95% CI, 1.14-1.26); and intellectual disability in 908 (0.9%) versus 9155 (0.9%) controls (HR: 1.12; 95% CI 1.04-1.20). No substantial differences were found between allergic and non-allergic asthma phenotypes, and neither allergic tendency nor respiratory infection was associated with a similar likelihood of neurodevelopmental disorders. Maternal asthma and allergic and non-allergic phenotypes showed weak associations with the offspring's neurodevelopmental disorders. The association is concerned especially with learning disabilities, ADHD, motor development, and autism.

Minimizing Indoor Allergen Exposure: What Works?

Allergic rhinitis and asthma morbidity has been linked to indoor allergen exposure. Common indoor allergens include dust mites, cats, dogs, rodents, and cockroaches. These allergens are ubiquitous and often difficult to remove from the home, making long-lasting reduction strategies difficult to achieve. Identifying strategies for reducing the presence of indoor allergens in homes could be utilized to decrease allergic disease burden, improve symptomology, reduce healthcare costs, and improve patients' quality of life. Studies have yielded mixed results with regard to specific environmental control measures in reducing indoor allergen levels and in improving clinical outcomes of allergic disease. In this review, we assess the available evidence of the effectiveness of environmental control measures in reducing indoor allergens and the potential clinical impact of these measures.

Allergy Modulation: Exploring the Role of Prebiotics, Probiotics, and Synbiotics in Enhancing Health Outcomes - A Literature Review

This literature review explores the role of prebiotics, probiotics, and synbiotics in the prevention and management of allergic diseases, including eczema, asthma, allergic rhinitis, and food allergies. The review delves into the mechanisms by which these dietary interventions modulate the gut microbiome, influence immune system responses, and enhance the epithelial barrier. While prebiotics promote the growth of beneficial gut bacteria and the production of short-chain fatty acids, probiotics introduce live microorganisms that restore balance in the gut ecosystem. Synbiotics combine both approaches to synergistically improve gut health. Despite the promising potential of these interventions, the evidence remains mixed, with their efficacy varying across different allergic conditions. This review underscores the need for further research to clarify the effectiveness of prebiotics, probiotics, and synbiotics in allergy prevention and management, highlighting the complexities involved in translating these findings into clinical practice.

Mycophenolate Mofetil, an Inhibitor of Inosine Monophosphate Dehydrogenase, and Tofacitinib, a Janus Kinase Inhibitor, Attenuate Airway Inflammation and Hyperresponsiveness in a Mouse Model of Allergic Asthma

Treatment-resistant asthma remains an unresolved clinical problem and a challenge for current medical science. Consequently, there is a growing and urgent need to develop novel or alternative therapeutic options for the treatment of asthma. The research problem raised in this study was to assess and compare mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase, and tofacitinib (TFB), a Janus kinase inhibitor, for anti-asthmatic properties, and consequently to determine whether these agents may have potential as alternative options for treatment of allergic asthma. For this purpose, we assessed the effect of administration of MMF and TFB on the development of a mouse model of allergic airway inflammation (AAI) and accompanying CD4+ (cluster of differentiation 4) T-cell immune response in the lung-draining mediastinal lymph nodes (MLNs) and lungs, i.e., in the inductive and effector sites, respectively, of the immune response underlying the development of allergic asthma. The results from a histopathological scoring system demonstrated that the administration of MMF and TFB did not prevent or abolish ovalbumin-induced AAI, but strongly attenuated its severity. The pulmonary function tests revealed that the treatment with MMF and TFB significantly reduced methacholine-induced bronchoconstriction. These results indicate that the treatment with TFB and MMF attenuated the development of ovalbumin-induced AAI. The magnitude of the anti-asthmatic effect was comparable between both agents. The study revealed that the impairment of the clonal expansion of effector CD4+ T cells in the MLNs is a critical event in the mechanism underlying the anti-asthmatic effect of MMF and TFB. Apart from this, the findings of the study strongly suggest that the suppression of the interleukin-33/suppression of tumorigenicity-2 signaling pathway may constitute an additional mechanism responsible for producing this effect. In turn, the results indicate that the anti-asthmatic action induced by the studied agents is not mediated by the generation of forkhead box protein 3-expressing CD4+ regulatory T cells. Clinical implication of the results: the results suggest that MMF and TFB may exert anti-asthmatic action, and thus they may be considered therapeutic options for the treatment of allergic asthma cases resistant to conventional/existing treatment.

Anti-Inflammatory Effects of SGLT1 Synthetic Ligand in In Vitro and In Vivo Models of Lung Diseases

Background. Several research findings suggest that sodium–glucose co-transporter 1 (SGLT1) is implicated in the progression and control of infections and inflammation processes at the pulmonary level. Moreover, our previous works indicate an engagement of SGLT1 in inhibiting the inflammatory response induced in intestinal epithelial cells by TLR agonists. In this study, we report the anti-inflammatory effects observed in the lung upon engagement of the transporter, and upon the use of glucose and BLF501, a synthetic SGLT1 ligand, for the treatment of animal models of lung inflammation, including a model of allergic asthma. Methods. In vitro experiments were carried out on human pneumocytes stimulated with LPS from Pseudomonas aeruginosa and co-treated with glucose or BLF501, and the production of IL-8 was determined. The anti-inflammatory effect associated with SGLT1 engagement was then assessed in in vivo models of LPS-induced lung injury, as well as in a murine model of ovalbumin (OVA)-induced asthma, treating mice with aerosolized LPS and the synthetic ligand. After the treatments, lung samples were collected and analyzed for morphological alterations by histological examination and immunohistochemical analysis; serum and BALF samples were collected for the determination of several pro- and anti-inflammatory markers. Results. In vitro experiments on human pneumocytes treated with LPS showed significant inhibition of IL-8 production. The results of two in vivo experimental models, mice exposed to aerosolized LPS and OVA-induced asthma, revealed that the engagement of glucose transport protein 1 (SGLT1) induced a significant anti-inflammatory effect in the lungs. In the first model, the acute respiratory distress induced in mice was abrogated by co-treatment with the ligand, with almost complete recovery of the lung morphology and physiology. Similar results were observed in the OVA-induced model of allergic asthma, both with aerosolized and oral BLF501, suggesting an engagement of SGLT1 expressed both in intestinal and alveolar cells. Conclusions. Our results confirmed the engagement of SGLT1 in lung inflammation processes and suggested that BLF501, a non-metabolizable synthetic ligand of the co-transporter, might represent a drug candidate for therapeutic intervention against lung inflammation states.

The VEGF-Mediated Cytoprotective Ability of MIF-Licensed Mesenchymal Stromal Cells in House Dust Mite-Induced Epithelial Damage.

Enhancing mesenchymal stromal cell (MSC) therapeutic efficacy through licensing with proinflammatory cytokines is now well established. We have previously shown that macrophage migration inhibitory factor (MIF)-licensed MSCs exerted significantly enhanced therapeutic efficacy in reducing inflammation in house dust mite (HDM)-driven allergic asthma. Soluble mediators released into the MSC secretome boast cytoprotective properties equal to those associated with the cell itself. In asthma, epithelial barrier damage caused by the inhalation of allergens like HDM drives goblet cell hyperplasia. Vascular endothelial growth factor (VEGF) plays a pivotal role in the repair and maintenance of airway epithelial integrity. Human bone marrow-derived MSCs expressed the MIF receptors CD74, CXCR2, and CXCR4. Endogenous MIF from high MIF expressing CATT7 bone marrow-derived macrophages increased MSC production of VEGF through the MIF CXCR4 chemokine receptor, where preincubation with CXCR4 inhibitor mitigated this effect. CATT7-MIF licensed MSC conditioned media containing increased levels of VEGF significantly enhanced bronchial epithelial wound healing via migration and proliferation in vitro. Blocking VEGFR2 or theuse of mitomycin C abrogated this effect. Furthermore, CATT7-MIF MSC CM significantly decreased goblet cell hyperplasia after the HDM challenge in vivo. This was confirmed to be VEGF-dependent, as the use of anti-human VEGF neutralising antibody abrogated this effect. Overall, this study highlights that MIF-licenced MSCs show enhanced production of VEGF, which has the capacity to repair the lung epithelium.

Prevalence of inhaled allergen sensitization among patients with suspected allergic diseases in Sichuan province: 3-year data from a single center.

Allergic diseases are becoming increasingly common, and they are a threat to people's health. Exploring the distribution characteristics of allergen-specific immunoglobulin E (sIgE) in people from Sichuan province, southwest China, can provide clinical epidemiological data. This study enrolled 12,204 consecutive patients with suspected allergies from May 2018 to May 2021. Among the patients, 4206 were diagnosed with allergic rhinitis or asthma. The Rayto Lumiray 1600 detection system and sIgE and total IgE (tIgE) detection kits were used to measure the levels of nine common sIgE and tIgE. sIgE ≥ 0.35 IU/mL was considered positive. The sensitization rate of D1 (Dermatophagoides pteronyssinus) is the highest (22.97%), followed by D2 (Dermatophagoides farinae) (23.33%); M3 (Aspergillus fumigatus) has the lowest positive rate (1.5%). E5 (Canis familiaris) and I6 (Blatella germanica) exhibited relatively high sensitization rates (8.64% and 12.35%, respectively). Allergen sensitization was significantly higher in men than in women. Moreover, 90.3% of sensitization samples from D1 were combined with at least one of the other eight allergens. Similarly, a positive correlation was demonstrated between D1, D2, and E1 (Felis domesticus). In addition, patients with allergic rhinitis (91.88% and 91.54%, respectively), allergic asthma (72.44% and 74.01%, respectively), and allergic rhinitis with asthma (92.12% and 93.22%, respectively) were mainly sensitized to D1 and D2. D1, D2, I6, and E5 are the main allergens. Moreover, D1 and D2 are the main allergens in patients with respiratory allergic diseases. Research focusing on the distribution of allergens and the characteristics of hypersensitivity in different people helps prevent, diagnose, and treat allergic diseases.

Biomarkers for house dust mite subcutaneous immunotherapy in allergic asthma

BackgroundAllergen immunotherapy (AIT) has demonstrated clinical efficacy in patients with allergic asthma. However, there is little information on biomarkers to evaluate the effect of house dust mite (HDM) subcutaneous immunotherapy (SCIT) on allergic asthma. ObjectiveTo evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SCIT. Methods139 patients with asthma sensitized to HDM were recruited, 75 subjects received SCIT as an add-on therapy to drug treatment, and 64 subjects received drug treatment alone. Spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total IgE (TIgE), serum specific IgE for HDM, and frequency of exacerbations (ACT scores) were measured at baseline, 6 months, and 12 months. The relationship between biomarkers and pulmonary function improvement was investigated. ResultsSCIT demonstrated a significant reduction in FeNO, serum IL-25 and ACT scores at 6 months and significantly improved airflow limitation at 12 months compared to pharmacotherapy. The changes in FEV1 were dramatically correlated with changes in blood eosinophils ( r =-0.35, P=0.002), FeNO ( r =-0.57, P＜0.0001), serum IL-25 ( r =-0.68, P＜0.0001) and ACT scores( r =0.562, P＜0.0001). The multivariate regression analysis revealed that the changes in serum IL-25 concentration and FeNO were independently associated with an increase in FEV1 (r2 = 0.514, P < 0.05, respectively) in patients with allergic asthma treated with HDM SCIT. ConclusionsAdding HDM SCIT to pharmacotherapy reduced serum IL-25 and FeNO and improved pulmonary function in allergic asthma. Serum IL-25 and FeNO may be useful biomarkers for predicting HDM SCIT in allergic asthma, even in the absence of significant improvement in airflow limitation.

Mechanisms of Mt.b Ag85B-Fc fusion protein against allergic asthma in mice by intranasal immunization.

Ag85B, the primary component of the Ag85 complex and an early secreted protein by Mycobacterium tuberculosis, has shown potential for the treatment of allergic asthma (AA) when used as a Fc-fusion protein. Administered via nasal immunization, Ag85B-Fc fusion protein significantly alleviated airway inflammation and reduced the proportions of some anaphylaxis related cells in lungs, with no significant histopathological injury to major organs in ovalbumin (OVA)-induced AA model mice. To investigate the underlying immune regulatory mechanisms of Ag85B protein, integrated proteomics and transcriptomics analyses were conducted, identifying the complement and coagulation cascades, and phagosomes as the two significantly enriched pathways at both gene and protein levels. Moreover, C3ar1 (C3aR1), Itgam (CD11b), Itgb2 (CD18), fgg (FGG), Cybb (CYBB), and Ncf4 (NCF4) were identified as core target factors that play a central role in allergic and asthmatic responses. Among them, C3aR1 and CR3 consisting of CD11b and CD18, are main complement receptors, indicating that Ag85B alleviated AA by regulating C3aR1- and CR3-mediated signal transduction. The validation results were consistent with the aforementioned findings. Overall, these results provide valuable insight into the application of mucosal immunotherapy in treatment of AA, positioning Ag85B-Fc fusion protein as a safe mucosal immunotherapeutic agent for AA.

The Association of Nasal and Blood Eosinophils with Serum IgE Level in Allergic Rhinitis and Asthma: A Case-Control Study.

Allergic rhinitis and asthma are two common respiratory diseases with allergic etiology in the world's population. Eosinophils and serum IgE levels have been known as inflammatory allergy markers for many years. This study aimed to evaluate the correlation of nasal and blood eosinophils with serum IgE levels in allergic rhinitis and asthma patients. This prospective study was done on patients (n = 78) diagnosed with asthma (n = 20), allergic rhinitis (n = 49), and chronic rhinosinusitis with nasal polyposis (CRSwNP) (n = 9) at our hospital in Ahvaz City, Iran. The age of participants in our study ranged from 3 to 73 years, and all of them were subjected to a complete blood count (CBC) test, nasal smear, and determination of serum IgE levels after their consent. There was no correlation between serum IgE level and nasal eosinophil count (p = 0.728) or between serum IgE level and blood eosinophil count (p = 0.657); however, a positive correlation was detected between blood and nasal eosinophil levels (p = 0.003). There is no significant relationship between serum IgE level and eosinophil count in the blood and nasal secretions. Serum IgE level and blood or nasal eosinophil count are both useful biomarkers for monitoring allergic rhinitis and asthma individually, but no diagnostic conclusion can be drawn from their correlation.

Efficacy and perceived satisfaction of 3-year SLIT in children with allergic rhinitis and asthma: a pilot study.

Despite the presence of robust evidence, there is very limited data on the efficacy of allergen immunotherapy (AIT) for selected patients. Accordingly, we aimed to evaluate the efficacy and perceived satisfaction of a 3-year course of sublingual immunotherapy (SLIT) in a paediatric population with allergic rhinitis and/or asthma. A pilot, monocentre, retrospective cohort study was performed. One hundred fifty-three children who fulfilled the criteria for allergic rhinitis and asthma and were either mono- or poly-sensitized were enrolled. A standardized questionnaire assessing perceived efficacy, use of rescue medication, disease control, number of exacerbations, quality of life, and perceived satisfaction was administered to each patient. Seventy patients (49 males, 21 females; mean age, 14.3±1.9 years) were included in the final analysis. All 70 patients received SLIT for up to 3 years, with 100% adherence to the treatment throughout the study. Significant improvements in symptoms and quality of life were reported (p<0.01). There was also a significant decrease in disease severity, use of rescue medication, and sleep disturbances (p<0.01). Additionally, a significant improvement in school performance was also recorded (p<0.01). Of the enrolled patients, 60 out of 70 (85.7%) reported being very satisfied, 6 out of 70 (8.57%) were much satisfied, and 4 out of 60 (5.71%) were satisfied. We were the first to demonstrate the efficacy and perceived satisfaction of a 3-year SLIT in a paediatric population, with 100% treatment adherence throughout the study.

GA2LEN ANACARE consensus statement: Potential of omalizumab in food allergy management.

Immunoglobulin E (IgE)-mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti-IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE-mediated food allergies by the US Food and Drug Administration (FDA). This GA2LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE-mediated food allergies, based on a systematic review and meta-analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE-mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation.

Targeting of the IL-5 pathway in severe asthma reduces mast cell progenitors

BackgroundTherapies targeting interleukin-5 (IL-5) or its receptor (IL-5Rα) are currently used to treat patients with severe eosinophilic asthma. ObjectiveTo investigate the impact of anti-IL-5 and anti-IL-5Rα biological therapies on mast cells (MCs) and their progenitors. MethodsSurface IL-5Rα expression was investigated on MCs and their progenitors in mouse lungs and bone marrow, and in human lungs and blood. Isolated human MC progenitors cultured in the presence or absence of IL-5 were analyzed in vitro. Circulating MC progenitors were quantified in patients with severe asthma, before and after anti-IL-5 (mepolizumab) or anti-IL-5Rα (benralizumab) therapy. Gene expression analysis of MC progenitors was performed before and after anti-IL-5Rα therapy. ResultsApproximately 50% of the human primary lung MCs, and 30% of the human MC progenitors from individuals with allergic asthma expressed IL-5Rα. In patients with mild-to-moderate allergic asthma and mice with acute allergic airway inflammation, the fraction of IL-5Rα + MC progenitors was elevated. Additionally, IL-5 promoted the proliferation and/or survival of isolated human MC progenitors. Further, patients with severe asthma from two independent cohorts demonstrated a reduction of blood MC progenitors after anti-IL-5 or anti-IL-5Rα treatment. This was associated with improved asthma control, as well as a decline in both blood eosinophils and Th2 cells. Finally, the blood MC progenitors remaining after anti-IL-5Rα (benralizumab) treatment exhibited a downregulated expression of genes involved in growth and proliferation. ConclusionThis study introduces the possibility that the clinical effects of targeting IL-5/IL-5Rα in severe asthma also may involve reduction of MC populations.

An updated review of the use of omalizumab for the treatment of uncontrolled pediatric allergic asthma

An updated review of the use of omalizumab for the treatment of uncontrolled pediatric allergic asthma

DES/O microemulsion for solubilizing and delivering curcumin via the nasal administration to treat acute asthma

As a natural small molecule drug derived from turmeric, curcumin is known for its good biosafety and a range of beneficial effects, including anti-inflammatory, anti-spasmodic, antioxidant, antibacterial, anti-tumor, and neuroprotective effects. Even though, its insolubility in water and instability severely limit its bioavailability and clinical applications. The present study developed a deep eutectic solvent (DES) in oil microemulsion (DES/O-ME) system loaded with Cur for intranasal administration, aiming to enhance both the solubility and permeability of Cur to significantly increase its bioavailability. The project first constructed and screened the optimal choline chloride-based DES. Subsequently, the DES/O-ME system was prepared and optimized to achieve uniform particle size and stability using a pseudo-ternary phase diagram and electrical conductivity measurements. The resulting DES/O-ME system was thoroughly evaluated for its solubilization efficacy, permeability, mucosal cytotoxicity, and stability. Additionally, the therapeutic efficacy of the Cur-DES/O-ME was assessed in vivo using a murine model of allergic asthma. This comprehensive evaluation highlights the potential of the DES/O-ME system as a promising intranasal drug delivery platform to overcome the limitations of curcumin’s bioavailability and clinical application.

Omalizumab Safety Concerns.

IgE and mast cells play key roles in the pathophysiology of allergic diseases, and omalizumab was the first monoclonal anti-IgE antibody licensed in the U.S. when initially FDA-approved for the treatment of allergic asthma in 2003. Since that time, the number of FDA-approved indications for treatment with omalizumab has grown to include chronic spontaneous urticaria, chronic rhinosinusitis with nasal polyps, and food allergy. Although omalizumab is generally considered relatively safe and well-tolerated, a number of safety concerns have been raised since its initial approval. These concerns focus on specific adverse events of interest that include anaphylaxis, pregnancy, malignancy, cardiovascular events, and infections. For each of these issues, data from clinical trials and post-marketing surveillance has been extensively evaluated. In this review, we examine this safety data, provide context for safety and risk assessments, and summarize a safety profile for each of the adverse events of interest. In doing so, we aim to provide a resource for shared-decision making when treatment with omalizumab is being considered.

Profile of immune response during nasal challenge with dermatophagoides pteronyssinus in subjects with allergic airway diseases

BackgroundT lymphocyte helper (Th) 2 plays the main role in pathogenesis of allergic airway diseases (AAD). Recent studies showed that interleukin (IL) 33, Th17 and Th22 also may be involved in allergic inflammation. The aim is to evaluate cytokine level before and after nasal challenge with Dermatophagoides pteronyssinus in patients with AAD.MethodsPatients with persistent allergic rhinitis (AR) with or without allergic asthma (AA) allergic to house dust mite and healthy individuals underwent nasal challenge with Dermatophagoides pteronyssinus. Measurements of IL-13, IL-17, IL-22 and IL-33 in serum and nasal lavage were performed before, 2 and 22 h after nasal challenge by ELISA.Results. Ten patients with AR only, 6 patients with AR and AA and 7 healthy individuals were involved in the study. Serum IL-22 level significantly increased in patients with AR and AA and nasal lavage IL-22 tended to increase in patients with AAD after nasal challenge. Serum IL-13 level tended to increase in patients with AR and AA. IL-13 level in nasal lavage fluid decreased at 22 h after nasal challenge in patients with AR only. IL-17 level in serum and nasal lavage decreased in patients with AAD. Serum IL-33 tended to increase after nasal challenge whereas IL-33 in nasal lavage significantly decreased.ConclusionCytokine profile differs between local and systemic compartments and between patients with allergic rhinitis only and patients with allergic rhinitis and asthma after nasal challenge.