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There has been extensive progress in understanding the cellular and molecular mechanisms of inflammation and immune regulation in allergic diseases of the skin and lungs during the last few years. Asthma and atopic dermatitis (AD) are typical diseases of type 2 immune responses. interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin are essential cytokines of epithelial cells that are activated by allergens, pollutants, viruses, bacteria, and toxins that derive type 2 responses. Th2 cells and innate lymphoid cells (ILC) produce and secrete type 2 cytokines such as IL-4, IL-5, IL-9, and IL-13. IL-4 and IL-13 activate B cells to class-switch to IgE and also play a role in T-cell and eosinophil migration to allergic inflammatory tissues. IL-13 contributes to maturation, activation, nitric oxide production and differentiation of epithelia, production of mucus as well as smooth muscle contraction, and extracellular matrix generation. IL-4 and IL-13 open tight junction barrier and cause barrier leakiness in the skin and lungs. IL-5 acts on activation, recruitment, and survival of eosinophils. IL-9 contributes to general allergic phenotype by enhancing all of the aspects, such as IgE and eosinophilia. Type 2 ILC contribute to inflammation in AD and asthma by enhancing the activity of Th2 cells, eosinophils, and their cytokines. Currently, five biologics are licensed to suppress type 2 inflammation via IgE, IL-5 and its receptor, and IL-4 receptor alpha. Some patients with severe atopic disease have little evidence of type 2 hyperactivity and do not respond to biologics which target this pathway. Studies in responder and nonresponder patients demonstrate the complexity of these diseases. In addition, primary immune deficiency diseases related to T-cell maturation, regulatory T-cell development, and T-cell signaling, such as Omenn syndrome, severe combined immune deficiencies, immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, and DOCK8, STAT3, and CARD11 deficiencies, help in our understanding of the importance and redundancy of various type 2 immune components. The present review aims to highlight recent advances in type 2 immunity and discuss the cellular sources, targets, and roles of type 2 mechanisms in asthma and AD., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Although airway remodeling in severe and/or fatal asthma is stil considered irreversible, its individual components as a cause of clinical symptoms and/or lung function changes remain largely unknown. While inhaled glucocorticoids have not consistently been shown to affect airway remodeling, biologics targeting specific pathways of airway inflammation have been shown to improve lung function, mucus plugging, and airway structural changes that can exceed those seen with glucocorticoids. This superiority of biologic treatment, which cannot be solely explained by insufficient doses or limited durations of glucocorticoid therapies, needs to be further explored. For this field of research, we propose a novel classification of the potential effects of biologics on airway remodeling into three temporal effects: early effects (days to weeks, primarily modulating inflammatory processes), late effects (months to years, predominantly affecting structural changes), and potential preventive effects (outcomes of early treatment with biologics). For the identification of potential preventive effects of biologics, we call for studies exploring the impact of early biological treatment on airway remodeling in patients with moderate-to-severe asthma, which should be accompanied by a long-term evaluation of clinical parameters, biomarkers, treatment burden, and socioeconomic implications., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The role of eosinophils in airway inflammation and asthma pathogenesis is well established, with raised eosinophil counts in blood and sputum associated with increased disease severity and risk of asthma exacerbation. Conversely, there is also preliminary evidence suggesting antiviral properties of eosinophils in the airways. These dual roles for eosinophils are particularly pertinent as respiratory virus infections contribute to asthma exacerbations. Biologic therapies targeting key molecules implicated in eosinophil-associated pathologies have been approved in patients with severe asthma and, therefore, the effects of depleting eosinophils in a clinical setting are of considerable interest. This review discusses the pathological and antiviral roles of eosinophils in asthma and exacerbations. We also highlight the significant reduction in asthma exacerbations seen with biologic therapies, even at the height of the respiratory virus season. Furthermore, we discuss the implications of these findings in relation to the role of eosinophils in inflammation and antiviral responses to respiratory virus infection in asthma., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background Genome-wide association studies ( GWASs) have identified various genes associated with asthma, yet, causal genes or single nucleotide polymorphisms ( SNPs) remain elusive. We sought to dissect functional genes/ SNPs for asthma by combining expression quantitative trait loci ( eQTLs) and GWASs. Methods Cis- eQTL analyses of 34 asthma genes were performed in cells from human bronchial epithelial biopsy ( BEC, n = 107) and from bronchial alveolar lavage ( BAL, n = 94). Results For TSLP- WDR36 region, rs3806932 (G allele protective against eosinophilic esophagitis) and rs2416257 (A allele associated with lower eosinophil counts and protective against asthma) were correlated with decreased expression of TSLP in BAL ( P = 7.9 × 10−11 and 5.4 × 10−4, respectively) and BEC, but not WDR36. Surprisingly, rs1837253 (consistently associated with asthma) showed no correlation with TSLP expression levels. For ORMDL3- GSDMB region, rs8067378 (G allele protective against asthma) was correlated with decreased expression of GSDMB in BEC and BAL ( P = 1.3 × 10−4 and 0.04) but not ORMDL3. rs992969 in the promoter region of IL33 (A allele associated with higher eosinophil counts and risk for asthma) was correlated with increased expression of IL33 in BEC ( P = 1.3 × 10−6) but not in BAL. Conclusions Our study illustrates cell-type-specific regulation of the expression of asthma-related genes documenting SNPs in TSLP, GSDMB, IL33, HLA- DQB1, C11orf30, DEXI, CDHR3, and ZBTB10 affect asthma risk through cis-regulation of its gene expression. Whenever possible, disease-relevant tissues should be used for transcription analysis. SNPs in TSLP may affect asthma risk through up-regulating TSLP mRNA expression or protein secretion. Further functional studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Inhaled glucocorticosteroids (ICS) are the mainstay of treatment in asthma. Fluticasone furoate (FF) is a novel, once-daily ICS asthma therapy. This study investigated the efficacy and safety of FF 50 meg in patients with mild-to-moderate persistent asthma. Methods: A 24-week, multicenter, randomized, placebo-controlled and active-con-trolled, double-blind, double-dummy, parallel-group phase III study. Three hun-dred and fifty-one patients (aged ≥12 years; uncontrolled by non-ICS therapy) were randomized to treatment (1:1:1) with once-daily FF 50 meg dosed in the evening, twice-daily fluticasone propionate (FP) 100 meg or placebo. The primary endpoint was change from baseline in evening trough forced expiratory volume in 1 s (FEV1) at Week 24. Secondary endpoints were change from baseline in the per-centage of rescue-free 24-h periods (powered endpoint), change from baseline in evening and morning peak expiratory flow, change from baseline in the percentage of symptom-free 24-h periods and number of withdrawals due to lack of efficacy. Results: Evening trough FEV, at Week 24 was not statistically significantly increased with FF 50 meg once-daily (37 ml [95% CI: -55, 128]; P = 0.430), but was with FP 100 meg twice daily (102 ml [10, 194]; P = 0.030), vs placebo. No consistent trends were observed across other endpoints, including the powered secondary endpoint. No safety concerns were raised for either active treatment. Conclusions: FP 100 meg twice daily improved evening trough FEV, in patients with mild-to-moderate persistent asthma, but FF 50 meg once daily did not dem-onstrate a significant effect. Secondary endpoints showed variable results. No safety concerns were identified for FF or FP. [ABSTRACT FROM AUTHOR]

Rackemann described the ‘intrinsic asthma’ population over 50 years ago as a unique subgroup that was characterized by onset of progressive loss of lung function beginning later in life, possibly after a respiratory infection. It has also been associated with a female predominance, aspirin-sensitive bronchospasm, and nasal polyposis. While the aetiology is not understood, we propose that persistent respiratory infections play a central role in the development of intrinsic asthma. [ABSTRACT FROM AUTHOR]

Background: Uncontrolled asthma is characterized by variability. Current asthma guidelines recommend focussing on the achievement and maintenance of control but few studies have examined in detail, using composite measures of control, the stability and potential duration of control once achieved. In this post-hoc analysis of the results of the Gaining Optimal Asthma controL (GOAL) study, we examine the association between the level of asthma control achieved during the step-up phase of the study and the stability of control experienced during the maintenance phase. Methods: GOAL was a 1-year, randomized, stratified, double-blind study of 3421 patients with uncontrolled asthma, which compared salmeterol/fluticasone propionate combination with fluticasone propionate in achieving two composite, guideline-based measures of control: totally controlled and well-controlled asthma. We analysed the proportion and duration of time spent in control, the effect of treatment on asthma stability, and the impact of asthma control stability on unscheduled use of healthcare resources. Results: In patients achieving well-controlled or totally controlled asthma, at least well-controlled asthma was maintained for a median of almost 3 and 6 months, and for more than 85% and 95% of weeks of follow-up, respectively. A high level of stability was confirmed in a Markov analysis investigating transitional probability of change in control status. Variability in control was associated with increased probability of an unscheduled healthcare resource use (odds ratio: 1.06, P < 0.001). Conclusions: Most patients achieving guideline-defined control can maintain at least a similar level of control with regular, stable dosing, with little likelihood of losing control. [ABSTRACT FROM AUTHOR]

The suitability of employing AIR Inhaled Insulin (AIR Insulin; AIR is a registered trademark of Alkermes) during acute upper respiratory tract infection (URI) has not been determined. Twenty-one healthy, non-diabetic subjects were enrolled in a single-sequence, two-period, euglycemic clamp study. Subjects received a single 12 U-equivalent dose of AIR Insulin before rhinovirus (RV16) inoculation and during symptomatic infection. Spirometry was used to evaluate pulmonary safety. AIR Insulin exposure (the area under the immunoreactive insulin (IRI) concentration vs time curve from time zero until the IRI concentrations returned to the predose baseline value (AUC0–t′)) and glucodynamic response (total amount of glucose infused (Gtot)) were comparable before and during RV infection (AUC0–t′ 46,300 vs 52,600 pmol min/l, P=0.21; Gtot 61,800 vs 68,700 mg, P=0.42, respectively). Variability of pharmacokinetic and pharmacodynamic parameters did not change during URI; either did the number or intensity of adverse events. No significant change in forced expiratory volume or forced vital capacity was observed following AIR Insulin administration or during URI. The AIR Insulin system provides similar pharmacokinetic and glucodynamic responses under conditions of an experimentally induced RV infection and is regarded as suitable for use in diabetic patients during URIs.Clinical Pharmacology & Therapeutics (2008) doi:10.1038/sj.clpt.6100286 [ABSTRACT FROM AUTHOR]

Background: The Gaining Optimal Asthma ControL (GOAL) study has shown the superiority of a combination of salmeterol/fluticasone propionate (SFC) compared with fluticasone propionate alone (FP) in terms of improving guideline defined asthma control. Methods: Clinical and economic data were taken from the GOAL study, supplemented with data on health related quality of life, in order to estimate the cost per quality adjusted life year (QALY) results for each of three strata (previously corticosteroid-free, low- and moderate-dose corticosteroid users). A series of statistical models of trial outcomes was used to construct cost effectiveness estimates across the strata of the multinational GOAL study including adjustment to the UK experience. Uncertainty was handled using the non-parametric bootstrap. Cost-effectiveness was compared with other treatments for chronic conditions. Result: Salmeterol/fluticasone propionate improved the proportion of patients achieving totally and well-controlled weeks resulting in a similar QALY gain across the three strata of GOAL. Additional costs of treatment were greatest in stratum 1 and least in stratum 3, with some of the costs offset by reduced health care resource use. Cost-effectiveness by stratum was £7600 (95% CI: £4800–10 700) per QALY gained for stratum 3; £11 000 (£8600–14 600) per QALY gained for stratum 2; and £13 700 (£11 000–18 300) per QALY gained for stratum 1. Conclusion: The GOAL study previously demonstrated the improvement in total control associated with the use of SFC compared with FP alone. This study suggests that this improvement in control is associated with cost-per-QALY figures that compare favourably with other uses of scarce health care resources. [ABSTRACT FROM AUTHOR]

Background: The effector function of eosinophils involves their release of toxic granule proteins, reactive oxygen species, cytokines, and lipid mediators. Murine studies have demonstrated that eosinophils can also enhance T cell function. Whether human eosinophils, in particular, airway eosinophils, have similar immunoregulatory activity has not been fully investigated. The aim of this study was to determine whether human blood and airway eosinophils can contribute to Th1 and Th2 cytokine generation from CD4+ T cells stimulated with superantigen. Methods: Eosinophils were obtained from blood or bronchoalveolar lavage fluid 48 h after segmental allergen bronchoprovocation. Purified eosinophils were co-cultured with autologous CD4+ blood T cells in the presence of staphylococcal enterotoxin B (SEB). Cytokine levels in the supernatant fluid were determined by enzyme-linked immunosorbent assay (ELISA). Eosinophil expression of major histocompatibility complex (MHC) class II and co-stimulatory molecules was assessed by flow cytometry before culture, 24 h after granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation, and 24 h after co-culture with CD4+ T cells and SEB. Results: Interleukin (IL)-5, IL-13, and interferon (IFN)- γ generation increased when CD4+ T cells were co-cultured with either blood or airway eosinophils in the presence of SEB. The ability of eosinophils to enhance cytokine generation was independent of their source (blood vs airway), activation by GM-CSF, or detectable expression of human leukocyte antigen (HLA)-DR, CD80, or CD86. Conclusion: Our data demonstrate that SEB-induced generation of Th1 and Th2 cytokines is increased in the presence of human blood and airway eosinophils. Thus, eosinophils can have an immunoregulatory function in pathogen-associated allergic diseases such as atopic dermatitis, chronic sinusitis, and asthma exacerbations. [ABSTRACT FROM AUTHOR]

Allergic rhinitis and asthma often co-exist and appear to produce a continuum of airway disease, but whether the clinical characteristics of asthma in patients with seasonal rhinitis differ from those of persistent asthma has not been examined. The aim of this retrospective study was to characterize the clinical features of patients with seasonal allergic rhinitis with concomitant asthma and to compare them with those in patients with persistent asthma. The patient populations for this study were derived hem nine prospective, placebo controlled planned clinical trials of similar design. Six studies (958 patients) enrolled patients with seasonal allergic rhinitis and concomitant asthma: three (607 patients) involved patients with persistent asthma. In all studies, patients were excluded from oral corticosteroid therapy in the preceding 3 months, and from inhaled corticosteroids in the preceding month. Patients with seasonal rhinitis and asthma bad a significantly (P<0.001) higher total asthma symptom score than those with persistent asthma. In particular, cough was three times more severe. The need for β-agonist as a rescue medication and the ratio of forced expiratory volume in 1 s forced vital capacity (FVC) were similar in the two groups whereas forced expiratory fraction 25- 75% FVC was significantly (P<0.02) reduced in the persistent asthmatics. Asthma and nasal symptom severity scores were correlated in patients with seasonal rhinitis and asthma (P < 0.0001). Patients with seasonal allergic rhinitis and concomitant astma appear to differ from those with persistent asthma. A prospective study should be designed to discover whether patients with seasonal rhinitis and asthma may represent a distinct nosological entity. ‘allergic airway disease’. [ABSTRACT FROM AUTHOR]

Summary Background Eosinophilic inflammation is a feature of asthma. However, serological markers to indicate eosinophil activation in this process are not fully defined. Objective To evaluate the relationship of serum eosinophil cationic protein (ECP) to asthma worsening and a marker for treatment effectiveness, 26 adult patients with an asthma exacerbation were identified. Methods Identified asthma subjects were treated with oral corticosteroids (prednisone) for 14 days. The lung function variables, forced expiratory volume in one second (FEV1 ) and peak expiratory flow (PEF), were determined as percentage of predicted and the blood total eosinophil count and serum ECP levels were measured. Patients were re-evaluated after 14 days of corticosteroid treatment and then every 3 months thereafter during a 12-month period. Results Eighteen patients responded to prednisone treatment, whereas eight did not, assessed as improvement of their lung function parameters. Different serum ECP patterns could be seen in the responders compared with the non-responders. All 18 responders had considerably increased serum ECP at the time of exacerbation, whereas the non-responders had lower serum ECP levels. The serum ECP levels decreased to a greater extent in the responder patient group than in the non-responder patients following prednisone treatment. This difference in patterns was not seen with total blood eosinophil counts. Conclusion Our findings suggest that serum ECP may be used to predict a response to corticosteroid therapy in adult patients with asthma. [ABSTRACT FROM AUTHOR]

Asthma, a pervasive pulmonary disorder, affects countless individuals globally. Characterized by chronic inflammation of the bronchial passages, its symptoms include cough, wheezing, dyspnea, and chest tightness. While many manage their symptoms through pharmaceutical interventions and self‐care, a significant subset grapples with severe asthma, posing therapeutic challenges. This study delves into the intricate etiology of asthma, emphasizing the pivotal roles of immune cells such as T cells, eosinophils, and mast cells in its pathogenesis. The recent emergence of monoclonal antibodies, including mepolizumab, reslizumab, and benralizumab, offers therapeutic promise, yet their efficacy varies due to the heterogeneous nature of asthma. Recognizing the potential of personalized medicine, this research underscores the need for a comprehensive understanding of asthma's immunological diversity. We employ single‐sample gene set enrichment analysis (ssGSEA) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms to identify differentially expressed immune cells and utilize machine learning techniques, including Extreme Gradient Boosting (XGBoost) and random forest, to predict severe asthma outcomes and identify key genes associated with immune cells. Using a murine asthma model and an online database, we aim to elucidate distinct immune‐centric asthma subtypes. This study seeks to provide novel insights into the diagnosis and classification of severe asthma through a transcriptomic lens. [ABSTRACT FROM AUTHOR]

Milk protein sensitivity is a major challenge in infant feeding, especially for infants who cannot receive adequate breastfeeding. Hydrolyzed milk protein is a mainstream way to address this difficulty. The aim of this study was to assess the effect of differences in whey protein concentrate (WPC) source and the degree of hydrolysis on blocking allergy and to analyze the possible mechanisms by which hydrolyzed infant formula (IF) blocks allergy through colony‐metabolism–immunity response. First, we prepared six groups of goat's milk IF with unhydrolyzed, partially, and extensively hydrolyzed WPC, which come from cow's milk WPC and goat's milk WPC. Subsequently, we evaluated their effects on allergy. The results showed that the hydrolyzed IF improved the allergic characteristics of mice, including low levels of total immunoglobulin E (IgE), specific IgE, histamine, and mucosal mast cell protease‐1 (mMCP‐1). Furthermore, the hydrolyzed IF promoted the immune response of T helper 1 (Th1) and regulatory T (Treg) cells by enhancing the messenger RNA (mRNA) expression of T‐box transcription factor 21 (T‐bet) and forkhead box protein P3 (Foxp3), which in turn suppressed the T helper 2 (Th2) overexpressed immune response in allergy (GATA‐binding protein 3 (GATA‐3) and retinoic‐acid‐receptor‐related orphan receptor gamma t (RORγt) mRNA expression, as well as interleukin 4 (IL‐4) and interleukin 5 (IL‐5) levels). Hydrolyzed IF promoted an increase in beneficial gut microbe Lactobacillus and Alistipes, which in turn promoted an increase in intestinal butyrate levels. The beneficial bacteria and their metabolized butyrate may have suppressed the abundance of the allergy‐characterizing bacterium Rikenellaceae‐RC9‐gut‐group. The final result we obtained was that for both cow's milk WPC and goat's milk WPC, at similar levels of hydrolysis, they did not bring about a significant effect on allergy symptoms. The hydrolyzed IF improved the allergic characteristics of mice, the deeper the degree of hydrolysis of WPC, the more obvious the effect of reducing allergic symptoms in model mice. [ABSTRACT FROM AUTHOR]

Wildfire smoke exposure leads to poorer health among those with pre‐existing conditions such as asthma. Particulate matter in wildfire smoke can worsen asthma control, cause acute exacerbations, and increase health resource utilization (HRU) and costs. Research to date has been retrospective with few opportunities to project changes in underlying asthma control and HRU given exposure to wildfire smoke. Using a microsimulation of 5,000 Californians with asthma, we calculated changes in asthma control distribution, risk of exacerbation, and HRU and cost outcomes in the 16 weeks during and after a wildfire. The model was calibrated against empirical values on asthma control distribution and increased HRU after exposure to wildfire smoke. Without smoke exposure, 48% of the cohort exhibited complete or well control of asthma, and 8% required acute healthcare per cycle. Following two consecutive weeks of wildfire smoke, complete or well control of asthma fell to 27%, with an additional 4% HRU. This corresponds to total additional $601,250 in all‐cause medical costs and eight fewer quality‐adjusted life years over 16 weeks of model time. Our model found increased asthma health and cost burden due to wildfire smoke that were aligned with empirical evidence from a historic wildfire event. This study establishes a framework for a more nuanced understanding of asthma impacts from wildfire smoke that can help inform the development of public health policies to mitigate harm and promote resilience among asthma patients in the face of climate change. Plain Language Summary: This study looks at how wildfire smoke affects people with asthma in California. It is known that wildfire smoke exposure can make asthma worse, but we wanted to understand exactly how it impacts asthma control, the risk of asthma attacks, and the need for asthma‐related healthcare. We created a computer simulation with 5,000 virtual Californians who have asthma and looked at what happened to them during and after a wildfire, compared to if there was no wildfire. Without wildfire smoke, about half of the virtual group had good control over their asthma, and only a small percentage needed to go to the hospital for asthma‐related reasons. During and after the wildfire, the number of people with good asthma control dropped as people were exposed to smoke, and more people needed to use healthcare services. This increase in asthma problems led to higher medical costs and reduced quality of life for the group exposed to wildfire smoke. Our findings were in line with observations made after a well‐documented past wildfire in California. This and similar computer models can help policymakers make better decisions to protect people with asthma from the effects of wildfire smoke. Key Points: Exposure to wildfire smoke worsens asthma outcomes, but microsimulation methods have rarely been applied to describe this associationOur novel microsimulation model accurately reflects altered distribution of asthma control and healthcare use after a wildfireSuch a model can be valuable for informing and evaluating preventive measures to reduce to burden of wildfire smoke on asthma [ABSTRACT FROM AUTHOR]

The recent elucidation of the inflammatory responses underlying asthma and allergic rhinitis has stimulated the development of new anti-asthma treatments, including numerous antileukotriene agents. These agents, which represent a new direction in targeted therapy, either antagonize the leukotriene receptor (e.g. zafirlukast) or block the synthesis of leukotrienes (e.g. zileuton). They have been used in preclinical and clinical studies involving normal subjects and patients with asthma or allergic rhinitis. These studies have generally supported the putative role of leukotrienes In the mechanisms of asthma and allergic rhinitis. With respect to asthma, the leukotrienes also appear to function as potent mediators of bronchoconstriction. The above cited results indicate that antileukotriene agents offer incremental improvements in airway caliber and may also attenuate the inflammatory response. Because they are orally administered, they should have the additional benefit of increasing patient compliance relative to other currently available treatments. In their current form, however, they may not be expected to replace the mainstays of current therapy but to act rather, as adjuvant therapy. Patients with relatively mild asthma may be able to achieve efficacy with an antileukotriene agent plus as needed β -adrenergic agonists; patients with more significant disease might use antileukotriene agents as a supplement to another ami-inflammatory agent, such as cromolyn, nedocromil, or corticosteroids. Studies of asthma patients have confirmed the ability of antileukotriene agents to attenuate asthma-associated bronchoconstriction. Antileukotriene agents appear to significantly attenuate aspirin-, allergen-, and exercise induced asthma, as well as the signs and symptoms of nocturnal and chronic asthma; they may have efficacy in other inflammation-associated disorders such as allergic rhinitis as well. [ABSTRACT FROM AUTHOR]

The article presents information about the role and contribution of viral respiratory infections to asthma. Many respiratory viruses causes a change in airway function such that bronchial obstruction is more likely to occur in patients with asthma, Furthermore, there is also evidence that viruses act through a number of pathways to enhance the likelihood of an inflammatory response. Subsequent observations must focus on the ability of viruses to stimulate cytokine production, which could then upregulate the allergic airway inflammatory response. With the unfolding of such observations, it is highly likely that greater insights into this major provoking factor in asthma will become more apparent as well as clearer insight into mechanisms of asthma.

Intranasal flunisolide is an effective treatment for allergic rhinitis. Flunisolide has high bioavailability when administered to normal subjects (50% of an intranasal dose reaches the systemic circulation) with minimal systemic effects. Bioavailability in patients with active rhinitis averages 62.4 ± 15.7%. The oral dose bioequivalent to 100 μg intranasally is 500 μg. To define the comparative trial and systemic effects of intranasal flunisolide in patients with active allergic rhinitis, a multicenter, randomized, double-blind, placebo-controlled study was conducted during the 1983 ragweed hayfever season. Ninety-nine patients with ragweed hayfever for &ges; 2 years and positive prick skin tests to ragweed were randomly allocated to one of three treatment groups: 0 = oral flunisolide 500 μg b.i.d. and intranasal placebo b.i.d.; N = intranasal flunisolide 50 μg per nostril b.i.d. and oral placebo b.i.d.; P = intranasal and oral placebo b.i.d. Treatment continued for 4 weeks. Patients kept daily symptom scores. Patients were evaluated by a blinded observer every 2 weeks and were globally evaluated at the study's end. Data were analyzed for each center and pooled. There were no significant differences in symptom severity of sneezing, nasal congestion, and throat itch in the 0 (oral flunisolide) and P (placebo) groups. N (nasal flunisolide) was significantly more effective than 0 or P (P &les; 0.005) for each symptom for at least one 2-week period. Global evaluation demonstrated control of overall hayfever severity for N (nasal flunisolide) but not for 0 (oral flunisolide). We conclude that the therapeutic efficacy of flunisolide is achieved by topical and not by systemic action. [ABSTRACT FROM AUTHOR]

A 10‐year‐old, neutered male, Golden Retriever dog presented for surgical correction of a descemetocele. Acepromazine (0.02 mg/kg) and methadone (0.5 mg/kg) were administered intramuscularly for sedation, propofol (2 mg/kg) and midazolam (0.2 mg/kg) were administered intravenously for anaesthetic induction and isoflurane in oxygen was utilised for anaesthetic maintenance. Rocuronium (0.5 mg/kg), a neuromuscular blocking agent, was administered intravenously to facilitate central positioning of the eye for surgery. Within 10 min of rocuronium administration, the dog became tachycardic and hypotensive. Hemodynamic aberrations did not resolve with initial interventions but were successfully mitigated with the administration of diphenhydramine (0.8 mg/kg) intravenously. The dog remained stable throughout the remainder of the procedure and experienced a smooth and uneventful recovery. While it is difficult to confirm that the hemodynamic changes observed in this clinical case resulted solely from administration of rocuronium, the observance of the cardiovascular changes, timing of events and response to therapy suggest that rocuronium elicited a histamine response that was successfully treated with diphenhydramine. [ABSTRACT FROM AUTHOR]

The inappropriate activation of eosinophils is a well-recognized driver of various human inflammatory diseases including asthma, chronic rhinitis, and various gastrointestinal diseases, including eosinophilic esophagitis. Steroids, both topical and systemic, remain a cornerstone of treatment and can be highly effective. However, some individuals suffer side effects, unresolved symptoms, or both. OmeGo, an enzymatically liberated fish oil, has demonstrated anti-inflammatory and antioxidant properties as well the reduction of the activation, migration, and survival of eosinophils. Two animal models of eosinophilic inflammation were used to further assess OmeGo's profile. A house dust mite model of induced asthma showed a significant reduction in eosinophilic lung inflammation compared to the negative control, linoleic acid. The CRTH2 antagonist fevipiprant showed a similar eosinophilic inhibitory profile to OmeGo. In contrast, cod liver oil had no impact on any measure of inflammation. A guinea pig model of mild intraperitoneal eosinophilia showed a significant reduction in eosinophil activity by OmeGo, assessed by chemotaxis and chemokinesis. Apolipoprotein A-IV, an endogenous human protein with anti-inflammatory actions, showed a similar but numerically lower effect. OmeGo therefore combines a consistent antieosinophilic action with the known anti-inflammatory effects of polyunsaturated fatty acids. Proof-of-concept studies in asthma are warranted., (© 2022 The Authors. Biotechnology and Applied Biochemistry published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Background: Omalizumab is the only licensed drug that serves as a third‐line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial. Therefore, this study aims to estimate the efficacy and safety of different doses of omalizumab in the treatment of CIU patients. Materials and methods: Four databases were searched from the database's creation to April 8, 2023. Several keywords such as omalizumab and urticarias were used to retrieve related studies. The meta‐analytical outcomes were analyzed in R 4.2.1 software and Stata 15.1 software. Cochrane risk‐of‐bias tool Ver. 2 was used to evaluate the risk of bias in randomized controlled trials (RCTs). Results: In total, 2331 patients were included. Five indexes were employed to assess, including weekly Itch Severity Score (ISS7), weekly Hive Severity Score (HSS7), weekly Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and adverse events (AE). A 300 mg dose of omalizumab was the optimum dose to treat CIU, followed by the 150 mg dose. Furthermore, 600 mg of omalizumab only showed a significant difference from the placebo in HSS7. No significant statistical difference was observed in AE. Meta‐regression analysis revealed that time, as a covariate, was statistically significant in the comparison of omalizumab 150 mg with placebo. Conclusion: 300 mg of omalizumab was the optimum dosage to treat CIU patients, with a 150 mg dose also exhibiting good efficacy. Further studies are required to explore the efficacy and safety of different doses of omalizumab in the treatment of CIU patients. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of allergies is mostly based on the patient's clinical history and allergen provocation tests. Determination of specific IgE (sIgE) profiles can be performed to support allergy diagnosis. This is commonly done in vivo by the skin prick test or in vitro with automated systems. Several platforms exist to quantify sIgE levels, but all these methods require access to specific instruments, often delaying the test's results. The IgE luciferase-linked immunosorbent assay (LuLISA) allows bioluminescent quantification of IgE against peanut in microliter samples, but this method awaits extension to other allergens. This study aimed to validate a new method, named LuLIPLEX, for multiplexed bioluminescent detection of sIgE against 20 major molecular allergens., Methods: Quantification of sIgE against 12 recombinant or purified food allergens and eight aeroallergens was performed by LuLIPLEX versus standard IgE detection methods (ImmunoCAP, ISAC, ALEX, or NOVEOS). Multiplexed detection of IgE against these 20 allergens was performed within 45 min using 50 μL of serum, plasma, or whole blood samples., Results: A head-to-head comparison between LuLIPLEX and standard IgE detection methods showed a high correlation among all allergens tested. sIgE profiles in polysensitized subjects could be determined within 45 min in serum and plasma samples, as well as using a single drop of capillary blood., Conclusions: LuLIPLEX is a rapid and sensitive method to quantify sIgE levels against multiple allergens. Given that the test is very fast and can be performed on small and inexpensive luminometers, the IgE LuLIPLEX could allow point-of-care testing of sIgE profiles in allergic subjects., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The impact of human IgE glycosylation on structure, function and disease mechanisms is not fully elucidated, and heterogeneity in different studies renders drawing conclusions challenging. Previous reviews discussed IgE glycosylation focusing on specific topics such as health versus disease, FcεR binding or impact on function. We present the first systematic review of human IgE glycosylation conducted utilizing the PRISMA guidelines. We sought to define the current consensus concerning the roles of glycosylation on structure, biology and disease. Despite diverse analytical methodologies, source, expression systems and the sparsity of data on IgE antibodies from non-allergic individuals, collectively evidence suggests differential glycosylation profiles, particularly in allergic diseases compared with healthy states, and indicates functional impact, and contributions to IgE-mediated hypersensitivities and atopic diseases. Beyond allergic diseases, dysregulated terminal glycan structures, including sialic acid, may regulate IgE metabolism. Glycan sites such as N394 may contribute to stabilizing IgE structure, with alterations in these glycans likely influencing both structure and IgE-FcεR interactions. This systematic review therefore highlights critical IgE glycosylation attributes in health and disease that may be exploitable for therapeutic intervention, and the need for novel analytics to explore pertinent research avenues., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: Salbutamol has been used to alleviate bronchospasm in airway disease for decades, while its potential risks have not been systematically investigated yet. The risk of any potential adverse events (AEs) in patients treated with salbutamol was assessed through systematic review and meta‐analysis. Methods: A systematic search of the literature was conducted, using EMBASE, PubMed and Cochrane library, until 3 April 2023. Once the AE incidence was evaluated, randomized controlled trials (RCTs) were eligible for review. The endpoints included the incidence of total AEs, severe AEs, treatment discontinuation and specific AEs. The pooled AEs incidence was analysed via random‐effects model in a single‐arm meta‐analysis. A subgroup study was carried out to examine whether the pooled incidence of AE differed by indications or formulations. Results: Of the 8912 studies that were identified, 58 RCTs met the inclusion criteria and involved 12 961 participants. The analysis showed the pooled incidences of total AEs, severe AEs and treatment discontinuation in patients treated with salbutamol were 34%, 2% and 3%, respectively. Subgroup analysis indicated that premature labour users and intravenous salbutamol users were more likely associated with total AEs. The most frequently observed specific AEs were palpitations or tachycardia. Conclusion: This meta‐analysis indicated that salbutamol was associated with a very common risk of palpitations or tachycardia. Clinical vigilance and research efforts are needed to optimize the safe use of salbutamol. [ABSTRACT FROM AUTHOR]

Background and Objective: This study compared the clinical outcomes of severe asthmatics treated with mepolizumab and benralizumab in a tertiary care severe asthma service setting. Methods: Patient data at baseline, six and 12 months were collected prospectively at two large tertiary hospital severe asthma clinics following treatment initiation. Two hundred and four patients received treatment with mepolizumab (117) or benralizumab (87). Baseline characteristics between groups were similar in regard to age, gender, body mass index, steroid dose and blood eosinophil count. However, the mepolizumab cohort had a higher Asthma Control Questionnaire Score (ACQ) at baseline (4.0 ± 1.1 vs. 3.6 ± 0.9, p = 0.018), accompanied by more frequent reliever medication usage and lower prebronchodilator FEV1% (56.0 ± 20.1 vs. 63.8 ± 18.9, p = 0.008). Results: After 6 months treatment, both treatments induced significant improvements in (i) ACQ of 2.3 ± 0.1 (p < 0.001), (ii) oral steroid requiring exacerbations (incident rate ratio 0.26 (0.18–0.37), p < 0.001) and (iii) FEV1. However, the improvement in FEV1 was 0.18 (0.05–0.30) litres greater with benralizumab than with mepolizumab (p = 0.002) even when adjusting statistically for baseline differences between groups. These differences were even more pronounced at 12 months post‐treatment initiation, when the improvement in exacerbation frequency with benralizumab was 64% greater than with mepolizumab (p = 0.01). Whilst both treatments significantly reduced the blood eosinophil count at 6 and 12 months, this reduction was substantially greater with benralizumab than mepolizumab (−260 cells/μL [−400 to −110, p = 0.001]). Conclusion: In this large group of severe eosinophilic asthmatics, mepolizumab and benralizumab both improved disease parameters. However, benralizumab treatment appeared significantly more effective than mepolizumab in reducing exacerbations, improving FEV1 and depleting blood eosinophils. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Not being well controlled by therapy with inhaled corticosteroids and long‐acting β2 agonist bronchodilators is a major concern for severe‐asthma patients. The current treatment option for these patients is the use of biologicals such as anti‐IgE treatment, omalizumab, as an add‐on therapy. Despite the accepted use of omalizumab, patients do not always benefit from it. Therefore, there is a need to identify reliable biomarkers as predictors of omalizumab response. Methods: Two novel computational algorithms, machine‐learning based Recursive Ensemble Feature Selection (REFS) and rule‐based algorithm Logic Explainable Networks (LEN), were used on open accessible mRNA expression data from moderate‐to‐severe asthma patients to identify genes as predictors of omalizumab response. Results: With REFS, the number of features was reduced from 28,402 genes to 5 genes while obtaining a cross‐validated accuracy of 0.975. The 5 responsiveness predictive genes encode the following proteins: Coiled‐coil domain‐ containing protein 113 (CCDC113), Solute Carrier Family 26 Member 8 (SLC26A), Protein Phosphatase 1 Regulatory Subunit 3D (PPP1R3D), C‐Type lectin Domain Family 4 member C (CLEC4C) and LOC100131780 (not annotated). The LEN algorithm found 4 identical genes with REFS: CCDC113, SLC26A8 PPP1R3D and LOC100131780. Literature research showed that the 4 identified responsiveness predicting genes are associated with mucosal immunity, cell metabolism, and airway remodeling. Conclusion and clinical relevance: Both computational methods show 4 identical genes as predictors of omalizumab response in moderate‐to‐severe asthma patients. The obtained high accuracy indicates that our approach has potential in clinical settings. Future studies in relevant cohort data should validate our computational approach. [ABSTRACT FROM AUTHOR]

Allergy is an ever‐evolving group of disorders, which includes asthma, atopic dermatitis, rhinitis and food allergies and that currently affects over 1 billion people worldwide. This group of disorders has exploded in incidence since around the start of the 20th century, implying that genetics is not solely responsible for its development but that environmental factors have an important role. Here, Fabio Luciani and Jonathan Coquet, in their role as editors at Immunology & Cell Biology, asked nine prominent researchers in the field of allergy to define the term 'allergy', discuss the role of genetics and the environment, nominate the most important discoveries of the past decade and describe the best strategies to combat allergy at the population level going forward. [ABSTRACT FROM AUTHOR]

Herein, desilication in increasingly harsh conditions was used to introduce mesopores into two different industrial ZSM‐5 catalysts (Si/Al ratio 11 or 29). For desilicated samples, increasing BET surface areas, mesopore volumes, and Si(OH) densities were noted. Brønsted acid site (BAS) densities increased upon desilication, as formerly inaccessible BAS in blocked pores became available, while the strength of the BAS was maintained upon desilication. Using KOH instead of NaOH as desilication agent can increase the mesopore volume generated per mass loss. The correlations between desilication strength and properties were largely determined by the parent Si/Al ratio. In general the introduced mesopores increased lifetimes in the ETA conversion, while additional Si(OH) groups introduced by desilication reduce the lifetime again. The lifetime is thus determined by a complex interplay of BAS density, improved reactant transport by introduced mesopores and Si(OH) density. There were no additional aromatics formed in desilicated samples during the conversion of ethanol and the samples were, in terms of aromatic yield, outperformed by a microporous parent. However, as result of longer lifetimes less ethanol was lost due to coke formation. It is concluded that desilication should be combined with other post‐modifications to increase aromatic production and lifetime. [ABSTRACT FROM AUTHOR]

Introduction: Suicide‐related behaviors are prevalent among college students, and several mental health problems associated with increased suicide risk have increased over time. Furthermore, notable cultural events (e.g., political changes, COVID‐19) have occurred in the past decade, which likely impact trends in suicide‐related behaviors. The current study examined how the prevalence of nonsuicidal self‐injury (NSSI), suicidal ideation (SI), and suicide attempts has changed from 2012 to 2022 across three different universities. Method: Archival datasets from multiple years of college student survey data were compiled, and different measures of NSSI, SI, and suicide attempts were dichotomized to assess prevalence. Chi‐square goodness‐of‐fit tests were used to identify changes in suicide‐related behaviors across time. Results: Results indicated significant increases in the prevalence of most behaviors across each university, with most increases occurring after 2018. Despite sharing a general trend of increased suicide‐related behaviors, each university differed considerably in their respective trends between various timepoints, suggesting that unique factors may differentially contribute to growing risk among college students. Conclusion: Overall, the current study identifies increasing trends in suicide‐related behaviors over the past decade and highlights the value of investigating these behaviors at the university level. [ABSTRACT FROM AUTHOR]

Alveolar macrophages (alvMs) play an important role for maintenance of lung function by constant removal of cellular debris in the alveolar space. They further contribute to defense against microbial or viral infections and limit tissue damage during acute lung injury. alvMs arise from embryonic progenitor cells, seed the alveoli before birth, and have life‐long self‐renewing capacity. However, recruited monocytes may also help to restore the alvM population after depletion caused by toxins or influenza virus infection. At present, the population dynamics and cellular plasticity of alvMs during allergic lung inflammation is poorly defined. To address this point, we used a mouse model of Aspergillus fumigatus‐induced allergic lung inflammation and observed that Th2‐derived IL‐4 and IL‐13 caused almost complete disappearance of alvMs. This effect required STAT6 expression in alvMs and also occurred in various other settings of type 2 immunity‐mediated lung inflammation or administration of IL‐4 complexes to the lung. In addition, Th2 cells promoted conversion of alvMs to alternatively activated macrophages and multinucleated giant cells. Given the well‐established role of alvMs for maintenance of lung function, this process may have implications for resolution of inflammation and tissue homeostasis in allergic asthma. [ABSTRACT FROM AUTHOR]