The epithelial barrier: The gateway to allergic, autoimmune, and metabolic diseases and chronic neuropsychiatric conditions.

Since the 1960 s, our health has been compromised by exposure to over 350,000 newly introduced toxic substances, contributing to the current pandemic in allergic, autoimmune and metabolic diseases. The "Epithelial Barrier Theory" postulates that these diseases are exacerbated by persistent periepithelial inflammation (epithelitis) triggered by exposure to a wide range of epithelial barrier-damaging substances as well as genetic susceptibility. The epithelial barrier serves as the body's primary physical, chemical, and immunological barrier against external stimuli. A leaky epithelial barrier facilitates the translocation of the microbiome from the surface of the afflicted tissues to interepithelial and even deeper subepithelial locations. In turn, opportunistic bacterial colonization, microbiota dysbiosis, local inflammation and impaired tissue regeneration and remodelling follow. Migration of inflammatory cells to susceptible tissues contributes to damage and inflammation, initiating and aggravating many chronic inflammatory diseases. The objective of this review is to highlight and evaluate recent studies on epithelial physiology and its role in the pathogenesis of chronic diseases in light of the epithelial barrier theory.

Mechanistic study of acupuncture on the pterygopalatine ganglion to improve allergic rhinitis: analysis of multi-target effects based on bioinformatics/network topology strategie.

One of the prevalent chronic inflammatory disorders of the nasal mucosa, allergic rhinitis (AR) has become more widespread in recent years. Acupuncture pterygopalatine ganglion (aPPG) is an emerging alternative therapy that is used to treat AR, but the molecular mechanisms underlying its anti-inflammatory effects are unclear. This work methodically demonstrated the multi-target mechanisms of aPPG in treating AR based on bioinformatics/topology using techniques including text mining, bioinformatics, and network topology, among others. A total of 16 active biomarkers and 108 protein targets related to aPPG treatment of AR were obtained. A total of 345 Gene Ontology terms related to aPPG of AR were identified, and 135 pathways were screened based on Kyoto Encyclopedia of Genes and Genomes analysis. Our study revealed for the first time the multi-targeted mechanism of action of aPPG in the treatment of AR. In animal experiments, aPPG ameliorated rhinitis symptoms in OVA-induced AR rats; decreased serum immunoglobulin E, OVA-sIgE, and substance P levels; elevated serum neuropeptide Y levels; and modulated serum Th1/Th2/Treg/Th17 cytokine expression by a mechanism that may be related to the inhibition of activation of the TLR4/NF-κB/NLRP3 signaling pathway. In vivo animal experiments once again validated the results of the bioinformatics analysis. This study revealed a possible multi-target mechanism of action between aPPG and AR, provided new insights into the potential pathogenesis of AR, and proved that aPPG was a promising complementary alternative therapy for the treatment of AR.

Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma.

Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.

Trajectory analysis of rhinitis in a birth cohort from lower-income New York City neighborhoods.

BACKGROUND: Rhinitis is a prevalent, chronic nasal condition associated with asthma. However, its developmental trajectories remain poorly characterized. OBJECTIVE: We sought to describe the course of rhinitis from infancy to adolescence and the association between identified phenotypes, asthma-related symptoms, and physician-diagnosed asthma. METHODS: We collected rhinitis data from questionnaires repeated across 22 time points among 688 children from infancy to age 11 years and used latent class mixed modeling (LCMM) to identify phenotypes. Once children were between ages 5 and 12, a study physician determined asthma diagnosis. We collected information on the following asthma symptoms: any wheeze, exercise-induced wheeze, nighttime coughing, and emergency department visits. For each, we used LCMM to identify symptom phenotypes. Using logistic regression, we described the association between rhinitis phenotype and asthma diagnosis and each symptom overall and stratified by atopic predisposition and sex. RESULTS: LCMM identified 5 rhinitis trajectory groups: never/infrequent; transient; late onset, infrequent; late onset, frequent; and persistent. LCMM identified 2 trajectories for each symptom, classified as frequent and never/infrequent. Participants with persistent and late onset, frequent phenotypes were more likely to be diagnosed with asthma and to have the frequent phenotype for all symptoms (P < .01). We identified interaction between seroatopy and rhinitis phenotype for physician-diagnosed asthma (P = .04) and exercise-induced wheeze (P = .08). Severe seroatopy was more common among children with late onset, frequent and persistent rhinitis, with nearly 25% of these 2 groups exhibiting sensitivity to 4 or 5 of the 5 allergens tested. CONCLUSIONS: In this prospective, population-based birth cohort, persistent and late onset, frequent rhinitis phenotypes were associated with increased risk of asthma diagnosis and symptoms during adolescence.

Clinical and Molecular Analysis of Longitudinal Rhinitis Phenotypes in an Urban Birth Cohort.

BACKGROUND: Chronic rhinitis symptoms cause significant health burden among children and can have a heterogeneous presentation. Defining phenotypes of childhood chronic rhinitis and associated pathobiology may lead to prevention or improved treatments. OBJECTIVES: To identify longitudinal patterns of rhinitis symptoms in childhood and determine their associations with early life risk factors, allergic comorbidities, and nasal epithelial cell gene expression. METHODS: Chronic rhinitis symptoms were evaluated from ages 1 through 11 years in 485 urban children at high risk for allergic disease in the Urban Environment and Childhood Asthma (URECA) birth cohort. We identified longitudinal rhinitis phenotypes and their relationships to early life exposures, atopic comorbidities, and patterns of nasal epithelial gene expression at age 11 years. RESULTS: Chronic rhinitis symptoms started early in many children and were a risk factor for developing aeroallergen sensitization. We identified four longitudinal rhinitis phenotypes: low/minimal disease, persistent, persistent decreasing, and late increasing. Persistent rhinitis was most closely linked to allergic sensitization and asthma. Risk factors for persistent rhinitis included frequent colds (p<0.001), antibiotic use (p<0.001), and reduced exposure to common indoor aeroallergens (p=0.003). Compared to low/minimal disease, rhinitis phenotypes were associated with increased expression of canonical Type 2 genes and decreased expression of immune response genes. CONCLUSIONS: In urban children, rhinitis symptoms often precede aeroallergen sensitization. Rhinitis phenotypes based on symptoms had distinct risk factors and nasal transcriptome. These results suggest that focusing on early life risk factors and distinct immune mechanisms may be a target to preventing chronic rhinitis in childhood.

The nasal basal cell population shifts toward a diseased phenotype with impaired barrier formation capacity in allergic rhinitis.

BACKGROUND: The integrity of the airway epithelium is guarded by the airway basal cells that serve as progenitor cells and restore wounds in case of injury. Basal cells are a heterogenous population, and specific changes in their behavior are associated with chronic barrier disruption-mechanisms that have not been studied in detail in allergic rhinitis (AR). OBJECTIVE: We aimed to study basal cell subtypes in AR and healthy controls. METHODS: Single-cell RNA sequencing (scRNA-Seq) of the nasal epithelium was performed on nonallergic and house dust mite-allergic AR patients to reveal basal cell diversity and to identify allergy-related alterations. Flow cytometry, immunofluorescence staining, and in vitro experiments using primary basal cells were performed to confirm phenotypic findings at the protein level and functionally. RESULTS: The scRNA-Seq, flow cytometry, and immunofluorescence staining revealed that basal cells are abundantly and heterogeneously present in the nasal epithelium, suggesting specialized subtypes. The total basal cell fraction within the epithelium in AR is increased compared to controls. scRNA-Seq demonstrated that potentially beneficial basal cells are missing in AR epithelium, while an activated population of allergy-associated basal cells is more dominantly present. Furthermore, our in vitro proliferation, wound healing assay and air-liquid interface cultures show that AR-associated basal cells have altered progenitor capacity compared to nonallergic basal cells. CONCLUSIONS: The nasal basal cell population is abundant and diverse, and it shifts toward a diseased state in AR. The absence of potentially protective subtypes and the rise of a proinflammatory population suggest that basal cells are important players in maintaining epithelial barrier defects in AR.

Allergic rhinitis phenotypes with distinct transcriptome profiles in children: A birth cohort.

BACKGROUND: Allergic rhinitis (AR) phenotypes in childhood are unclear. OBJECTIVES: This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic characteristics. METHODS: Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype. RESULTS: Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late-onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection-related defense response, whereas late-onset AR was associated with T cell-related immune response. CONCLUSIONS: Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late- and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well.

Nasal solitary chemosensory cells govern daily rhythm in mouse model of allergic rhinitis.

BACKGROUND: While the daily rhythm of allergic rhinitis (AR) has long been recognized, the molecular mechanism underlying this phenomenon remains enigmatic. OBJECTIVE: We aimed to investigate the role of circadian clock in AR development and to clarify the mechanism by which the daily rhythm of AR is generated. METHODS: AR was induced in mice with ovalbumin. Toluidine blue staining, liquid chromatography-tandem mass spectrometry analysis, real-time quantitative PCR, and immunoblotting were performed with AR and control mice. RESULTS: Ovalbumin-induced AR is diurnally rhythmic and associated with clock gene disruption in nasal mucosa. In particular, Rev-erbα is generally downregulated and its rhythm retained, but with a near-12-hour phase shift. Furthermore, global knockout of core clock gene Bmal1 or Rev-erbα increases the susceptibility of mice to AR and blunts AR rhythmicity. Importantly, nasal solitary chemosensory cells (SCCs) are rhythmically activated, and inhibition of the SCC pathway leads to attenuated AR and a loss of its rhythm. Moreover, rhythmic activation of SCCs is accounted for by diurnal expression of ChAT (an enzyme responsible for the synthesis of acetylcholine) and temporal generation of the neurotransmitter acetylcholine. Mechanistically, Rev-erbα trans-represses Chat through direct binding to a specific response element, generating a diurnal oscillation in this target gene. CONCLUSION: SCCs, under the control of Rev-erbα, are a driver of AR rhythmicity; targeting SCCs should be considered as a new avenue for AR management.

Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVES: We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR. METHODS: The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses. CONCLUSIONS: Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.

Accurate determination of house dust mite sensitization in asthma and allergic rhinitis through cytometric detection of Der p 1 and Der p 2 binding on basophils (CytoBas).

BACKGROUND: House dust mite (HDM) is the most common allergen trigger globally for allergic rhinitis and atopic asthma. OBJECTIVES: To expedite accurate confirmation of allergen sensitization, we designed fluorescent allergen tetramers to directly stain specific IgE on basophils to detect specific allergen sensitization using the flow cytometric CytoBas assay. METHODS: Recombinant proteins of major HDM allergens (component), Der f 1, Der p 1, and Der p 2 were biotinylated and conjugated with fluorochrome streptavidins as tetramers. Blood samples from 64 patients who are HDM-allergic and 26 controls that are non-HDM-sensitized were incubated with allergen tetramers for evaluation of basophil binding (CytoBas) and activation (BAT) with flow cytometry. RESULTS: The tetramers effectively bound and activated basophils from patients who are allergic but not from controls who are nonsensitized. CytoBas with Der p 1 as a single allergen had comparable sensitivity and specificity (92% and 100%) to BAT (91% and 100%) in detecting allergen sensitization, as did CytoBas with Der p 2 (95% and 96%) to BAT (95% and 87%). A positive staining for Der p 1 and/or Der p 2 in CytoBas was 100% sensitive and 96% specific for HDM allergy. CONCLUSIONS: CytoBas has diagnostic accuracy for group 1 and group 2 HDM allergens that is comparable to BAT, but with additional advantages of multiple allergen components in a single tube and no requirement for in vitro basophil activation. These findings endorse a single, multiplex CytoBas assay for accurate and component-resolved diagnosis of aeroallergen sensitization in patients with allergic asthma and/or rhinitis.

IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen.

BACKGROUND: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. OBJECTIVE: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities. METHODS: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7. RESULTS: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). CONCLUSIONS: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

Identification of plasma protein markers of allergic disease risk: a mendelian randomization approach to proteomic analysis.

BACKGROUND: While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework. METHODS: Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications. RESULTS: Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR. CONCLUSION: Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets.

Understanding the nose-brain axis and its role in related diseases: A conceptual review.

The nose-brain axis (NBA), a critical component of the body-brain axis, not only serves as a drug transport route for the treatment of brain diseases but also mediates changes such as neuroimmune disorders, which may be an important mechanism in the occurrence and development of some nasal or brain diseases. Despite its importance, there are substantial gaps that remain in our understanding of the characteristics of NBA-mediated diseases and of the cellular and molecular mechanisms underlying the bidirectional NBA crosstalk. These gaps have limited the translational application of NBA-related research findings to some extent. Therefore, this review aims to address the conceptual framework of NBA and highlight its values in representative diseases by combining existing literature with new research results from our group. We hope that this paper will provide a basis for further in-depth research in this field, and facilitate the clinical translation of NBA.

P2X7 receptor of olfactory bulb microglia plays a pathogenic role in stress-related depression in mice with allergic rhinitis.

The aim of this study was to explore the role and mechanism of the olfactory bulb (OB) microglial P2X7 receptor (P2X7R) in allergic rhinitis (AR)-related depression, with the objective of identifying a potential clinical target. An AR mouse model was induced using ovalbumin (OVA), while chronic stress was employed to induce depression. The study used P2X7R-specific antagonists and OB microglia-specific P2X7R knockdown mice as crucial tools. The results showed that mice in the OVA + stress group exhibited more pronounced depressive-like phenotypes. Furthermore, there was an observed increase in microglial activation in the OB, followed by a rise in the level of inflammation. The pharmacological inhibition of P2X7R significantly mitigated the depression-like phenotype and the OB inflammatory response in OVA + stress mice. Notably, the specific knockdown of microglial P2X7R in the OB resulted in a similar effect, possibly linked to the regulation of IL-1ß via the "ATP-P2X7R-Caspase 1" axis. These findings collectively demonstrate that microglial P2X7R in the OB acts as a direct effector molecule in AR-related depression, and its inhibition may offer a novel strategy for clinical prevention and treatment.

Potential Protective Factors for Allergic Rhinitis Patients Infected with COVID-19.

At the beginning of the 2019 coronavirus disease (COVID-19) pandemic, airway allergic diseases such as asthma and allergic rhinitis (AR) were considered as risk factors for COVID-19, as they would aggravate symptoms. With further research, more and more literature has shown that airway allergic disease may not be a high-risk factor, but may be a protective factor for COVID-19 infection, which is closely related to its low-level expression of the ACE2 receptor and the complex cytokines network as underlying molecular regulatory mechanisms. In addition, steroid hormones and age factors could not be ignored. In this review, we have summarized some current evidence on the relationship between COVID-19 and allergic rhinitis to highlight the underlying mechanisms of COVID-19 infection and provide novel insights for its prevention and treatment. The key findings show that allergic rhinitis and its related molecular mechanisms may have a protective effect against COVID-19 infection.

Astragalus membranaceus, Nigella sativa, and Perilla frutescens as Immunomodulators-Molecular Mechanisms and Clinical Effectiveness in Allergic Diseases.

Plants are the source of numerous remedies in modern medicine, and some of them have been studied due to their potential immunomodulatory activity. Astragalus membranaceus Fisch. ex Bunge (A. membranaceus), Nigella sativa L. (N. sativa), and Perilla frutescens (L.) Britton (P. frutescens) are plant species used in traditional medicine for the treatment of various diseases. Their potential to act as immunomodulatory, anti-inflammatory, and anti-allergic agents makes them interesting for investigating their clinical potential in alleviating the symptoms of allergic diseases. Allergy affects a large number of people; according to some sources more than 30% of the world population suffer from some type of allergic reaction, with pollen allergy as the most common type. Treatment is usually pharmacological and may not be completely effective or have side effects. Thus, we are seeking traditional medicine, mostly medicinal plants, with promising potential for alleviating allergy symptoms. A literature overview was conducted employing databases such as Scopus, PubMed, Web of Science, Springer, and Google Scholar. This manuscript summarizes recent in vivo preclinical and clinical studies on three species with immunomodulatory activity, provides a comparison of their anti-allergic effects, and underlines the potential of their application in clinical practice. The obtained results confirmed their efficacy in the in vivo and clinical studies, but also emphasize the problem of phytochemical characterization of the species and difference between tested doses. More clinical trials with standardized protocols (defined active molecules, dosage, side effects) are required to obtain safe and effective herbal drugs.

The Role of WNT3A Protein and Gene Variants in Allergic Rhinitis: A Case-Control Study.

Allergic rhinitis (AR) is a prevalent inflammatory disorder of the upper respiratory tract, driven by allergen exposure. Understanding mechanisms and identifying biomarkers for AR could significantly impact diagnosis and treatment. This study aimed to investigate the association between serum Wingless-Type MMTV Integration Site Family, Member 3A (WNT3A) protein levels, WNT3A polymorphisms, and AR. A cohort of 92 AR patients and 86 healthy controls was recruited. Serum WNT3A levels were measured by enzyme-linked immunosorbent assay (ELISA). WNT3A gene polymorphisms (rs752107 and rs3121310) were analyzed using Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. The study revealed significantly higher serum WNT3A levels in AR patients compared to controls (p < 0.0001). The impact of WNT3A in the differential diagnosis of AR was determined to be moderate, with an area under the curve (AUC) value of 0.67 (95% Confidence Interval: 0.59-0.75) based on the receiver operating characteristic (ROC) curve analysis. The rs3121310 polymorphism showed a significant association with the GA genotype more prevalent in controls (p < 0.05). However, no significant relationship was observed between rs3121310 genotypes and clinical parameters of the patients. These findings suggest a role for WNT3A in AR pathogenesis, given the elevated serum levels in patients. Larger cohort studies are needed to validate these findings and explore serum WNT3A levels as a biomarker for AR diagnosis and treatment monitoring.

Influence of light at night on allergic diseases: a systematic review and meta-analysis.

BACKGROUND: Allergic diseases impose a significant global disease burden, however, the influence of light at night exposure on these diseases in humans has not been comprehensively assessed. We aimed to summarize available evidence considering the association between light at night exposure and major allergic diseases through a systematic review and meta-analysis. METHODS: We completed a search of six databases, two registries, and Google Scholar from inception until December 15, 2023, and included studies that investigated the influence of artificial light at night (ALAN, high vs. low exposure), chronotype (evening vs. morning chronotype), or shift work (night vs. day shift work) on allergic disease outcomes (asthma, allergic rhinitis, and skin allergies). We performed inverse-variance random-effects meta-analyses to examine the association between the exposures (ALAN exposure, chronotype, or shiftwork) and these allergic outcomes. Stratification analyses were conducted by exposure type, disease type, participant age, and geographical location along with sensitivity analyses to assess publication bias. RESULTS: We included 12 publications in our review. We found that exposure to light at night was associated with higher odds of allergic diseases, with the strongest association observed for ALAN exposure (OR: 1.88; 95% CI: 1.04 to 3.39), followed by evening chronotype (OR: 1.35; 95% CI: 0.98 to 1.87) and exposure to night shift work (OR: 1.33; 95% CI: 1.06 to 1.67). When analyses were stratified by disease types, light at night exposure was significantly associated with asthma (OR: 1.62; 95% CI: 1.19 to 2.20), allergic rhinitis (OR: 1.89; 95% CI: 1.60 to 2.24), and skin allergies (OR: 1.11; 95% CI: 1.09 to 1.91). We also found that the association between light at night exposure and allergic diseases was more profound in youth (OR: 1.63; 95% CI: 1.07 to 2.48) than adults (OR: 1.30; 95% CI: 1.03 to 1.63). Additionally, we observed significant geographical variations in the association between light at night exposure and allergic diseases. CONCLUSIONS: Light at night exposure was associated with a higher prevalence of allergic diseases, both in youth and adults. More long-term epidemiological and mechanistic research is required to understand the possible interactions between light at night and allergic diseases.

English tweets on allergy: Content analysis and association with surveillance data.

BACKGROUND: Analysis of X (formerly Twitter) posts can inform on the interest/perceptions that social media users have on health subjects. In this study, we aimed to analyse tweets on allergic conditions, comparing them with surveillance data. METHODS: We retrieved tweets from England on "allergy," "asthma," and "allergic rhinitis," published between 2016 and 2021. We estimated the correlation between the frequency of tweets on "asthma" and "allergic rhinitis" and English surveillance data on the incidence of asthma and allergic rhinitis medical visits. We performed sentiment analysis, computing a score informing on the emotional tone of assessed tweets. We applied a topic modelling approach to identify topics (clusters of words frequently occurring together) for tweets on each assessed condition. RESULTS: We analysed a total of 13,605 tweets on "allergy," 7767 tweets on "asthma," and 11,974 tweets on "allergic rhinitis." Food-related words were preponderant on tweets on "allergy," while "eyes" was the most frequent meaningful word on "allergy rhinitis" tweets. We observed seasonal patterns for tweets on "allergic rhinitis," both in their frequency and sentiment - the incidence of allergic rhinitis medical visits was moderately to strongly correlated with the frequency (ρ = 0.866) and sentiment (ρ = -0.474) of tweets on "allergic rhinitis." For tweets on "asthma," no such patterns/correlations were observed. The average sentiment score was negative for all assessed conditions, ranging from -0.004 ("asthma") to -0.083 ("allergic rhinitis"). CONCLUSIONS: Tweets on "allergic rhinitis" displayed a seasonal pattern regarding their frequency and sentiment, which correlated with surveillance data. No such patterns were observed for "asthma."

Component-specific clusters for diagnosis and prediction of allergic airway diseases.

BACKGROUND: Previous studies which applied machine learning on multiplex component-resolved diagnostics arrays identified clusters of allergen components which are biologically plausible and reflect the sources of allergenic proteins and their structural homogeneity. Sensitization to different clusters is associated with different clinical outcomes. OBJECTIVE: To investigate whether within different allergen component sensitization clusters, the internal within-cluster sensitization structure, including the number of c-sIgE responses and their distinct patterns, alters the risk of clinical expression of symptoms. METHODS: In a previous analysis in a population-based birth cohort, by clustering component-specific (c-s)IgEs, we derived allergen component clusters from infancy to adolescence. In the current analysis, we defined each subject's within-cluster sensitization structure which captured the total number of c-sIgE responses in each cluster and intra-cluster sensitization patterns. Associations between within-cluster sensitization patterns and clinical outcomes (asthma and rhinitis) in early-school age and adolescence were examined using logistic regression and binomial generalized additive models. RESULTS: Intra-cluster sensitization patterns revealed specific associations with asthma and rhinitis (both contemporaneously and longitudinally) that were previously unseen using binary sensitization to clusters. A more detailed description of the subjects' within-cluster c-sIgE responses in terms of the number of positive c-sIgEs and unique sensitization patterns added new information relevant to allergic diseases, both for diagnostic and prognostic purposes. For example, the increase in the number of within-cluster positive c-sIgEs at age 5 years was correlated with the increase in prevalence of asthma at ages 5 and 16 years, with the correlations being stronger in the prediction context (e.g. for the largest 'Broad' component cluster, contemporaneous: r = .28, p = .012; r = .22, p = .043; longitudinal: r = .36, p = .004; r = .27, p = .04). CONCLUSION: Among sensitized individuals, a more detailed description of within-cluster c-sIgE responses in terms of the number of positive c-sIgE responses and distinct sensitization patterns, adds potentially important information relevant to allergic diseases.