Allergic rhinitis (AR) is an IgE-mediated, non-infectious inflammatory disorder of the nasal mucosa, and accurate diagnosis is important for individualized treatment. Over the past decade, diagnostic strategies for AR have evolved substantially from conventional methods, such as skin prick testing and serum-specific IgE testing, toward advanced approaches, including molecular allergen diagnostics, biomarker profiling, functional imaging, and artificial intelligence-assisted assessment. This review provides a systematic overview of these developments by summarizing the underlying principles, clinical utility, strengths, and limitations of each method. It also discusses the integration of multi-omics and digital health technologies, which have the potential to support truly precise and individualized diagnostics. By critically reviewing current strategies and future research directions, this article aims to help clinicians optimize patient management and promote further development in the field of AR diagnostics.

Chronic upper and lower airway inflammatory diseases (such as allergic rhinitis, chronic rhinosinusitis, and bronchial asthma) are a group of highly heterogeneous disorders primarily characterized by immune imbalance and persistent inflammation as their core features, which seriously affect patients’ quality of life. As an important component of the immune system, macrophages can undergo functional polarization in response to distinct inflammatory microenvironments, exerting divergent pro-inflammatory or anti-inflammatory effects. They also form intricate interaction networks with other immune cells to jointly regulate the progression of chronic airway inflammation. Although the regulation of macrophage plasticity is regulated by multiple aspects, metabolic reprogramming has emerged as a pivotal mechanism modulating macrophage polarization and function. This review systematically summarizes the interplay between macrophage polarization and other immune cells, focusing on the impact of distinct phenotypes and their regulatory pathways on chronic airway inflammatory diseases. Furthermore, we discuss the therapeutic potential of targeting metabolic reprogramming, providing new insights for the precise treatment of chronic upper and lower airway inflammatory diseases.

Objective:To analyze the current status,hotspots,and development trends of research in the field of seasonal allergic rhinitis(SAR)using bibliometric methods,providing references for clinical diagnosis and treat-ment and research directions.Methods:Based on SAR-related literature from the Web of Science Core Collection(WoSCC)database from 2014 to 2024,CiteSpace 6.4.R1 software was used to construct national/institutional collaboration networks,keyword co-occurrence,and emergent maps,combined with cluster analysis to explore the evolution of research hotspots.Results:A total of 1 037 articles were identified;annual output peaked in 2021.The most productive countries were the United States(241 articles),Germany(146),and China(135).Institutions in Berlin showed the tightest collaborative ties.The core prolific authors include Ludger Klimek,Ste-phen R.Durham,and Luo Zhang,and their teams.High-frequency keywords included"asthma","double-blind trial",and"efficacy".Cluster analysis indicated that systematic reviews and immunotherapy dominated the past e-leven years.Since 2019,cross-reactivity,birch pollen,food allergy,and pollen allergy have emerged as new fron-tiers.Conclusion:SAR research is shifting from empirical therapy validation to precision medicine.Deciphering cross-reactivity mechanisms and expanding biological agents will be central to future work.Although China's scholarly output has grown markedly,stronger transnational collaboration is still warranted.Systematic reviews,molecular diagnostics,and targeted therapies are expected to optimize SAR management strategies.

Allergic rhinitis (AR) is a prevalent chronic inflammatory disorder characterized by complex pathophysiological mechanisms. Nasal mucosal epithelial cells serve as crucial “immune sentinels” that detect allergens and initiate immune responses, thereby playing a pivotal role in disease progression. Intracellular calcium signaling, as a vital second messenger, regulates epithelial barrier integrity and modulates immune functions within these cells. This review summarizes current understanding of the immune surveillance role of nasal mucosal epithelial cells in AR, emphasizing the regulatory mechanisms of calcium signaling pathways in barrier disruption and the amplification of inflammatory cycles. Recent studies reveal that aberrant calcium signaling contributes to nasal epithelial barrier dysfunction and excessive activation of inflammatory cells, which perpetuate chronic inflammation and exacerbate symptom severity. By integrating emerging evidence on calcium-mediated cellular processes, this article highlights the critical involvement of calcium signaling in maintaining epithelial homeostasis and controlling inflammatory responses in AR. Understanding these mechanisms provides novel insights into the pathogenesis of AR and identifies potential therapeutic targets aimed at restoring epithelial barrier function and modulating inflammatory cascades, thereby offering new directions for clinical intervention.

Allergic rhinitis (AR) is an IgE-dependent, Th2 cell-mediated disorder that significantly impairs patients’ quality of life. In recent years, molecular innate immune regulation has emerged as a pivotal area of research, especially focusing on the use of Toll-like receptor (TLR) agonists as adjuvants in allergen immunotherapy (AIT). TLRs, key components of the innate immune system, recognize pathogen-associated molecular patterns and activate dendritic cells, thereby modulating adaptive immune responses to promote anti-allergic immune deviation. This review provides a comprehensive overview of the role of TLRs in the development of AR vaccines, summarizing the progress made with various TLR agonists and their potential applications in AIT. Emphasis is placed on the immunoregulatory characteristics of these molecules and the current status of clinical trials, aiming to offer a theoretical foundation and research direction for the design of more effective and fast-acting therapeutic strategies for allergic rhinitis.

Chronic rhinosinusitis (CRS) is a systemic, complicated, inflammatory disease which results in a significant burden on the patient's quality of life. Although the prevalence has been increasing worldwide, our therapeutic advances have been limited by the complexity of immune imbalance in addition to epithelial breakdown. Although murine models have always been the default of choice of mechanistic studies because of their relative affordability and genetic tractability, they are often insufficient to reflect the anatomical and physiological reality of the human nasal sinus. As an example, the sheep model provides a much more convincing explanation of the process of human sinus drainage, and porcine models offer a specialized perspective on the recalcitrant epithelial remodeling that characterizes severe CRS. In this review we go further than the listing of the species. Rather we focus on evaluating the efficiency of these models in representing specific human phenotypes, such as from eosinophilic overproliferation in type 2 inflammation to phenotypes in non-type 2 diseases. Through a new strategic decision framework, we would guide researchers out of paradigms of models of convenience, to models of clinical relevance, eventually facilitating the translation of bench discoveries to patient-centered therapy.

INTRODUCTION:This retrospective study evaluated real-world data on subcutaneous immunotherapy for house dust mites (HDM-SCIT) in children and adults with AR over a period exceeding 10 years and aimed to observe the long-term efficacy of HDM-SCIT lasting more than 10 years in children and adults. METHODS:Sixty-six patients, including 31 children and 35 adults who were allergic to house dust mite and received SCIT, were retrospectively analysed. All patients completed an immunotherapy course lasting 2-3 years. Questionnaire data were collected before and at the end of SCIT, and telephone follow-up was conducted to evaluate the long-term efficacy after 10 years. RESULTS:Nasal and ocular symptoms in children and adults remained better controlled 10 years after the completion of HDM-SCIT (all p < 0.05). The efficacy for nasal and ocular symptoms in children persisted after 10 years (all p < 0.05), whereas the efficacy of other related symptoms declined (p = 0.414). The efficacy for nasal symptoms in adults remained stable (p = 0.888), whereas the efficacy for ocular symptoms and ear-itching symptoms declined (all p < 0.05). No statistically significant difference between children and adults (p = 0.607, p = 0.764). No adverse reactions persisted for 10 years or more. CONCLUSIONS:Up to 10 years after completing HDM-SCIT, both children and adults continued to exhibit significant improvement in their symptoms. The safety profile during treatment for both adults and children remained excellent even 10 years later.

Background:Saline nasal irrigation is widely used in the management of nasal diseases; however, its inability to replicate the physicochemical properties of airway surface liquid (ASL) may limit its long-term efficacy. We aimed to investigate the protective mechanisms of sodium hyaluronate (hyaluronic acid, HA) nasal spray on the nasal mucosa and to compare its effects with conventional saline. Methods:BALB/c mice were subjected to intranasal mugwort allergen exposure and treated with either saline or sodium hyaluronate nasal spray for 1-7 days. Behavioral assessments and nasal crusting scores were recorded. Cytokine levels (IL-4, IL-25, IL-33, TSLP) were quantified using ELISA. Histological analyses (H&E, PAS, Alcian Blue) and immunohistochemistry (ZO-1, Occludin) were performed. Ex vivo mucociliary clearance (MCC) was assessed under different liquid environments. Results:HA treatment significantly reduced nasal scratching and attenuated crust formation following prolonged allergen exposure. This was accompanied by suppression of Th2 cytokines and epithelial-derived alarmins in both nasal mucosa and serum. HA preserved mucus layer thickness and goblet cell density and significantly delayed the decline in MCC. Tight junction protein expression remained unchanged. Conclusion:Sodium hyaluronate nasal spray confers mucosal protection primarily through preservation of ASL homeostasis and MCC function rather than modulation of epithelial tight junctions. These findings highlight HA as a promising alternative to saline for long-term management of nasal mucosal disorders.

Allergic rhinitis (AR) is a chronic nasal disease primarily mediated by immunoglobulin E (IgE). This condition significantly impairs patients' quality of life. Current treatments have limited clinical effectiveness. Although TH2 lymphocytes are well established as key regulators in AR pathogenesis, recent evidence underscores the pivotal role of M2 macrophages, particularly the M2a subtype, in exacerbating type 2 inflammation through recruitment of TH2 cells. To address this, 2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) is developed, a positively charged macromolecular polysaccharide that is water-soluble and has good biocompatibility. In vitro experiments demonstrate its ability to reprogram M2a macrophages into the M1 phenotype and suppress their release of chemotactic factors. In vivo studies further confirm that HACC effectively alleviated AR symptoms in a mouse model, significantly reducing inflammatory cell infiltration in the nasal mucosa, and partially reversed the TH1-TH2 imbalance in a mouse model. Notably, its therapeutic efficacy is comparable to cetirizine, a clinically approved treatment for AR. This study highlights modulation of macrophage phenotypes as a promising strategy to inhibit type 2 inflammation and achieve effective management of allergic rhinitis.

Objective:To investigate the clinical efficacy of endoscopic ethmoid infundibulum expansion surgery（EEIES） combined with Stapokibart in the treatment of type 2 chronic rhinosinusitis with nasal polyps（CRSwNP）. Methods:A prospective, randomized, single-blind, self-controlled study was conducted. A total of 18 patients with bilateral CRSwNP and type 2 inflammatory phenotype admitted to the Department of Otorhinolaryngology Head and Neck Surgery in our hospital from April 2025 to August 2025 were enrolled. Patients' bilateral nasal cavities were randomly assigned to undergo either EEIES or full-house endoscopic sinus surgery（full-house ESS）. EEIES described in this study refers to precise ventilation reconstruction of the middle/superior meatus centered on the ethmoid infundibulum. All patients received routine treatments including nasal corticosteroids and nasal irrigation postoperatively. Subcutaneous injection of Stapokibart 300 mg was administered every 2 weeks starting at 2 weeks after surgery for 24 consecutive weeks. The nasal symptom visual analogue scale（VAS）, sino-nasal outcome test-22（SNOT-22） score, nasal polyp score（NPS）, Lund-Kennedy score of nasal endoscopy, and sinus CT Lund-Mackay score were compared before and 24 weeks after surgery, and the efficacy differences between the two surgical procedures were analyzed. Results:At 24 weeks postoperatively, all scores of patients were significantly improved compared with preoperative baseline（all P<0.01）. The NPS, Lund-Kennedy score, and Lund-Mackay score were significantly improved in both EEIES side and full-house ESS side compared with baseline（all P<0.01）, with no statistically significant differences between the two sides（all P>0.05）. Conclusion:The short-term clinical efficacy of EEIES combined with Stapokibart in the treatment of type 2 CRSwNP is comparable to that of full-house ESS combined with Stapokibart. EEIES can precisely alleviate ventilation disorders and the hypoxic microenvironment in the middle and superior nasal meatus, while maximizing preservation of the natural sinus ostium and integrity of the sinus mucosa. Combined with Stapokibart, it can effectively block the type 2 inflammatory pathway and promote nasal mucosal homeostasis reconstruction. The restoration of sinus ventilation and drainage function critically depends on the recovery and integrity of nasal mucosal ciliary function, rather than mechanical enlargement of the sinus ostium. Therefore, EEIES can provide a more minimally invasive and biologically rational surgical treatment option for patients with type 2 CRSwNP.

INTRODUCTION:The epithelial cells of the airway mucosa, as the initiating factors of airway inflammation, regulate the occurrence of innate and acquired immune responses. According to the same airway theory and the latest research results on pericytes in the lower respiratory tract, there may also be interactions or information transmission between the epithelial cells and pericytes of the airway mucosa in the upper respiratory tract. METHODS:In this study, primary mucosal epithelial cells of nasal polyps (NP) were first isolated and cultured to establish a stimulation system of house dust mite (HDM) extract. Then, a coculture system of primary mucosal epithelial cells of NP and human microvascular pericytes was established using transwell chambers. The migration of pericytes in each group after coculture was determined by using the plate scratch test. Transcriptomics was applied to study the differences in gene expression of pericytes in each group after coculture. The expression of cytokines and chemokines in the culture supernatants of each group was detected by ELISA. Finally, the protein expression of the related pathways after coculture was detected by the WB method. RESULTS:The results of this study show that the pericytes migration in the eosinophilic coculture group is significantly higher than that in the other groups. Compared with the model group, the coculture group increased the cell viability of human nasal mucosal epithelial cells stimulated by HDM. The migration ability of human nasal mucosal epithelial cells decreased after HDM stimulation, and the migration ability was restored after coculture. The results indicated that in the coculture group, POSTN, VCAM-1, and CCL-5 expressed by pericytes were the most numerous. The WB detection results revealed that the PDGF pathway in pericytes was activated, and the expressions of related proteins all changed accordingly. CONCLUSION:This study indicates that in the coculture model of mucosal epithelial cells of NP and pericytes, the stimulated epithelial cells can upregulate the expression of factors such as POSTN, VCAM-1, and CCL-5 in pericytes. There exists a PDGF/PI3K/AKT/NF-κB signaling pathway between mucosal epithelial cells of NP and pericytes.

The prevalence of allergic rhinitis (AR) continues to rise, severely impairing patients’ quality of life and causing enormous social and economic burdens. For refractory AR that cannot be adequately controlled by standardized firstline therapies, neurotomy has become an important secondline therapeutic option. However, due to various remaining controversial issues, there is currently a lack of internationally unified clinical guidelines, which restricts its clinical application and generalization. To better guide the clinical practice of neurotomy for AR in China, 49 experts in the field of rhinology and allergy nationwide, led by the Third Affiliated Hospital of Sun Yat-sen University, carried out the work of formulating a consensus. Using the Delphi method, we focused on seven dimensions: the purpose and significance of neurotomy for AR, relevant applied anatomy, pathophysiological basis, surgical indications and contraindications, surgical techniques, efficacy and evaluation criteria, and surgical complications and their management, ultimately generating a series of core viewpoints. This consensus is expected to further promote the standardized development of neurotomy for AR in China, and help improve the overall prevention and management of AR.

BackgroundThe airway epithelial barrier is the first defence against aeroallergens. Nasal epithelial cells (NECs) are vital in regulating innate and adaptive mucosal immunity in allergic rhinitis (AR). Tregs produce cytokines essential for the immunomodulatory activities in allergen immunotherapy. Understanding the relationship between NECs and Tregs in the airway hyperresponsiveness network is essential for developing novel treatments.MethodsUsing an in vitro human Treg-NEC co-culture system of AR and health control group, the chemokine expression profiles of NECs were examined using immunohistochemistry, RT-PCR, and ELISA, and functional surface markers of Tregs were detected using flow cytometric analysis. Correlation analysis was performed between cytokines derived from NECs and surface markers of CD4+CD8+Foxp3+ Tregs in the AR group after co-culture, including TSLP/CTLA4, CCL1/CTLA4, TSLP/CTLA4, TSLP/CCR8, and CCL1/CCR8.ResultsCCR8 and CTLA-4 expressions after co-culturing were higher than single culture. Following Derp1 stimulation, TSLP, IL-25 and TGF-β expressions in the AR + Derp1 group were increased. CCL1 mRNA was lower in the AR + Derp1 group than control group. In the AR + Derp1 group, TSLP was higher, and CCL1 protein levels were decreased. There were no significant differences in IL-25, TGF-β and IL-10. When Treg co-culture group added, changes were similar to that observed in pNECs. After co-culture, CCL1/CCR8 was positively correlated in AR.ConclusionHuman pNECs can communicate with Tregs directly, CCL1/CCR8 may be the pathway between NECs and Tregs in vitro and may play a key role in the immune network of AR.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.

BACKGROUND:The causal links between gut microbiota, inflammatory cytokines, and chronic rhinosinusitis are unclear. METHODS:A Mendelian randomization study used data from the MiBioGen consortium (211 microbiota taxa, n = 18,340), genome-wide association studies of 91 inflammatory cytokines, and chronic rhinosinusitis data from the FinnGen consortium. RESULTS:Five microbiota taxa were causally linked to chronic rhinosinusitis. The genera Ruminococcaceae NK4A214 group and Victivallis were risk factors, while Lachnospiraceae NC2004 group, Ruminococcus2, and Subdoligranulum were protective. Elevated levels of axin-1, C-X-C motif chemokine 10, interleukin-18 receptor 1, interleukin-1-alpha, and vascular endothelial growth factor A increased risk, whereas C-C motif chemokine 19, CD40L receptor, and Fractalkine were protective. The Ruminococcaceae NK4A214 group id.11358 increased risk through reduced Fractalkine and elevated vascular endothelial growth factor A levels. CONCLUSIONS:The study supports a causal link between Ruminococcaceae NK4A214 group id.11358 and chronic rhinosinusitis, mediated by Fractalkine and vascular endothelial growth factor A levels.

Environmental pollution and climate change seriously affect human health, leading to the onset and exacerbation of chronic respiratory diseases, such as allergic rhinitis and lung diseases. Over the past several decades, increasing air pollution and environmental exposure owing to global urbanization, industrialization, and rapid economic growth have led to an increase in the prevalence of allergic and respiratory diseases. Allergic rhinitis and lung diseases are global health problems affecting people of all ages. This article summarizes the effects of environmental pollution and accompanying climate change on allergic rhinitis and lung diseases and discusses the interactions between the pathogenesis of allergic rhinitis and lung diseases and environmental pollution. The molecular mechanisms of allergic rhinitis and lung diseases and their common features are discussed. The prevention and control measures of allergic rhinitis and lung diseases caused by air pollution and climate change are described. Given that climate change could bring about numerous unforeseen and enduring impacts on allergic respiratory conditions, healthcare practitioners ought to champion efficient measures for mitigation and adaptation to curtail its adverse effects on respiratory health.

Background There is no trial to assess the benefits of periodically using biologics during the pollen season in patients with uncontrolled seasonal allergic rhinitis (SAR), who have moderate -to -severe symptoms even after standard -ofcare. This trial aimed to evaluate the efficacy and safety of the add-on administration of stapokibart, a humanised monoclonal antibody that targets interleukin-4 receptor alpha, in patients with uncontrolled SAR. Methods In this investigator -initiated, randomised, double-blind, placebo -controlled trial, eligible patients received either stapokibart 600-300 mg weekly (QW), every 2 weeks (Q2W), or placebo QW for 4 weeks. All patients were given mometasone furoate nasal spray and loratadine throughout the trial. The primary endpoint was the mean change from baseline in daily reflective total nasal symptom score (rTNSS) during 2 -week treatment. Secondary efficacy outcomes included: the mean change from baseline in daily rTNSS during 4 -week treatment; the mean changes and the mean percentage changes from baseline during 2 -week and 4 -week treatment in 1) daily rTNSS and reflective total ocular symptom score (rTOSS), 2) morning (AM)/evening (PM) rTNSS and rTOSS, 3) AM instantaneous total nasal symptom score (iTNSS) and instantaneous total ocular symptom score (iTOSS), 4) individual nasal and ocular symptoms; the change from baseline in Rhinoconjunctivitis Quality of -Life Questionnaire score during 4 -week treatment. Exploratory endpoints included the change of prespecified markers related to type 2 inflammation pre- and post -treatment. Safety, immunogenicity, and pharmacokinetics were also evaluated. This study is registered with www.clinicaltrials.gov (NCT05470647). Findings Between August 17, 2022, and December 28, 2022, 92 patients with uncontrolled SAR were enrolled from 4 centres in China and randomly assigned to receive stapokibart 600-300 mg QW (n = 31), stapokibart 600-300 mg Q2W (n = 30), or placebo QW (n = 31), of whom 86 (93%) completed the study. Both stapokibart Q2W and QW did not significantly improve mean change from baseline in daily rTNSS compared with placebo in 2 weeks. The leastsquares (LS) mean differences (97.5% confidence interval [CI]) compared with placebo were -1.0 (-2.3, 0.2) in stapokibart Q2W group (p = 0.065) and -0.2 (-1.5, 1.0) in stapokibart QW group (p = 0.67). For the secondary outcomes, compared with placebo, stapokibart Q2W presented significant improvements in the mean percentage change from baseline in daily rTNSS in 2 weeks (LS mean difference -12.9%, 95% CI -25.3%, -0.4%, p = 0.043), as well as AM iTNSS over 2 weeks (LS mean difference -17.4%, 95% CI -31.0%, -3.8%, p = 0.013) and 4 weeks 2024;69: Published https://doi.org/10. 1016/j.eclinm.2024. 102467 (LS mean difference -15.4%, 95% CI -29.0%, -1.9%, p = 0.026). Additionally, the nasal congestion score was significantly lower in stapokibart Q2W than placebo during 2 -week (LS mean difference -0.4, 95% CI -0.7, -0.1, p = 0.014) and 4 -week (LS mean difference -0.4, 95% CI -0.7, -0.04, p = 0.028) treatment. Treatment -emergent adverse events (TEAEs) occurred in 48% (15/31), 33% (10/30), and 61% (19/31) of patients receiving stapokibart QW, Q2W, and placebo, respectively. Most reported TEAEs were sinus bradycardia, hyperlipidaemia, and blood uric acid increased.

BackgroundTRP protein is sensitive to external temperature changes, but its pathogenic mechanism in the upper airway mucosa is still unclear.ObjectiveTo investigate the mechanism of TRPV1and TRPA1 in regulating the secretion of inflammatory factors in nasal epithelial cells.MethodsThe expression of TRPV1 and TRPA1 in nasal mucosal epithelial cells was investigated using immunofluorescence assays. Epithelial cells were stimulated with TRPV1 and TRPA1 agonists and antagonists, and changes in Ca2+ release and inflammatory factor secretion in epithelial cells were detected. TSLP secretion stimulated with the calcium chelating agent EGTA was evaluated. The transcription factor NFAT was observed by immunofluorescence staining.ResultsTRPV1 and TRPA1 expression was detected in nasal epithelial cells, and Ca2+ influx was increased after stimulation with agonists. After the activation of TRPV1 and TRPA1, the gene expression of TSLP, IL-25, and IL-33 and the protein expression levels of TSLP and IL-33 were increased, and only TSLP could be inhibited by antagonists and siRNAs. After administration of EGTA, the secretion of TSLP was inhibited significantly, and the expression of the transcription factor NFAT in the nucleus was observed after activation of the TRPV1 and TRPA1 proteins in epithelial cells.ConclusionActivation of TRPV1 and TRPA1 on nasal epithelial cells stimulates the generation of TSLP through the Ca2+/NFAT pathway. It also induces upregulation of IL-25 and IL-33 gene expression levels and increased levels of IL-33 protein, leading to the development of airway inflammation.

Background: The clinical outcomes of drug treatments and surgical interventions for chronic sinusitis with nasal polyps (CRSwNPs) are suboptimal, and the high recurrence rate remains a significant challenge in clinical practice. Targeted therapies such as biologics provide new perspectives and directions for treating CRSwNP. Summary: With the continuous investigation of signaling pathways, RAS/RAF/MEK/ERK signaling pathway and other signaling pathways including Hippo, JAK-STAT, Wnt, TGF-β, PI3K, Notch, and NF-κB were confirmed to play an important role in the progression of CRSwNP. Among them, the abnormality of RAS/RAF/MEK/ERK signaling pathway is accompanied by the abnormality of this apoptotic component, which may provide new research directions for targeting the components of signaling pathways to mediate apoptosis. Key Messages: Abnormalities in signaling pathways are particularly important in studying the pathogenesis and treatment of CRSwNP. Therefore, this review summarizes the ongoing investigation and characterization of RAS/RAF/MEK/ERK signaling pathway and other signaling pathways in CRSwNP, which provides constructive ideas and directions for improving the treatment of CRSwNP.