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ObjectivesPrevious research has suggested connections between specific inflammatory cytokines and nasal conditions, including Allergic Rhinitis (AR), Chronic Rhinosinusitis (CRS), and Nasal Polyps (NP). However, a lack of robust research establishing the causal underpinnings of them. This Mendelian Randomization (MR) study aims to evaluate the causal relationships between 41 inflammatory cytokines and the incidence of AR, CRS and NP.MethodsThis study employed a two-sample MR design, harnessing genetic variations derived from publicly accessible genome-wide association studies (GWAS) datasets. AR data was sourced from a GWAS with 25,486 cases and 87,097 controls (identifier: ukb-b-7178). CRS data originated from a GWAS encompassing 1,179 cases and 360,015 controls (identifier: ukb-d-J32). NP data was extracted from a GWAS involving 1,637 cases and 335,562 controls (identifier: ukb-a-541). The data for 41 inflammatory cytokines were obtained from an independent GWAS encompassing 8,293 participants. Inverse variance weighted (IVW), MR Egger regression and Weighted median were used to evaluate the causalities of exposures and outcomes. A range of sensitivity analyses were implemented to assess the robustness of the results.ResultsThe results revealed significant associations between elevated circulating levels of MIP-1α (odds ratio, OR: 1.01798, 95% confidence interval, CI: 1.00217–1.03404, p = 0.02570) and TNF-α (OR: 1.01478, 95% CI: 1.00225–1.02746, p = 0.02067) with an augmented risk of AR in the IVW approach. Heightened levels of circulating IL-2 exhibited a positive correlation with an increased susceptibility to NP in the IVW approach (OR: 1.00129, 95% CI: 1.00017–1.00242, p = 0.02434), whereas elevated levels of circulating PDGF-BB demonstrated a decreased risk of NP (OR: 0.99920, 95% CI: 0.99841–0.99999, p = 0.047610). The MR analysis between levels of 41 inflammatory cytokines and the incidence of CRS yielded no positive outcomes.ConclusionThis investigation proposes a potential causal association between elevated levels of MIP-1α and TNF-α with an elevated risk of AR, as well as an increased risk of NP linked to elevated IL-2 levels. Furthermore, there appears to be a potential association between increased levels of circulating PDGF-BB and a reduced risk of NP.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have been shown to protect against fine particulate matter <2.5 μm in aerodynamic diameter (PM2.5)-induced hazards. However, limited evidence is available for respiratory health, particularly in pregnant women and their offspring. OBJECTIVES: We aimed to investigate the association of prenatal exposure to PM2.5 and its chemical components with allergic rhinitis (AR) in children and explore effect modification by maternal erythrocyte PUFAs. METHODS: This prospective birth cohort study involved 657 mother–child pairs from Guangzhou, China. Prenatal exposure to residential PM2.5 mass and its components [black carbon (BC), organic matter (OM), sulfate (SO42- ), nitrate (NO3 - ), and ammonium (NH4 +)] were estimated by an established spatiotemporal model. Maternal erythrocyte PUFAs during pregnancy were measured using gas chromatography. The diagnosis of AR and report of AR symptoms in children were assessed up to 2 years of age. We used Cox regression with the quantile-based g-computation approach to assess the individual and joint effects of PM2.5 components and examine the modification effects of maternal PUFA levels. RESULTS: Approximately 5.33% and 8.07% of children had AR and related symptoms, respectively. The average concentration of prenatal PM2.5 was 35.50 ± 5.31 μg/m³. PM2.5 was positively associated with the risk of developing AR [hazard ratio (HR)= 1.85; 95% confidence interval (CI): 1.16, 2.96 per 5 μg/m³] and its symptoms (HR = 1.79; 95% CI: 1.22, 2.62 per 5 μg/m³) after adjustment for confounders. Similar associations were observed between individual PM2.5 components and AR outcomes. Each quintile change in a mixture of components was associated with an adjusted HR of 3.73 (95% CI: 1.80, 7.73) and 2.69 (95% CI: 1.55, 4.67) for AR and AR symptoms, with BC accounting for the largest contribution. Higher levels of n-3 docosapentaenoic acid and lower levels of n-6 linoleic acid showed alleviating effects on AR symptoms risk associated with exposure to PM2.5 and its components. CONCLUSION: Prenatal exposure to PM2.5 and its chemical components, particularly BC, was associated with AR/symptoms in early childhood. We highlight that PUFA biomarkers could modify the adverse effects of PM2.5 on respiratory allergy. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential alleviation effect of Cang'erzi powder on inflammation in a mice model of allergic rhinitis through modulation of toll-like receptor 4/nuclear factor-kappa B signaling pathway. The allergic rhinitis mouse model was established via ovalbumin induction. The mice were divided into groups; phosphate buffer saline group, ovalbumin group, ovalbumin+low-dose Cang'erzi powder group, ovalbumin+high-dose Cang'erzi powder group, and ovalbumin+dexamethasone group. The number of sneezing and nasal scratching episodes was recorded. Histopathological examination of the nasal mucosa was performed using hematoxylin-eosin staining. Levels of inflammatory cytokines in the serum were assessed via enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. Oxidative stressrelated markers were quantified using specific assay kits. Protein levels of toll-like receptor 4 and nuclear factor-kappa B in the nasal mucosa were determined using Western blot analysis. In the allergic rhinitis mouse model, Cang'erzi powder administration significantly reduced the number of ovalbumin induced sneezing and nasal scratching episodes. Furthermore, Cang'erzi powder treatment effectively attenuated the ovalbumin induced secretion of pro-inflammatory factors, including toll-like receptor 4 and interleukin-5. Notably, Cang'erzi powder also demonstrated antioxidant effects by reducing the levels of reactive oxygen species, malondialdehyde, and myeloperoxidase, while enhancing the activity of the antioxidant enzyme superoxide dismutase. Additionally, Cang'erzi powder treatment led to a reduction in the protein levels of tolllike receptor 4 and nuclear factor-kappa B in the nasal mucosa. These findings indicate that Cang'erzi powder possesses anti-inflammatory properties and can alleviate inflammation in allergic rhinitis mice by modulating the toll-like receptor 4/nuclear factor-kappa B signaling pathway. Thus, Cang'erzi powder may hold promise as a potential therapeutic agent for the management of allergic rhinitis and warrants further investigation for its clinical application in inflammatory disorders. [ABSTRACT FROM AUTHOR]