(1) Background: Allergic rhinitis (AR) is a common disease in otolaryngology and novel biological therapies are required for clinical needs. To assess the tolerability of monoclonal antibodies, justifying their clinical applications, we presented a comprehensive safety profile of biologics in AR; (2) Methods: A systematic literature search was conducted following PRISMA guidelines for randomized clinical trials comparing monoclonal antibodies and placebo in AR. PubMed, Web of Science, Medline, and Cochrane were searched up until 9 January 2023. Among 3590 records in total, 12 studies with more than 2600 patients were included. Quality was assessed for all studies using Cochrane risk-of-bias tool for randomized trials, and subgrouped meta-analysis was performed; (3) Results: We accomplished an up-to-date literature overview and analysis on adverse events of monoclonal antibodies in AR. Total, common, severe, discontinuation-causing, and serious adverse events failed to reach statistical significance. Country was an essential factor for heterogeneity, and urticaria was the adverse event at highest risk (RR 2.81, 95% CI 0.79–9.95); (4) Conclusions: Monoclonal antibodies are considered well tolerated and relatively safe in patients with AR. The regions of patients and hypersensitive adverse reactions such as urticaria require a special caution in biological treatments in AR.

Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by type 2 inflammation, including M2 macrophage infiltration. Baicalein is a flavonoid with anti-inflammatory properties. This study aimed to investigate the therapeutic effect of baicalein in a papain-induced eosinophilic rhinosinusitis model and to determine whether it acts through arachidonate 15-lipoxygenase (ALOX15)-dependent M2 macrophage function. Clinical nasal samples from controls, non-eosinophilic CRSwNP (neCRSwNP), and eCRSwNP were analyzed for ALOX15 expression and localization. THP-1 cells were differentiated and polarized toward M2 macrophages, and the effects of baicalein on ALOX15 expression, lipid peroxidation, cytokine secretion, and transcriptomic profile were examined. The ALOX15 inhibitor PD146176 was used for target validation. A murine eosinophilic rhinosinusitis model was established by intranasal papain instillation, followed by baicalein treatment. Mucosal inflammation, IgE levels, proteoglycan 2 (PRG2)/ALOX15 expression, and immune cell infiltration were evaluated. ALOX15 was upregulated in eCRSwNP tissues and localized to CD68⁺CD206⁺ M2 macrophages. In vitro, M2 polarization increased ALOX15 expression and lipid peroxidation. Baicalein suppressed ALOX15 expression, lipid peroxidation, and the secretion of CCL22, CCL2, CXCL12, FGF-2, and IL-15. PD146176 produced similar effects, and baicalein showed no additional effect after ALOX15 blockade. RNA sequencing revealed transcriptional remodeling in M2 macrophages after baicalein treatment. In vivo, papain increased ethmoid sinus mucosal thickening, serum IgE, PRG2/ALOX15 positive cells, and infiltration of CD45⁺ immune cells, CD170⁺ eosinophils, F4/80⁺ macrophages, and B220⁺ B cells. Baicalein significantly alleviated all these pathological changes. In conclusion, baicalein attenuates papain-induced eCRSwNP-like inflammation by inhibiting lipid peroxidation and ALOX15-associated M2 macrophage secretory function. The ALOX15/M2 macrophage axis may represent a potential therapeutic target for eCRSwNP.

Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) share overlapping inflammatory mechanisms while retaining distinct disease biology. Although lipid metabolism is increasingly implicated in airway inflammation, the nasal fluid lipidomic landscape across AR and CRSwNP and its relationship to local eosinophilic inflammation and clinical burden remain incompletely understood. We performed widely targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) lipidomics on nasal fluid from 73 participants, including 22 controls, 23 patients with AR, and 28 patients with CRSwNP. Group differences were evaluated using multivariate analysis and models adjusted for age, sex, and smoking status, followed by trajectory clustering and residual-correlation network analysis. Within CRSwNP, adjusted models were used to assess lipid associations with tissue eosinophilia, the 22-item Sinonasal Outcome Test (SNOT-22), overall visual analog scale (VAS), and Lund–Mackay computed tomography score. Lipid subclass patterns were examined by ranked enrichment and focused subclass score analyses. AR was characterized mainly by higher relative abundances of TG species, whereas CRSwNP showed broader increases involving triacylglycerol species, plasmalogen phosphatidylethanolamines, and lysophospholipids. Exploratory clustering of 147 lipids showing nominally significant differences (p < 0.05) in at least one covariate-adjusted pairwise group comparison yielded four modules with differing biochemical compositions, although the partition was sensitive to the input lipid set. Among these, the diacylglycerol–lysophosphatidic acid-related module displayed strong internal network connectivity, suggesting coordinated variation within the identified module. Within CRSwNP, ranked analysis of lipid associations with tissue eosinophilia showed negative enrichment of plasmalogen phosphatidylethanolamine, sphingomyelin, and ether-linked lysophosphatidylcholine, and positive enrichment of glycerolipid and acylcarnitine subclasses. Clinical burden showed only partial overlap with this pattern: plasmalogen phosphatidylethanolamine was inversely associated with both tissue eosinophilia and patient-reported symptom burden, whereas conventional lysophosphatidylcholine showed stronger positive associations with symptomatic and radiographic burden. These findings suggest distinct and coordinated nasal fluid lipidomic features associated with the upper-airway inflammatory phenotype, local eosinophilic inflammation, and clinical disease burden.