ArticleThe Journal of allergy and clinical immunology2021
Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease.
Article in The Journal of allergy and clinical immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 85 citations in OpenAlex.
- Studies of the role of basophils in aspirin-exacerbated respiratory disease pathogenesis.The Journal of allergy and clinical immunology · 2021Trial
- ALOX15-driven ω-6 fatty acid metabolism promotes type 2 inflammation in eosinophilic chronic rhinosinusitis with nasal polyps.The journal of allergy and clinical immunology. Global · 2026Article
- Baicalein Attenuates Eosinophilic Rhinosinusitis by Suppressing ALOX15-Mediated M2 Macrophage Function.International journal of molecular sciences · 2026Article
- Integrated Immune, Epithelial and Lipid Pathways in NSAID-Exacerbated Respiratory Disease.Clinical and translational allergy · 2026Review
- Toward precision medicine in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease.ERJ open research · 2026Article
- Harnessing machine learning and multi-scale modeling to discover novel ALOX15 inhibitors from marine natural products.Molecular diversity · 2026Article
- Dupilumab Dampens Mucosal Type 2 Response During Acetylsalicylic Acid Challenge in N-ERD Patients.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Article
- Nrf2: A Promising Therapeutic Target for Glucocorticoid-Resistant Chronic Rhinosinusitis.Clinical and experimental otorhinolaryngology · 2026Review
- Multi-Omics Insights into Chronic Rhinosinusitis with Nasal Polyps: A Review of Lipidomics, Proteomics, and Transcriptomics.Journal of inflammation research · 2026Review
- Biologic therapies targeting type 2 inflammation in NSAID-exacerbated respiratory disease.Frontiers in immunology · 2026Review
- Review
- Lung function impairment and eosinophilia in patients with eosinophilic chronic rhinosinusitis.The journal of allergy and clinical immunology. Global · 2025Article
- Single-cell transcriptomic profiling of eosinophils and airway immune cells in childhood asthma.The Journal of allergy and clinical immunology · 2025Article
- Sputum Eosinophil and Macrophage Changes After Aspirin Challenge in Patients With Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease.Clinical and translational allergy · 2025Article
- Asthma Phenotypes and Biomarkers.Respiratory care · 2025Review
- Accumulation of long-chain unsaturated fatty acids in the airway inflammatory microenvironment drives eosinophil etosis and corticosteroid resistance.Cell communication and signaling : CCS · 2025Article
- Clinical and mechanistic advancements in aspirin exacerbated respiratory disease.The Journal of allergy and clinical immunology · 2025Review
- SLC27A2 marks lipid peroxidation in nasal epithelial cells driven by type 2 inflammation in chronic rhinosinusitis with nasal polyps.Experimental & molecular medicine · 2025Article
- Analysis of human neutrophils from nasal polyps by single-cell RNA sequencing reveals roles of neutrophils in chronic rhinosinusitis.The Journal of allergy and clinical immunology · 2025Article
- Aspirin hypersensitivity diagnostic index (AHDI): In vitro test for diagnosing of N-ERD based on urinary 15-oxo-ETE and LTEAllergy · 2025Article
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD.
objectiveOur aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD.
methodsSingle-cell RNA sequencing (10× Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence.
resultsThe gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P < .05) or controls (P < .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r = 0.56; P < .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P < .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LO
conclusionsEpithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD.
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