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BackgroundNonsteroidal anti‐inflammatory drugs–exacerbated respiratory disease (NSAIDs‐ERD) is characterized by altered arachidonic acid (AA) metabolism. Aspirin hypersensitivity is diagnosed using aspirin challenge, while induced sputum is collected to perform cell counts and to identify local biomarkers in induced sputum supernatant (ISS). This study aimed to assess the levels of a newly identified eicosanoid, 15‐oxo‐eicosatetraenoic acid (15‐oxo‐ETE), in ISS at baseline and during aspirin‐induced bronchospasm in patients with NSAIDs‐ERD.MethodsOral aspirin challenge was performed in 27 patients with NSAIDs‐ERD and in 17 patients with aspirin‐tolerant asthma (ATA) serving as controls. Sputum was collected before and after aspirin challenge to determine eosinophil, neutrophil, macrophage, and lymphocyte counts as well as the concentration of AA metabolites via 15‐lipoxygenase‐1 (15‐LOX‐1) and 5‐LOX pathways in ISS. Chromatography–tandem mass spectrometry was used to measure ISS levels of 15‐oxo‐ETE, 15‐hydroxyeicosatetranoic acid (15‐HETE), and leukotriene E4 (LTE4).ResultsAt baseline, ISS levels of 15‐oxo‐ETE were higher in NSAIDs‐ERD than in ATA (p = 0.04). In contrast, baseline 15‐HETE levels in ISS were lower in patients with NSAIDs‐ERD (p = 0.03). After aspirin challenge, 15‐oxo‐ETE levels decreased only in patients with NSAIDs‐ERD (p = 0.001) who developed bronchospasm. In both study groups, there was a reduction in sputum macrophage count after aspirin challenge (p = 0.03 and p = 0.02, respectively) irrespective of bronchospasm.ConclusionsPatients with NSAIDs‐ERD are characterized by higher baseline 15‐oxo‐ETE levels in ISS than patients with ATA. Aspirin‐induced bronchospasm inhibited the local generation of 15‐oxo‐ETE.
BackgroundNonsteroidal anti‐inflammatory drugs–exacerbated respiratory disease (NSAIDs‐ERD) is characterized by altered arachidonic acid (AA) metabolism. Aspirin hypersensitivity is diagnosed using aspirin challenge, while induced sputum is collected to perform cell counts and to identify local biomarkers in induced sputum supernatant (ISS). This study aimed to assess the levels of a newly identified eicosanoid, 15‐oxo‐eicosatetraenoic acid (15‐oxo‐ETE), in ISS at baseline and during aspirin‐induced bronchospasm in patients with NSAIDs‐ERD.MethodsOral aspirin challenge was performed in 27 patients with NSAIDs‐ERD and in 17 patients with aspirin‐tolerant asthma (ATA) serving as controls. Sputum was collected before and after aspirin challenge to determine eosinophil, neutrophil, macrophage, and lymphocyte counts as well as the concentration of AA metabolites via 15‐lipoxygenase‐1 (15‐LOX‐1) and 5‐LOX pathways in ISS. Chromatography–tandem mass spectrometry was used to measure ISS levels of 15‐oxo‐ETE, 15‐hydroxyeicosatetranoic acid (15‐HETE), and leukotriene E4 (LTE4).ResultsAt baseline, ISS levels of 15‐oxo‐ETE were higher in NSAIDs‐ERD than in ATA (p = 0.04). In contrast, baseline 15‐HETE levels in ISS were lower in patients with NSAIDs‐ERD (p = 0.03). After aspirin challenge, 15‐oxo‐ETE levels decreased only in patients with NSAIDs‐ERD (p = 0.001) who developed bronchospasm. In both study groups, there was a reduction in sputum macrophage count after aspirin challenge (p = 0.03 and p = 0.02, respectively) irrespective of bronchospasm.ConclusionsPatients with NSAIDs‐ERD are characterized by higher baseline 15‐oxo‐ETE levels in ISS than patients with ATA. Aspirin‐induced bronchospasm inhibited the local generation of 15‐oxo‐ETE.
Background This study aims to explore the potential of utilizing the expression levels of cannabinoid receptor 2 (CB2), μ-opioid receptor (MOR), MCP-1, IL-17, IFN-γ, and osteopontin as predictors for the severity of SARS-CoV-2 infection. The overarching goal is to delineate the pathogenic mechanisms associated with SARS-CoV-2. Methods Using quantitative Real-time PCR, we analyzed the gene expression levels of CB2 and MOR in nasopharynx specimens obtained from patients diagnosed with SARS-CoV-2 infection, with 46 individuals classified as having severe symptoms and 46 as non-severe. Additionally, we measured the circulating levels of MCP-1, IL-17, IFN-γ, and osteopontin using an ELISA assay. We examined the predictive capabilities of these variables and explored their correlations across all patient groups. Results Our results demonstrated a significant increase in MOR gene expression in the epithelium of patients with severe infection. The expression of CB2 receptor was also elevated in both male and female patients with severe symptoms. Furthermore, we observed concurrent rises in MCP-1, IL-17, IFN-γ, and osteopontin levels in patients, which were linked to disease severity. CB2, MOR, MCP-1, IL-17, IFN-γ, and osteopontin showed strong predictive abilities in distinguishing between patients with varying degrees of SARS-CoV-2 severity. Moreover, we identified a significant correlation between CB2 expression and the levels of MOR, MCP-1, osteopontin, and IFN-γ. Conclusions These results underline the interconnected nature of molecular mediators in a sequential manner, suggesting that their overexpression may play a role in the development of SARS-CoV-2 infections. Graphical Abstract
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