leukotriene-d4 and Sinusitis

Aspirin is not only one of the best-documented medicines in the world, but also one of the most frequently used drugs of all times. In addition to its role as an analgesic, aspirin is being increasingly used in the prophylaxis of ischemic heart disease and strokes. The prevalence of aspirin intolerance is around 5 to 6%. Up to 20% of the asthmatic population is sensitive to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) and present with a triad of rhinitis, sinusitis, and asthma when exposed to the offending drugs. This syndrome is referred to as aspirin-induced asthma (AIA). The pathogenesis of AIA has implicated both the lipoxygenase (LO) and the cyclooxygenase (COX) pathways. By inhibiting the COX pathway, aspirin diverts arachidonic acid metabolites to the LO pathway. This also leads to a decrease in the levels of prostaglandin (PG) E(2), the anti-inflammatory PG, along with an increase in the synthesis of cysteinyl leukotrienes (LTs). Evidence suggests that patients with AIA have increased activity of LTC(4) synthase, the rate-limiting enzyme in the cysteinyl LT synthesis, in their bronchial biopsy specimens, thereby tilting the balance in favor of inflammation. LT-modifying drugs are effective in blocking the bronchoconstriction provoked by aspirin and are used in the treatment of this condition. Aspirin desensitization has a role in the management of AIA, especially in patients who need prophylaxis from thromboembolic diseases, myocardial infarction, and stroke. This review covers the latest understanding of pathogenesis, clinical features, and management of AIA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acids; Aspirin; Asthma; Bronchial Hyperreactivity; Cyclooxygenase Inhibitors; Desensitization, Immunologic; Dinoprostone; Drug Hypersensitivity; Glutathione Transferase; Humans; Leukotriene Antagonists; Leukotriene D4; Lipoxygenase; Rhinitis; Sinusitis

Topics: Acetates; Asthma; Bronchi; Cyclopropanes; Humans; Hydroxyurea; Indoles; Leukotriene Antagonists; Leukotriene D4; Lipoxygenase Inhibitors; Membrane Proteins; Phenylcarbamates; Quinolines; Receptors, Leukotriene; Rhinitis; Sinusitis; Sulfides; Sulfonamides; Tosyl Compounds

Eosinophils are multifunctional granulocytes capable of releasing various cytokines, chemokines, and lipid mediators. We previously reported dysregulated fatty acid metabolism in peripheral blood-derived eosinophils from patients with severe asthma. However, functional characteristics of eosinophils present in allergic inflammatory tissues remain largely uncharacterized.. We established a method for isolating CD69. Lipidomic analysis revealed impaired synthesis of prostaglandins and 15-lipoxygenase (15-LOX)-derived mediators, and selective upregulation of leukotriene D. Inflammatory tissue-derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.

Topics: Adult; Arachidonate 15-Lipoxygenase; Blood Donors; Cells, Cultured; Chronic Disease; Cytokines; Eosinophils; Fatty Acids; Female; gamma-Glutamyltransferase; Humans; Leukotriene D4; Male; Middle Aged; Nasal Polyps; Phenotype; Prostaglandin-Endoperoxide Synthases; Proteome; Rhinitis; Signal Transduction; Sinusitis; Transcriptome

Topics: Aspirin; Drug Hypersensitivity; Enzyme-Linked Immunosorbent Assay; Humans; Leukocytes; Leukotriene C4; Leukotriene D4; Leukotriene E4; Rhinitis, Allergic, Perennial; Sensitivity and Specificity; Sinusitis

Chronic sinusitis is a recurrent disorder commonly found in atopic individuals, yet few studies have explored the role of inflammatory mediators in sinusitis. Sinus lavage fluid from ten patients with chronic sinusitis obtained during endoscopic surgery was analyzed for total cell counts and then assayed for histamine, immunoreactive leukotriene C4/D4/E4 (LTC4/D4/E4), and prostaglandin D2 (PGD2). All ten patients had been unresponsive to medical treatment, including oral corticosteroids in most cases. High concentrations of histamine, LTC4/D4/E4 and PGD2 were found in sinus fluid and were comparable to levels seen in nasal secretions of allergic rhinitis patients following allergen challenge. In the sinus fluid, inflammatory cells were predominantly neutrophils with only low percentages of mast cells, basophils or eosinophils. On the basis of the histamine and PGD2 concentrations in sinus fluid, we conclude that mast cell/basophil activation does occur in chronic sinusitis and may contribute to the persistent inflammation present in sinusitis.

Topics: Adolescent; Adult; Aged; Basophils; Body Fluids; Cell Count; Cell Degranulation; Child; Chronic Disease; Female; Histamine; Humans; Leukotriene C4; Leukotriene D4; Leukotriene E4; Male; Mast Cells; Middle Aged; Prostaglandin D2; Sinusitis; Therapeutic Irrigation