leukotriene-c4 and Rhinitis

Topics: Arachidonic Acid; Aspirin; Asthma; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Inflammation; Leukotriene C4; Nasal Polyps; Prostaglandin-Endoperoxide Synthases; Rhinitis; Sinusitis

Twenty five years after the structure elucidation of slow reacting substance of anaphylaxis, antileukotrienes are established as a new therapeutic modality in asthma. The chapter reviews the biochemistry and pharmacology of leukotrienes and antileukotrienes with particular focus on the different usage of antileukotrienes for treatment of asthma and rhinitis in Europe and the US. Further research needs and new areas for leukotriene involvement in respiratory diseases are also discussed.

Topics: Acetates; Animals; Asthma; Clinical Trials as Topic; Cyclopropanes; Humans; Hydroxyurea; Leukotriene Antagonists; Leukotriene C4; Leukotriene D4; Leukotriene E4; Lipoxygenase Inhibitors; Membrane Proteins; Quinolines; Receptors, Leukotriene; Respiratory System; Rhinitis; Sulfides

This study investigated the early, prolonged immediate, and late-phase reactions of dust-mite-sensitive subjects undergoing long-term challenge in the Vienna challenge chamber (VCC) in terms of clinical symptoms and inflammatory mediator level patterns in nasal lavage fluids. A concentration of 70 ng Der p 1/m3 of air (feces of Dermatophagoides) was maintained over 8 h in the VCC. To show the clinical impact of this challenge model, the effect of a histamine H1-receptor antagonist that also has some antiallergic properties (loratadine) was also investigated. The study followed a double-blind, placebo-controlled, crossover design. Medication was given orally over 7 days before the provocation at a dose of 10 mg once daily. All 12 patients, whose dust-mite sensitivity was confirmed by disease history, skin prick test, and RAST, completed the challenge session. The documentation of the chosen parameters was performed every 30 min. Subjective nasal and ocular symptoms were assessed via a visual analog scale of 100 mm, nasal flow was recorded by active anterior rhinomanometry, and mediator release was evaluated with nasal lavages. Clinical aspect: the whole sample population showed a rise of nasal and ocular symptom severity and a nasal flow reduction, which were perceptibly, but not significantly attenuated by active drug treatment. Mediator pattern: in each patient, prostaglandin (PG)D2 and leukotriene (LT)C4 levels peaked within the first 2 h of provocation, PGD2 then moving toward baseline levels, and LTC4 then again rising continuously. Eosinophil cationic protein (ECP) exhibited a constant level increase over the whole provocation period, and tryptase levels did not change significantly. Whereas the area under the curve values of tryptase and ECP were higher in drug-treated patients than the placebo group, the early PGD2 peak occurring during the first two challenge hours seemed to be mitigated by loratadine. These results reveal that there is no link between the clinical symptoms, the drug efficacy, and the released mediators (LTC4, PGD2, ECP, and tryptase).

Topics: Adult; Antigens, Dermatophagoides; Blood Proteins; Bronchial Provocation Tests; Chymases; Cross-Over Studies; Double-Blind Method; Eosinophil Granule Proteins; Eye Diseases; Female; Glycoproteins; Histamine H1 Antagonists; Humans; Inflammation Mediators; Leukotriene C4; Loratadine; Male; Nasal Lavage Fluid; Pilot Projects; Prostaglandin D2; Radioallergosorbent Test; Respiratory Hypersensitivity; Rhinitis; Ribonucleases; Serine Endopeptidases; Skin Tests; Tryptases

A role of prostaglandins (PGs) and leukotrienes (LTs) in the pathogenesis of nasal polyps has been recently suggested. Cyclooxygenase (CO) products (thromboxane B2, PGE2 and 6-keto PGF1 alpha) and lipoxygenase (LO) products (LTB4 and LTC4) were investigated by radioimmunoassay in polyps, hypertrophic turbinates and nasal mucosa from 14 patients with non-allergic (n = 6), allergic chronic rhinitis (n = 6) and aspirin-sensitive asthma (ASA) (n = 2), who underwent polypectomy. In all tissues CO metabolite levels were found higher than LO products (P < 0.01). Nasal polyps showed a significantly lower (P < 0.05) arachidonic acid (AA) metabolism in comparison to nasal mucosa. In polyps of allergic patients significantly higher LTB4 levels (P < 0.001) and a tendency to produce higher amounts of CO products in comparison to non-allergic subjects were observed, whereas in turbinates of non-allergic patients LT levels were significantly higher in comparison to those of allergic ones (P < 0.01). In ASA patients a decreased CO/LO ratio was found supporting the hypothesis of an imbalance of AA metabolism in this syndrome. These findings seem to indicate that the occurrence of nasal polyps may represent the result of different chronic inflammatory stimuli, regulated in part by AA metabolites.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acid; Asthma; Dinoprostone; Humans; Leukotriene B4; Leukotriene C4; Lipoxygenase; Middle Aged; Nasal Mucosa; Nasal Polyps; Prostaglandin-Endoperoxide Synthases; Rhinitis; Thromboxane B2; Turbinates