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Background: Aspirin desensitization followed by daily aspirin therapy is effective add-on treatment for patients with aspirin-exacerbated respiratory disease. Prior studies used 650 mg of aspirin twice daily, but studies at lower dosages were inconclusive. Objective: We sought to determine the optimal daily dosage of aspirin treatment. Methods: We studied 137 patients who had undergone successful aspirin desensitization and randomized them into 2 groups, 650 mg twice daily versus 325 mg twice daily. After 1 month, patients either increased or decreased their dosage based on their symptom control and continued that dosage for the remainder of the year. Results: Patients taking either 650 mg twice daily or 325 mg twice daily showed significant improvements in number of sinus infections, sinus operations, and hospitalizations for asthma (all P < .0001). Anosmia, nasal/sinus symptoms, and asthma symptoms also improved in both groups (all P < .03). Systemic corticosteroid dosages decreased by 3- and 4-fold in the 325 mg twice daily and 650 mg twice daily groups, respectively. Of the 137 patients, 32 had adverse effects from or discontinued aspirin therapy: 14 (44%) of 32 from the group randomized to taking 650 mg twice daily and 18 (56%) of 32 from the group randomized to 325 mg twice daily. The most common adverse effect was dyspepsia. Conclusion: Both dosages were efficacious, and side effects occurred in both groups at similar frequencies. Some patients initially taking 325 mg twice daily required an increase to 650 mg twice daily for optimal symptom control. Clinical implications: We recommend that patients begin daily aspirin therapy with 650 mg twice daily and subsequently decrease to the lowest effective dosage (usually 325 mg twice daily). [Copyright &y& Elsevier]

Summary: Background: Inhalation of swine house dust induces acute airway inflammation and increased bronchial responsiveness in healthy subjects. Objective: The aim of the study was to investigate whether 5-lipoxygenase products such as leukotrienes may have a role in this reaction. Methods: Twenty-three healthy subjects were randomised into two groups receiving treatment with either zileuton (600mg) or placebo four times a day. After 5 days of treatment, all subjects were exposed for 3h in a swine barn. Bronchial responsiveness, exhaled nitric oxide (NO), and mediators in nasal lavage (NAL), blood and urine were measured before and after the exposure. Results: The exposure induced an increased bronchial responsiveness to methacholine in both groups with 2–3 doubling concentration steps, no significant difference between treatments. Leukotriene E4 in urine increased significantly following exposure in the placebo group from 37.3 (29.1–45.6) (mean (95% confidence interval)) ng/mmol creatinine to 47.7 (36.3–59.0) ng/mmol creatinine (), but not in the zileuton group. The post-exposure increase of LTB4 levels in NAL fluid was totally abolished in the zileuton group ( vs. the placebo). The levels of exhaled NO increased significantly (), two-fold in both groups. The PGD2 metabolite 9α, 11β-PGF2 increased in placebo-treated subjects (; vs. zileuton), strengthening mast cell participation. Neutrophil counts and levels of IL-6 in peripheral blood increased in both groups, with a significantly larger increase in zileuton treated subjects ( and , respectively compared to placebo). Conclusions: Pre-treatment with clinically recommended doses of the 5-lipoxygenase inhibitor zileuton did not affect the increase of bronchial reactivity induced by swine dust exposure. The intervention totally abolished the LTB4 release in NAL fluid, but only partially inhibited the formation of leukotrienes as monitored by urinary levels. The enhanced increase of neutrophils and IL-6 in peripheral blood in the zileuton group, suggests that inhibition of 5-lipoxygenase may have pro-inflammatory effects. [Copyright &y& Elsevier]