Nedocromil sodium and airway inflammation in vivo and in vitro.

We conducted a series of studies investigating the antiinflammatory effects of nedocromil sodium, with particular reference to its effects on human bronchial epithelial cells and eosinophils in vitro and on eosinophils in vivo. Nedocromil sodium produced a dose-related inhibition of ozone-induced IL-8 release from human bronchial epithelial cells and also attenuated the release of granulocyte macrophage colony-stimulating factor, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule 1. The culture medium from human bronchial epithelial cell cultures, containing the proinflammatory cytokines IL-8, granulocyte macrophage colony-stimulating factor, "regulated on activation, normal T expressed and secreted," IL-1 beta, and tumor necrosis factor-alpha, increased eosinophil chemotaxis and eosinophil adhesion to cultured human endothelial cells. The chemotaxis and increased adhesion were blocked in the presence of nedocromil sodium. The drug also abrogated the epithelial cell dysfunction (assessed as ciliary beat frequency) induced by the presence of activated eosinophils and blocked the release of eosinophil cationic protein from the eosinophils. We also conducted a double-blind placebo-controlled study of the effects of regular albuterol 200 micrograms or nedocromil sodium 4 mg, both given four times daily for 16 weeks, on inflammatory cell numbers in bronchial biopsy and bronchoalveolar lavage samples. Assessed in terms of total and activated eosinophils in biopsy samples, inflammation decreased with nedocromil sodium and was significantly different from a deterioration with albuterol, although neither of these changes was significantly different from that with placebo treatment. Levels of eosinophil cationic protein in bronchoalveolar lavage samples showed a similar trend.

Effect of six-hour exposure to nitrogen dioxide on early-phase nasal response to allergen challenge in patients with a history of seasonal allergic rhinitis.

BACKGROUND: Recent studies have suggested that exposure to air pollutants may enhance the airway responsiveness of susceptible individuals to inhaled allergen. METHODS: To investigate the effect of exposure to nitrogen dioxide (NO2) on nasal airways resistance (NAR) and inflammatory mediators in nasal lavage fluid, eight subjects with a history of seasonal allergic rhinitis, who were tested out of season, were exposed in a randomized single-blind, crossover study to either air or 400 ppb NO2 for 6 hours. The changes in NAR and eosinophil cationic protein (ECP), mast cell tryptase (MCT), neutrophil myeloperoxidase (MPO), and interleukin-8 (IL-8) in nasal lavage fluid before and after exposure were evaluated. Another group of eight subjects with a history of seasonal allergic rhinitis were also randomized to exposure to air or 400 ppb NO2 for 6 hours and then challenged with allergen, before evaluation for changes in NAR and changes in ECP, MCT, MPO, and IL-8 in nasal lavage fluid. RESULTS: Exposure to air or NO2 did not alter either NAR or the levels of ECP, MCT, MPO, or IL-8 in nasal lavage fluid. Allergen challenge after exposure to both air and NO2 significantly (p < 0.05) increased levels of MCT, but not MPO and IL-8 in the nasal lavage fluid. In addition, allergen challenge after exposure to NO2 but not air, significantly increased levels of only ECP in nasal lavage fluid (p < 0.05). CONCLUSIONS: These results suggest that acute exposure to NO2 at concentrations found at the curbside in heavy traffic during episodes of pollution, may "prime" eosinophils for subsequent activation by allergen in individuals with a history of seasonal allergic rhinitis.

Nitrogen dioxide increases eosinophil activation in the early-phase response to nasal allergen provocation.

Recent studies have suggested that exposure to air pollutants may sensitise susceptible individuals to allergen. We have investigated the effect of exposure for 6 h to 400 ppb NO2 on nasal airways resistance (NAR) and changes in inflammatory mediators (IMs) in nasal lavage in subjects with a history of seasonal allergic rhinitis. In this single blind crossover study, 8 patients were randomised to exposure to either air or 400 ppb NO2 in air and evaluated for changes in NAR and IM, before and after exposure. Another 8 patients were further challenged with allergen after similar exposure regimes and then evaluated for changes in NAR and IMs. Exposure to air or NO2 did not alter either NAR or the levels of eosinophil cationic protein (ECP), mast cell tryptase (MCT), myeloperoxidase (MPO) or interleukin (IL)-8 in nasal lavage. MCT was significantly increased after allergen challenge following exposure to both air and NO2. In contrast, ECP was significantly increased by allergen challenge only after exposure to NO2. Neither MPO nor IL-8 were altered after allergen challenge. These results suggest that NO2 may increase eosinophil activation in the early-phase response to nasal allergen provocation in allergic rhinitis.

The effects of topical fluticasone propionate on allergen-induced immediate nasal airways response and eosinophil activation: preliminary results.

Nasal application of grass pollen allergen in atopic individuals with seasonal rhinitis leads to an early rise in nasal airways resistance. The effects of fluticasone propionate, a powerful, topically active glucocorticosteroid, on nasal airways resistance and cellular infiltration of the nasal mucous membrane were investigated. Fluticasone propionate blunted the rise in nasal airway resistance following allergen challenge (P = 0.089). Although this glucocorticosteroid did not affect the total number of eosinophils in biopsies of nasal mucous membrane, the number of activated eosinophils was significantly reduced (P less than 0.05).