fluticasone and Pseudomonas-Infections

To determine the concentration of exhaled H(2)O(2) in patients with bronchiectasis, and to study the relationship between levels of exhaled H(2)O(2), extent of disease, symptoms score, spirometry, and cellular composition obtained from induced sputum; furthermore, to account for possible confounding effects of inhaled corticosteroids (ICS) usage, long-term oral antibiotic treatment, and chronic colonization with Pseudomonas aeruginosa.. Cross-sectional study.. Thirty patients with steady-state bronchiectasis.. Mean (95% confidence interval [CI]) exhaled H(2)O(2) levels were significantly elevated in patients with bronchiectasis compared to normal subjects: 1.1 (0.87 to 1.29) microM vs 0.3 (0.19 to 0.36) microM, respectively (p < 0.0001). Patients treated with ICS had similar values as steroid-naïve patients. The group of patients with P aeruginosa colonization showed a significantly increased concentration of H(2)O(2) compared to the group without P aeruginosa colonization. Patients receiving long-term oral antibiotic treatment had significantly higher values of H(2)O(2) compared to those not receiving antibiotics. There was a significant positive correlation between H(2)O(2) and either the percentage of neutrophils in induced sputum or the extent of the disease as defined by high-resolution CT. A significant negative correlation was found between H(2)O(2) and FEV(1) percent predicted. Finally, there was a significant positive correlation between H(2)O(2) and the symptoms score.. Patients with bronchiectasis in stable condition showed increased levels of exhaled H(2)O(2). The above-mentioned levels were not decreased either by ICS or long-term oral antibiotic treatment, but were significantly affected by chronic colonization with P aeruginosa. H(2)O(2) levels could be an indirect index of neutrophilic inflammation, impairment of lung function, and extension and severity of the disease.

Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Bacterial Agents; Breath Tests; Bronchiectasis; Budesonide; Confidence Intervals; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrogen Peroxide; Leukocyte Count; Long-Term Care; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Spirometry; Sputum; Vital Capacity

The purpose of this study was to investigate the effect of the corticosteroid, fluticasone propionate (FP), on Pseudomonas aeruginosa infection of the respiratory mucosa of an organ culture model in vitro. Organ cultures infected with P. aeruginosa had significantly (p< or =0.05) elevated levels of mucosal damage and significantly (p< or =0.05) less ciliated cells compared to controls. Preincubation of tissue with FP (10(-6) or 10(-5) but not 10(-7) M) prior to P. aeruginosa infection significantly (p< or =0.05) reduced the bacterially induced mucosal damage in a concentration-dependent manner. FP (10(-5) M) also significantly (p< or =0.05) prevented loss of ciliated cells. FP did not alter the density of bacteria adherent to the different mucosal features of the organ cultures, but did reduce total bacterial numbers due to the reduced amount of damaged tissue, which is a preferred site of P. aeruginosa adherence. It has previously been shown that the long-acting beta2-agonist salmeterol (4 x 10(-7)M) also reduces the mucosal damage caused by P. aeruginosa infection, probably via elevation of intracellular cyclic adenosine monophosphate concentrations. Preincubation of tissue with both 10(-7)M FP and 10(-7)M salmeterol, concentrations at which they did not by themselves influence the effect of P. aeruginosa infection, significantly (p< or =0.05) reduced P. aeruginosa-induced loss of cilia. However, there was no additional benefit from adding 4 x 10(-7)M salmeterol to 10(-6)M FP. In conclusion fluticasone propionate reduced mucosal damage caused by P. aeruginosa infection in vitro and preserved ciliated cells. There was a synergistic action with salmeterol in the preservation of ciliated cells.

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Bacterial Adhesion; Bronchodilator Agents; Culture Techniques; Dose-Response Relationship, Drug; Fluticasone; Humans; Microscopy, Electron, Scanning; Mucociliary Clearance; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Mucosa; Respiratory Tract Infections; Salmeterol Xinafoate