Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma.

The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV1) 94% predicted), steroid doses (800 microg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV1 and peak expiratory flow decreased in both groups (p<0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p<0.05). Night-time symptoms were slightly elevated with placebo (p<0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation.

In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation.

Systemic corticosteroids have been recommended as a therapeutic option in patients with moderate to severe COPD. In an early stage of the disease, i.e. chronic bronchitis with mild or no airflow obstruction, a trial with inhaled steroids could reveal potential benefits, particularly in terms of a modulation of airway inflammation. We therefore investigated the effect of inhaled fluticasone (1000 microg day(-1)) on markers of airway inflammation in 19 patients with chronic bronchitis (mean+/-SEM FEV1, 83.4+/-3.0% predicted; FEV1/VC, 67.5+/-2.4%) in a double-blind, cross-over, placebo-controlled manner. Visits were performed before and after two 4-week treatment periods. separated by a 4-week washout period. Lung function, the concentration of exhaled nitric oxide, differential cell counts in induced sputum and the number of cells positive for iNOS, as well as the levels of LDH, ECP, neutrophil elastase and IL-8 in sputum supernatants were determined. Although the total cell number decreased significantly after fluticasone (geometric mean 12.3 vs. 7.7 x 10(6)/ml; P<0.05) it was not significantly different from the change observed after placebo (14.2 vs. 10.6 x 10(6)/ml; n.s.). None of the other parameters showed statistically significant changes after fluticasone or placebo and the results did not depend on the presence of airway hyperresponsiveness. We conclude that in patients with chronic bronchitis short-term treatment with inhaled corticosterids did not improve lung function or inflammatory parameters to an extent which was statistically significant as compared to spontaneous variability.

The concentration of hydrogen peroxide in exhaled air depends on expiratory flow rate.

Hydrogen peroxide (H2O2) is known to be detectable in exhaled air. The present study aimed to determine whether the concentration of exhaled H2O2 depends on expiratory flow rate in order to make inferences on the site of its production within the lung. Breath condensate was collected in cooled Teflon tubes, at three different expiratorv flow rates, in 15 healthy or mild asthmatic subjects. Tests were repeated 2-5 times to assess reproducibility. Mean+/-SEM concentrations of H2O2 at flow rates of 140, 69 and 48 mL.s(-1) were 0.12+/-0.02, 0.19+/-0.02 and 0.32+/-0.03 microM, respectively. These values differed significantly from each other (p<0.001). For comparison, average coefficients of variability within repeated measurements at each of the three flow rates were 68, 62 and 82%, respectively. These data demonstrate that the concentration of exhaled hydrogen peroxide depends on expiratory flow rate. Since flow dependence is an indicator of production within the airways, this result suggests that, to a large extent, the exhaled hydrogen peroxide originates within the airways. However, even under strictly controlled conditions, a high degree of variability persists, which may limit the usefulness of exhaled hydrogen peroxide as a marker of airway inflammation.