Inhaled corticosteroids are now first-line therapy for most patients with asthma. However, it has been shown that there is ongoing airway inflammation and airway hyperresponsiveness even in the presence of low dose inhaled corticosteroids. To ensure a maximal therapeutic potential we investigated the effect of 3 mo of a very high dose of a new inhaled corticosteroid, fluticasone propionate (FP) (equivalent to 4,000 micrograms daily of beclomethasone dipropionate [BDP]. Twenty asthmatics with mild-to-moderate disease were recruited into this single-blind study. Baseline data were compared with those from 26 normal subjects. Differences in inflammatory indices between asthmatics and normal subjects were detected in both BAL and endobronchial biopsies. After the FP treatment period there was a significant improvement in symptom scores, lung function, and airway responsiveness by a mean 2.8 doubling dilutions of methacholine. Reduction in the airway lymphocyte load and lymphocyte activation was demonstrated and is likely to be an important mechanism mediating the effects of inhaled corticosteroids. Decreased mast cell numbers and activity in atopic asthma suggest that corticosteroids may have additional targets in different types of asthma. Reduced lymphocyte and mast cell activity was found with high dose FP even in those receiving low dose maintenance BDP prior to the study, suggesting a dose-response effect of inhaled corticosteroids on airway inflammation. BAL eosinophilia was still present after FP, indicative of a component of asthmatic airway inflammation that is relatively resistant to corticosteroid therapy.

Background-Beta-2 agonists protect against non-specific bronchoconstricting agents such as methacholine, but it has been suggested that the protection afforded by long acting P)2 agonists wanes rapidly with regular treatment. Methods-The changes in airway responsiveness were investigated during and after eight weeks of regular treatment with salmeterol 50 ug twice daily in 26 adult asthmatic patients, 19 of whom were receiving maintenance inhaled corticosteroids. The study was of a randomised, placebo controlled, double blind design. Airway responsiveness to methacholine was measured as PD,0 by a standardised dosimeter technique 12 hours after the first dose, at four weeks and eight weeks during treatment (12 hours after the last dose of test medication), and at 60 hours, one week and two weeks after stopping treatment. Results-There were no significant differences between the baseline characteristics of the two groups. A significant improvement in PD20 was seen at all points during treatment with salmeterol compared with the placebo group, with no significant fall off with time. PD20 measurements returned to baseline values after cessation of treatment with no significant difference from the placebo group. Conclusions-Salmeterol gave significant protection against methacholine induced bronchoconstriction 12 hours after administration. This protection was of small magnitude, but there was no significant attenuation with eight weeks of regular use and no rebound increase in airway responsiveness on stopping treatment in a group of moderate asthmatic patients, the majority of whom were receiving inhaled corticosteroids.

We quantified the influence of lapsed time, measurement of gas-transfer factor (TLCO), and passive smoking on expired carbon monoxide (CO) levels, and then evaluated the accuracy of smoking histories against expired CO measurements in patients newly attending 'occupational' compared with 'general' chest clinics. Expired CO levels had an estimated average rate of decline of 3.4 ppm/h in the presumed absence of further smoking, though individual rates depended necessarily on the initial levels (2.1, 3.9, 5.7 and 7.5 ppm/h, respectively, when the initial levels were 10, 20, 30 and 40 ppm). TLCO measurement was associated with a median increase in expired CO of 4.0 ppm, but passive exposure to tobacco smoke in non-smokers had negligible effect. Expired CO levels indicative of current smoking (> 8 ppm) were noted much more commonly in the current cigarette smokers (88%) than those who claimed to be current non-smokers (6.0%), but without significant difference between the non-smokers attending the occupational and general clinics (6.6% vs 5.3%). We conclude that the lapse of 1 h and the measurement of TLCO exert mild but important influences on the expired CO level, but that passive smoking does not. 'Occupational' and 'general' patients give similarly false declarations of current non-smoking when presenting initially for clinical evaluation.

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