A randomized double-blind placebo-controlled parallel group study with inhaled fluticasone propionate over 6 weeks, designed to quantify the beneficial effect on airway responsiveness, and so assess whether short pulses of intermittent prophylactic treatment might serve as an alternative means of managing mild asthma, is reported.The 20±50-yr-old participants, who were recruited from an epidemiological study of the general population, had never knowingly received any regular treatment for asthma. Fluticasone propionate at the maximum recommended dose level (2,000 mg daily) and placebo were administered via metered-dose inhalers, and airway responsiveness was quantified conventionally by the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20) at 2-week intervals during the treatment phase and at various intervals subsequently.Compared with placebo fluticasone propionate was associated with a highly significant decrease in airway responsiveness (1.9 doublings of the geometric mean PD20), which was maximal at the end of the 6-week treatment period. No persisting benefit was detectable at the next measurement 2 weeks later, or thereafter. Multiple linear regression analysis showed that the magnitude of the fluticasone propionate effect was significantly greater in males than in females (3.2 versus 1.2 doublings respectively of the geometric mean PD20), but was uninfluenced by current smoking, age or FEV1.In conclusion, in the absence of any possibility of tachyphylaxis, inhaled fluticasone propionate at this dose causes a steadily increasing improvement in airway responsiveness over a 6-week period, which is modified by sex but lost almost immediately on treatment cessation. Short pulses of intermittent prophylactic treatment would not, therefore, be useful as a means of managing mild asthma. Eur Respir J 2000; 15: 19±24. In an epidemiological study of a normal population of males and females many subjects were identified in whom airway responsiveness could be quantified but who had never knowingly received corticosteroid treatment, whether for asthma or other diseases, nor knowingly received any regular medication for asthma for >3 months [1]. The majority were not recognized to have (or to have had) asthma. Volunteers from among them were sought to evaluate the effect on airway responsiveness of inhaled fluticasone propionate, a potent topical steroid thought to have an enhanced benefit-risk ratio because of a high level of "first pass" hepatic metabolism and low oral bioavailability [2].The aim of this study was to quantify the effect of 6 weeks treatment at the maximum recommended dose by its peak and duration over the following 20 weeks. It was wondered whether short "pulses" of intermittent prophylactic treatment might offer an alternative means of management of mild asthma (or a means of preventing 'subclinical asthma' from becoming symptomatic) if the initial effect was sufficiently strong and sufficiently prolonged. The secondary aims were to...

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.