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...

Background -To assess the possible magnitude of differences between normal populations an epidemiological investigation ofasthma was conducted in two strongly contrasting districts of northern England -rural West Cumbria on the west coast and urban Newcastle upon Tyne on the east coast. Methods -A cross sectional survey of randomly identified men aged 20-44 years was conducted in two phases: phase 1, a postal survey of respiratory symptoms and asthma medication in 3000 men from each district; and phase 2, a clinical assessment of 300 men from each district comprising investigator administered questionnaires, skin prick tests, spirometry, and methacholine challenge tests. Results -The phase 1 (but not phase 2) study showed a small excess of "ever wheezed" in Newcastle (44% versus 40%), but neither phase showed differences between the two districts for recent wheeze or for other symptoms characteristic of asthma. There were also no differences with regard to diagnosed asthma, current asthma medication, spirometric parameters, or airways responsiveness. The prevalence of quantifiable airways responsiveness (PD20 < 6400 dg) was 27 7% in West Cumbria and 28-2% in Newcastle. Regression analyses showed that PD20 was negatively associated with atopy and positively with forced expiratory volume in one second (FEV,); that an association between PD20 and current smoking could be explained by diminished FEV,; and that PD20 was not related to geographical site of residence. Conclusions -Neither airways responsiveness nor the other parameters of diagnostic relevance to asthma varied much between the two study populations, despite the apparent environmental differences. The most obvious of these were the levels of outdoor air pollution attributable to vehicle exhaust emissions, the ambient levels of which were 2-10 fold greater in Newcastle. Our findings consequently shed some doubt over the role of such pollution in perceived recent increases in asthma prevalence. It is possible, however, that an air pollution effect in Newcastle has been balanced by asthmagenic effects of other agents in West Cumbria. (Thorax 1996;51:169-174) Keywords: asthma, epidemiology, airways responsiveness, air pollution.There is concern at present over reported increases in asthma symptoms, diagnosis, medication, sickness absence, hospital admission, and death.'-7 These apparent increases in morbidity and mortality have occurred despite advances in the understanding and management of the disease,89 and despite diminishing morbidity and mortality from other diseases amenable to effective preventive and therapeutic intervention.'0 A plausible and popular explanation is that the incidence of asthma is increasing, though trends may have been exaggerated by changes in diagnostic fashion."Migration and twin studies have shown that asthma is largely an acquired disease determined by environmental factors. 1-14 A logical step towards their elucidation is standardised investigation of populations living under different environmental conditions. Al...

To clarify whether asthma may be caused by fume from welding mild steel and to evaluate the possible strength of such an effect, we quantified airway responsiveness among young shipyard workers with different levels of fume exposure. Clinical investigation comprised a cross-sectional survey of 19- to 27-yr-old workers who were completing 3 to 9 yr of employment in various trades, and a control group of 15- to 17-yr-old school leavers who were applying for apprenticeships within the same trades. Both groups were subdivided into negligible-, ambient-, or high-exposure subgroups according to expected levels of fume exposure. Actual exposures were assessed in a parallel environmental survey. Participants were investigated by questionnaire, skin prick tests, spirometry, and methacholine tests. Complete data sets were obtained from 1,024 of the 1,070 eligible subjects (96%). Among the workers but not the school leaver controls, there was an increasing prevalence of positive methacholine tests across the exposure subgroups-negligible 37%, ambient 44%, high 49% (p < 0.05). Regression analyses showed that in males after allowing for the effects of atopy, current smoking, and age, the estimated geometric mean level of airway responsiveness of regular welders was twice that of workers with negligible exposure after 5 yr of work. This implies that fume exposure may have been critical in causing asthma in about 1% of the welders. A lesser effect (though not significantly so) was noted among the workers with ambient exposure.

Conclusions -If airways responsiveness is related to dietary sodium the relationship is not likely to be strong. (Thorax 1995;50:941-947)