Effect of inhaled fluticasone propionate on airway responsiveness in treatment-naive individuals--a lesser benefit in females

• Published in: The European respiratory journal Vol. 15; no. 1; pp. 19 - 24
• Main Authors: Convery, RP, Leitch, DN, Bromly, C, Ward, RJ, Bartlett, G, Hendrick, DJ
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01-01-2000; Maney
• Subjects: Administration, Inhalation; Administration, Topical; Adult; Airway Resistance - drug effects; Androstadienes - administration & dosage; Androstadienes - adverse effects; Anti-Asthmatic Agents - administration & dosage; Anti-Asthmatic Agents - adverse effects; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Asthma - diagnosis; Asthma - drug therapy; Biological and medical sciences; Bronchial Provocation Tests; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Respiratory system; Sex Factors; Treatment Outcome; Human; Corticosteroid; Respiratory disease; Treatment efficiency; Antiinflammatory agent; Sex; Exploration; Male; Fluticasone; Antiasthma agent; Asthma; Inhalation; Respiratory tract; Chemotherapy; Reactivity; Treatment; Female; Obstructive pulmonary disease; Comparative study
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00.15101900

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 microg 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.