Effects of varying doses of fluticasone propionate on the physiology and bronchial wall immunopathology in mild-to-moderate asthma

Objectives: Inhaled corticosteroids (ICS) are typically associated with a flat dose-response curve when traditional efficacy values are examined (eg, FEV1). The aim of the present study was to investigate if a dose-response relationship exists for lung function and inflammatory cell numbers in bronchial biopsy specimens. Methods: Bronchial biopsy specimens were obtained from 36 patients randomized to receive 100 mug, 500 mug, or 2,000 mug/d of fluticasone propionate (FP). Lung physiology and bronchial biopsies were performed at baseline and after 2 weeks of treatment. Results: Improvement in lung function and suppression of airway inflammation were optimal at a dose of 500 mug/d of FP. Significant changes from baseline following treatment were documented in FEV1 (p=0.02), forced expiratory flow (p=0.002), FEV1/FVC (p=0.007), provocative concentration of histamine causing a 20% fall in FEV1 (PC20) [p=0.02], T-cell numbers (p=0.0005), activated eosinophils (p=0.01), and numbers of macrophages (p=0.01) in the group treated with 500 mug/d of FP. Comparison between groups administered different doses of FP failed to demonstrate a dose-response relationship for change from baseline in PC20 (p=0.43), any of the lung function parameters, T-cell numbers (p=0.64), activated T cells (p=0.46). eosinophils (p=0.53), activated eosinophils (p=0.48), or macrophage numbers (p=0.68). Conclusion: The apparent lack of a dose-response for ICS treatment in patients with asthma further validates the preferential use of add-on therapy over increasing the dose of ICS.