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Effects of Varying Doses of Fluticasone Propionate on the Physiology and Bronchial Wall Immunopathology in Mild-to-Moderate Asthma^*

^* From the Department of Clinical Immunology (Drs. O’Sullivan and Poulter), Royal Free and University College Hospital Medical School, London, UK; and Department of Respiratory Medicine (Mr. Cormican, Ms. Murphy, and Dr. Burke), James Connolly Memorial Hospital, Dublin, Ireland.

Correspondence to: Siobhán O’Sullivan, PhD, Department of Clinical Immunology, Royal Free and University College School of Medicine, Pond St, NW3 2QG, London, UK; e-mail: sioosu{at}indigo.ie

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 µg, 500 µg, or 2,000 µg/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 µg/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 µg/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.

Key Words: dose-response • inflammation • inhaled corticosteroids

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