Effect of inhaled fluticasone with and without salmeterol on airway inflammation in asthma

Wallin, Annika, Sue-Chu, Malcolm, Bjermer, Leif, Ward, Jonathan, Sandström, Thomas, Lindberg, Anne, Lundbäck, Bo, Djukanovic, Ratka, Holgate, Stephen and Wilson, Susan (2003) Effect of inhaled fluticasone with and without salmeterol on airway inflammation in asthma. Journal of Allergy and Clinical Immunology, 112 (1), 72-78. (doi:10.1067/mai.2003.1518).

Abstract

Background: The clinical benefit of combining long-acting ?2-agonists with inhaled corticosteroids rather than doubling the dose of corticosteroid has been well-documented. However, there are concerns that this might result in a masking of underlying airway inflammation.

Objective: The aim of this study was to test the hypothesis that the addition of the long-acting ?2-agonist salmeterol (SALM) to a low dose of the inhaled corticosteroid fluticasone propionate (FP) has a steroid-sparing effect and does not result in a worsening of bronchial inflammation compared to doubling the dose of inhaled corticosteroid.

Methods: Fifty-six asthmatic subjects, previously not well-controlled on inhaled corticosteroids, were randomized to receive 3 months of treatment with inhaled FP 500 ?g twice a day (FP 1000) or FP 200 ?g twice a day plus SALM 50 ?g twice a day (FP 400 + SALM). Fluticasone propionate 200 ?g twice a day served as the control (FP400). Bronchial mucosal biopsy specimens, bronchial washings (BW), and bronchoalveolar lavage were obtained before and after treatment. The primary end points for the study were submucosal mast cell and eosinophil counts.

Results: There was a significant improvement in FEV1 in the FP400 + SALM group compared to both the FP400 and FP1000 groups. This was accompanied by a significant improvement in peak expiratory flow in the FP400 + SALM group in both the morning and evening compared to the FP1000 group. There were no significant between treatment differences in the change in the number of submucosal mast cells or eosinophils. However, in the FP400 + SALM group there was a significant decrease in submucosal mast cells after 12 weeks of treatment. The addition of SALM to FP was not associated with any increases in airway inflammation in the biopsy specimens, bronchoalveolar lavage, or bronchial washings.

Conclusion: These findings confirm that addition of SALM to FP has clinical benefits but does not mask or exacerbate airway inflammation and suggest that long-acting ?2-adrenoceptor agonists might influence mast cell numbers.

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Contributors

Author: Jonathan Ward

Author: Ratka Djukanovic

Author: Susan Wilson

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