Asthma, Rhinitis, other Respiratory Diseases
Effect of inhaled fluticasone with and without salmeterol on airway inflammation in asthma,☆☆

https://doi.org/10.1067/mai.2003.1518Get rights and content

Abstract

Background: The clinical benefit of combining long-acting β2-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 β2-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 μg twice a day (FP 1000) or FP 200 μg twice a day plus SALM 50 μg twice a day (FP 400 + SALM). Fluticasone propionate 200 μg 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 β2-adrenoceptor agonists might influence mast cell numbers. (J Allergy Clin Immunol 2003;112:72-8.)

Section snippets

Study design

This was a randomized double-blind, parallel group, control study, which comprised a 2- to 4-week run-in period followed by a 12-week treatment period conducted outside the pollen season. During the run-in period and after treatment, a methacholine bronchial provocation test and fiberoptic bronchoscopy were undertaken. After the first bronchoscopy the subjects were randomized to receive FP 200 μg twice a day (FP 400), 500 μg twice a day (FP 1000), or 200 μg twice a day together with SALM 50 μg

Results

Baseline characteristics of the subjects in the 3 groups were evenly distributed with respect to gender, asthma duration, measures of pulmonary function, and reversibility. For the baseline PC20 there was a significant difference (P < .05) between the subjects randomized to FP 1000 when compared with FP400 (Fig 1).

Fifty-six subjects were randomized, of which 51 underwent both bronchoscopies. Of the 5 who failed to complete the study, 2 were withdrawn because of an asthma exacerbation (FP 1000

Discussion

The present study was designed to test the hypothesis that the addition of the long-acting β2-agonist SALM to a low dose of the inhaled corticosteroid FP has a steroid-sparing effect and does not result in a worsening of bronchial inflammation compared to doubling the dose of inhaled corticosteroid.

By using objective measures of pulmonary function the present study has confirmed previous observations11, 12, 13, 14, 15, 16 that the addition of the long-acting β2-agonist SALM to a low dose of FP

Acknowledgements

We would like to thank Kevin Kane (GlaxoSmithKline) for undertaking the statistical analysis of the clinical data.

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    Supported by a grant from Glaxo Wellcome R&D, United Kingdom.

    ☆☆

    Reprint requests: Susan Wilson, PhD, Infection, Inflammation and Repair, Mailpoint 810 (RCMB), Level D, Centre Block, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.

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