ASTHMA

Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma

J G Koopmans¹, R Lutter², H M Jansen¹, J S van der Zee¹

¹ Department of Pulmonology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
² Laboratory of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Correspondence to:
Dr J S van der Zee
Academic Medical Center, Department of Pulmonology, F4-208, P O Box 22700, 1100 DE Amsterdam, The Netherlands; j.s.vanderzee{at}amc.uva.nl

Background: Addition of the long acting ß₂ agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma.

Methods: After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 µg with or without salmeterol 50 µg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 µg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period.

Results: Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p<0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p>0.05). However, adding salmeterol significantly reduced sputum ratios of ₂-macroglobulin and albumin during the treatment period (p = 0.001).

Conclusions: The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting ß₂ agonist is combined with inhaled corticosteroids.

Abbreviations: ECP, eosinophil cationic protein; FEV₁, forced expiratory volume in 1 second; IL, interleukin; MPO, myeloperoxidase; PC₂₀histamine, concentration of histamine provoking a fall in FEV₁ of at least 20%; RCE_s, relative coefficient of excretion in induced sputum

Keywords: asthma; inflammation; sputum; bronchodilator agents; anti-inflammatory agents

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