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1 Lung Pathology Unit, Dept of Gene Therapy, National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, UK. 2 Asthma Research Centre, University of Uppsala, Uppsala, Sweden. 3 University Hospital, Dept of Pulmonary Medicine, Gentofte, Denmark. 4 University Hospital, Dept of Pulmonary Medicine, Aarhus, Denmark
CORRESPONDENCE: P.K. Jeffery, Lung Pathology, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. Fax: 44 20 73518435. E-mail: p.jeffery@ic.ac.uk
Keywords: asthma, biopsy, inflammation, neutrophil, salmeterol xinafoate
Received: April 26, 2002
Accepted July 12, 2002
This study was supported by GlaxoSmithKline Research & Development Ltd, London, UK.
Although the anti-inflammatory effects of inhaled corticosteroids in the treatment of asthma are established, the effects of long-acting ß2-adrenergic receptor agonists on inflammation are the subject of debate. The aim of the present study was to determine the effect of salmeterol on the numbers of inflammatory cells in biopsy samples of distinct immunophenotype and those expressing the genes for interleukin-4 and -5, regulatory cytokines particularly relevant to asthma.
Twenty patients (aged 18–55 yrs) with mild stable asthma were randomised in a three-way crossover study to 6 weeks of treatment with: 1) salmeterol (50 µg b.d.; SM50); 2) fluticasone propionate (250 µg b.d.; FP250), or 3) placebo.
Compared with placebo, SM50 significantly reduced the numbers of neutrophils in bronchial biopsy samples and the concentrations of myeloperoxidase and soluble E-selectin in serum, each of which reflect neutrophil involvement. Compared with FP250, SM50 reduced neutrophil number and human neutrophil lipocalin level in bronchial lavage fluid and intercellular adhesion molecule-1 level in bronchoalveolar lavage fluid. Compared with placebo, FP250 significantly reduced the numbers of (CD3+) T-lymphocytes, (CD4+) T-helper cells, (CD45RO+) activated T-helper cells and eosinophils in the biopsy samples; it also reduced the percentage of eosinophils and soluble intercellular adhesion molecule-1 in serum. The percentage of symptom-free days and nights and airways hyperresponsiveness improved significantly after SM50 compared to both placebo and FP250.
In conclusion, a novel antineutrophilic effect of the inhaled long-acting ß2-adrenergic receptor agonist, salmeterol, in mild asthma is reported.
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