The long‐acting β2‐agonist salmeterol xinafoate: effects on airway inflammation in asthma

Abstract

Salmeterol xinafoate is an inhaled long-acting beta2-adrenoceptor agonist recently introduced for the treatment of asthma. Both in vitro and animal studies suggest that it may have anti-inflammatory activities of benefit in this disease. To assess this directly, the effects of 6 weeks' treatment with salmeterol on indices of clinical activity, airway dysfunction and inflammation in subjects with stable atopic asthma were investigated. In a double blind study, asthmatic patients were randomized to 6 weeks' treatment with either salmeterol 50 microg twice daily (n=14) or placebo (n=12). They underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy immediately before starting treatment and again after 6 weeks. Treatment with salmeterol improved clinical indices of asthma activity, but there were no changes in BAL differential cell counts or mediator levels, and no change in T-cell numbers or activation status. In the biopsy specimens there were no changes in numbers of inflammatory cells, sub-basement membrane collagen deposition or mast cell degranulation. Regular treatment with salmeterol improves clinical indices of asthma but has no effect on the underlying inflammatory process. These findings strengthen guideline recommendations that long-acting beta2-agonists should not be prescribed as sole antiasthma medication.

Effects of fluticasone vs. fluticasone/salmeterol on airway calibre and airway hyperresponsiveness in mild persistent asthma

“…This in turn can be quantified from methacholine bronchoprovocation. The superiority of FP/SM vs. FP alone on AHR is therefore likely to be explained by an additive airway stabilizing effect, since SM has been shown to have no clinically meaningful in vivo anti-inflammatory activity [12][13][14]. This would also be consistent with the same trend showing superiority of FP/SM vs. FP on measures of airway calibre.…”

Long-Acting β2-Adrenoceptor Agonists Synergistically Enhance Glucocorticoid-Dependent Transcription in Human Airway Epithelial and Smooth Muscle Cells

“…Explanations for this effect include two generic possibilities: 1) LABAs and ICS activate distinct processes to produce additive effects; 2) LABAs and ICS activate processes that combine to produce common synergistic effects. In this context, LABAs, as a monotherapy in vivo are not considered to be anti-inflammatory, which argues against mechanisms that combine to elicit additive effects (Roberts et al, 1999;Howarth et al, 2000). In contrast, exacerbation rates and asthma severity are reduced to a greater extent in asthmatics taking formoterol/budesonide combination than in those patients taking budesonide alone (Pauwels et al, 1997).…”

Effects of salmeterol on mucosal inflammation in asthma: a placebo-controlled study

“…An early study of salmeterol in mild asthma demonstrated no pro-inflammatory effect on either bronchoalveolar lavage (BAL) fluid differential cell counts or inflammatory cell numbers in biopsy samples [12]. A study of formoterol, another long-acting b 2 -agonist, in asthmatics, even demonstrated a reduction in the number of biopsy mast cells [13].…”