In-vitro data suggest that long-acting b 2 -agonists may have a neutrophilstabilising effect. A reduction in airway wall eosinophil number following introduction of salmeterol in persistent asthma has previously been described. There is currently interest in the "neutrophil system" in asthma, and thus the aim of the present study was to investigate the effect of salmeterol on interleukin (IL)-8, neutrophils and myeloperoxidase (MPO) in persistent asthma.In the same 12-week double-blind parallel-group placebo-controlled study as described previously, the effects on bronchoalveolar lavage fluid (BALF) IL-8, neutrophils and MPO of introducing salmeterol (50 mg b.i.d.) or giving additional inhaled corticosteroid (fluticasone 100 mg b.i.d.) in 45 subjects with persistent asthma already on low/moderate doses of inhaled corticosteroids were further investigated.At baseline, BALF IL-8 but not neutrophil or MPO levels were significantly raised in the asthmatic subjects compared to normal controls. MPO levels correlated strongly with IL-8 levels, and weakly with BALF neutrophil numbers in the asthmatics. Fluticasone treatment resulted in significantly elevated neutrophil numbers, but not MPO or IL-8 levels. In contrast, introducing salmeterol significantly reduced IL-8 and MPO levels, but did not affect BALF neutrophil numbers. Interestingly, salmeterol and fluticasone showed significantly contrasting effects on MPO and neutrophils, and there was a divergent effect on IL-8 levels that almost reached significance.Excessive interleukin-8 levels may be relevant to asthma pathogenesis, even in the setting of moderate-dose inhaled corticosteroid therapy. Reduction in interleukin-8 production and possibly stabilisation of airway neutrophil numbers may explain the greater clinical benefit of adding a long-acting b 2 -agonist rather than merely increasing inhaled corticosteroid doses. Indeed, high-dose inhaled corticosteroid therapy alone may promote airway neutrophilia. Asthma is characterised by airway inflammation, bronchial hyperresponsiveness and reversible airflow obstruction. The asthmatic inflammatory response consists of infiltration into the airway of a variety of activated inflammatory cells with release of mediators of asthma pathophysiology. The eosinophil has an established role as an effector cell in asthma but the pro-inflammatory role of other granulocytes, in particular the neutrophil, remains less well defined [1,2].Increased numbers of airway neutrophils have been described in severe steroid-dependent asthma, during acute exacerbations and in cases of sudden-onset fatal disease [3][4][5]. An increase in neutrophil activation, but not numbers, in mild chronic asthma has previously been shown [6]. The role of airway neutrophils in the pathogenesis of persistent asthma despite mild/moderate inhaled corticosteroid (ICS) doses has not been established. However, more recent data confirm considerable heterogeneity of the asthma phenotype and many subjects may exhibit an airway disease characterised by sputu...