In adolescents and adults with sub-optimal control on low dose ICS monotherapy, the combination of LABA and ICS is modestly more effective in reducing the risk of exacerbations requiring oral corticosteroids than a higher dose of ICS. Combination therapy also led to modestly greater improvement in lung function, symptoms and use of rescue ß2 agonists and to fewer withdrawals due to poor asthma control than with a higher dose of inhaled corticosteroids. Apart from an increased rate of tremor and less oral candidiasis with combination therapy, the two options appear relatively safe in adults although adverse effects associated with long-term ICS treatment were seldom monitored. In children, combination therapy did not lead to a significant reduction, but rather a trend towards an increased risk, of oral steroid-treated exacerbations and hospital admissions. These trends raised concern about the safety of combination therapy in view of modest improvement in children under the age of 12 years.
An antiinflammatory effect of salmeterol, a long-acting beta(2) agonist, assessed in airway biopsies and bronchoalveolar lavage in asthma.
The addition of long-acting beta(2) agonists to inhaled corticosteroid (ICS) therapy in symptomatic patients with asthma improves clinical status more than increasing the dose of ICS. It has been suggested that these benefits could be at the cost of an increase in airway inflammation, but few histopathological studies have been performed in the relevant group. In a double-blind, parallel-group, placebo-controlled study, we randomly assigned 50 symptomatic patients with asthma who were receiving ICS (range, 100 -500 microgram/d) to 12 wk of supplementary treatment with salmeterol (50 microgram twice daily) or fluticasone (100 microgram twice daily) or placebo. Bronchial biopsies and BAL were obtained from 45 patients before and after treatment and analyzed. After treatment with salmeterol there was no deterioration of airway inflammation as assessed by mast cells, lymphocytes, or macrophages in BAL or biopsies, but rather a significant fall in EG1-positive eosinophils in the lamina propria (from a median 18.3 to 7.6 cells/mm, p = 0.01), which was not seen after treatment with fluticasone. The only cellular effect of added fluticasone was a decrease in BAL lymphocyte activation. There was a concurrent improvement in clinical status, more marked with salmeterol than with increased ICS. Thus, adding salmeterol to ICS is not associated with increased "allergic" airway inflammation, but conversely with a complementary antieosinophil effect.