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.
Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group.
Guidelines on asthma management recommend that in patients who still have symptoms on treatment with low-dose inhaled corticosteroids the first step should be an increase in inhaled corticosteroid dose. The addition of long-acting inhaled beta 2-adrenoceptor agonists is another option. We have compared these two strategies in a randomised, double-blind, parallel-group trial. We studied 429 adult asthmatic patients who still had symptoms despite maintenance treatment with 200 micrograms twice daily inhaled beclomethasone dipropionate (BDP). 3 did not provide verifiable data. Of the others, 220 were assigned salmeterol xinafoate (50 micrograms twice daily) plus BDP and 206 were assigned higher-dose BDP (500 micrograms twice daily) for 6 months. The mean morning peak expiratory flow increased from baseline in both groups, but the increase was greater in the salmeterol/BDP group than in the higher-dose BDP group at all time points (differences 16-21 L/min, p < 0.05). Mean evening PEF also increased with salmeterol/BDP but not with higher-dose BDP. There were significant differences in favour of salmeterol/BDP in diurnal variation of PEF (all time points) and in use of rescue bronchodilator (salbutamol) and daytime and night-time symptoms (some time points). There was no significant difference between the groups in adverse effects or exacerbations of asthma, indicating that in this group of patients regular beta 2-agonist therapy was not associated with any risk of deteriorating asthma control over 6 months. This study suggests a need for a flexible approach to asthma management.