Recent Studies Characterising the Role of Beta2 Agonists
There are now a number of studies that show adding a long-acting beta2 agonist may be preferable to simply increasing the dose of inhaled corticosteroids in symptomatic, moderate asthma.
Patients taking beclomethasone diproprionate (BDP) 200m g b.d. with persistent symptoms were randomly allocated to two treatment groups - either a higher dose of BDP (500m g b.d.) or additional treatment with salmeterol (50m g b.d,) - and observed over a period of 6 months. Those taking salmeterol had improved lung function, improved morning and evening peak flow rates, and less nocturnal asthma.1
A second study of 738 symptomatic patients taking even higher doses of BDP (500m g b.d.), carried out over 24 weeks, found similar results. Combined treatment with BDP (500m g b.d.) plus salmeterol (50m g or 100m g b.d) was more effective than higher doses of BDP (1000m g b.d.) in controlling nocturnal asthma and improving morning and evening peak flow rates.2
The improvement in control of asthma symptoms with additional use of salmeterol has also been demonstrated with eformoterol. In a study of 852 patients taking inhaled corticosteroids, but experiencing persistent symptoms, random treatments included high or low dose budesonide (100m g or 400m g b.d.) with either eformoterol (12mg b.d.) or placebo. The greatest benefit in symptom control and peak flow rates was seen in the group taking budesonide 400m g b.d. with eformoterol.3
Of importance was the significant effect of
the higher dose of inhaled corticosteroid.
Furthermore, the study found a reduced rate
of mild and severe exacerbations of asthma
in those on eformoterol and budesonide.
Using specific recommendations for dose
reduction a further study, carried out over
6 months, examined 101 patients with mild or
moderate asthma taking over 200m g per day
of budesonide or BDP. It found that the
addition of salmeterol 50m g b.d. resulted
in dose reductions in steroid use.4
- Asthma control in moderate and severe asthma is best achieved with the combination of an inhaled steroid at optimal dose and a long acting beta2 agonist.
- Dose reduction of oral or inhaled corticosteroids may be achieved using long-acting beta2 agonists, possibly reducing the incidence of systemic side effects.
- Inhaled corticosteroids are still required in moderate to severe asthma to control the underlying inflammatory process.
Until recently, systemic effects of inhaled corticosteroids have been considered to be of Little clinical importance, although indices of bone metabolism and adrenal function have been found to be suppressed in patients taking over 1000mg daily of BDP or equivalent. Studies now indicate that posterior subcapsular cataracts may occur more frequently in those with a cumulative lifetime dose of over 2000mg of BDP or equivalent.5 Some evidence suggests that them is an increased risk of glaucoma related to the rise of high-dose inhaled corticosteroids, particularly in the elderly.6
References
1. Greening AP, Ind PW. Northfield M et al. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing corticosteroid. Lancet 1997:334:219-24.
2. Woolcock A, Lundback B, Ringdal N et al. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit Care Med 1996;143:1481-8
3. Pauwels RA, Lofdahl C-G, Postma DS et al for the Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med 1997;337:1405-11.
4. Wilding P, Clark M, Thompson J et al. Effects of long term treatment with salmeterol on asthma control: a double blind, randomised crossover study. Br Med J 1997;314:1441-6·
5. Cumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997;337:8-14·
6. Garbe E, Le Loirer J Boivin ]-F et al. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. JAMA 1997;227:722-7.