Influence of inhaled steroids and chromones on long-term effects of beta-agonists in asthma

The effects of nedocromil sodium (NS) and beclomethasone dipropionate (BDP) were assessed in 21 asthmatic subjects who had previously showed an impairment in lung function and an increase in bronchial hyperresponsiveness (BHR), after 4-week regular treatment with inhaled salbutamol (S) (200 mg MDI q.i.d.). After 2 weeks of wash out, patients were randomly assigned to take, for 4 weeks, one of the following 2 treatments in addition to S (200 mg MDI q.i.d.): 11 subjects inhaled NS (4 mg MDI q.i.d.); 10 subjects took BDP (250 mg MDI q.i.d.). Finally, after 2 weeks of wash out, patients were treated for 4 weeks with the medication above described, but S dose was halved (100 mg q.i.d.). After every period patients performed forced spirometry and methacholine (mch) challenge test. Peak Expiratory Flow Rates (PEFR) and asthma symptoms were monitored by the patients during the whole study. All the changes induced by S treatment disappeared after 2 weeks of wash out. When BDP was added to S treatment there was a significant improvement in airway caliber and reactivity as well as in asthma control; these effects were more evident, although not significantly, when S dose was halved. NS treatment, combined with full-dose as well as with half-dose of S was not associated to any significant change in spirometric parameters, BHR or in clinical status data. However, the increase in BHR induced by S was fully prevented by the addition of NS. Thus, we confirm that regular use of β2- agonists as monotherapy may be deleterious in asthma treatment. However, both topic steroids and chromones are able to prevent these unfavourable effects.