As-needed inhaled beta2-adrenoceptor agonists in moderate-to-severe asthma: current recommendations

Intermediate-acting inhaled beta2-agonists (e.g. albuterol [salbutamol]), once recommended for round-the-clock bronchodilation, are now recommended to be used exclusively as-needed. Guidelines advise that asthma should be controlled with anti-inflammatory therapeutic strategies so that the as-needed requirement for inhaled beta2-agonists should be infrequent; ideally less than several times per week, up to once a day for exercise, and none at night. These recommendations are based upon the recognition that asthma is primarily an inflammatory condition and that the major thrust of therapy should be anti-inflammatory, including environmental control and administration of inhaled corticosteroids (ICS), leukotriene-receptor antagonists, and possibly oral theophylline and inhaled cromones; the cromones include cromolyn sodium (sodium cromogylcate) and nedocromil. While this is the primary rationale behind the as-needed infrequent prescription of the inhaled beta2-agonist paradigm, there are a number of detrimental effects that can be seen with regularly scheduled (or frequent as-needed) use of inhaled beta2-agonists. These include tolerance to the bronchodilator and particularly the bronchoprotective effects, increased airway responsiveness to allergen, worsened asthma control, and, probably most importantly, over-reliance on an excellent symptom reliever leading to undertreatment. Any or all of these could be responsible for the demonstrated dose-response relationship between inhaled beta2-agonist overuse and death from asthma. Several controlled clinical trials, which have included many patients with at least moderately severe asthma, have failed to demonstrate any obvious advantage to the regular scheduled use of inhaled beta2-agonists compared with as-needed inhaled beta2-agonists. On the other hand, despite no obvious advantage, regular use of albuterol 1000-1200 microg/day appears to be well tolerated and reasonably safe. When asthma is treated using an as-needed, infrequent inhaled beta2-agonist, the requirements for beta2-agonists become a useful marker of whether or not the asthma is adequately controlled. When inhaled beta2-agonists are required inordinately frequently (i.e. when asthma is not adequately controlled), after ensuring compliance with ICS, the most common strategy is to add one of the long-acting inhaled beta2-agonists twice daily. On the basis of the available evidence, the as-needed intermediate-acting inhaled beta2-agonist therapeutic strategy appears appropriate for patients with moderate-to-severe asthma.