Management of Asthma and Chronic Airflow Limitation (Part 5)
A second major weakness is that although the majority of other studies employed aerosol beta agonists, the doses used may have been suboptimal. It has been shown that the dose of these drugs may need to be individualized in patients with chronic asthma. Simple cumulative dose-response curves may need to be done in these patients, since the dose required for the maximal bronchodilating effect may be greater than the two-puff dose usually used for maintenance therapy. Until recently, none of the studies purporting to show superiority of combined bronchodilator treatment had utilized dose titration to establish a therapeutic plateau for the beta agonist. It is thus questioned whether, if larger doses of the aerosol beta2 agonist had been used, theophylline would have been redundant. A recent well-designed study that specifically addressed this question showed that in poorly reversible asthma, maximal bronchodilation can almost always be achieved by dose titration of the P-agonist up to a therapeutic plateau. A further response of at least 200 ml could be achieved in 15 percent of the patients with a large dose (160 |xg) of ipratropium bromide, but not in any of the patients given aminophylline intravenously to achieve therapeutic serum levels.
Theophylline has become the most widely prescribed medication for children with asthma in the United States. However, this drug, as will be discussed later, has significant potential toxicity. Because of this, several groups of investigators have conducted trials to assess the effectiveness of cromolyn as an alternative for the management of mild to moderately severe chronic asthma in children.* These studies concluded that cromolyn was as effective as theophylline in treating this group of patients and was without associated side effects. Other studies suggest that cromolyn, but not theophylline, may improve bronchial hyperreactivity as measured by a methacholine challenge test, suggesting that cromolyn may produce an improvement in the underlying inflammation.