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Department of Medicine, University of Maryland School of Medicine, Division of Pulmonary and Critical Care Medicine
Correspondence to: John G. Teeter, MD, FCCP, Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, 10 South Pine Street, 800 MSTF, Baltimore, MD 21201; e-mail: jteeter@umaryland.edu
Preventing exacerbations of bronchospasm is one of the main goals of the management of chronic asthma.1 Despite this therapeutic goal, emergency department (ED) visits for acute bronchospasm/status asthmaticus continue to be an important clinical problem. The most recent data from the Centers for Disease Control and Prevention estimate that there were more than 1.8 million ED visits for status asthmaticus in 1995.2 In 1994, approximately $348 million was spent providing care to acutely ill asthmatics in EDs.3 Because of this common and expensive aspect of asthma care, better treatment strategies are needed to improve outcomes and to reduce the morbidity and expense associated with status asthmaticus.
The pharmacologic treatment of status asthmaticus includes high-dose inhaled bronchodilators and the early administration of oral or IV corticosteroids.1 ,4 ,5 The selective ß2-agonists are considered to be the bronchodilators of choice for patients with acute bronchospasm.1 ,4 When inhaled in high doses, these agents are rapidly effective and well tolerated in most patients.5 ,6 ,7 Aminophylline,8 ,9 magnesium,10 ,11 and ipratropium bromide12 ,13 ,14 ,15 ,16 ,17 ,18 ,19 ,20 ,21 ,22 have all been administered in combination with ß2-agonists to treat status asthmaticus. In this issue of CHEST (see page 937), Weber and colleagues report the results of a prospective, randomized, controlled clinical trial examining the effect of combined high-dose inhaled albuterol and ipratropium bromide on the clinical outcomes of patients presenting to a municipal ED with acute bronchospasm. These authors were unable to demonstrate significant improvements in pulmonary function, ED length of stay, or the need for hospitalization in the patients who received prednisone and combined high-dose inhaled bronchodilator therapy, compared to patients who received standard therapy with high-dose albuterol and prednisone. As the authors note, there was a reduced statistical power to detect small but significant differences between the bronchodilator therapies because of the relatively small number of patients enrolled in their study. Nonsignificant trends favoring combination therapy were apparent for all three of the primary outcomes examined by Weber and colleagues.
Other prospective, controlled studies examining the efficacy of high-dose combined selective ß2-agonist and ipratropium bromide inhalation therapy in status asthmaticus have demonstrated mixed results. Most of these studies,12 ,13 ,14 ,15 ,16 ,17 ,18 ,19 as well as a recent meta-analysis,20 have demonstrated small but significant improvements in airway obstruction and/or clinical outcomes favoring combination therapy, while two have not.21 ,22 When present, the improvement in airway obstruction in patients receiving combination therapy over that produced by high-dose ß2-agonist therapy alone has been relatively small. Garrett et al14 demonstrated a difference in FEV1 of 113 mL favoring combination therapy in acutely ill adult asthmatics 90 min after receiving treatment. A meta-analysis of the efficacy of ipratropium bromide in acute childhood asthma concluded that there was a 12.5% improvement in airway obstruction conferred by combination therapy compared to therapy with ß2-agonists alone.23 Combination therapy may be particularly beneficial in children with acute asthma, as demonstrated now in five prospective, randomized, controlled clinical trials,12 ,13 ,15 ,17 ,19 and in patients who present with a greater degree of airway obstruction.12 ,15 ,16 As in this month's report from Weber and colleagues, all of these studies have demonstrated the safety of administering selective ß2-agonists and ipratropium bromide together in high doses.12 ,13 ,14 ,15 ,16 ,17 ,18 ,19 ,20 ,21 ,22
Thus, while neither aminophylline8 ,9 nor magnesium10 ,11 confers additional benefit to high-dose ß2-agonists and corticosteroids in patients with status asthmaticus, the benefit of ipratropium seems to be small but significant. As long as more than 1.8 million asthmatics with acute bronchospasm continue to present to our EDs, however, combination bronchodilator therapy with selective ß2-agonists and ipratropium bromide may result in significant overall improvements in patient outcomes and cost.
Maintaining proper asthma controller therapies in patients at risk for status asthmaticus should help to reduce the incidence of ED visits for asthma. It is telling that only slightly more than half of the patients enrolled in the study reported by Weber and coworkers were taking inhaled corticosteroids. Inhaled corticosteroids are the cornerstone of controller therapy for patients with persistent asthma.1 ,4 The regular use of these agents has been shown to reduce the need for ED therapy and hospitalization, and to reduce the cost of asthma care for these patients.24 ,25 Thus, while the treatment of status asthmaticus is being refined, ongoing efforts to identify and treat our more severely affected patients with appropriate levels of controller medications should help to reduce the overall incidence of acute exacerbations of asthma.
References
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