Inhaled Corticosteroids in Asthma
ABSTRACT & COMMENTARY
Source: Suissa S, et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000; 343:332-336.
Many studies have addressed the importance of inhaled corticosteroids in preventing life-threatening exacerbations of asthma and associated end points such as frequent hospitalizations. However, no study has demonstrated that this therapy can prevent death from asthma.
The authors used a clever research tool—the Saskatchewan Health databases—which enabled them to track prescription use and associated demographics and outcomes such as hospitalizations and deaths. They formed a population-based cohort of all subjects 5-44 years of age who were using anti-asthma drugs from 1975 to 1991. They conducted a nested case-control study in which subjects who died of asthma were matched with controls within the cohort. Adjustments were made for subject age and gender; the number of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled beta-adrenergic agonists used in the year prior to the index date; and the number of hospitalizations for asthma in the two years before the index date. This enabled them to create a control group of patients with asthma of similar severity.
The cohort consisted of 30,569 subjects. Of 562 deaths, 66 were classified as due to asthma and had complete data available. There were 2681 controls. Roughly one-half of each group had used inhaled corticosteroids the previous year, most commonly low-dose beclo-methasone. The mean number of canisters used in the prior year was 1.18 for the patients who died and 1.57 for the controls. Even more telling was the percentage of patients using more than six canisters in the previous year (1.5% of the patients who died vs. 7.4% of the controls). On the basis of a continuous dose-response analysis, the authors calculated that the rate of death from asthma decreased by 21% with each additional canister of inhaled corticosteroids used in the previous year (adjusted rate ratio, 0.79; 95% CI, 0.65-0.97). Interestingly, the rate of death from asthma during the first three months after discontinuation of inhaled corticosteroids was higher than the rate among patients who continued to use the drugs. The authors conclude that the regular use of low-dose inhaled corticosteroids is associated with a decreased risk of death from asthma and that cessation of corticosteroid use poses a particular risk.
Of particular interest are the characteristics of the case vs. control groups. Although not statistically different, the case patients had more hospitalizations for asthma and more prescriptions for oral corticosteroids, inhaled beta-adrenergic agonists, nebulized beta-adrenergic agonists, oral beta-adrenergic agonists, and theophylline. The average age was about 30 in each group, and the case group was slightly more often male.
COMMENT BY RICHARD j. HAMILTON, MD, FAAEM, ABMT
I found this research very compelling. In 1991, the notion that ED physicians should start patients on inhaled steroids after treatment for an acute exacerbation of asthma was just taking hold. Which patients should be started on this therapy and why was not entirely clear. Some nine years later, the authors provide evidence from that period demonstrating that patients who used more inhaled steroids were less likely than controls to die from asthma. On balance, the control group used more inhaled steroids and less of every other asthma therapy than the case group. One could argue that this just indicates a trend toward more severe asthma in the case group. However, it is my feeling that this is perhaps another marker for the success of inhaled corticosteroids. Other studies support the finding that patients on inhaled steroids are hospitalized less often, and use less inhaled beta agonists and oral corticosteroids. In the year 2000, ED physicians should learn this lesson, since they treat the "worst of the worst" asthma. I believe this research supports the practice of discharging all patients treated for asthma in the ED with a prescription for inhaled corticosteroids and a brief educational session on their use. It also suggests that patients who are on inhaled corticosteroids should rarely have their prescription for this drug discontinued. The care and consideration we give to prescribing this drug saves lives.
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