Correspondence
Albuterol in Mild Asthma
N Engl J Med 1997; 336:729-730March 6, 1997
- Article
To the Editor:
The study by Drazen et al. (Sept. 19 issue)1 demonstrates the safety of the regular use of inhaled β-agonists in a controlled setting among patients with mild asthma. We fear, however, that this result may create a false sense of security among patients and their physicians that could be conducive to the inappropriate use of these very effective bronchodilators. We would like to remind readers that our long-term epidemiologic studies have shown that the excessive use of β-agonists is associated with a very high risk of fatal or near-fatal asthma 2 and that the threshold of safety is around one and a half canisters per month.3 Monitoring the monthly use of β-agonists is vital, since we also found that a pattern of increasing use over time is a more important predictor of an imminent fatal or near-fatal asthma attack than regular use, even regular use of excessive quantities.4 Practically, this implies that over a six-month period, an increase of one canister in the monthly use of β-agonists or a doubling of the monthly use is a critical warning sign of an impending serious asthma attack. Consequently, this signal should be used to reassess the patient's care and to initiate or modify antiinflammatory therapy — specifically, to initiate or increase treatment with inhaled corticosteroids, which are clearly associated with a decrease in morbidity.5 The importance of β-agonist requirements as a marker of poor asthma control, in conjunction with the lack of benefit derived from regular use, argues strongly for the use of inhaled β-agonists only as needed in most patients.
5 ReferencesSamy Suissa, Ph.D.
Pierre Ernst, M.D.
Royal Victoria Hospital, Montreal, QC H3A 1A1, Canada1
Drazen JM ,Israel E ,Boushey HA , et al. Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. N Engl J Med 1996;335:841-847
Full Text | Web of Science | Medline2
Spitzer WO ,Suissa S ,Ernst P , et al. The use of β-agonists and the risk of death and near death from asthma. N Engl J Med 1992;326:501-506
Full Text | Web of Science | Medline3
Suissa S ,Ernst P ,Boivin JF , et al. A cohort analysis of excess mortality in asthma and the use of inhaled β-agonists. Am J Respir Crit Care Med 1994;149:604-610
Web of Science | Medline4
Suissa S ,Blais L ,Ernst P . Patterns of increasing β-agonist use and the risk of fatal or near-fatal asthma. Eur Respir J 1994;7:1602-1609
CrossRef | Web of Science | Medline5
Ernst P ,Spitzer WO ,Suissa S , et al. Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use. JAMA 1992;268:3462-3464
CrossRef | Web of Science | Medline
To the Editor:
Drazen and colleagues randomly assigned patients with mild asthma to receive inhalations of albuterol either on a scheduled basis or only as needed. No major differences were found between the two groups in various outcome measures, and the authors concluded that patients with mild asthma should use albuterol only as needed.
By design, patients who were considered for inclusion in the study were first evaluated during a run-in period, during which they received placebo inhalations on a scheduled basis and albuterol as needed. Only patients whose asthma remained stable during these six weeks were considered for randomization. The number of patients who were excluded after this initial run-in period is not mentioned, and it is thus difficult to judge the generalizability of the authors' findings to a broader population of patients with mild asthma. The study may be more accurately described as showing that patients whose asthma remains stable during six weeks of albuterol treatment as needed are likely to continue to have stable asthma with this regimen and that switching to scheduled albuterol treatment in such patients is unwarranted. Elimination of the run-in period would be necessary to support the more general conclusion of the authors.
Doron Zahger, M.D.
Hadassah University Hospital, Jerusalem 91240, IsraelAuthor/Editor Response
The authors reply:
To the Editor: Suissa and Ernst are concerned that the regularly scheduled use of inhaled albuterol could mask one of the indicators of an impending serious asthma attack — namely, an increase in the frequency of use of inhaled albuterol. Although our data clearly show that in patients with mild asthma there is no benefit to be derived from the regular use of inhaled albuterol, we also showed that regular use did not produce deleterious effects in these patients. Thus, although we agree that regular use might theoretically blunt the ability to detect an increase in the frequency of use of inhaled albuterol, we observed no difference in the occurrence of exacerbations of asthma between the two treatment groups. In our patients, exacerbations of asthma were easily identified through the combined use of symptom recording and peak-flow monitoring. This reinforces our belief that it is important for patients with asthma to receive adequate instruction in the techniques of disease management and for patients and physicians to work together to ensure that an adequate plan of action is in place, ready for implementation should the need arise.
Dr. Zahger is concerned that many of the patients who were originally enrolled in the trial did not undergo randomization because their asthma was unstable during the six-week run-in period. We regret that space limitations did not allow us to include the outcomes of patients who entered the study but who were not admitted into the randomized-treatment section of the trial. A total of 319 patients were enrolled in the trial, and 64 dropped out before randomization. Of these patients, 6 exceeded the study limits in terms of their albuterol use, 6 were unable to comply with the study procedures, 11 had exacerbations of asthma, 18 left because of personal reasons (e.g., there were unresolvable conflicts between the demands presented by participation in the trial and the patient's capacity to meet these demands), and 23 withdrew consent because they found the trial requirements onerous. Thus, less than 3 percent of the patients initially enrolled dropped out because of worsening of their asthma.
Jeffrey M. Drazen, M.D.
Elliot Israel, M.D.
Brigham and Women's Hospital, Boston, MA 02115for the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network
