Original Article
Effect of a Short Course of Prednisone in the Prevention of Early Relapse after the Emergency Room Treatment of Acute Asthma
N Engl J Med 1991; 324:788-794March 21, 1991
- Abstract
- Abstract
Background.
Relapse after the treatment of acute asthma in the emergency room is common (occurring in 25 to 30 percent of cases) and is not accurately predicted by any available measurements. We studied the usefulness of prednisone in reducing this high rate of relapse.
Methods.
One hundred twenty-two patients treated in the emergency room for acute exacerbations of asthma were assigned in a randomized, double-blind fashion to receive at discharge either prednisone for eight days (the dose being tapered from 40 to 0 mg per day) or matching placebo. Ninety-three were subsequently discharged from the emergency room and participated in the trial. On days 1, 7, and 14 after discharge, the patients were assessed during home visits with spirometry and diary-card review; they were contacted by telephone on day 21. Relapse was defined as an unscheduled medical visit occasioned by the patient's perceived need for further asthma treatment.
Results.
The overall risk of relapse was significantly lower in the prednisone group (P<0.05), with a significantly reduced rate of relapse during the first 10 days of follow-up (3 of 48, as compared with 11 of 45 in the placebo group; P<0.05). Thereafter (days 11 though 21), there was no further significant difference in relapse rates between treatment groups (five in the prednisone group and six in the placebo group). During the first week after discharge, patients receiving prednisone reported significantly lower mean (±SD) daily symptom scores for shortness of breath (1.4±0.4 vs. 2.5±0.4, P<0.01 ) and less frequent use of an inhaled bronchodilator (5.2±0.5 vs. 6.9±0.2 puffs per day, P<0.05) than patients receiving placebo. Subsequently, symptom scores and bronchodilator use were similar in the two groups.
Conclusions.
A short course of prednisone reduced early relapse rates after the treatment of acute asthma in the emergency room, an effect limited to the period of steroid administration. (N Engl J Med 1991; 324: 788–94.)
Media in This Article
Figure 1
Kaplan–Meier Survival Curve16 Showing the Probability of Remaining Relapse-free after Emergency Room Treatment for Patients Receiving Prednisone (Solid Line) and Those Receiving Placebo (Broken Line).Figure 2
Shortness-of-Breath Scores (Panel A) and Use of Inhaled β2-Agonists (Panel B) in Patients Receiving Prednisone (Solid Line) and Those Receiving Placebo (Broken Line) after Emergency Room Treatment for Asthma.Article Activity
- Article
PHYSICIANS who treat patients with acute asthmatic attacks can base their therapeutic decisions on numerous studies directed specifically to the care of such patients in the emergency department.1 2 3 If hospitalization is required, there is also an extensive body of literature that addresses early in-hospital and intensive care management.2 3 4 The decision to admit these patients or discharge them from the emergency room is more problematic. There are no reliable indicators that ensure that patients with asthma who are considered to be well enough to go home from the emergency room will remain well,3 , 5 6 7 and available data indicate that 25 to 30 percent will have a relapse within 10 days of discharge.8 , 9 Instructions for follow-up are provided infrequently, and it is unclear what those instructions should be in this critical period.10 In short, researchers' attention has been focused on the first hour or two of palliation of acute exacerbations of asthma in the emergency room, and less attention has been paid to the subsequent weeks of clinical instability.2
How might relapse of recently discharged patients with asthma be prevented? In acute, severe asthma, parenteral corticosteroids administered in a hospital setting can be lifesaving.11 For the management of stable asthma in ambulatory patients, oral or inhaled corticosteroids are clearly effective.12 , 13 It would appear reasonable, then, to administer oral corticosteroids during the critical period following the management of asthma in the emergency room. Nonetheless, this potentially useful therapeutic approach has not yet been validated objectively. Accordingly, we conducted a placebo-controlled, doubleblind, randomized trial of a short course of oral prednisone in the prevention of relapse in the first three weeks after a visit to the emergency room for the treatment of asthma.
Methods
Patients
During the 21-month study, emergency room physicians at Toronto Western Hospital and Toronto General Hospital were asked to refer patients treated in the emergency room for acute exacerbations of asthma who met previously established inclusion criteria and who, in the judgment of the treating physician, were likely to be sent home on completion of therapy. The inclusion criteria required eligible patients to be at least 16 years of age, to fulfill the American Thoracic Society criteria for the diagnosis of asthma,14 to be free of complicating medical illnesses, to have taken no oral or parenteral corticosteroids in the preceding four weeks, to be free of known contraindications to the administration of systemic corticosteroids, and for premenopausal women, to be neither pregnant nor breast-feeding. The referred patients were then assessed in the emergency room by a member of the Asthma Centre research team for possible enrollment. Written, informed consent was obtained from all patients; the form described both the risk of relapse and the possible side effects of medications used. For patient safety, all family physicians were notified by mail, and all patients carried a note describing their participation in the study. Sealed envelopes containing the study code were available to be opened by an independent pharmacist at any time at the request of emergency room or family physicians. The protocol was approved by the Human Subjects Review Committee of the University of Toronto.
Treatment Protocol
The dosage, method of administration, and frequency of medications were determined by the referring emergency room physician, although a recommended treatment protocol was made available to all. The recommended therapy consisted of supplemental oxygen, a nebulized β2-agonist every 30 minutes, and when response was judged inadequate by the emergency room physician, nebulized ipratropium bromide or intravenous aminophylline. For the purpose of the present study, the administration of parenteral corticosteroids and subsequent admission to the inpatient service were considered exclusion criteria. The decision to discharge patients with asthma was made at the discretion of the treating emergency room physician and was based on his or her clinical judgment. The physician had access to the results of flow-volume spirometry performed by members of the trial team, but these nonphysician research assistants refrained from discussing the spirometric data or the decision about discharge. Physicians of the Asthma Centre did not participate in treatment or discharge decisions concerning the patients referred to the trial; patients referred to a physician at the Asthma Centre for medical management were excluded from the trial.
Patients agreeing to participate in the trial were assigned in a randomized, double-blind fashion to receive an eight-day tapering course of oral prednisone or matching placebo. Patients assigned to the active drug received 40 mg of prednisone (eight 5-mg tablets) at the time of discharge and a supply of tablets with instructions to take 40 mg the following day, with subsequent doses decreasing by 5 mg per day until the supply was exhausted. Patients assigned to placebo received inert tablets identical in appearance and taste to the active drug. In addition to the trial medication, all patients inhaled a β2-agonist regularly. They were instructed to use their usual inhaled β2-agonist at least four times daily unless otherwise directed by the emergency room physician. If their own supplies of medication were inadequate or if a β2-agonist had not been prescribed, the patients were supplied with metered-dose inhalers (Ventolin, Glaxo, Toronto) designed to provide 100 μg of albuterol per puff, and their inhalation technique was reviewed. Twice-daily oral therapy with sustained-release theophylline was continued for all patients already taking this medication and was supplied (Theo-Dur, 200 to 300 mg twice daily depending on body weight; Astra Pharmaceuticals, Mississauga, Ont., Canada) to all those not already taking this medication unless there was a known contraindication to its use or a reported intolerance to the drug. Each patient's usual inhaled maintenance therapy was continued in unchanged dosage throughout the trial, thereby allowing regular continued inhalation of ipratropium bromide, cromolyn sodium, and beclomethasone (up to 400 μg daily), alone or in combination.
The patients were supplied with diary cards on which they were instructed to record use of medications, perceived side effects, and asthma-symptom scores daily for 14 days after discharge. Five symptoms related to the severity of asthma — "tightness or wheezing," "cough or congestion," "shortness of breath," feeling "tired or worn out," and "difficulty sleeping" — were scored daily on a scale from 0 to 10; according to printed guidelines given to patients, 0 represented no symptoms, 1 to 3 mild symptoms, 4 to 6 moderate symptoms, and 7 to 10 severe symptoms.
The patients were visited in their homes or workplaces by a research assistant on days 1, 7, and 14 after discharge for spirometric measurements, a review of diary cards, and pill counts to verify compliance. The patients were asked whether they had sought further treatment of their asthma, and if they had, the details of the visit to the physician were recorded. A similar inquiry was made by telephone by the research assistant on day 21. The chief outcome variable, relapse, was defined as an unscheduled visit to a physician's office or a return to the emergency department occasioned by the patient's perception of worsening or unresponsive asthma. (Although a change in therapy was not a criterion in this definition, such visits invariably prompted a modification of therapy.) Relapse during days 1 through 10, the follow-up interval of most previous studies, was designated early relapse. Before the study code was broken and patients' assignments to active drug or placebo were known, all instances of possible relapse were reviewed by two members of the research team and were confirmed or rejected as actual relapses.
Pulmonary function was monitored objectively by flow-volume spirometry at the time of discharge and during prearranged visits at approximately the same time of day to the patient's home or workplace on day 1 (the day after emergency room treatment) and days 7 and 14. Patients were asked to refrain whenever possible from using inhaled bronchodilators for five hours before spirometry. Spirometric measurements at follow-up (and at discharge from the emergency room) were made by one of three trained research assistants using a portable pneumotachygraph (Vitalograph Compact spirometer, Lenexa, Kans.) that was calibrated twice weekly; variables were recorded from the best of three maximal forced expiratory maneuvers as determined by American Thoracic Society criteria,15 with a printout of graphic and numerical data retained for subsequent analyses. Flow-volume loops were rejected as suboptimal unless the two best results for the sum of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) differed by 5 percent or less. Peak flow was recorded from the pneumotachygraph flow signal during the spirometric maneuver rather than measured by a separate expiratory maneuver with a peak-flow meter.
Statistical Analysis
Results are expressed as means ±SD. The risk of relapse was compared between groups by estimates of product-limit survival,16 and tested for significance by the log-rank test.16 Two such analyses were performed. In one analysis, data on patients for whom outcome was unknown because of premature withdrawal from the study were regarded as censored observations. In a second analysis, such patients were regarded as having had treatment failures or as having relapses on an intention-to-treat basis. Means were compared between prednisone and placebo groups or relapse and nonrelapse groups by unpaired t-test. Proportions were compared between treatment groups or relapse and nonrelapse groups by Fisher's exact test (two-tailed) for two-by-two contingency tables. Three or more proportions were compared by the chi-square test. Repeated-measures analysis-of-variance techniques were used to compare diary-card data between the groups over time. One-way analysis of variance was used to analyze whether there were significant differences among the study technicians and between emergency room sites in the mean discharge FEV1 values obtained, as a check for observer and site bias, respectively. Results were considered to indicate significance at a P value of less than 0.05.
Results
Patients
One hundred twenty-two patients with asthma were assessed in the emergency room and agreed to participate in the trial. Of these, 20 did not begin the trial, 11 because they were subsequently admitted to the hospital from the emergency room, 6 because they were discovered not to meet inclusion criteria (e.g., suspected pregnancy), and 3 because they subsequently received at least one bolus of intravenous corticosteroids at the direction of the emergency room physician. Nine of these patients had been randomly assigned to receive prednisone, and 11 placebo. Of the remaining 102 patients who left the emergency room with the stated intention of participating in the outpatient trial, 8 (2 assigned to prednisone and 6 to placebo) were lost to follow-up immediately and 1 was inadvertently not given the study medication (prednisone) at the time of discharge. Of those lost to follow-up, six had clearly provided false addresses or telephone numbers and two were known to have moved from the region. The 93 patients remaining (48 assigned to prednisone and 45 to placebo) participated in the primary analysis, a comparison of relapse rates over the 21-day follow-up period.
The characteristics of the patients in the prednisone and placebo groups are shown in Table 1Table 1
Characteristics of the Patients in the Prednisone and Placebo Groups.*. The groups did not differ significantly with respect to mean age, sex, duration of asthma, smoking history, previous use of oral steroids for exacerbations of asthma, or previous hospitalizations for the treatment of asthma. The maintenance antiasthmatic medications used regularly at the time of presentation were not significantly different in the two groups. The types of medications administered in the emergency room were similar in both groups; all received a nebulized β2-agonist, 2 percent in each group received nebulized ipratropium bromide (commercially available during only the final few weeks of the trial), and 19 and 13 percent of the patients subsequently randomly assigned to receive prednisone and placebo, respectively, were given intravenous aminophylline while in the emergency room. The duration of emergency room care (3.0±2.5 hours for prednisone-treated patients as compared with 3.2±1.5 hours for patients receiving placebo) did not differ significantly between groups.Spirometric measures at the time of discharge were similar in the treatment groups (Table 2Table 2
Pulmonary Function in Patients Receiving Prednisone and Those Receiving Placebo before and after Treatment in the Emergency Room and Improvement over the Course of Treatment.*). In the majority of patients, spirometric measurements were also recorded on arrival in the emergency room. The mean pretreatment FVC was 2.74 liters (62 percent of the predicted value), and the mean FEV1 was 1.73 liters (46 percent of the predicted value). By the time the patients were discharged, these values had increased by 43 and 47 percent of base-line values, respectively. Pretreatment spirometric measurements and the level of improvement after treatment did not differ significantly between the prednisone and placebo groups (Table 2). The mean FEV1 values obtained at discharge did not differ significantly among the three research assistants recording them or between the two sites at which patients were recruited.Although the proportion of patients with asthma using oral theophylline regularly at the time of the emergency room assessment was similar in the two groups, more patients in the placebo group than in the prednisone group reported tolerance to the drug and had oral theophylline added to their regimens by the time of discharge. As a result, significantly more patients in the placebo group than in the prednisone group were taking theophylline during the follow-up period (80 percent vs. 49 percent, P<0.01).
Relapse Rates
The risk of relapse was significantly lower in the prednisone group than in the placebo group (P<0.05). The difference was most evident in the first half of the follow-up period. During days 1 through 10, significantly fewer patients in the prednisone group than in the placebo group relapsed (3 of 48 vs. 11 of 45, P<0.05). On days 11 through 21, five additional patients in the prednisone group and six in the placebo group relapsed, but the difference between the groups was not significant. In a second analysis, five patients (two receiving prednisone and three placebo) who withdrew from the trial prematurely and whose clinical outcome could not be verified were regarded as having had treatment failures on an intention-to-treat basis. Once again, the risk of relapse was significantly lower in the prednisone-treated group (P<0.05) (Fig. 1Figure 1
Kaplan–Meier Survival Curve16 Showing the Probability of Remaining Relapse-free after Emergency Room Treatment for Patients Receiving Prednisone (Solid Line) and Those Receiving Placebo (Broken Line).). When the data were analyzed according to intention to treat, fewer patients in the prednisone group than in the placebo group relapsed between day 1 and day 10 (5 of 48 vs. 13 of 45, P<0.05). Between day 11 and day 21, five additional patients receiving prednisone and seven receiving placebo relapsed. No relapse resulted in death, and none were severe enough to warrant admission to the intensive care unit or prolonged hospitalization. No relapse appeared to be provoked by the request that patients refrain from taking inhaled bronchodilators, if possible, before spirometry. All but four postdischarge events were easily categorized as relapses or nonrelapses. These four involved visits to family practitioners; three were ultimately designated relapses.We examined our data to see whether the benefit of steroid therapy was limited to any particular high-risk group and found no effect of age, concomitant medication use, previous hospitalizations, or the duration of exacerbation of asthma. However, the relapse-reducing effect of prednisone was most evident in, if not confined to, the group of patients discharged from the emergency room with an FEV1 below 59 percent of the predicted value, the median discharge value. In this subgroup, the rates of relapse were 50 percent in those receiving placebo and 13 percent in those receiving prednisone (P<0.05). Among those with an FEV1 exceeding 59 percent at discharge, the relapse rates were 30 percent in the placebo group and 33 percent in the prednisone group.
Symptom Scores
During the first week after discharge, patients receiving prednisone reported significantly lower mean daily symptom scores in the "shortness of breath" category (1.4±0.4 vs. 2.5±0.4, P<0.01) (Fig. 2Figure 2
Shortness-of-Breath Scores (Panel A) and Use of Inhaled β2-Agonists (Panel B) in Patients Receiving Prednisone (Solid Line) and Those Receiving Placebo (Broken Line) after Emergency Room Treatment for Asthma.A). Other symptom scores did not differ significantly between treatment groups during this period, although there was a trend toward lower mean scores for "difficulty sleeping" as the result of asthma in prednisone-treated patients (1.7±0.8 vs. 2.8±0.4, P = 0.06). Prednisone-treated patients with asthma also reported less frequent daily use of an inhaled β2-agonist (5.2±0.5 vs. 6.9±0.2 puffs per day, P<0.05) (Fig. 2B). Compliance with the oral study medication exceeded 80 percent of the prescribed dose among patients who neither relapsed nor withdrew before day 10.Outcome According to Relapse Status
The group of patients who relapsed during the 21-day follow-up was compared with the group that did not relapse. In addition, a subgroup of the former group, patients who relapsed early (days 1 through 10), was compared with the group that remained relapse-free. Patients who relapsed were not significantly different from those who did not with respect to age, sex, duration of asthma, duration of the current exacerbation, history of hospitalizations for the treatment of asthma, or types of maintenance medications reported as being used at the time of the emergency room visit. In particular, the use of inhaled steroids was not significantly different in the relapse and nonrelapse groups (17 and 21 percent, respectively). However, a significantly higher proportion of patients who relapsed early (days 1 through 10) reported previous use of oral steroids: 55 percent of those who relapsed as compared with 34 percent of those who did not (P<0.05).
Mean values for spirometric measurements revealed no significant differences between the groups at the time of the emergency room visit (Table 3Table 3
Pulmonary Function before Treatment in the Emergency Room and at the Time of Discharge and Improvement Observed during the First Home Visit after Treatment, According to the Presence or Absence of Relapse at Any Time during the 21-Day Follow-up.*). However, FVC at the time of discharge was significantly lower in the subgroup of patients who relapsed early (days 1 through 10) than in the group of patients who remained well (expressed as a percentage of the predicted normal value, 70±16 vs. 83±19 percent; P<0.05). Although spirometric measurements were made on days 1, 7, and 14 after discharge, a meaningful comparison between the relapse and nonrelapse groups was possible only for the data obtained on day 1; most relapses occurred before day 7 or 14, so spirometric measures at the time of relapse were unavailable. Four measurements of flow showed different patterns of response to therapy in the relapse and nonrelapse groups by day 1. Expressed as the percentage change from the value at discharge from the emergency room, FEV1, maximal midexpiratory flow rate, instantaneous expiratory flow at 50 percent of vital capacity, and instantaneous expiratory flow at 25 percent of vital capacity were all significantly lower among patients who relapsed than among those who did not (Table 3). Neither FVC nor peak flow rate distinguished the relapse from the nonrelapse group (Table 3).When examined during the first week after discharge, patients who relapsed during the first 10 days reported significantly higher scores for four of five asthma-related symptoms than patients who did not relapse; too few patients relapsed after day 10 to make continued comparisons meaningful. The mean scores for the early-relapse and the nonrelapse groups were 3.98±3.7 and 2.06±4.8 for "tightness or wheezing" (P<0.05), 5.14±4.7 and 2.66±5.4 for "cough or congestion" (P<0.01), 3.21±1.1 and 1.59±3.9 for "shortness of breath" (P<0.01), 4.10±3.7 and 2.31±5.1 for feeling "tired or worn out" (P<0.05), and 3.83±6.3 and 2.12±6.1 for "difficulty sleeping" (P = 0.09). The use of inhaled bronchodilators did not differ significantly between the early-relapse and nonrelapse groups. Similar but nonsignificant trends for symptom scores and albuterol use were noted when those who relapsed at any time during the 21-day follow-up were compared with those who did not relapse.
Discussion
The use of short courses of oral corticosteroids after discharge from the emergency room has been recommended previously, although it has not been tested objectively as part of a comprehensive treatment regimen in a representative group of patients with asthma. For example, Shapiro et al. reported that children with asthma improved more rapidly after emergency therapy when treated with oral steroids.17 In that study, there were no relapses in either the treatment or the control group, suggesting that patients with mild disease were studied. In adults, Fiel et al. reported a decrease in the relapse rate from 21 to 6 percent in patients given a tapering course of methylprednisolone,18 which included an intravenous bolus of the drug. As maintenance therapy their patients received only an inhaled bronchodilator for intermittent "rescue" therapy, and follow-up consisted of a single telephone call, with no documentation of pulmonary-function changes or follow-up beyond 10 days. Littenberg and Gluck advocated a single intravenous bolus of methylprednisolone at the time of presentation to the emergency room as a strategy for reducing the rates of immediate hospitalization.19 They reported that fewer patients with asthma who had received methylprednisolone were hospitalized by physicians, but did not give objective criteria on which these decisions were based. There were no significant differences in pulmonary function or other objective measures between their treatment groups, and postdischarge outcome was not reported. By contrast, we have demonstrated a significant benefit of low-cost oral steroid therapy in a large population of patients with asthma, most of whom also received regular maintenance therapy throughout the trial, including inhaled corticosteroids in some cases. The rates of relapse, which in the control group were comparable to those reported in the literature,8 , 9 were reduced significantly in the group receiving steroids, and a significantly different pattern of spirometric response to therapy emerged as early as the first day after the administration of oral steroids. Because we followed the patients for 21 days after their visits to the emergency room, we can be sure that relapse was not simply postponed by 8 days of oral prednisone; at the same time, we caution that the rate of late relapse (after prednisone was discontinued) was not affected by the regimen tested. Prednisone would appear to be of particular benefit to patients with asthma whose FEV1 at discharge is low, but this post hoc observation must be interpreted cautiously and requires prospective validation.
We chose to add theophylline to the treatment regimen of all patients after discharge (when tolerated) for two reasons. First, we thought that it was ethical to ensure that the patients given placebo received some form of supplemental maintenance therapy, given the reported rates of relapse in this high-risk group. Second, we wished to emulate a common clinical practice, thereby enhancing the general applicability of our results. Unfortunately, more patients given placebo than given prednisone received maintenance theophylline treatment during the follow-up period. This did not reflect a difference in the severity of disease between groups; a nonphysician member of the trial team routinely gave theophylline to all patients who did not report previous intolerance of the drug or a contraindication to its use. In one sense, the direction of this chance difference between the prednisone and placebo groups was fortunate; one would expect that adding theophylline more often in the placebo group would bias the trial against finding an advantage for prednisone treatment. We suspect, therefore, that the true benefits of prednisone treatment may be even greater than suggested by the present data. We cannot rule out entirely the possibility that theophylline somehow contributed to the higher rate of relapse among the patients given placebo, but we consider this unlikely; theophylline is of demonstrable benefit in the maintenance treatment of asthma, and its side effects, troublesome to a minority of patients, are unlikely to have provoked a relapse, since patients received theophylline only if they reported previous tolerance of the agent.20 , 21 Our data suggest indirectly that theophylline therapy is of minimal benefit as compared with oral steroids in reducing the rate of relapse after acute attacks of asthma.
Our study appears to confirm the usefulness of oral steroids in the care of patients with asthma after treatment in the emergency room, regardless of their concurrent therapy, and should encourage more widespread adoption of this strategy. However, we believe that we must also recommend caution and highlight some limits to the general application of our data. We enrolled approximately 14 percent, or one in seven, of the patients with asthma who were discharged from the participating emergency departments during the study period (as determined by a 10-year survey of emergency room visits for asthma, described elsewhere).22 No doubt many were not referred because they did not meet the circulated inclusion criteria. However, it seems likely that patients with mild asthma were more likely to be referred than those with severe asthma; emergency room physicians spoke of their reluctance to risk the possible random assignment of some patients to placebo and were less likely to refer patients in the middle of the night, despite the availability by long-range pager of research staff members most nights during the study period. Although patients who agreed to participate in our blinded trial were almost certainly more compliant and cooperative than average as a group, a considerable number of them did not make themselves available for follow-up care; 13 percent were lost to follow-up or withdrew prematurely from the study. Most surprising to us were patients who gave false names and addresses and could not be located for further assessment. These observations suggest that a subgroup of patients with asthma who present in the emergency room will be poor candidates for an oral regimen requiring compliance for eight days. Others have suggested repository steroid therapy as an alternative approach.23 Our study may not reflect optimal steroid use for all or even the majority of patients with asthma. The duration of the oral-steroid course chosen might be too short and the dosage too low for some patients. Tapering of the dosage, although it reduces the likelihood of a sudden flare-up of asthma during steroid withdrawal, may also complicate the regimen unnecessarily. For patients with asthma who have protracted exacerbations requiring prolonged courses of antiinflammatory therapy, high-dose inhaled corticosteroids may offer substantial risk—benefit advantages over the oral approach,24 although we detected no serious side effects or toxicity from the short-term use of prednisone. For these reasons, we believe that further research is required to determine the optimal glucocorticoid regimens in the care of ambulatory patients with asthma after their treatment in the emergency room.
Supported by a research grant from the PSI Foundation.
We are indebted to the following emergency room physicians, whose enthusiastic cooperation made this study possible: Drs. M.B.T. Rowat (clinical director of emergency room services, Toronto General Hospital), D.P. Colohan (clinical director of emergency room services, Toronto Western Hospital), P. Arnold, D. Austin, D. Berg, R.C. Beveridge, J. Carstoniu, A. Gareau, L. Greenspan, G.V. Hill, D. Jones, R. Lindzon, A. McCallum, A.J. Nazareth, C. Rubes, A. Shellam, J. Tomarken, and J. Yaphe; to the anonymous reviewers of the PSI Foundation, whose constructive criticisms were invaluable; to Drs. Hoffstein, Slutsky, and Zamel, whose insights were helpful in the preparation of this paper; and to Ms. A. Stewart for her assistance in the preparation of the manuscript.
Source Information
From the Asthma Centre of the Toronto Hospital, Toronto. Address reprint requests to Dr. Chapman at the Toronto Hospital Asthma Centre, 399 Bathurst St., 4th Fl., Edith Cavell Wing, Toronto, ON M5T 2S8, Canada.
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Michelle Gill, Scott Walker, Aqeel Khan, Steven M. Green, Lillian Kim, Shaun Gray, Baruch Krauss. (2005) Exhaled Nitric Oxide Levels during Acute Asthma Exacerbation. Academic Emergency Medicine 12:7, 579-586
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D. Cunnington, N. Smith, K. Steed, P. Rosengarten, A.M. Kelly, H. Teichtahl. (2005) Oral versus intravenous corticosteroids in adults hospitalised with acute asthma. Pulmonary Pharmacology & Therapeutics 18:3, 207-212
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Kelly Butler, William O. Cooper. (2004) Adherence of Pediatric Asthma Patients With Oral Corticosteroid Prescriptions Following Pediatric Emergency Department Visit or Hospitalization. Pediatric Emergency Care 2:11, 730-735
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