FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 343:332-336 August 3, 2000 Number 5 Next

Abstract PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article PubMed Citation

ABSTRACT

Background Although inhaled corticosteroids are effective for the treatment of asthma, it is uncertain whether their use can prevent death from asthma.

Methods We used the Saskatchewan Health data bases to form a population-based cohort of all subjects from 5 through 44 years of age who were using antiasthma drugs during the period from 1975 through 1991. We followed subjects until the end of 1997, their 55th birthday, death, emigration, or termination of health insurance coverage, whichever came first. We conducted a nested case–control study in which subjects who died of asthma were matched with controls within the cohort according to the length of follow-up at the time of death of the case patient (the index date), the date of study entry, and the severity of asthma. We calculated rate ratios after adjustment for the subject's age and sex; the number of prescriptions of theophylline, nebulized and oral ß-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled ß-adrenergic agonists used in the year before the index date; and the number of hospitalizations for asthma in the two years before the index date.

Results The cohort consisted of 30,569 subjects. Of the 562 deaths, 77 were classified as due to asthma. We matched the 66 subjects who died of asthma for whom there were complete data with 2681 controls. Fifty-three percent of the case patients and 46 percent of the control patients had used inhaled corticosteroids in the previous year, most commonly low-dose beclomethasone. The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. On the basis of a continuous dose–response analysis, we calculated that the rate of death from asthma decreased by 21 percent with each additional canister of inhaled corticosteroids used in the previous year (adjusted rate ratio, 0.79; 95 percent confidence interval, 0.65 to 0.97). 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.

Conclusions The regular use of low-dose inhaled corticosteroids is associated with a decreased risk of death from asthma.

Trends in several countries indicate that during the 1980s and 1990s, sales of inhaled corticosteroids increased as the yearly rates of death from asthma decreased.^10,11,12 Three case–control studies from New Zealand and a cohort study from Saskatchewan, Canada, which were designed to assess the effects of ß-adrenergic agonists on death from asthma, found no association between the use of inhaled corticosteroids and death from asthma.^{2,13,14,15,16} This may have been because of the low rates of use of inhaled corticosteroids during the 1980s. However, inhaled corticosteroids significantly reduced the combined risk of near-fatal and fatal asthma.⁵ There have been no studies of the dose–response relation in inhaled corticosteroid therapy. Such studies are desirable because of the increasing doses used in many countries and the potential adverse effects associated with prolonged use of higher doses, especially ocular side effects in adults and decreased growth in children.^17,18,19,20

We conducted a population-based epidemiologic study to determine whether and to what extent the use of inhaled corticosteroids prevents death from asthma.

Methods

Subjects and Source of Data

The cohort of patients with asthma whom we studied has been described in detail elsewhere.^8,9 Briefly, the computerized data bases of Saskatchewan Health formed the primary source of data on the cohort. These data bases were developed as a result of the universal health insurance provided to all residents of the province since 1975. Two million people have been covered by this program since it began. The data bases have been used extensively to study the effects of several prescription drugs at the population level.²¹ We selected from this population all 30,569 beneficiaries 5 through 44 years of age who received at least three prescriptions for an antiasthma medication in any one-year period from September 1975 through December 1991. The medications included all antiasthma drugs that were covered by the health insurance plan during the study period, except for oral corticosteroids. These drugs were beclomethasone, budesonide, triamcinolone, flunisolide, cromolyn sodium, ketotifen, nedocromil, albuterol, fenoterol, terbutaline, isoproterenol, metaproterenol, procaterol, epinephrine bitartrate, ipratropium bromide, and any compound of theophylline. We initially omitted oral corticosteroids in order to exclude subjects with conditions other than asthma. However, we later obtained data on all prescriptions for oral corticosteroids for all selected subjects.

The subjects were followed until their 55th birthday, death, emigration from the province, the end of their coverage by the health insurance plan, or December 31, 1997, whichever occurred first.

Outcome

All deaths from any cause that occurred during follow-up of the 30,569 members of the study cohort were identified, and the death certificates were obtained. Two pulmonary physicians, who were unaware of the drugs used by the patients, independently reviewed the death certificates to identify deaths due to asthma. The case patients were cohort members whose deaths were attributed primarily to asthma by both physicians. Deaths that occurred during or within a year after the 18-month period from July 1987 through December 1988 were excluded, because Saskatchewan Health did not collect data on medications during this period.

Study Design

We used a nested case–control design within the cohort to allow precise assessment of the changes over time in the use of antiasthma drugs. Each patient who died of asthma was matched with all available controls within the cohort on the basis of several factors. First, all matched controls had to have been followed for at least as long as the corresponding case patient at the time of the date of death, which was designated the index date. Moreover, to control for trends over time in the use of inhaled corticosteroids, we required that the matched controls have entered the cohort on the same date (±3 months) as the case patient. Because we expected the case patients to be those with more severe disease, we used the following additional matching factors to control for the severity of disease: the occurrence of hospitalization for asthma during the two years before the index date and the number of canisters of ß-adrenergic agonist dispensed (18 or fewer vs. more than 18), the use of theophylline, the use of nebulized ß-adrenergic agonists, and the use of oral corticosteroids during the year before the index date. The 16 case patients who could not be matched with at least 2 controls who had entered the cohort on the same date (±3 months) were matched with additional controls who had entered the cohort during the 12 months (14 case patients) or 36 months (2 case patients) preceding or following the date of entry of the case patient.

Exposure to Inhaled Corticosteroids

We determined the number of canisters dispensed in each prescription for inhaled corticosteroids to the case and control patients during the year before the index date. When two or more canisters were dispensed by the same prescription, the canisters were considered to have been used during successive months. Patients who had received at least one canister during each quarter of the previous year were considered to have used inhaled corticosteroids regularly and without interruption throughout that year.

Statistical Analysis

To quantify the amount of exposure to inhaled corticosteroids, we determined the number of canisters dispensed to each case patient during the year before and during the six months before the index date. To assess the effect of discontinuation of inhaled corticosteroids, we divided the case patients into four groups: those who had used inhaled corticosteroids without interruption during the year before the index date, and those who had discontinued inhaled corticosteroids within three, six, and nine months before the index date.

Because controls were matched with case patients and the number of controls per case patient was variable, crude descriptive statistics for the characteristics of the controls could not be used. To allow unbiased comparisons with case patients, these statistics were weighted by the inverse of the number of controls in each matched set, a procedure equivalent to standardizing the number of controls to one control per case.

Conditional logistic regression for matched case–control data was used to estimate the adjusted rate ratios for death from asthma that were associated with the use of inhaled corticosteroids. To assess the dose–response effect, we first stratified inhaled-corticosteroid use as follows: no use, use of less than one-half canister per month, and use of one-half canister or more per month. To maximize the power of the analysis, we used conditional logistic regression to estimate the rate ratio for death from asthma as a function of the number of canisters of inhaled corticosteroids dispensed among users of these drugs, with the nonusers as the reference group. Both analyses were repeated for the one-year and six-month periods before the index date. To assess the effect of discontinuation of inhaled corticosteroids, we used conditional logistic regression to estimate the rate of death from asthma among subjects who discontinued inhaled corticosteroids within three, six, and nine months before the index date, relative to the rate among those who used inhaled corticosteroids without interruption during the entire year before the index date.

To control for any confounding that might remain after matching for the severity of asthma, we adjusted all estimates of rate ratios according to the quantities of prescribed antiasthma drugs. These quantities were expressed by the number of dispensed prescriptions for theophylline, nebulized and oral ß-adrenergic agonists, and oral corticosteroids and by the number of canisters of inhaled ß-adrenergic agonists dispensed in the year before the index date. We also adjusted for the number of hospitalizations for asthma during the two years before the index date and for the subject's age and sex.

Results

There were 562 deaths in the cohort, of which 77 were classified as being due to asthma. We excluded 11 of these deaths because they occurred during or up to a year after the 18-month period when Saskatchewan Health did not collect data on medications. The remaining 66 case patients were matched with 2681 controls from the cohort. The mean age of the case patients was 30 years (range, 9 to 54). Seventeen of the case patients were less than 18 years old. The case patients and their matched controls had severe asthma. Fifty-three percent had been hospitalized for asthma in the previous two years, and during the previous year, 48.5 percent had used oral corticosteroids, 57.6 percent had used more than 18 canisters of inhaled ß-adrenergic agonists, 25.8 percent had used nebulized ß-adrenergic agonists, and 63.6 percent had used theophylline.

The case patients were older and more likely to be men than the controls (Table 1). Moreover, although case and control patients were matched according to the presence or absence of several markers of the severity of asthma, the frequency of these markers remained somewhat higher among case patients than among controls. As compared with controls, the case patients had more hospitalizations for asthma and more prescriptions for oral corticosteroids, inhaled ß-adrenergic agonists, nebulized ß-adrenergic agonists, oral ß-adrenergic agonists, and theophylline. Ninety-three percent of the prescribed canisters of inhaled corticosteroids contained low-dose beclomethasone (200 puffs per canister, with 50 µg of drug delivered per puff).

View this table: [in this window] [in a new window]   Table 1. Characteristics of the Study Subjects.

 
Table 2 presents the crude and adjusted matched rate ratios for death from asthma in relation to the use of inhaled corticosteroids during the previous year. The adjusted rate ratio for any use of inhaled corticosteroids during this period as compared with nonuse was essentially 1. However, the adjusted rate ratio for the use of six or more canisters of inhaled corticosteroids during this period was 0.15 (95 percent confidence interval, 0.02 to 1.22). Only one case patient had used six or more canisters during the previous year. From the continuous dose–response analysis, we calculated that the rate of death from asthma among users of inhaled corticosteroids decreased by 21 percent (rate ratio, 0.79; 95 percent confidence interval, 0.65 to 0.97) for every additional canister of inhaled corticosteroids used during the year. The rate was reduced by 54 percent (rate ratio, 0.46; 95 percent confidence interval, 0.26 to 0.79) for every additional canister of inhaled corticosteroids used during the previous six months.

View this table: [in this window] [in a new window]   Table 2. Crude and Adjusted Rate Ratios for Death from Asthma in Relation to the Use of Inhaled Corticosteroids during the One-Year and Six-Month Periods before the Index Date.

 
Figure 1 shows the fitted dose–response curve for the one-year period. The rate of death from asthma among users of inhaled corticosteroids as compared with nonusers was reduced by about 50 percent with the use of more than six canisters per year. A similar curve (not shown) was found for the six-month period. Figure 1 also suggests that sporadic use of inhaled corticosteroids (fewer than four canisters per year) may be associated with higher rates of death from asthma.

View larger version (5K): [in this window] [in a new window]   Figure 1. Fitted Rate Ratio for Death from Asthma as a Function of the Number of Canisters of Inhaled Corticosteroids Used during the Year before the Index Date. The index date for case patients and matched controls was the date of each case patient's death from asthma. The rate ratio is adjusted for the age and sex of the patient; the number of prescriptions for theophylline, nebulized and oral ß-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled ß-adrenergic agonists dispensed in the year before the index date; and the number of hospitalizations for asthma during the two years before the index date.

 
As Table 3 shows, 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 (rate ratio, 4.6; 95 percent confidence interval, 1.1 to 19.1). The rate ratios after longer periods of interruption were also elevated, but not significantly so.

View this table: [in this window] [in a new window]   Table 3. Crude and Adjusted Rate Ratios for Death from Asthma in Relation to Discontinuation of Inhaled Corticosteroid Use.

 
Discussion

We found that the use of low-dose inhaled corticosteroids, such as several puffs of beclomethasone per day, is associated with a decreased risk of death from asthma. Our data also suggest that the discontinuation of inhaled corticosteroids can be detrimental.

The validity of our findings is strengthened by the increase in benefit observed with increased regularity of use and by the increase in risk with discontinuation of inhaled corticosteroids. The benefits occur at doses of corticosteroids that are lower than those associated with adverse ocular effects in adults and with decreased growth in children. Such doses are also associated with little or no biochemical evidence of systemic effects.²² A prior study using the Saskatchewan data bases, although it suggested that inhaled corticosteroids had a beneficial effect in reducing the risk of life-threatening asthma, had insufficient power to examine death from asthma as the sole outcome.⁵ Data on trends over time also suggest an association between declining death rates from asthma and increasing sales of inhaled corticosteroids, but the potential for bias makes such studies appropriate for generating hypotheses rather than proving them.^12,23

Nonrandomized studies such as ours are susceptible to bias due to confounding by indication. Such bias would have occurred in the present study if patients with less severe asthma were more likely to have used inhaled corticosteroids. If there is any bias at all, it appears to have been in the reverse direction, since there was a slightly higher risk of death from asthma among subjects who received at least one prescription for inhaled corticosteroids in the previous 12 months than among those who used no inhaled corticosteroids during that period. Furthermore, the greater benefit seen with increasing use and the high risk associated with discontinuation of therapy suggest that patients with more severe asthma may have been more likely to receive inhaled corticosteroids. Finally, we were able to adjust for many of the factors previously shown to be markers of the severity of asthma and the risk of death, such as prior hospitalization, use of oral corticosteroids, and excessive use of short-acting inhaled ß-adrenergic agonists.

We believe that the most likely explanation of the excess risk of death from asthma shortly after the discontinuation of inhaled corticosteroid therapy is that such therapy was necessary to prevent death in these patients with asthma. The doses of inhaled corticosteroids used by most patients in this study were too low to result in adrenal insufficiency, a potential complication of the abrupt cessation of treatment with oral corticosteroids.

We excluded 11 deaths from consideration because they occurred during or within 1 year after an 18-month hiatus in the collection of information about drug prescriptions. There is no reason to believe that there was any significant difference between these 11 patients and the 66 patients whose deaths were included in the final analysis in terms of the severity of their asthma or the treatment they received. A strength of our study is that all deaths in this cohort of patients with asthma were identified, and that the cohort included all patients who were initially 5 through 44 years of age in the province of Saskatchewan to whom antiasthma drugs were dispensed on more than an occasional basis. We may have missed some deaths from asthma, because we included only deaths that two pulmonary physicians independently judged to have been due to asthma. There is no reason to believe, however, that missed case patients were more or less likely to have been prescribed inhaled corticosteroids, and therefore selection bias seems unlikely.

In conclusion, we found that the regular use of low-dose inhaled corticosteroids is associated with a decreased risk of death from asthma. This finding has important implications for the treatment of patients with asthma.

Supported by grants from the Medical Research Council of Canada, Astra Draco, Boehringer Ingelheim, and Zeneca Pharmaceuticals. Dr. Suissa is the recipient of a Senior Scientist Award from the Medical Research Council. Mr. Benayoun, Dr. Baltzan, and Mr. Cai received studentships from the Medical Research Council during the study period. The McGill Pharmacoepidemiology Research Unit is funded by an infrastructure grant from the Fonds de la Recherche en Santé du Québec. This study is based in part on data provided by the Saskatchewan Department of Health. The interpretation and conclusions contained herein do not necessarily represent those of the government of Saskatchewan or the Saskatchewan Department of Health.

Dr. Suissa is a consultant to Boehringer Ingelheim. Dr. Ernst is a consultant to Glaxo–Wellcome and Merck.

Source Information

From the Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University Health Centre, and the Departments of Epidemiology and Biostatistics and of Medicine, McGill University (S.S., P.E., S.B., M.B., B.C.); and the Division of Respiratory Medicine, McGill University Health Centre (P.E.) — all in Montreal.

Address reprint requests to Dr. Suissa at the Division of Clinical Epidemiology, Royal Victoria Hospital, 687 Pine Ave. West, Ross 4.29, Montreal, QC H3A 1A1, Canada, or at samy.suissa{at}clinepi.mcgill.ca.

References

1. Sears MR. Descriptive epidemiology of asthma. Lancet 1997;350:Suppl II:1-4. [Medline]
2. Suissa S, Ernst P, Boivin J-F, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med 1994;149:604-610. [Abstract]
3. Rea HH, Scragg R, Jackson R, Beaglehole R, Fenwick J, Sutherland DC. A case-control study of deaths from asthma. Thorax 1986;41:833-839. [Abstract]
4. Arrighi HM. US asthma mortality: 1941 to 1989. Ann Allergy Asthma Immunol 1995;74:321-326. [Medline]
5. 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. [Abstract]
6. Donahue JG, Weiss ST, Livingston JM, Goetsch MA, Greineder DK, Platt R. Inhaled steroids and the risk of hospitalization for asthma. JAMA 1997;277:887-891. [Abstract]
7. Barnes PJ. Current issues for establishing inhaled corticosteroids as the antiinflammatory agents of choice in asthma. J Allergy Clin Immunol 1998;101:S427-S433. [CrossRef][Medline]
8. Blais L, Suissa S, Boivin JF, Ernst P. First treatment with inhaled corticosteroids and the prevention of admissions to hospital for asthma. Thorax 1998;53:1025-1029. [Free Full Text]
9. Blais L, Ernst P, Boivin JF, Suissa S. Inhaled corticosteroids and the prevention of readmission to hospital for asthma. Am J Respir Crit Care Med 1998;158:126-132. [Free Full Text]
10. Garrett J, Kolbe J, Richards G, Whitlock T, Rea H. Major reduction in asthma morbidity and continued reduction in asthma mortality in New Zealand: what lessons have been learned? Thorax 1995;50:303-311. [Abstract]
11. Devoy MAB, Fuller RW, Palmer JBD. Asthma mortality and ß-agonists. Chest 1995;108:1768-1768.
12. Suissa S, Ernst P. Optical illusions from visual data analysis: example of the New Zealand asthma mortality epidemic. J Clin Epidemiol 1997;50:1079-1088. [CrossRef][Medline]
13. Crane J, Pearce N, Flatt A, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study. Lancet 1989;1:917-922. [Medline]
14. Pearce N, Grainger J, Atkinson M, et al. Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81. Thorax 1990;45:170-175. [Abstract]
15. Grainger J, Woodman K, Pearce N, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study. Thorax 1991;46:105-111. [Abstract]
16. Spitzer WO, Suissa S, Ernst P, et al. The use of ß-agonists and the risk of death and near death from asthma. N Engl J Med 1992;326:501-506. [Abstract]
17. Garbe E, LeLorier J, Boivin JF, Suissa S. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. JAMA 1997;277:722-727. [Abstract]
18. Cumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997;337:8-14. [Free Full Text]
19. Garbe E, Suissa S, LeLorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA 1998;280:539-543. [Erratum, JAMA 1998;280:1830.] [Free Full Text]
20. Simons FE. Benefits and risks of inhaled glucocorticoids in children with persistent asthma. J Allergy Clin Immunol 1998;102:S77-S84. [Medline]
21. Strand LM, Downey W. Health databases in Saskatchewan. In: Strom BL, ed. Pharmacoepidemiology. 2nd ed. Chichester, England: John Wiley, 1994:217-29.
22. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 1999;159:941-955. [Free Full Text]
23. Ernst P, Suissa S. Study designs of adverse events in asthma treatment. Eur Respir J 1992;5:773-775. [Medline]

Abstract PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article PubMed Citation

This article has been cited by other articles:

• Joos, S, Miksch, A, Szecsenyi, J, Wieseler, B, Grouven, U, Kaiser, T, Schneider, A (2008). Montelukast as add-on therapy to inhaled corticosteroids in the treatment of mild to moderate asthma: a systematic review. Thorax 63: 453-462 [Abstract] [Full Text]  
• Mehuys, E., Van Bortel, L., De Bolle, L., Van Tongelen, I., Annemans, L., Remon, J. P., Brusselle, G. (2008). Effectiveness of pharmacist intervention for asthma control improvement. Eur Respir J 31: 790-799 [Abstract] [Full Text]  
• Suissa, S. (2008). Immortal Time Bias in Pharmacoepidemiology. Am J Epidemiol 167: 492-499 [Abstract] [Full Text]  
• Bateman, E. D., Hurd, S. S., Barnes, P. J., Bousquet, J., Drazen, J. M., FitzGerald, M., Gibson, P., Ohta, K., O'Byrne, P., Pedersen, S. E., Pizzichini, E., Sullivan, S. D., Wenzel, S. E., Zar, H. J. (2008). Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 31: 143-178 [Abstract] [Full Text]  
• Skoner, D. P., Maspero, J., Banerji, D., and the Ciclesonide Pediatric Growth Study Group, (2008). Assessment of the Long-term Safety of Inhaled Ciclesonide on Growth in Children With Asthma. Pediatrics 121: e1-e14 [Abstract] [Full Text]  
• Nieto, A., Mazon, A., Pamies, R., Linana, J. J., Lanuza, A., Jimenez, F. O., Medina-Hernandez, A., Nieto, F. J. (2007). Adverse Effects of Inhaled Corticosteroids in Funded and Nonfunded Studies. Arch Intern Med 167: 2047-2053 [Abstract] [Full Text]  
• Mangione-Smith, R., DeCristofaro, A. H., Setodji, C. M., Keesey, J., Klein, D. J., Adams, J. L., Schuster, M. A., McGlynn, E. A. (2007). The Quality of Ambulatory Care Delivered to Children in the United States. NEJM 357: 1515-1523 [Abstract] [Full Text]  
• Cazzola, M., Matera, M. G. (2007). Review: Safety of long-acting {beta}2 -agonists in the treatment of asthma. Therapeutic Advances in Respiratory Disease 1: 35-46 [Abstract]  
• Suissa, S., McGhan, R., Niewoehner, D., Make, B. (2007). Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 4: 535-542 [Abstract] [Full Text]  
• Papi, A., Canonica, G. W., Maestrelli, P., Paggiaro, P., Olivieri, D., Pozzi, E., Crimi, N., Vignola, A. M., Morelli, P., Nicolini, G., Fabbri, L. M., the BEST Study Group, (2007). Rescue Use of Beclomethasone and Albuterol in a Single Inhaler for Mild Asthma. NEJM 356: 2040-2052 [Abstract] [Full Text]  
• Wechsler, M. E., Shepard, J.-A. O., Mark, E. J. (2007). Case 15-2007 -- A 20-Year-Old Woman with Asthma and Cardiorespiratory Arrest. NEJM 356: 2083-2091 [Full Text]  
• Butz, A. M., Tsoukleris, M., Donithan, M., Hsu, V. D., Mudd, K., Zuckerman, I. H., Bollinger, M. E. (2006). Patterns of Inhaled Antiinflammatory Medication Use in Young Underserved Children With Asthma. Pediatrics 118: 2504-2513 [Abstract] [Full Text]  
• Barnes, P. J. (2006). Treatment with (R)-Albuterol Has No Advantage over Racemic Albuterol.. Am. J. Respir. Crit. Care Med. 174: 969-972 [Full Text]  
• Barnes, P. J. (2006). Rebuttal by Dr. Barnes. Am. J. Respir. Crit. Care Med. 174: 974-974 [Full Text]  
• Halterman, J. S., Fisher, S., Conn, K. M., Fagnano, M., Lynch, K., Marky, A., Szilagyi, P. G. (2006). Improved preventive care for asthma: a randomized trial of clinician prompting in pediatric offices.. Arch Pediatr Adolesc Med 160: 1018-1025 [Abstract] [Full Text]  
• Schuh, S., Dick, P. T., Stephens, D., Hartley, M., Khaikin, S., Rodrigues, L., Coates, A. L. (2006). High-Dose Inhaled Fluticasone Does Not Replace Oral Prednisolone in Children With Mild to Moderate Acute Asthma. Pediatrics 118: 644-650 [Abstract] [Full Text]  
• Humbert, M. (2006). The Right Tools at the Right Time. Chest 130: 29S-40S [Abstract] [Full Text]  
• Williams, D. M. (2006). Considerations in the long-term management of asthma in ambulatory patients. Am J Health Syst Pharm 63: S14-S21 [Abstract] [Full Text]  
• Murray, C S, Poletti, G, Kebadze, T, Morris, J, Woodcock, A, Johnston, S L, Custovic, A (2006). Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax 61: 376-382 [Abstract] [Full Text]  
• Lim, D L, Ma, S, Wang, X S, Cutter, J, Chew, S K, Lim, T K, Lee, B W (2006). Trends in sales of inhaled corticosteroids and asthma outcomes in Singapore.. Thorax 61: 362-362 [Full Text]  
• Scarfone, R. J., Zorc, J. J., Angsuco, C. J. (2006). Emergency Physicians' Prescribing of Asthma Controller Medications. Pediatrics 117: 821-827 [Abstract] [Full Text]  
• Lange, P, Scharling, H, Ulrik, C S, Vestbo, J (2006). Inhaled corticosteroids and decline of lung function in community residents with asthma. Thorax 61: 100-104 [Abstract] [Full Text]  
• Nelson, H. S., Weiss, S. T., Bleecker, E. R., Yancey, S. W., Dorinsky, P. M., the SMART Study Group, (2006). The Salmeterol Multicenter Asthma Research Trial: A Comparison of Usual Pharmacotherapy for Asthma or Usual Pharmacotherapy Plus Salmeterol. Chest 129: 15-26 [Abstract] [Full Text]  
• Strek, M. E. (2006). Difficult asthma.. Proc Am Thorac Soc 3: 116-123 [Abstract] [Full Text]  
• Miller, M., Cho, J. Y., McElwain, K., McElwain, S., Shim, J. Y., Manni, M., Baek, J. S., Broide, D. H. (2006). Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 290: L162-L169 [Abstract] [Full Text]  
• Schatz, M., Nakahiro, R., Crawford, W., Mendoza, G., Mosen, D., Stibolt, T. B. (2005). Asthma Quality-of-Care Markers Using Administrative Data. Chest 128: 1968-1973 [Abstract] [Full Text]  
• Eurich, D. T., Majumdar, S. R., McAlister, F. A., Tsuyuki, R. T., Johnson, J. A. (2005). Improved Clinical Outcomes Associated With Metformin in Patients With Diabetes and Heart Failure. Diabetes Care 28: 2345-2351 [Abstract] [Full Text]  
• O'Sullivan, S. M. (2005). Asthma Death, CD8+ T Cells, and Viruses. Proc Am Thorac Soc 2: 162-165 [Abstract] [Full Text]  
• Boushey, H. A., Sorkness, C. A., King, T. S., Sullivan, S. D., Fahy, J. V., Lazarus, S. C., Chinchilli, V. M., Craig, T. J., Dimango, E. A., Deykin, A., Fagan, J. K., Fish, J. E., Ford, J. G., Kraft, M., Lemanske, R. F. Jr., Leone, F. T., Martin, R. J., Mauger, E. A., Pesola, G. R., Peters, S. P., Rollings, N. J., Szefler, S. J., Wechsler, M. E., Israel, E., the National Heart, Lung, and Blood Institute's As, (2005). Daily versus As-Needed Corticosteroids for Mild Persistent Asthma. NEJM 352: 1519-1528 [Abstract] [Full Text]  
• Senthilselvan, A., Lawson, J. A., Rennie, D. C., Dosman, J. A. (2005). Regular Use of Corticosteroids and Low Use of Short-Acting {beta}2-Agonists Can Reduce Asthma Hospitalization. Chest 127: 1242-1251 [Abstract] [Full Text]  
• Hertzman, P. A., Kelly, H. W., Coultas, D. (2005). Chronic Illness Care in Russia: A Pilot Project To Improve Asthma Care in a "Closed City". Chest 127: 861-865 [Abstract] [Full Text]  
• Masoli, M, Weatherall, M, Beasley, R (2005). Optimal starting dose of inhaled corticosteroids in adult asthma: why has it taken so long?. Thorax 60: 93-94 [Full Text]  
• Jayaram, L, Pizzichini, E, Lemiere, C, Man, S F P, Cartier, A, Hargreave, F E, Pizzichini, M M M (2005). Steroid naive eosinophilic asthma: anti-inflammatory effects of fluticasone and montelukast. Thorax 60: 100-105 [Abstract] [Full Text]  
• Anderson, H R., Ayres, J. G, Sturdy, P. M, Bland, J M., Butland, B. K, Peckitt, C., Taylor, J. C, Victor, C. R, for the Mortality and Severe Morbidity Group of th, (2005). Bronchodilator treatment and deaths from asthma: case-control study. BMJ 330: 117- [Abstract] [Full Text]  
• Reddel, H.K. (2004). Goals of asthma treatment: how high should we go?. Eur Respir J 24: 715-717 [Full Text]  
• Tattersfield, A. E., Harrison, T. W., Hubbard, R. B., Mortimer, K. (2004). Safety of Inhaled Corticosteroids. Proc Am Thorac Soc 1: 171-175 [Abstract] [Full Text]  
• Suissa, S. (2004). From the authors. Eur Respir J 24: 711-711 [Full Text]  
• Colice, G. L. (2004). Categorizing Asthma Severity: An Overview of National Guidelines. Clin Med Res 2: 155-163 [Abstract] [Full Text]  
• Sin, D. D., Man, J., Sharpe, H., Gan, W. Q., Man, S. F. P. (2004). Pharmacological Management to Reduce Exacerbations in Adults With Asthma: A Systematic Review and Meta-analysis. JAMA 292: 367-376 [Abstract] [Full Text]  
• Stempel, D. A., Roberts, C. S., Stanford, R. H. (2004). Treatment Patterns in the Months Prior to and After Asthma-Related Emergency Department Visit. Chest 126: 75-80 [Abstract] [Full Text]  
• Eurich, D. T., Majumdar, S. R., Tsuyuki, R. T., Johnson, J. A. (2004). Reduced Mortality Associated With the Use of ACE Inhibitors in Patients With Type 2 Diabetes. Diabetes Care 27: 1330-1334 [Abstract] [Full Text]  
• O'Byrne, P. M. (2004). Pharmacologic Interventions to Reduce the Risk of Asthma Exacerbations. Proc Am Thorac Soc 1: 105-108 [Abstract] [Full Text]  
• Suissa, S., Baltzan, M., Kremer, R., Ernst, P. (2004). Inhaled and Nasal Corticosteroid Use and the Risk of Fracture. Am. J. Respir. Crit. Care Med. 169: 83-88 [Abstract] [Full Text]  
• Marcus, P. (2003). Dosing Inhaled Steroids in Asthma: Is Once-a-Day Administration Effective?. Chest 124: 1196-1198 [Full Text]  
• Campbell, J.L., Kiebert, G.M., Partridge, M.R. (2003). Development of the Satisfaction with Inhaled Asthma Treatment Questionnaire. Eur Respir J 22: 127-134 [Abstract] [Full Text]  
• Verona, E, Petrov, D, Cserhati, E, Hofman, J, Geppe, N, Medley, H, Hughes, S (2003). Fluticasone propionate in asthma: a long term dose comparison study. Arch. Dis. Child. 88: 503-509 [Abstract] [Full Text]  
• Green, R H, Brightling, C E, Pavord, I D, Wardlaw, A J (2003). Management of asthma in adults: current therapy and future directions. Postgrad. Med. J. 79: 259-267 [Abstract] [Full Text]  
• Suissa, S., Ernst, P. (2003). Use of anti-inflammatory therapy and asthma mortality in Japan. Eur Respir J 21: 101-104 [Abstract] [Full Text]  
• Lozano, P., Finkelstein, J. A., Hecht, J., Shulruff, R., Weiss, K. B. (2003). Asthma Medication Use and Disease Burden in Children in a Primary Care Population. Arch Pediatr Adolesc Med 157: 81-88 [Abstract] [Full Text]  
• Irvine, L., Crombie, I.K., Alder, E.M., Neville, R.G., Clark, R.A. (2002). What predicts poor collection of medication among children with asthma? A case-control study. Eur Respir J 20: 1464-1469 [Abstract] [Full Text]  
• Lynd, L. D., Guh, D. P., Pare, P. D., Anis, A. H. (2002). Patterns of Inhaled Asthma Medication Use: A 3-Year Longitudinal Analysis of Prescription Claims Data From British Columbia, Canada. Chest 122: 1973-1981 [Abstract] [Full Text]  
• Johnson, J. A., Majumdar, S. R., Simpson, S. H., Toth, E. L. (2002). Decreased Mortality Associated With the Use of Metformin Compared With Sulfonylurea Monotherapy in Type 2 Diabetes. Diabetes Care 25: 2244-2248 [Abstract] [Full Text]  
• Leigh, R., Vethanayagam, D., Yoshida, M., Watson, R. M., Rerecich, T., Inman, M. D., O'Byrne, P. M. (2002). Effects of Montelukast and Budesonide on Airway Responses and Airway Inflammation in Asthma. Am. J. Respir. Crit. Care Med. 166: 1212-1217 [Abstract] [Full Text]  
• Weinberger, M., Murray, M. D., Marrero, D. G., Brewer, N., Lykens, M., Harris, L. E., Seshadri, R., Caffrey, H., Roesner, J. F., Smith, F., Newell, A. J., Collins, J. C., McDonald, C. J., Tierney, W. M. (2002). Effectiveness of Pharmacist Care for Patients With Reactive Airways Disease: A Randomized Controlled Trial. JAMA 288: 1594-1602 [Abstract] [Full Text]  
• Soriano, J.B., Vestbo, J., Pride, N.B., Kiri, V., Maden, C., Maier, W.C. (2002). Survival in COPD patients after regular use of fluticasone propionate and salmeterol in general practice. Eur Respir J 20: 819-825 [Abstract] [Full Text]  
• Suissa, S, Ernst, P, Kezouh, A (2002). Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma. Thorax 57: 880-884 [Abstract] [Full Text]  
• Barr, R. G., Somers, S. C., Speizer, F. E., Camargo, C. A. Jr (2002). Patient Factors and Medication Guideline Adherence Among Older Women With Asthma. Arch Intern Med 162: 1761-1768 [Abstract] [Full Text]  
• Lanes, S F, Garcia Rodriguez, L A, Huerta, C (2002). Respiratory medications and risk of asthma death. Thorax 57: 683-686 [Abstract] [Full Text]  
• Pinto Pereira, L. M., Clement, Y., Da Silva, C. K., McIntosh, D., Simeon, D. T. (2002). Understanding and Use of Inhaler Medication by Asthmatics in Specialty Care in Trinidad* : A Study Following Development of Caribbean Guidelines for Asthma Management and Prevention. Chest 121: 1833-1840 [Abstract] [Full Text]  
• Allen;, D. B., Sharek, P. J., Bergman, D. A. (2001). Effect of Inhaled Corticosteroids on Growth. Pediatrics 108: 1234-1235 [Full Text]  
• Kips, J. C. (2001). Treating Asthma, or Is Simple Too Simple?. Am. J. Respir. Crit. Care Med. 164: 1336-1338 [Full Text]  
• Kozyrskyj, A. L., Mustard, C. A., Cheang, M. S., Simons, F. (2001). Income-based drug benefit policy: impact on receipt of inhaled corticosteroid prescriptions by Manitoba children with asthma. CMAJ 165: 897-902 [Abstract] [Full Text]  
• Kips, J C, Pauwels, R A (2001). Low dose inhaled corticosteroids and the prevention of death from asthma. Thorax 56: ii74-78 [Full Text]  
• SIN, D. D., TU, J. V. (2001). Inhaled Corticosteroids and the Risk of Mortality and Readmission In Elderly Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 164: 580-584 [Abstract] [Full Text]  
• Rabe, K.F., Schmidt, D.T. (2001). Pharmacological treatment of asthma today. Eur Respir J 18: 34S-40s [Abstract] [Full Text]  
• Eisner, M. D., Abramson, M., Bailey, M., Couper, F., Driver, J., Drummer, O., Forbes, A., McNeil, J., Walters, E. H., Victorian Asthma Mortality Study Group, t. (2001). INHALED BETA AGONISTS AND DEATH FROM ASTHMA: REVISITING THE CONTROVERSY. Am. J. Respir. Crit. Care Med. 163: 1502-1502 [Full Text]  
• Kelly, H. W. (2001). The Management of Acute Severe Asthma. Journal of Pharmacy Practice 14: 91-107 [Abstract]  
• Bourdet, S. V., Williams, D. (2001). Management Considerations for Chronic Asthma. Journal of Pharmacy Practice 14: 108-125 [Abstract]  
• Mapp, C. E. (2000). Inhaled Glucocorticoids in Chronic Obstructive Pulmonary Disease. NEJM 343: 1960-1961 [Full Text]  
• Myers, K. A. (2000). New evidence of a link between inhaled corticosteroid use and osteoporosis. CMAJ 163: 1335-1335 [Full Text]