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Ambulatory Use of Inhaled [[Beta].sub.2]-Agonists for the Treatment of Asthma in Quebec - .Abstract - )
From CHEST, 5/1/01 by Regis Blais

Study objectives: To assess whether the utilization of inhaled short-acting [[Beta].sub.2]-agonists (ISAB) and inhaled long-acting [[Beta].sub.2]-agonists (ILAB) for the treatment of asthma was appropriate according to the 1996 Canadian Asthma Consensus Conference recommendations.

Design: Population-based retrospective drug utilization review using pharmacists' billing data of the Prescription Drug Insurance Plan administered by the Quebec health insurance board. However, the database used did not contain complete patient clinical information to accurately assess severity of asthma.

Setting: Province of Quebec, Canada.

Patients: Persons who received at least one outpatient prescription of ISAB (age range, 5 to 45 years) or ILAB (age range, 12 to 45 years) for the treatment of asthma between August 1997 and April 1998.

Measurements: Percentages of patients whose use was appropriate according to three criteria regarding the average daffy dose of ISAB (criterion 1), the renewal interval of ILAB (criterion 2), and the concomitant daffy use of corticosteroids for the expected length of utilization of ILAB (criterion 3).

Results: Overall proportions of appropriate use according to criterion 1 were as follows: 75% (without inhaled corticosteroids [ICS]) and 84% and 43% (with one or more than one prescription of ICS, respectively). Appropriateness was slightly higher for female patients, younger patients (5 to 18 years old), and those treated by pediatricians. However, appropriateness was only 9% among patients who received at least two prescriptions of ISAB during the study period. The proportion of appropriate use was 19% according to criterion 2 and 15% according to criterion 3; there were few differences by gender or by age, but the appropriateness according to criterion 2 was somewhat higher for patients of respirologists.

Conclusion: Compared to the 1996 Canadian asthma consensus conference recommendations, ISAB are overused, ICS are underused, and ILAB are often used improperly. Close collaboration between health professionals and patients is essential to improve the pharmacotherapy of asthma. (CHEST 2001; 119:1316-1321)

Key words: asthma; Canadian; consensus; corticosteroids; drug utilization review; inhaled [[Beta].sub.2]-agonists

Abbreviations: ICS = inhaled corticosteroids; ILAB = inhaled long-acting [[Beta].sub.2]-agonists; ISAB = inhaled short-acting [[Beta].sub.2]-agonists; RAMQ = Regie de l'assurance maladie du Quebec

A Population-Based Utilization Review

Asthma is the most common chronic respiratory disease of young North Americans, affecting about 5 to 10% of individuals aged from 0 to 45 years. In Canada alone, in 1990, the direct and indirect costs of asthma were already estimated to be from $504 to $648 million,[1] and have increased since then. Sixty-one percent of these costs were direct, and drugs were the most important item, followed by hospital and physician services.

The understanding and treatment of asthma have improved in recent years, especially with the advent of new and more effective drugs. In 1992, the US National Institutes of Health published guidelines for the diagnosis and management of asthma based on scientific evidence.[2] In 1996, a Canadian Asthma Consensus Conference developed similar guidelines.[3] In particular, recommendations were formulated about the use of inhaled [[Beta].sub.2]-agonists, coupled with inhaled corticosteroids (ICS) when needed. The Canadian consensus statement has been publicized among physicians and pharmacists, through several local continuing medical education programs across Canada and by publications of these guidelines in local journals.[4,5] Yet, previous experiences have shown that guideline dissemination alone does not guarantee change in clinical practice.[6] We suspected that this could also be the case for the drugs recommended for asthma. Identifying instances where drug treatment is less than optimal would help design interventions to improve the effectiveness of therapy.

The objective of this study was to assess the appropriateness of use of inhaled short-acting [[Beta].sub.2]-agonists (ISAB) and inhaled long-acting [[Beta].sub.2]-agonists (ILAB) for the treatment of asthma, according to specific criteria based on the recommendations of the 1996 Canadian asthma consensus conference. Using a large population-based approach, this study quantifies the problem of appropriateness of pharmacotherapy for asthma and identifies potential predictors, which has rarely been done before.


This study was a retrospective drug utilization review of ISAB and ILAB in Quebec, the second largest Canadian province (population 7.4 million).[7] Data came from the Prescription Drug Insurance Plan administered by the Regie de l'assurance maladie du Quebec (RAMQ), the Quebec health insurance board. The RAMQ plan covers about 3 million people classified into three groups: the elderly ([is greater than or equal to] 65 years old), welfare recipients, and those who do not have access to a private group plan.

The study population included the persons who received at least one outpatient prescription of ISAB or ILAB for the treatment of asthma, between August 1, 1997 and April 30, 1998. To simplify the analysis and because they were few, users of [[Bets].sub.2]-agonists administered with a nebulizer were not selected. To compensate for the absence of valid diagnostic information in the RAMQ database and retain actual asthma subjects, a number of exclusions were made. Patients [is greater than] 45 years old were excluded because of a higher prevalence of COPD in this age group. For the analysis of ISAB, children [is less than] 5 years old were excluded because of the difficulty of diagnosing asthma and to avoid including cases of bronchiolitis, which is common at that age. For the analysis of ILAB, children [is less than] 12 years old were excluded because the medication is not officially indicated for this age group. Subjects who took certain drugs (acetylcysteine, racemic epinephrine, ipratropium alone or in combination with salbutamol, morphine, pancreatin, pancrelipase, and tobramycin) were excluded because they could have received inhaled [[Beta].sub.2]-agonists for medical conditions other than asthma. Among those who used ISAB, we also excluded subjects who took oral corticosteroids during the study period, in order to exclude those with severe asthma who may temporarily require higher doses of ISAB during acute asthma episodes. As the appropriate consumption of ISAB is difficult to assess in patients with more severe asthma, we excluded subjects who received estimated daily doses of inhaled beclomethasone or its equivalent: [is greater than] 800 [micro]g for those aged between 5 years and 11 years, or 1,000 [micro]g for those [is greater than or equal to] 12 years old. Finally, among subjects who had only one prescription of ISAB during the study period, we excluded those for whom the interval between the date the prescription was filled and the end of the observation period was [is less than] 100 days for salbutamol consumption (other periods apply for other drug denominations according to number of inhalations per device) because the time frame was then too short to assess the appropriateness of use.

Two databases from the RAMQ were used and linked at the patient level using unique encrypted health insurance numbers. The pharmacist billing database provided information on the drugs dispensed (type of drug, duration of treatment, and date where prescription was filled) and the identification of the prescriber (including specialty) and the patient. The beneficiary database contained the patient age, gender, and region of residence. The validity of the Quebec prescription claims databases for pharmacoepidemiologic research has been established.(8)

Study subjects were classified into four mutually exclusive groups: users of ISAB without ICS (n = 20,633), with one (n = 6,716) or more than one (n = 6,067) prescription of ICS during the study period, and users who received ILAB with or without ISAB (n = 775). The generic names of the study drugs for ISAB are fenoterol, pirbuterol, salbutamol, and terbutaline; those for ILAB are formoterol and salmeterol; and those for ICS are beclomethasone, budesonide, flunisolide, fluticasone and triamcinolone. Based on the dates when the prescriptions were filled and the use of appropriate equivalence factors related to beclomethasone for different ICS, average daily consumption of ISAB and ICS (of beclomethasone dipropionate equivalent) was calculated. Table 1 presents the approximate equivalence of different ICS used in this study and estimated from various expert sources.[9-12] However, there are yet no definite equivalence factors because the mode of administration and absorption varies by drug.

For each subject in the database, the first prescription of inhaled [[Beta].sub.2]-agonists was identified. We then assessed whether the use of this prescription was appropriate according to three criteria developed by a panel of experts. Those criteria were based on the 1996 Canadian Asthma Consensus Conference guidelines.[3] One criterion was developed to assess the use of ISAB and two applied to the use of ILAB. These three criteria are as follows:

Criterion 1: Use of ISAB was considered appropriate if two inhalations per day or less of equivalent salbutamol were taken, either with or without ICS. The Canadian consensus guidelines recommend a maximum of two inhalations of [[Beta].sub.2]-agonists three times a week, excluding use to prevent symptoms due to exercise. Since the available data contained no information on use of [[Beta].sub.2]-agonists for exercise-induced symptoms, a less stringent criterion was employed to allow for such use. The appropriateness of the daily dosage was assessed both according to the quantity dispensed and by measuring the time interval between two dispensings of [[Beta].sub.2]-agonists. In the event that only one prescription of ISAB was present in the database during the study period, use was automatically found appropriate because the interval between the date the prescription was filled and the end of the observation period was at least equivalent to 100 days of salbutamol consumption (ie, two inhalations per day).

Criterion 2: Use of ILAB was considered appropriate if they were refilled between 25 days and 35 days after filling of the initial prescription. According to the experts, if the prescription was refilled before 25 days, consumption was considered too high; if it was after 35 days, consumption was deemed insufficient to control asthma properly.

Criterion 3: If an inhaled or oral corticosteroid was concurrently taken (the exact close varies with each patient condition although it is generally accepted that the dose of ICS should be at least 400 [micro]g/d) during the full period of the prescription for ILAB, utilization was considered appropriate. According to the Canadian asthma consensus guidelines, ICS should not be interrupted during treatment with ILAB.

For each of the four study groups, we calculated the proportion (percentage) of patients whose use of [[Beta].sub.2]-agonists was appropriate according to the specified criteria, broken down by patient characteristics (age, gender, and region of residence) and physician specialty. The numerator was the number of patients whose use was appropriate and the denominator was the total number of patients in each category. The analysis of associations between appropriateness of use and physician and patient characteristics as do e using Pearson [chi square] test.


Results are presented separately for ISAB and ILAB. Table 2 shows the demographic characteristics of the study population using ISAB and the proportion of appropriate use according to these characteristics. Most users are adult female patients, and most have had, their prescriptions written by general practitioners.

In the group not concurrently taking ICS, the overall proportion of appropriate use was 75%. Appropriateness was higher among female and younger subjects and those treated by pediatricians, although the latter represent only 5% of cases. It varied little across the different regions of subject residence (70 to 79%), with the exception of Northern Quebec (65%), where only 24 patients came from (data not shown). It is worth noting that 72% of patients had no second prescription of ISAB during the study period, thus automatically making their use appropriate according to criterion 1. By excluding them from the analysis, the proportion of appropriate use drops to 9% (482 of 5,675 subjects) and the differences between subgroups of patients remain more or less the same.

In the group using both ISAB and ICS, the overall proportion of appropriate use was 84% among subjects who had only one prescription of ICS and 43% among those who had more than one. Considering only the subjects who had at least two prescriptions of ISAB during the study period, appropriateness drops to 11% (126 of 1,173 subjects) and 8% (282 of 3,758 subjects), respectively. Overall, appropriateness was quite similar for male and female subjects, but was higher for younger ones, especially among those who had more than one prescription of ICS during the study period (57% among subjects 5 to 11 years old, 35% among subjects 19 to 45 years old). Subjects treated by pediatricians had a higher proportion of appropriate use. The proportion varied somewhat less across regions in the group with one prescription of ICS (81 to 89%) than with two or more prescriptions (36 to 48%).

The Canadian consensus guidelines suggested that for people [is greater than or equal to] 12 years old who are not optimally controlled with low doses of ICS (400 [micro]g/d), this dose should be increased up to 1,000 [micro]g of beclomethasone or equivalent. This study shows that 63% of subjects in this age group whose use of ISAB was considered questionable took on average [is less than] 400 [micro]g/d of inhaled beclomethasone or its equivalent, ie, probably not enough to be adequately controlled. For younger children, the recommended dosage is more variable, so a similar assessment is more difficult to make. Yet, 57% of children aged between 5 years and 11 years used daily doses [is less than] 200 [micro]g of inhaled beclomethasone or its equivalent.

Only 775 users of ILAB were identified. There were more female than male subjects and many more adults than adolescents in this group (Table 3). Unlike subjects taking ISAB, nearly half of the subjects received the prescription of their long-acting preparations from respirologists and about one third from general practitioners. The interval for refilling a prescription of ILAB (criterion 2) was considered appropriate for 19% of users. Few (5%) refilled their initial prescription of ILAB too early, ie, before 25 days, while 76% did so [is greater than] 35 days after. Appropriateness was even lower for criterion 3 (15%) regarding the necessity to use corticosteroids concurrently. For both criteria, appropriateness did not vary by gender or by age, but for criterion 2, it was somewhat higher for subjects treated by respirologists than other physicians. Analysis by region was not conducted because many regions had too few eases.

The Canadian consensus guidelines recommended that ICS be continued during a treatment with ILAB. During the study period, 8% of subjects received no ICS. Among those who received ICS and whose quantity could be estimated, 32% took [is less than] 400 [micro]/d, which is generally considered insufficient. Alternatively, 25% of subjects received 400 to 800 [micro]g of ICS, 20% received 800 to 1,000 [micro]g, and 23% received [is greater than] 1,000 [micro]g daily.

Finally, the 1996 Canadian consensus guidelines stated that when a patient is treated with ILAB, ISAB could also be used if needed, but at the lowest possible dosage.[2] The concurrent use of ISAB among users of ILAB was thus examined. Results showed that 47% of the latter group also took on average more than the two maximum recommended inhalations of salbutamol or its equivalent daily.


The three main findings of this study are that, compared to the recommendations of the Canadian Asthma Consensus Conference, (1) ISAB are overused, (2) ICS seem to be underused, and (3) ILAB are often used improperly. This means that, despite their dissemination among physicians, the Canadian consensus guidelines are far from having been put into practice. Other studies[13-18] also have shown that treatment for asthma was suboptimal. More generally, it has often been demonstrated that simple dissemination of guidelines or consensus statements does not change clinical practice, particularly prescribing patterns.[19,20]

Explanations for suboptimal drug use could be related the characteristics of patients, health-care providers, policies, and the drugs themselves. First, higher proportion of appropriate use of ISAB among 5- to 18-year-old patients may be due to the fact that parents take charge of the treatment of children, especially younger ones, and monitor it closely. Second, erroneous negative perceptions about the potential side effects of ICS among asthmatic patients may be a barrier to adherence to optimal treatment.[21] Finally, the inappropriate use of ILAB may be explained by the lack of knowledge among users as to the specific role of the various medications employed in the treatment of asthma, ie, ISAB, ILAB, and ICS.

For health-care professionals, several factors may contribute to the nonadherence to clinical recommendations (eg, unawareness of recent knowledge, practice setting, mode of remuneration).[22] In this study, the fact that pediatricians (for ISAB),and respirologists (for ILAB) prescribe more appropriately than general practitioners may be due to differences in training and practice volume.[23,24] Alternatively, inappropriate or insufficient patient education by providers may also lead to inadequate use of medication.

Policies such as cost-sharing arrangements could also influence the appropriateness of drug use. The cost of corticosteroids is much higher than the cost of [[Beta].sub.2]-agonists. Despite the public drug plan coverage in Quebec, co-payment by users may reduce compliance to optimal treatment of asthma. Under the RAMQ drug plan, prescribed medications are free of charge for children up to 18 years old. Gratuity for this category of subjects may then explain why the proportion of appropriate use (especially with ICS) is higher since economical accessibility is a facilitator.

The characteristics of the drugs themselves may also condition their optimal use. The overuse of ISAB and underuse of ICS by patients may be due to the fact that the former provide immediate relief of acute symptoms compared to the latter, a long-term controller whose effect can take more than a week to show. Patients may prefer the medication they actually feel is beneficial, while failing to properly treat the underlying inflammatory cause of their symptoms. The difficulty in taking this type of medication could also cause problem. For example, wrong techniques of administration of inhalers may reduce their effect and contribute to their overuse, especially in the case when a drug, such as [[Beta].sub.2]-agonists, is taken for immediate relief.

Since the use of drugs is the outcome of a process involving mainly the physician, the pharmacist, and the patient, behavioral change should be sought in all three to improve the pharmacotherapy of asthma. For ISAB, since general practitioners are the main prescribers, they should be the principal target of interventions aimed at changing physician behavior. Adult male patients should receive special attention because of their lower appropriate use of ISAB. In the case of ILAB, everyone needs to be reminded that ICS should not be interrupted during a treatment with ILAB (criterion 3).

Various types of interventions could be implemented to improve the quality of drug prescribing and utilization, and many of them have been reviewed elsewhere.[19,22,25-27] In any case, close collaboration between health professionals and patients is essential. Here are some proposals that apply especially to the subject of this study. For example, an algorithm for the treatment of asthma should be distributed to physicians and pharmacists to ensure that a consistent message is delivered to asthmatic patients. Physicians and pharmacists should have inhaler placebo demonstrators in their work settings to teach patients how to use this type of device. Public authorities should support the implementation of centers where physicians and pharmacists can refer asthmatic patients for education and informative material about environmental risk factors and treatments for asthma.[28] Professionals themselves should participate in continuing education activities to improve their knowledge and skills regarding this disease.

This study has a number of limitations, especially related to the use of administrative databases. The main limitation is the absence of valid information about the clinical indication for treatment. The large number of subjects who had only one prescription for ISAB during the study period makes us think that, despite our efforts, the selection of asthmatic patients was not perfect. The absence of diagnostic information in the database also precludes adjustment of appropriateness for case severity, which would be useful when comparing regions or physicians by specialty. Another limitation comes from the fact that the study is based on claims that pharmacists send to the RAMQ when they fill a prescription. Information on actual consumption of medication delivered is not known for sure but only assumed. Yet the RAMQ drug prescriptions database has been shown to be both reliable and valid,s Finally, the data source employed did not include samples that were given to subjects by physicians nor medications received by patients who were admitted to hospitals. As a consequence, given that criterion 1 is based on the refill patterns of ISAB, the proportion of appropriate use may have been overestimated. Conversely, daily dosages of ICS that were calculated may have been underestimated.

In summary, this study suggests that the recommendations of the 1996 Canadian Asthma Consensus Conference were far from being followed by physicians and/or their patients. A new Canadian asthma consensus report has now been published.[29] In the light of our result, it seems that special actions need to be taken to make 'sure that the new guidelines are not only disseminated but implemented by all involved parties.

ACKNOWLEDGMENT: The clinicians of the expert panel who worked on the criteria of appropriate use of the study drugs were Dr. Jacques Bouehard, general practitioner; Dr. Louis-Philippe Boulet, respirologist; Dr. Andre Cartier, respirologist; Dr. Pierre Larivee, respirologist; and Mrs. Rachel Rouleau, pharmacist.


[1] Krahn MD, Berka C, Langlois P, et al. Direct and indirect costs of asthma in Canada, 1990. Can Med Assoc J 1996; 154:821-831

[2] Fitzgerald ST. National asthma education program expert panel report: guidelines for the diagnosis and management of asthma. AAOHN J 1992; 40:376-382

[3] Ernst P, FitzGerald JM, Spier S, et al. Canadian Asthma Consensus Conference: summary of recommendations. Can Respir J 1996; 3:89-100

[4] Boulet LP, Thivierge RL, Cartier A. L'asthme: interventions educatives, plan d'action et suivi. Le Clinicien 1996; juin: 109-127

[5] Ernst P, Berube D, Boulet LP. Consensus sur le bilan et le traitement de l'asthme. Le Clinicien 1996; mai:122-138

[6] Lomas J, Anderson GM, Domnick-Piere K, et al. Do practice guidelines guide practice? The effect of a consensus statement on the practice of physicians. N Engl J Med 1989; 321:1306-1311

[7] Comite de revue de l'utilisation des medicaments. Revue de l'utilisation des agonistes [[Beta].sub.2] inhales employes dans le traitement de l'asthme: rapport d'etude. Quebec, Canada: Comite de revue de l'utilisation des medicaments, 1999

[8] Tamblyn R, Lavoie G, Petrella L, Monette J. The use of prescription claims databases for pharmacoepidemiological research: the accuracy and comprehensiveness of the prescription claims databases in Quebec. J Clin Epidemiol 1995; 48:999-1009

[9] Barnes PJ. Inhaled glucocorticoids for asthma. N Engl J Med 1995; 13:868-875

[10] Canadian Pharmacists Association. Compendium of Pharmaceuticals and Specialties. Ottawa, Canada: Canadian Pharmacists Association, 1998

[11] Conseil consultatif de pharmacologie. L'aerosoltherapie dans le traitement de l'asthme et des autres bronchopneumopathies obstructives. Info-medicaments 1995; mai:1-20

[12] Kelly HW. Comparison of inhaled corticosteroids. Ann Pharmacother 1998; 32:220-232

[13] Boulet LP. L'asthme: notions de base, education, intervention. Quebec, Canada: Les Presses de l'Universite Laval, 1997

[14] Habbick B, Baker MJ, McNutt M, et al. Recent trends in the use of inhaled [[Beta].sub.2]-adrenergic agonists and inhaled corticosteroids in Saskatchewan. Can Med Assoc J 1995; 153:1437-1443

[15] Hartert TV, Windom HH, Peebles RS Jr, et al. Inadequate medical outpatient therapy for patients with asthma admitted to two urban hospitals. Am J Med 1996; 100:386-394

[16] Jatulis DE, Meng YY, Elashoff RM, et al. Preventive pharmacologic therapy among asthmatics: five years after publication of guidelines. Ann Allergy Asthma Immunol 1998; 81:82-88

[17] Legorreta AP, Christian-Herman J, O'Connor RD, et al. Compliance with national asthma management guidelines and specialty care: a health maintenance organization experience. Arch Intern Med 1998; 158:457-464

[18] Diette GB, Wu AW, Skinner EA, et al. Treatment patterns among adult patients with asthma: factors associated with overuse of inhaled [Beta]-agonists and underuse of inhaled corticosteroids. Arch Intern Med 1999; 159:2697-2704

[19] Anderson GM, Lexchin J. Strategies for improving prescribing practice. Can Med Assoc J 1996; 154:1013-1017

[20] Soumerai SB, Lipton HL. Evaluating and improving physician prescribing. In: Strom BL, ed. Pharmacoepidemiology. 2nd ed. New York, NY: Wiley, 1994; 395-412

[21] Boulet LP. Perception of the role and potential side effects of inhaled corticosteroids among asthmatic patients. Chest 1998; 113:587-592

[22] Lexchin J. Improving the appropriateness of physician prescribing. Int J Health Serv 1998; 28:253-267

[23] Storms B, Olden L, Nathan R, et al. Effect of allergy specialist care on the quality of life in patients with asthma. Ann Allergy Asthma Immunol 1995; 75(6 pt 1):491-494

[24] Hardy CC, Donovan H, Bell C. Do general physicians really manage asthma as effectively as chest physicians [abstract]? Am J Respir Crit Care Med 1994; 149(suppl):A1077

[25] Lavoie GY. L'utilisation optimale des medicaments chez les personnes agees. L'omnipraticien 1998; 19 fevrier:24-33

[26] Liddell MJ, Goldman SP. Attitudes to and use of a modified prescription form by general practitioners and pharmacists. Med J Aust 1998; 168:322-325

[27] Roberts MS, Stokes JA. Prescriptions, practitioners and pharmacists. Med J Aust 1998; 168:317-318

[28] Boulet LP, Boutin H, Cote J, et al. Evaluation of an asthma self-management education program J Asthma 1995; 32:199-206

[29] Boulet LP, Becker A, Berube D, et al. Canadian asthma consensus report, 1999. Can Med Assoc J 1999; 161(11 Suppl):S1-S62


In addition to Dr. Blais and Dr. Gregoire, the members of the Comite de revue de l'utilisation des medicaments are Dr. Michelle Lussier-Montplaisir, Mrs, Diane Lamarre, Mr. Elie Assal, Mrs. Danielle Doyon, Dr. Yvon Grand'Maison, Dr. Serge Langlois, and Mr. Pierre Madore. Mrs. Diane Blais, Mrs. Louise Barnard, Mrs. Joelle Mimeault, and Mr. Marc Saindon acted as a support staff.

Regis Blais, PhD; Jean-Pierre Gregoire, PhD; Rachel Rouleau, MSc; Andre Cartier, MD; Jacques Bouchard, MD; and Louis-Philippe Boulet, MD; and the Comite de revue de l'utilisation des medicaments([dagger])

(*) From the Departement d'administration de la sante et Groupe de recherche interdisciplinaire en sante (Dr. Blais), Universite de Montreal, Montreal; Faculte de pharmacie et Groupe de recherche en Epidemiologie (Dr. Gregoire), Universite Laval, Quebec city; Centre universitaire de sante de l'Estrie (Ms. Rouleau), Sherbrooke; Service de pneumologie (Dr. Cartier), Hopital du Sacre-Coeur de Montreal, Montreal; Centre hospitalier St-Joseph de La Malbaie (Dr. Bouchard), La Malbaie; and Centre de pneumologie de l'Hopital Laval (Dr. Boulet), Institut de cardiologie et de pneumologie de l'Universite Laval, Quebec City, Quebec, Canada.

([dagger]) A complete list of participants is given in the Appendix. This study was funded by the Comite de revue de l'utilisation des medicaments of the province of Quebec.

Manuscript received February 1, 2000; revision accepted November 16, 2000.

Correspondence to: Regis Blais, PhD, Groupe de recherche interdisciplinaie en sante, Universite de Montreal, PO Box 6128, Station Centre-ville, Montreal, QuEbec, Canada H3C 3J7; e-mail:

COPYRIGHT 2001 American College of Chest Physicians
COPYRIGHT 2001 Gale Group

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