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American Journal of Epidemiology Advance Access published online on November 24, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn309
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Original Contribution

Determinants of the Incidence of Childhood Asthma: A Two-Stage Case-Control Study

Marie-Josée Martel, Évelyne Rey, Jean-Luc Malo, Sylvie Perreault, Marie-France Beauchesne, Amélie Forget and Lucie Blais

Correspondence to Dr. Lucie Blais, Faculté de pharmacie, Université de Montréal, C.P. 6128, succursale Centre-ville, Montréal, Québec H3C 3J7, Canada (e-mail: lucie.blais{at}umontreal.ca).

Received for publication December 14, 2007. Accepted for publication September 8, 2008.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Extensive literature exists on potential risk factors for childhood asthma. To the authors’ knowledge, no investigators have yet attempted to disentangle the effects of those determinants within a single study setting. The authors aimed to evaluate the independent effects of 47 potential determinants (from the prenatal, perinatal, and childhood periods) of asthma development in children within the first 10 years of life. From a Canadian birth cohort of 26,265 children (1990–2002), a 2-stage case-control study was conducted. In the first stage, 20 controls per case were selected from 3 administrative databases. In the second stage, selected mothers were mailed questionnaires for assessment of additional determinants. Increased risks of childhood asthma were found for ≥1 previous diagnosis of bronchopulmonary disease and atopic dermatitis in the child, oxygen administration after birth, prescription of antibiotics within the first 6 months of life, male gender, asthma during pregnancy, use of antibiotics during pregnancy, maternal receipt of social aid, paternal asthma, and asthma in siblings. Protective effects included use of intranasal corticosteroids during pregnancy, having a wood-burning fireplace, having pets in the home prior to the index date, breastfeeding, and day-care attendance. This study allowed the authors to identify, within a single setting, the most influential determinants of childhood asthma among 47 predictors assessed for the prenatal, perinatal, and childhood periods.

asthma; case-control studies; child; databases as topic; epidemiologic factors; Quebec; questionnaires; risk factors

Abbreviations: ICD-9, International Classification of Diseases, Ninth Revision; MED-ECHO, Maintenance et Exploitation des Données pour l'Étude de la Clientèle Hospitalière; RAMQ, Régie de l'assurance-maladie du Québec


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
The prevalence of childhood asthma has been increasing over the last few decades, as has its related burden (1, 2). In addition to the personal and social impacts of childhood asthma, increases in emergency-room visits, hospitalizations, and missed school days due to asthma exacerbations in children have emphasized the need to understand the development of childhood asthma and identify its key determinants, especially modifiable ones (3, 4).

The presence of asthma and atopy in the family, most importantly maternal history of asthma, is one of the many risk factors reported in the literature (5, 6). Furthermore, the timing of exposure is also of interest, as there is evidence that some of the atopic response of the child could be primed in utero and influenced after birth (6–8).

However, while the literature on potential determinants of childhood asthma is extensive, results obtained are sometimes mitigated and/or could still be confounded, since most investigators have been providing risk estimates adjusted only for subsets of risk factors, leaving the estimates unadjusted for several other determinants. Furthermore, in some well-performed studies, investigators gathered data on a wide variety of potential determinants, but those data were analyzed by subgroup, thereby limiting the ability to disentangle the independent effects of those individual variables (9–15). The above-mentioned limitations could be due to the unavailability of necessary information or to small sample sizes, precluding the investigation of several determinants at the same time.

Thus, we conducted the current study to obtain a more complete picture of the development of childhood asthma. Using the rich source of data provided by large administrative health databases and a mailed questionnaire, we aimed at identifying the independent effects of 47 potential predictors, measured during pregnancy and after birth, on the incidence of asthma development in children within the first 10 years of life.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Study design and sources of data
A case-control study with a 2-stage sampling strategy was the design retained. It involved data originating from 3 interlinked administrative health databases in Quebec, Canada (the Régie de l'assurance-maladie du Québec (RAMQ) medical and pharmaceutical services database, the Maintenance et Exploitation des Données pour l'Étude de la Clientèle Hospitalière (MED-ECHO) hospitalizations database, and the Birth and Death Registry) and a mailed questionnaire. A portion of the data available from those sources has been used to investigate, among children of asthmatic mothers, the effect of maternal asthma control and severity on the incidence of childhood asthma (Martel et al., Université de Montréal, unpublished manuscript, 2007). In the present study, we focused on the analysis of all available and pertinent determinants and included children of both asthmatic mothers and nonasthmatic mothers. The databases and their linkage have been described elsewhere (16).

From the databases, a cohort of pregnant women and their children was formed. It consisted of all asthmatic women and a sample of nonasthmatic women who had had at least 1 singleton pregnancy ending in a livebirth between 1990 and 2002. If a woman had had more than 1 pregnancy during the study period, only the latest pregnancy was retained in the cohort. To be considered as having asthma during a pregnancy, a woman had to have filled 1 or more prescriptions for asthma medication and had to have 1 or more asthma diagnoses (International Classification of Diseases, Ninth Revision (ICD-9), code 493) recorded in the RAMQ or MED-ECHO database 2 years before or during the pregnancy of interest. Nonasthmatic women did not receive any diagnostic code for asthma or fill any prescriptions for asthma medication during the 1990–2002 study period. Nonasthmatic women were randomly selected from the RAMQ. They represented 33% of all nonasthmatic women covered by the RAMQ for their medications with 1 or more pregnancies during the 1990–2002 period.

The cohort included 8,226 asthmatic women and 18,039 nonasthmatic women and their 26,265 children (Figure 1). Children entered the cohort at birth and were followed until the end of governmental drug insurance coverage, their 10th birthday, December 31, 2002, or asthma development, whichever occurred first.


Figure 1
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  		Figure 1. Course of a 2-stage nested case-control study of childhood asthma, Quebec, Canada, 1990–2002. First, a cohort of children of asthmatic and nonasthmatic mothers was isolated. Second (stage 1), cases and matched controls were selected from the cohort. In the first stage of sampling, asthma cases were identified within the cohort and 20 controls were selected from the "risk set" of children who were at risk of asthma at the time of case occurrence. Third (stage 2), balanced sampling was performed to obtain a subsample of cases and controls to which questionnaires were mailed. In the second stage, balanced sampling of cells of the first-stage exposure-outcome cross-table was performed, allowing overrepresentation of small cells and an increase in statistical power. Therefore, in this stage of sampling, the asthma status of the mother and the occurrence of childhood asthma were considered. Random sampling without replacement was used; cases could only contribute as cases to the sampling pool; and controls were selected among noncases at the end of follow-up. Estimates obtained for maternal asthma in the statistical analyses were corrected using sampling fractions and maternal asthma estimates from the first stage of the study. Information on questionnaire responses is also provided in the figure.

 
The first stage of the study consisted of a case-control study, nested in the cohort of children. A child was considered a case if he/she had received at least 1 diagnosis for asthma (ICD-9 code 493) and had had at least 1 prescription for asthma medication filled within a 2-year period. The case's index date was the latter of 2 dates: the first occurrence of an asthma diagnostic code and a filled prescription for asthma medication within a 2-year period. Twenty controls per case were selected using density sampling, and controls were matched to cases on age at asthma occurrence (the index date for controls was the date of selection, i.e., the index date of the matched case) (17).

For the second stage of the study, a questionnaire was mailed to a subsample of mothers of cases and controls to obtain more information on variables not available in databases. Balanced sampling of cells of the first-stage exposure-outcome cross-table was performed. This allowed the overrepresentation of small cells and an increase in statistical power (18, 19).

The addresses of the mothers were obtained from the RAMQ for this subsample. Only women whose mailing address was in Quebec, who were alive, and whose child was alive and had the same mailing address as the mother were contacted for the second stage of the study. The questionnaire included 40 questions on 15 pages and was available in both French and English. To increase the questionnaire's response rate, we sent a postal reminder card and a second copy of the questionnaire to the mothers 1 month apart and issued Can$10 compensation to women who sent back a completed questionnaire. The questionnaire was pretested, and double-entry of questionnaire information was carried out independently by 2 research assistants in 2 Microsoft Access databases (Microsoft Corporation, Seattle, Washington) in order to ensure the quality of the data.

Approvals to conduct this study were obtained from the Commission d'accès à l'information du Québec and the ethics board of the Hôpital du Sacré-Coeur de Montréal.

Determinants of childhood asthma
We conducted a systematic review in order to identify determinants to be considered. Data on 47 determinants were retrieved from either the administrative databases or the questionnaire. Their sources and definitions are detailed below.

Maternal risk factors.
From the databases, we obtained information on maternal asthma during pregnancy, use of intranasal corticosteroids during pregnancy, mean number of antibiotic prescriptions filled per month during pregnancy, number of prenatal visits, obstetrician visits during pregnancy, mode of delivery, having had a pregnancy in the preceding year, chronic hypertension, pregnancy-induced hypertension, diabetes mellitus, and gestational diabetes. From the questionnaire, we obtained information on history of allergy and atopy, maternal weight gain during pregnancy, smoking (during pregnancy and prior to the index date), and duration of breastfeeding.

Paternal risk factors.
For paternal risk factors, we obtained information on history of asthma, history of allergy and atopy, and paternal smoking (during pregnancy and prior to the index date) from the questionnaire.

Childhood risk factors.
From the databases, we obtained information on male gender, being born small for gestational age, diagnosis of allergic rhinitis (ICD-9 code 477) or atopic dermatitis (ICD-9 code 691) prior to the index date, and having at least 1 prescription for antibiotics filled prior to the index date or within the first 6 months of life. From the questionnaire, we obtained information on the development of atopy indicators prior to the index date (reported allergies to acetylsalicylic acid, animals, dust mites, hay fever, pollen, other aeroallergens, mold, metal, or cutaneous allergies), and diagnosis of bronchopulmonary disease, administration of oxygen to the newborn after birth, and history of asthma, allergy, and atopy in the child's siblings.

Socioeconomic and environmental risk factors.
From the databases, we obtained information on maternal age at conception, maternal receipt of social welfare (in the year before or during pregnancy), maternal education at delivery, and living in a rural area. From the questionnaire, we obtained information on family income during the year of delivery, whether the child had always lived with the mother prior to the index date, day-care attendance from birth to the index date, the presence of pets in the home (for ≥2 months during pregnancy and ≥2 months prior to the index date), the presence of a wood-burning fireplace in the house (during pregnancy and prior to the index date), primary type of heating source (during pregnancy and prior to the index date), area of residence (during pregnancy and prior to the index date), reporting of the presence of mold in the mother's bedroom during pregnancy, and reporting of the presence of mold in the child's bedroom between birth and the index date.

Statistical analyses
Crude rates of childhood asthma for children of asthmatic and nonasthmatic mothers were estimated from the cohort. For the first stage of the study, we obtained crude and adjusted rate ratios using conditional logistic regression and a backward selection strategy (20).

For the analysis using the subsample of cases and controls for which database and questionnaire information was available, we obtained crude and adjusted odds ratios using unconditional logistic regression. Because 47 variables were evaluated, we used 4 steps to identify determinants of childhood asthma. 1) From the univariate analyses, we identified determinants associated with childhood asthma with a P value of, at most, 0.20. 2) We fitted 2 independent models, using a backward selection strategy with variables identified in step 1: one including variables measured during pregnancy (model 1) and another including variables measured after the birth of the child (model 2). 3) We combined the 2 reduced models obtained in step 2 into 1 final model, which was subsequently reduced using backward selection (20). 4) In the model obtained in step 3, we reentered, one by one, all variables excluded in steps 1 and 2, leaving in the final model those found to have a P value of 0.05 or less. Finally, estimates obtained for maternal asthma were corrected using sampling fractions and maternal asthma estimates from the first stage of the study, as described by Collet et al. (18). The correction was done only for maternal asthma, because the second-stage selection had been made using the maternal asthma–childhood asthma cross-table and was not influenced by the prevalence of the other determinants investigated (18).

We conducted a number of sensitivity analyses: 1) subgroup analyses based on maternal asthma status during pregnancy (first-stage analysis only); 2) removing the variable "diagnosis of bronchopulmonary conditions prior to the index date" from the pool of determinants studied; 3) among patients available at the second stage of sampling, analyzing variables available from the first stage, with and without adjustment for variables obtained via the mailed questionnaires; and 4) testing a definition of childhood asthma based on the occurrence of 2 or more diagnoses and 1 prescription for asthma. Questionnaire responders and nonresponders were compared using Pearson chi-square tests for the 20 variables for which information was available in databases.

We calculated 95% confidence intervals for all estimates. All analyses were performed using SAS 9.1 (SAS Institute Inc., Cary, North Carolina).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
The incidences of childhood asthma were 32.6% (95% confidence interval: 31.6, 33.6) and 14.1% (95% confidence interval: 13.6, 14.6) among the 8,226 children of asthmatic mothers and the 18,039 children of nonasthmatic mothers, respectively. From the cohort, 5,226 cases of childhood asthma were identified and 104,520 matched controls were selected for the first stage of the study. Table 1 displays characteristics available at the first stage for cases and controls, crude rate ratios, and adjusted rate ratios from the multivariate first-stage analysis. The most important determinants associated with the incidence of childhood asthma, in terms of rate ratio magnitude, were asthma during pregnancy, a previous diagnosis of allergic rhinitis and atopic dermatitis in the child prior to the index date, having at least 1 prescription for antibiotics filled prior to the index date or within the first 6 months of life, male gender, and use of antibiotics during pregnancy.


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  		Table 1. Characteristics of Childhood Asthma Cases and Matched Controls Obtained From 3 Administrative Databases (First Stage of Sampling), Quebec, Canada, 1990–2002

 
At the end of the 23 weeks allocated for the questionnaire collection process, 43.5% of the 3,804 mailed questionnaires had been received (780 cases and 873 controls) (Figure 1). After discarding 75 questionnaires that had been completed for the wrong child, we had questionnaire information on 745 cases and 833 controls available for use in the second-stage analysis (639 cases and 724 controls born to asthmatic mothers and 106 cases and 109 controls born to nonasthmatic mothers). Questionnaire responders and nonresponders were similar with regard to most of the 20 variables available in the databases, except for small statistically significant differences for receipt of social welfare, level of education, area of residence, mode of delivery, and pregnancy in the preceding year (data available upon request). Table 2 displays the distribution of second-stage potential determinants for questionnaire responders, along with crude odds ratios for childhood asthma.


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  		Table 2. Characteristics of Childhood Asthma Cases and Matched Controls Whose Mothers Answered the Postal Questionnaire (Second Stage of Sampling), Quebec, Canada, 1990–2002

 
In final multivariate analyses (Table 3), several determinants were statistically significantly associated with increased risk of childhood asthma: a previous diagnosis of bronchopulmonary disease in the child prior to the index date, oxygen administration after birth, a prior diagnosis of atopic dermatitis, maternal receipt of social welfare, filling of 1 or more antibiotic prescriptions for the child prior to the index date or within the first 6 months of life, maternal asthma during pregnancy, maternal report of asthma in the child's father, male gender, asthma in the child's siblings, and use of antibiotics during pregnancy.


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  		Table 3. Results from the Final Multivariate Analysis of Determinants of Asthma Incidence in Offspring (Combining First- and Second-Stage Variables), Quebec, Canada, 1990–2002

 
Statistically significant protective effects were observed for having a wood-burning fireplace in the home between birth and the index date, use of intranasal corticosteroids during pregnancy, having pets in the home for ≥2 months between birth and the index date, breastfeeding, and day-care attendance.

Since the hazard function may not be constant over age, we conducted subgroup analyses based on age at diagnosis. Subgroups of children (cases and matched controls) were formed on the basis of age at asthma onset (<3 years and ≥3 years). Table 4 presents results of the first-stage subgroup analyses. Maternal asthma remained a strong risk factor in both age groups, as did child-related characteristics, but it was difficult to draw conclusions regarding the differences between models because of the difference in the statistical power of these analyses. The second-stage subgroup analyses had very low power, thereby preventing the presentation of informative comparative analyses. Overall, other sensitivity analyses conducted did not sizably modify the results obtained (data available upon request).


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  		Table 4. Results from the Multivariate First-Stage Analysis for Subgroups of Children (Cases with Asthma and Matched Controls) Selected on the Basis of Age at Asthma Onset, Quebec, Canada, 1990–2002

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
The present study allowed for identification of the independent effects of numerous potential determinants of childhood asthma, obtained for different time periods of child development, including in utero. To our knowledge, this is the largest study to date to have considered such a variety of potential determinants of this condition within a single study setting.

Our results show that a prior diagnosis of atopic dermatitis, asthma during pregnancy, maternal report of asthma in the child's father, and asthma in the child's siblings were associated with an increased risk of childhood asthma (9, 11, 12, 21–28). Asthma and atopy are known to "run" in families, via a genetic predisposition and/or the shared environment of the child and his/her siblings. Diagnostic bias is also possible, since these well-known associations may cause a physician to diagnose this condition more quickly in children of asthmatic mothers, and those mothers could also be more likely to contact a physician when noticing asthma-like symptoms in their children.

Several additional determinants were associated with an increased risk of childhood asthma. A previous diagnosis of bronchopulmonary disease in the child prior to the index date was the determinant with the strongest association with childhood asthma. Some investigators report that early-life infections increase childhood asthma risk and that some of the symptoms could be due to early manifestations of asthma not yet diagnosed in the child (9, 12, 15, 24, 27). Other risk factors include male gender (9, 24, 25, 29), maternal receipt of social welfare (30–32), oxygen administration after birth (23, 27), filling of 1 or more antibiotic prescriptions for the child prior to the index date or within the first 6 months of life (8, 15, 24), and use of antibiotics during pregnancy (13, 33). Protective effects were seen for having pets in the home during infancy, breastfeeding, and day-care attendance (5, 6). However, it is possible that part of the protective effect of the presence of pets in the home could be due to pet avoidance by families of at-risk children.

Interestingly, having a wood-burning fireplace in the home between birth and the index date was associated with a reduction in childhood asthma risk. This could be an indicator of adequate ventilation, which would be generated by the presence of a chimney (34), or a decline in household humidity levels and a subsequent reduction in mold exposure resulting from wood heating (35). Use of intranasal corticosteroids during pregnancy was associated with a reduced risk of childhood asthma. This determinant could act as an indicator of maternal behaviors which would tend to limit exposure to environmental triggers of atopic manifestations. Additionally, intranasal corticosteroids have been associated with a reduction of asthma-related emergency department visits and hospitalizations in adults, and "allergic rhinitis and asthma are frequently comorbid conditions and appropriate management of allergic rhinitis can lead to more effective asthma control" (36, p. 1076). This could therefore enhance maternal asthma control, which has been associated with a reduced risk of childhood asthma (Martel et al., Université de Montréal, unpublished manuscript, 2007).

Although we had adequate statistical power to evaluate the independent effects of a large number of determinants in this study, some usually recognized risk factors, such as parental cigarette smoking, were not found to be statistically significantly associated with the risk of childhood asthma in the multivariate analyses. Crude odds ratios for maternal and paternal smoking during pregnancy and after childbirth were borderline-statistically significant. It may be that the population studied here was relatively homogeneous and did not allow for the distinction of a difference between the high proportions of smokers seen in this study. The higher proportion of female smokers is in accordance with the situation in Quebec, since women aged 25–44 years are those who smoke the most and a high prevalence of smoking has been reported in persons of lower socioeconomic status (3, 37).

This study had strengths and limitations. The large sample of children of asthmatic and nonasthmatic mothers, along with the combination of databases and the questionnaire, through the use of the 2-stage sampling method, allowed us to study multiple and diverse determinants of childhood asthma and disentangle their independent effects. Administrative databases provide information collected prospectively and independently of the outcome under study. The length of follow-up is also notable, as incident cases of asthma could be identified up to 10 years after birth. The case definition for childhood asthma was designed to increase specificity and positive predictive value, since a child had to have received a diagnosis and used medication for asthma within a 2-year period. Although this does not entirely prevent residual confounding from affecting the results, the substantial number of variables included in the analyses greatly minimized its potential influence.

Another key feature of this study is that for many determinants, the timing of the exposures was considered. Several risk factors were measured for 2 distinct periods: during pregnancy and after the child's birth. To reduce the likelihood of collinearity, variables related to the maternal and child environments, such as variables for tobacco smoke exposure (37, 38), were evaluated in 2 distinct models. Those models were also useful in attempting to distinguish different effects of a risk factor when the exposure occurred in 2 different time periods. For example, allergen exposure has been suggested to intervene prenatally in the neonatal switching from T-helper 1 lymphocytes to T-helper 2 lymphocytes, as well as postnatally via allergic sensitization (6, 39). In this study, stronger crude estimates were obtained for environmental determinants assessed for the period following the child's birth compared with assessment of the same determinants during pregnancy. In multivariate analysis, the only environmental determinants remaining in the final reduced model were measured for the period following childbirth. This may reflect a stronger influence of these exposures on the risk of childhood asthma, the intensity and/or length of exposure, or the more precise measurement that may have been obtained for this period.

However, despite the extent of the data collection efforts, information on some potential risk factors was not available. The data sources sometimes did not allow for precise data ascertainment; for example, use of antibiotics prior to the index date or within the first 6 months of life, used as a proxy for infections, could also reflect the reverse-causation phenomenon, since antibiotics could have been more often prescribed in cases of worsening asthmatic symptoms (8, 15, 24, 40). Recall bias in the questionnaire responses is also possible; but while this might have influenced the accuracy of some of the associations measured, information bias is potentially limited, since the crude and adjusted associations were consistent with the magnitude of the effects reported in the literature. The questionnaire response rate was also not as high as expected, but selection bias, if present, is likely to have been minimal, since responders and nonresponders were similar with regard to most of the 20 database variables. Finally, it would have been of interest to present the second-stage subgroup analyses based on age at asthma diagnosis for children aged <3 years and ≥3 years, to allow the inclusion in the models of the full range of available variables. Finer subgroups would also have been interesting to investigate, but the lower power that would have resulted from such segmentation of the cases and controls prevented this analysis.

Several theories have been proposed to explain the observed increased prevalence of childhood asthma and provide a basis for conceptual frameworks, such as the hygiene hypothesis and the concept of "fetal programming," in which multiple known and suspected risk factors would be interconnected (5, 6, 8, 41, 42). This is a complex task, and although genetic and environmental influences are important components to consider, the timing of exposures is also a key element for understanding this multifactorial disease (5–8, 41). Combining multiple sources of data provides the opportunity to draw the most complete picture of childhood asthma development. This study allowed us to identify, within a single setting, the most influential risk factors for childhood asthma among a wide variety of determinants assessed for the prenatal, perinatal, and childhood periods.


   ACKNOWLEDGMENTS
 
Author affiliations: Faculty of Pharmacy, Université de Montréal, Montréal, Québec, Canada (Marie-Josée Martel, Sylvie Perreault, Marie-France Beauchesne, Lucie Blais); Department of Obstetrics and Gynecology, CHU Sainte-Justine, Montréal, Québec, Canada (Évelyne Rey); Research Center, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada (Jean-Luc Malo, Amélie Forget, Lucie Blais); and Pharmacy Department, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada (Marie-France Beauchesne).

This study was funded by the Canadian Institutes for Health Research.

The authors thank Marie-Claude Giguère from the Régie de l’assurance maladie du Québec, Chantal Girard from the Institut de la statistique du Québec, and Louise Légaré from the Ministère de la Santé et des Services sociaux du Québec for assistance with the data. The authors are grateful to M. Daniel Bourassa of the Commission d’accès à l’information du Québec for authorizing the study. The authors also thank Karine Chouinard and Myriam Fortin for data entry and Karine Chouinard for helping with the logistics of the study.

M.-J. Martel has received a doctoral research scholarship from the K. M. Hunter Foundation–Canadian Institutes for Health Research. E. Rey has received grant support from Pfizer Canada and is on the speakers’ bureau for Duschenay. M. F. Beauchesne has received grant support from Bayer Canada, GlaxoSmithKline Canada, Merck Frosst, and AstraZeneca Canada for some research projects; has received honoraria for oral presentations from Pfizer Canada, AstraZeneca, GlaxoSmithKline Canada, and Boehringer Ingelheim Canada; and cochairs the Astra-Zeneca Endowment Pharmaceutical Chair in Respiratory Health. J.-L. Malo has received support for clinical assays of various antiasthma drugs produced by several pharmaceutical companies (Altana Pharma, GlaxoSmithKline, Hoffmann-LaRoche, and AstraZeneca). S. Perreault is the recipient of Chercheur Boursier Senior II salary support from the Fonds de la recherche en santé du Québec. L. Blais has received grant support from AstraZeneca, Amgen Canada, and GlaxoSmithKline; cochairs the AstraZeneca Endowment Pharmaceutical Chair in Respiratory Health; and is the recipient of Chercheur Boursier Junior II salary support from the Fonds de la recherche en santé du Québec.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

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