BACKGROUND: Adjustable maintenance dosing with budesonide/formoterol in a single inhaler (Symbicort, AstraZeneca, Lund, Sweden) may provide a convenient means of maintaining asthma control with the minimum effective medication level. OBJECTIVES: To compare adjustable and fixed maintenance dosing regimens of budesonide/formoterol in asthma. METHODS: This was an open-label, randomized, parallel-group, multicentre, Canadian study of asthma patients (aged 12 years or older, postbronchodilator forced expiratory volume in 1 s 70% or greater of predicted normal). Following a one-month run-in on budesonide/formoterol (100/6 mg or 200/6 mg metered doses, two inhalations twice daily), 995 patients were randomly assigned either to continue on this fixed dosing regimen or to receive budesonide/formoterol adjustable dosing (step down to one inhalation twice daily if symptoms were controlled or temporarily step up to four inhalations twice daily for seven or 14 days if asthma worsened). The primary efficacy variable was the occurrence of exacerbations (requiring oral or inhaled corticosteroids, emergency department treatment, serious adverse events or added maintenance therapy because of asthma). RESULTS: With adjustable dosing, significantly fewer patients experienced exacerbations compared with fixed dosing (4.0% versus 8.9%, P=0.002; number needed to treat=21 [95% CI 13 to 59]). Patients required 36% fewer overall doses of budesonide/formoterol (2.5 versus 3.9 inhalations/day, P
Airflow obstruction is relatively uncommon in young adults, and may indicate potential for the development of progressive disease. The objective of the present study was to enumerate and characterize airflow obstruction in a random sample of Canadians aged 20 to 44 years.
The sample (n=2962) was drawn from six Canadian sites.
A prevalence study using the European Community Respiratory Health Survey protocol was conducted. Airflow obstruction was assessed by spirometry. Bronchial responsiveness, skin reactivity to allergens and total serum immunoglobulin E were also measured. Logistic regression was used for analysis.
Airflow obstruction was observed in 6.4% of the sample, not associated with sex or age. The risk of airflow obstruction increased in patients who had smoked and in patients who had lung trouble during childhood. Adjusted for smoking, the risk of airflow obstruction was elevated for subjects with past and current asthma, skin reactivity to allergens, elevated levels of total immunoglobulin E and bronchial hyper-responsiveness. Of the subjects with airflow obstruction, 21% were smokers with a history of asthma, 50% were smokers without asthma, 12% were nonsmokers with asthma and 17% were nonsmokers with no history of asthma. Bronchial hyper-responsiveness increased the prevalence of airflow obstruction in each of these groups.
Smoking and asthma, jointly and individually, are major determinants of obstructive disorders in young adults. Bronchial hyper-responsiveness contributes to obstruction in both groups.
Cites: CMAJ. 2001 Apr 3;164(7):995-100111314453
Cites: Am J Respir Crit Care Med. 1999 Jan;159(1):179-879872837
Cites: MMWR Surveill Summ. 2002 Aug 2;51(6):1-1612198919
Increasing evidence links air pollution to the risk of cardiovascular disease. This study investigated the association between ischemic heart disease (IHD) prevalence and exposure to traffic-related air pollution (nitrogen dioxide [NO2], fine particulate matter [PM2.5], and ozone [O3]) in a population of susceptible subjects in Toronto. Local (NO2) exposures were modeled using land use regression based on extensive field monitoring. Regional exposures (PM2.5, O3) were modeled as confounders using inverse distance weighted interpolation based on government monitoring data. The study sample consisted of 2360 patients referred during 1992 to 1999 to a pulmonary clinic at the Toronto Western Hospital in Toronto, Ontario, Canada, to diagnose or manage a respiratory complaint. IHD status was determined by clinical database linkages (ICD-9-CM 412-414). The association between IHD and air pollutants was assessed with a modified Poisson regression resulting in relative risk estimates. Confounding was controlled with individual and neighborhood-level covariates. After adjusting for multiple covariates, NO2 was significantly associated with increased IHD risk, relative risk (RR) = 1.33 (95% confidence interval [CI]: 1.2, 1.47). Subjects living near major roads and highways had a trend toward an elevated risk of IHD, RR = 1.08 (95% CI: 0.99, 1.18). Regional PM2.5 and O3 were not associated with risk of IHD.
A recurring epidemic of asthma exacerbations in children occurs annually in September in North America when school resumes after summer vacation.
Our goal was to determine whether montelukast, added to usual asthma therapy, would reduce days with worse asthma symptoms and unscheduled physician visits of children during the September epidemic.
A total of 194 asthmatic children aged 2 to 14 years, stratified according to age group (2-5, 6-9, and 10-14 years) and gender, participated in a double-blind, randomized, placebo-controlled trial of the addition of montelukast to usual asthma therapy between September 1 and October 15, 2005.
Children randomly assigned to receive montelukast experienced a 53% reduction in days with worse asthma symptoms compared with placebo (3.9% vs 8.3%) and a 78% reduction in unscheduled physician visits for asthma (4 [montelukast] vs 18 [placebo] visits). The benefit of montelukast was seen both in those using and not using regular inhaled corticosteroids and among those reporting and not reporting colds during the trial. There were differences in efficacy according to age and gender. Boys aged 2 to 5 years showed greater benefit from montelukast (0.4% vs 8.8% days with worse asthma symptoms) than did older boys, whereas among girls the treatment effect was most evident in 10- to 14-year-olds (4.6% [montelukast] vs 17.0% [placebo]), with nonsignificant effects in younger girls.
Montelukast added to usual treatment reduced the risk of worsened asthma symptoms and unscheduled physician visits during the predictable annual September asthma epidemic. Treatment-effect differences observed between age and gender groups require additional investigation.
To compare the cost-effectiveness of budesonide-formoterol in a single inhaler used as both maintenance and reliever medication versus clinician-directed titration of salmeterol-fluticasone as maintenance medication, plus salbutamol taken as needed, in controlling asthma in adults and adolescents.
A Canadian economic evaluation was conducted based on the results of a large (n=2143), open-label, randomized, controlled effectiveness trial in which health resource use was prospectively collected. The primary outcome measurement was the time to the first severe exacerbation. Costs included direct medical costs (physician and emergency room visits, hospitalizations, asthma drug costs, etc) and productivity (absenteeism). The time horizon was one year, which corresponded to the duration of the clinical trial. Prices were obtained from 2005 Canadian sources. Both health care and societal perspectives were considered, and deterministic univariate sensitivity analyses were conducted.
In the clinical trial, budesonide-formoterol as maintenance and reliever treatment was superior to salmeterol-fluticasone with respect to the time to the first severe exacerbation, overall rate of exacerbations and use of as-needed reliever medication. The annualized rate of severe exacerbations was 0.24 events/patient in the budesonide-formoterol arm and 0.31 events/patient in the salmeterol-fluticasone arm (P=0.0025). From a health care perspective, the mean cost per patient-year was $1,315 in the budesonide-formoterol arm versus $1,541 in the salmeterol-fluticasone arm. From a societal perspective, the mean cost per patient-year was $1,538 in the budesonide-formoterol arm and $1,854 in the salmeterol-fluticasone arm. Budesonide-formoterol was dominant (more effective and less expensive) in the base case analysis from both perspectives. The results were robust under sensitivity testing.
The strategy that allows budesonide-formoterol to be used in a single inhaler as both maintenance and reliever medication proved to be more effective and less expensive than a strategy of clinician-directed titration of salmeterol-fluticasone with salbutamol as reliever therapy.
Cites: J R Coll Physicians Lond. 1993 Oct;27(4):387-908289159
Chronic exposure to traffic-related air pollution (TRAP) may contribute to premature mortality, but few studies to date have addressed this topic.
In this study we assessed the association between TRAP and mortality in Toronto, Ontario, Canada.
We collected nitrogen dioxide samples over two seasons using duplicate two-sided Ogawa passive diffusion samplers at 143 locations across Toronto. We calibrated land use regressions to predict NO2 exposure on a fine scale within Toronto. We used interpolations to predict levels of particulate matter with aerodynamic diameter
Cites: Chronic Dis Can. 2000;21(3):104-1311082346
Cites: Environ Health Perspect. 2008 Feb;116(2):196-20218288318
Cites: J Epidemiol Community Health. 2002 Aug;56(8):588-9412118049
Cites: J Air Waste Manag Assoc. 2002 Sep;52(9):1032-4212269664
Cites: Lancet. 2002 Oct 19;360(9341):1203-912401246
Cites: J Environ Monit. 2003 Aug;5(4):557-6212948227
Cites: Circulation. 2004 Jan 6;109(1):71-714676145
Cites: Environ Health Perspect. 2004 Apr;112(5):610-515064169
Cites: Am J Epidemiol. 2004 Jul 15;160(2):173-715234939
Cites: J Air Waste Manag Assoc. 2004 Jun;54(6):644-8015242147
Cites: Epidemiology. 2005 Jan;16(1):33-4015613943
Cites: Environ Health Perspect. 2005 Feb;113(2):201-615687058
Cites: Science. 2005 May 6;308(5723):804-615879201
Cites: Environ Health Perspect. 2005 Aug;113(8):987-9216079068
Cites: Environ Health Perspect. 2005 Oct;113(10):1447-5416203261
Studies in Europe and North America have reported that living in a disadvantaged neighbourhood is associated with an increased incidence of coronary heart disease. The aim of this study was to test the hypotheses that exposure to traffic and air pollution might account for some of the socioeconomic differences in mortality rates in a city where residents are covered by universal health insurance.
Cohort mortality study. Individual postal codes used to derive: (1) socioeconomic status from census data; (2) mean air pollution levels from interpolation between governmental monitoring stations; (3) proximity to traffic from the geographical information system. Analysis conducted with Cox proportional hazards models.
Hamilton Census Metropolitan Area, Ontario, Canada, on the western tip of Lake Ontario (population about 480,000).
5228 people, aged 40 years or more, identified from register of lung function laboratory at an academic respirology clinic between 1985 and 1999.
Circulatory disease (cardiovascular and stroke) mortality rates were related to measures of neighbourhood deprivation. Circulatory disease mortality rates were also associated with indices of long term ambient pollution at the subjects' residences (relative risk 1.06, 1.00 to 1.13) and with proximity to traffic (relative risk 1.40, 1.08 to 1.81). Subjects in more deprived neighbourhoods had greater exposure to ambient particulate and gaseous pollutants and to traffic.
At least some of the observed social gradients in circulatory mortality arise from inequalities in environmental exposure to background and traffic air pollutants.
Cites: Epidemiology. 2000 Jan;11(1):11-710615837
Cites: Am J Epidemiol. 1999 Nov 15;150(10):1094-810568625
Cites: Chronic Dis Can. 2000;21(3):104-1311082346
Cites: Environ Health Perspect. 2001 Apr;109(4):341-711335181
Cites: N Engl J Med. 2001 Jul 12;345(2):99-10611450679
Cites: N Engl J Med. 2001 Jul 12;345(2):134-611450663
Cites: Eur Heart J. 2001 Jul;22(14):1198-20411440492
Cites: CMAJ. 2001 Sep 4;165(5):565-7011563208
Cites: J Epidemiol Community Health. 2002 Jan;56(1):29-3511801617
Geographic variability in reported prevalences of asthma worldwide could in part relate to interpretation of symptoms and diagnostic biases. Bronchial responsiveness measurements provide objective evidence of a common physiologic characteristic of asthma. We measured bronchial responsiveness using the standardized protocol of the European Community Respiratory Health Survey (ECRHS) in six sites in Canada, and compared prevalences across Canada with international sites.
Samples of 3,000 to 4,000 adults aged 20 to 44 years were randomly selected in Vancouver, Winnipeg, Hamilton, Montreal, Halifax, and Prince Edward Island, and a mail questionnaire was completed by 18,616 individuals (86.5%). Preselected random subsamples (n = 2,962) attended a research laboratory for examination including more detailed questionnaires, lung function testing including methacholine challenge, and skin testing with 14 allergens.
Prevalences of bronchial hyperresponsiveness, measured as cumulative dose of methacholine required to produce a 20% fall from the post-saline solution FEV1
The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding.
We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing.
We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia-Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity.
These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.