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2.  Mortality among subjects with chronic obstructive pulmonary disease or asthma at two respiratory disease clinics in Ontario 
Chronic obstructive pulmonary disease (COPD) accounts for nearly three million deaths annually, with approximately 5% of deaths in Canada attributed to COPD in 2004. Mortality rates among individuals with COPD or asthma, however, are not extensively studied in North America. Certainly, follow-up of individuals with respiratory diseases can shed light on mortality risks and contribute valuable information to prevent premature death. Accordingly, this retrospective study investigated mortality rates and examined risk factors for premature death among patients diagnosed with respiratory diseases identified from two lung function testing databases of two respiratory clinics in Ontario during the 1990s.
Chronic obstructive pulmonary disease (COPD) and asthma are common; however, mortality rates among individuals with these diseases are not well studied in North America.
To investigate mortality rates and risk factors for premature death among subjects with COPD.
Subjects were identified from the lung function testing databases of two academic respiratory disease clinics in Hamilton and Toronto, Ontario. Mortality was ascertained by linkage to the Ontario mortality registry between 1992 and 2002, inclusive. Standardized mortality ratios were computed. Poisson regression of standardized mortality ratios and proportional hazards regression were performed to examine the multivariate effect of risk factors on the standardized mortality ratios and mortality hazards.
Compared with the Ontario population, all-cause mortality was approximately doubled among subjects with COPD, but was lower than expected among subjects with asthma. The risk of mortality in patients with COPD was related to cigarette smoking, to the presence of comorbid conditons of ischemic heart disease and diabetes, and to Global initiative for chronic Obstructive Lung Disease severity scores. Individuals living closer to traffic sources showed an elevated risk of death compared with those who lived further away from traffic sources.
Mortality rates among subjects diagnosed with COPD were substantially elevated. There were several deaths attributed to asthma among subjects in the present study; however, overall, patients with asthma demonstrated lower mortality rates than the general population. Subjects with COPD need to be managed with attention devoted to both their respiratory disorders and related comorbidities.
PMCID: PMC3267622  PMID: 22187688
Asthma; Cohort study; COPD; Mortality; Risk factors
6.  Can we predict which patients with community-acquired pneumonia are likely to have positive blood cultures? 
Blood cultures (BC) are commonly ordered during the initial assessment of patients with community-acquired pneumonia (CAP), yet their yield remains low. Selective use of BC would allow the opportunity to save healthcare resources and avoid patient discomfort. The study was to determine what demographic and clinical factors predict a greater likelihood of a positive blood culture result in patients diagnosed with CAP.
A structured retrospective systematic chart audit was performed to compare relevant demographic and clinical details of patients admitted with CAP, in whom blood culture results were positive, with those of age, sex, and date-matched control patients in whom blood culture results were negative.
On univariate analysis, eight variables were associated with a positive BC result. After logistic regression analysis, however, the only variables statistically significantly associated with a positive BC were WBC less than 4.5 × 109/L [likelihood ratio (LR): 7.75, 95% CI=2.89-30.39], creatinine >106 μmol/L (LR: 3.15, 95%CI=1.71-5.80), serum glucose<6.1 mmol/L (LR: 2.46, 95%CI=1.14-5.32), and temperature > 38 °C (LR: 2.25, 95% CI =1.21-4.20). A patient with all of these variables had a LR of having a positive BC of 135.53 (95% CI=25.28-726.8) compared to patients with none of these variables.
Certain clinical variables in patients with CAP admitted to hospitals do appear to be associated with a higher probability of a positive yield of BC, with combinations of these variables increasing this likelihood. We have identified a subgroup of CAP patients in whom blood cultures are more likely to be useful.
PMCID: PMC4129722  PMID: 25215022
Community-acquired pneumonia; Blood cultures
7.  Montelukast as an alternative to low-dose inhaled corticosteroids in the management of mild asthma (the SIMPLE trial): An open-label effectiveness trial 
To evaluate the effectiveness of montelukast as monotherapy for patients with mild asthma who remain uncontrolled or unsatisfied while on inhaled corticosteroid (ICS) monotherapy.
A multicentre, open-label study. Patients (six years of age or older) had ICS therapy discontinued and were treated with orally administered montelukast once daily for six weeks.
The primary outcome measure was the rate at which asthma symptom control was achieved or maintained after six weeks of treatment. The secondary outcome measures were to compare compliance and physician satisfaction, and to further assess the safety and tolerability of montelukast.
Of the 534 patients enrolled, 481 (90.1%) completed the study. Mean (± SD) age was 27.8±19.0 years. The number of patients with uncontrolled symptoms decreased from 455 (85.2%) at baseline to 143 (26.8%) at week 6 (P<0.001), and mean Asthma Control Questionnaire score decreased from 1.4±0.8 to 0.6±0.6 (P<0.001), representing a clinically significant improvement. Of the 79 patients with controlled asthma symptoms at baseline, 73.4% maintained asthma control at week 6. Compliance to asthma therapy increased from 41% at baseline for ICS to 88% at week 6 for montelukast (P<0.001). Physician satisfaction with treatment increased from 43% to 85% (P<0.001) and patient satisfaction increased from 45% at baseline to 94% at week 6. No serious adverse events were reported over the course of the study.
Montelukast is an effective and well-tolerated alternative to ICS treatment in patients with mild asthma who are uncontrolled or unsatisfied with low-dose ICS therapy.
PMCID: PMC3486709  PMID: 19557207
Adherence; Allergic rhinitis; Asthma; Inhaled corticosteroids (ICS); Montelukast
8.  Montelukast as add-on therapy to inhaled corticosteroids in the management of asthma (the SAS trial) 
To evaluate the effectiveness of montelukast as add-on therapy for asthmatic patients who remain uncontrolled with low, moderate or high doses of inhaled corticosteroid monotherapy.
An eight-week, multicentre, open-label, observational study.
Of 320 patients enrolled, 288 (90.0%) completed the study. Of patients who had uncontrolled asthma symptoms (Canadian Asthma Consensus Guidelines Update, 2003) but were controlled according to the Asthma Control Questionnaire (ACQ score of less than 1.5), 93.9% maintained asthma control at week 8. Of patients with uncontrolled asthma at baseline for both definitions, 63.5% achieved asthma control by week 8. The mean ± SD ACQ score decreased from 1.13±0.28 to 0.57±0.50 (P<0.001) for controlled patients at baseline and from 2.38±0.73 to 1.03±0.80 (P<0.001) for patients who were uncontrolled at baseline, each representing a clinically significant improvement.
Montelukast add-on therapy is an effective alternative to inhaled corticosteroid monotherapy.
PMCID: PMC3486710  PMID: 19557206
Asthma; Inhaled corticosteroids; Montelukast add-on
9.  Montelukast as add-on therapy with inhaled corticosteroids or inhaled corticosteroids and long-acting beta-2-agonists in the management of patients diagnosed with asthma and concurrent allergic rhinitis (the RADAR trial) 
To evaluate the effectiveness of montelukast as add-on therapy for patients diagnosed with asthma and concurrent allergic rhinitis who remain uncontrolled while receiving inhaled corticosteroid (ICS) monotherapy or ICS/long-acting beta-2-agonist (LABA) therapy in a community practice setting.
An eight-week, multicentre, open-label, observational study. Patients were 15 years of age or older and, while treated with an ICS or ICS/LABA, had allergic rhinitis and uncontrolled asthma symptoms by at least two criteria as per the Canadian Asthma Consensus Guidelines. The primary outcome measure was the percentage of patients with controlled asthma symptoms after eight weeks of treatment with montelukast 10 mg once daily added to ICS or ICS/LABA therapy.
In total, 1004 patients participated in the survey phase of the study. Of these patients, 319 continued in the treatment phase and 301 (94.4%) completed the eight-week assessment. At baseline, all patients had uncontrolled asthma symptoms based on the Canadian Asthma Consensus Guidelines; at the eight-week assessment, 229 patients (76.1%) achieved asthma control. According to the Asthma Control Questionnaire (as determined by scores of 0.75 or less), 164 patients (54.7%) achieved well-controlled asthma at week 8. The mean (± SD) Asthma Control Questionnaire score decreased from 2.03±0.80 to 0.92±0.80 (P<0.001) for all patients, representing a clinically significant improvement. A statistically and clinically significant reduction in the overall Mini Rhinitis Quality of Life Questionnaire score was achieved with a decrease from 2.57±1.20 to 1.12±1.00 (–1.45±1.35; P<0.001). Patient and physician satisfaction rates with montelukast add-on therapy were also significantly increased when compared with baseline treatment.
Montelukast add-on therapy is effective for managing asthma and allergic rhinitis symptoms in patients who were previously uncontrolled with ICS or ICS/LABA treatment.
PMCID: PMC3486712  PMID: 19557208
Allergic rhinitis; Asthma; Inhaled corticosteroids; Long-acting beta-2-agonist; Montelukast
10.  Management of asthma in adults 
PMCID: PMC2789128  PMID: 19786471
11.  Diagnosis of asthma in adults 
PMCID: PMC2774375  PMID: 19770241
12.  Influence of current or former smoking on asthma management and control 
In patients with asthma, smoking has been associated with accelerated decline in pulmonary function, poor disease control and reduced responsiveness to corticosteroids.
To assess the influence of current and former smoking on self-reported asthma control and health care use in a large population of asthma patients.
The present analysis was conducted following a telephone survey of adult Canadians aged 18 to 54 years who had physician-diagnosed asthma and a smoking history of less than 20 pack-years.
Of 893 patients, 268 were former smokers and 108 were current smokers. Daytime and nighttime symptoms, absenteeism from work or school, emergency care use for asthma in the past year, and use of a short-acting bronchodilator without controller medication were reported more frequently by current smokers than non-smokers and former smokers. Former smokers were not significantly different from nonsmokers with respect to most asthma outcomes.
Current smokers with asthma show evidence of poorer asthma control and greater acute care needs than lifelong nonsmokers or former smokers. These observations stress the importance of smoking cessation to help achieve asthma control.
PMCID: PMC2679551  PMID: 18716691
Asthma; Asthma control; Asthma management; Smoking
15.  Overdiagnosis of asthma in obese and nonobese adults 
It is unclear whether asthma is overdiagnosed in developed countries, particularly among obese individuals, who may be more likely than nonobese people to experience dyspnea.
We conducted a longitudinal study involving nonobese (body mass index 20–25) and obese (body mass index ≥ 30) individuals with asthma that had been diagnosed by a physician. Participants were recruited from 8 Canadian cities by means of random-digit dialing. A diagnosis of current asthma was excluded in those who did not have evidence of acute worsening of asthma symptoms, reversible airflow obstruction or bronchial hyperresponsiveness, despite being weaned off asthma medications. We stopped asthma medications in those in whom a diagnosis of asthma was excluded and assessed their clinical outcomes over 6 months.
Of 540 individuals with physician-diagnosed asthma who participated in the study, 496 (242 obese and 254 nonobese) could be conclusively assessed for a diagnosis of asthma. Asthma was ultimately excluded in 31.8% (95% confidence interval [CI] 26.3%–37.9%) in the obese group and in 28.7% (95% CI 23.5%–34.6%) in the nonobese group. Overdiagnosis of asthma was no more likely to occur among obese individuals than among nonobese individuals (p = 0.46). Of those in whom asthma was excluded, 65.5% did not need to take asthma medication or seek health care services because of asthma symptoms during a 6-month follow-up period.
About one-third of obese and nonobese individuals with physician-diagnosed asthma did not have asthma when objectively assessed. This finding suggests that, in developed countries such as Canada, asthma is overdiagnosed.
PMCID: PMC2582787  PMID: 19015563
17.  Approach to chronic obstructive pulmonary disease in primary care 
Canadian Family Physician  2008;54(5):706-711.
To review the diagnosis, assessment of severity, and management of chronic obstructive pulmonary disease (COPD) and to address the systemic manifestations associated with COPD.
PubMed was searched from January 2000 to December 2007 using the key words COPD, practice guidelines, randomized controlled trials, therapy, and health outcomes. The Canadian Thoracic Society guideline on management of COPD was carefully reviewed. The authors, who have extensive experience in care of patients with COPD, provided expert opinion.
Chronic obstructive pulmonary disease is a common systemic disease caused primarily by smoking. Spirometry is essential for diagnosis of COPD and should be integrated into primary care practice. Pharmacologic and nonpharmacologic therapy improves symptoms, capacity for exercise, and quality of life. Smoking cessation is the only intervention shown to slow disease progression. The systemic manifestations and comorbidity associated with COPD need to be identified and addressed to optimize health and quality of life.
An evidence-based approach to managing COPD along with a primary care chronic disease management model could improve quality of life for patients with COPD.
PMCID: PMC2377210  PMID: 18474704
18.  Asthma control in Canada remains suboptimal: The Reality of Asthma Control (TRAC) study 
Two Canadian studies showed that 55% of patients with asthma had daily symptoms (in 1996) and that 57% of patients suffered from poorly controlled asthma (in 1999).
To assess the state of asthma control of adult Canadians, and asthma knowledge and practices of Canadian physicians actively involved in the care of patients with asthma.
Telephone interviews were conducted with adults 18 to 54 years of age who had been diagnosed with asthma at least six months before the survey, who did not have chronic obstructive pulmonary disease and who had a smoking history of fewer than 20 pack-years. Physicians were surveyed by telephone and mail. The surveys took place between April and August 2004.
Almost all (97%) of the 893 patients believed that they had controlled asthma; however, only 47% had controlled disease according to symptom-based guideline criteria. Just 39% of 463 physicians based their treatment recommendations on the Canadian asthma guidelines most or all of the time, despite having a high awareness of them. Only 11% of patients had written action plans, and one-half of patients with action plans did not use them regularly. Almost three-quarters of patients expressed concerns about taking inhaled corticosteroids.
Since the last major national survey, guideline implementation has not resulted in significant changes in asthma-related morbidity. Effective means of knowledge transfer should be developed and implemented to improve the translation of guideline recommendations into care.
PMCID: PMC2683303  PMID: 16896426
Adults; Antiasthmatic agents; Asthma; Canada; Health surveys; Self care
19.  The role of omalizumab in the treatment of severe allergic asthma 
A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.
To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.
A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use.
Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or fourweek intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumab-treated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment.
Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.
PMCID: PMC2806789  PMID: 16909166
Asthma severity; Atopy; IgE; Monoclonal antibodies
20.  Le rôle de l’omalizumab dans le traitement de l’asthme allergique grave 
Un nouveau traitement anti-immunoglobuline E (anti-IgE) contre l’asthme, l’omalizumab, a été approuvé au Canada.
Passer en revue les données fondamentales et cliniques sur l’omalizumab et examiner le rôle possible de ce médicament dans la prise en charge de l’asthme au Canada.
Une recherche documentaire a été effectuée dans MEDLINE afin de repérer les études menées de 1960 à 2006 sur l’omalizumab. La recherche a également porté sur les résumés de réunions scientifiques récentes dans le domaine des maladies respiratoires et des allergies; par ailleurs, toute donnée non publiée a été demandée au fabricant. Après avoir revu et résumé les données, un comité mixte constitué de spécialistes des maladies respiratoires et des allergies a rédigé un ensemble de recommandations relatives à l’utilisation de l’omalizumab.
L’omalizumab est un anticorps monoclonal humanisé qui se lie au domaine C epsilon 3 de la molécule d’IgE pour former des complexes immuns solubles qui sont éliminés par le système réticulo-endothélial. L’administration d’injections sous-cutanées espacées de deux ou de quatre semaines à la dose recommandée entraîne une diminution rapide des taux d’IgE circulantes libres. Lors de deux essais cliniques de phase III menés auprès de 1 405 adultes et adolescents atteints d’asthme modéré à grave qui recevaient des doses moyennes stables de corticostéroïdes en inhalation (CSI), l’omalizumab a diminué les taux d’exacerbation par rapport au placebo et a été associé à une amélioration des symptômes ainsi qu’à une épargne plus importante des corticostéroïdes. Dans un essai mené auprès de 419 patients atteints d’asthme grave non maîtrisé malgré l’utilisation de doses élevées de CSI et de la prise concomitante d’agonistes bêta-2 à action prolongée, les exacerbations graves étaient de 50 % moins fréquentes chez les patients traités par l’omalizumab que chez les sujets témoins. Des analyses rétrospectives ont permis d’identifier les caractéristiques des patients les plus susceptibles de répondre au traitement par l’omalizumab.
L’omalizumab pourrait être envisagé comme traitement d’appoint dans les cas atopiques d’asthme grave non maîtrisé avec des traitements classiques par des doses optimales de CSI et un traitement d’appoint approprié (p. ex. : agonistes bêta-2 à action prolongée). En général, les patients sont classés en fonction de leur recours – traitement court et fréquent ou continu et oral – aux corticostéroïdes. Il ne faut amorcer le traitement qu’après avoir consulté un spécialiste pour confirmer le diagnostic et s’assurer que le traitement classique est optimal.
PMCID: PMC2806788
anticorps monoclonaux; atopie; gravité de l’asthme; IgE
21.  The SMART study 
Canadian Family Physician  2007;53(4):687-688.
PMCID: PMC1952599  PMID: 17872720
22.  Asthma control in Canada 
Canadian Family Physician  2007;53(4):672-677.
To determine whether asthma control in Canada had improved since the last major survey in 1999 by exploring how well patients’ asthma was controlled, how much they knew about asthma control, and how they used health care resources.
National telephone survey of patients between April and August 2004.
Eight hundred ninety-three adults 18 to 54 years old diagnosed with asthma more than 6 months before the survey.
Patients’ control of their asthma, patients’ knowledge about asthma, the frequency and duration of periods of worsening asthma, and patients’ use of health care resources to manage those periods.
In total, 26 210 households listed in a consumer database were contacted. Excluding ineligible households and households with a language barrier, a member of 13% of the households completed the 35-minute survey. Based on definitions in Canadian guidelines, 53% of patients had symptomatic uncontrolled asthma. In the previous year, almost all asthma patients had experienced worsening of symptoms that lasted on average 13.6 days for patients with uncontrolled asthma and 8.0 days for patients with controlled asthma (P < .02). Markedly more patients with uncontrolled asthma used health care resources for episodes of asthma than patients with controlled asthma did (72% vs 15% for urgent office visits, P < .01; 32% vs 3% for emergency department visits, P < .01; and 7% vs 0% for hospitalizations, P < .01) in the year before the survey. Patients were confused about the differences between reliever and controller medications. One third of patients claimed that no one had taught them about asthma medications, and one quarter said they had received no training on how to recognize the early signs of asthma worsening.
Asthma control and management remained suboptimal in Canada and relatively unchanged since the previous major survey in 1999.
PMCID: PMC1952597  PMID: 17872718
23.  SMART therapy 
PMCID: PMC1513407  PMID: 16880449
24.  Antimicrobials in acute exacerbations of chronic obstructive pulmonary disease - An analysis of the time to next exacerbation before and after the implementation of standing orders 
To compare the mean time to next exacerbation in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) before and after the implementation of standing orders.
Tertiary care hospital, Halifax, Nova Scotia, Canada.
The records of 150 patients were analyzed, 76 were in the preimplementation group, 74 in the postimplementation group.
The management and outcomes of patients admitted with an acute exacerbation of COPD before and after the implementation of standing orders were compared.
A retrospective chart review.
There was no difference in the mean time to next exacerbation between treatment groups (preimplementation group: 310 days, postimplementation group: 289 days, P=0.53). Antibiotics were used in 90% of the cases (preimplementation group: 87%, postimplementation group: 93%). The postimplementation group had a 20% increase in the use of first-line agents over the preimplementation group. Overall, first-line agents represented only 37% of the antibiotic courses.
The implementation of standing orders encouraged the use of first-line agents but did not influence subsequent symptom resolution, length of hospital stay, or the infection-free interval in patients with acute exacerbations of COPD.
PMCID: PMC2094950  PMID: 18159466
Antibiotics; Chronic obstructive pulmonary disease; Exacerbation

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