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2.  Comparative efficacy of indacaterol in chronic obstructive pulmonary disease 
Long-acting bronchodilators have been shown to improve multiple clinical outcomes in chronic obstructive pulmonary disease (COPD) including lung function, symptoms, dyspnea, quality of life, and exacerbations. Indacaterol is a novel, inhaled, long-acting β2-agonist providing 24-hour bronchodilation with once-daily dosing. It is currently approved for the maintenance treatment of COPD to be administered as 150 or 300 μg once-daily doses as licensed in many countries and 75 μg as licensed in the US by means of a single-dose dry powder inhaler. The data from clinical development support a favorable safety and tolerability profile within the β2-agonist drug class, with no relevant issues identified. Current evidence indicates that indacaterol is suitable for use as first-line monotherapy in COPD patients with moderate disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II) and beyond that do not require an inhaled corticosteroid (ICS) as per GOLD guidelines, or in combination with an ICS in severe or very severe patients with repeated exacerbations. Data from trials with the novel once-daily β2-agonist, indacaterol, indicate superior bronchodilation and clinical efficacy over twice-daily long-acting β2-agonists and at least equipotent bronchodilation as once-daily tiotropium. Bronchodilators are central in the symptomatic management of COPD. It is likely that once-daily dosing of a bronchodilator would be a significant convenience and probably a compliance-enhancing advantage, leading to improved overall clinical outcomes in patients with COPD.
doi:10.2147/COPD.S19805
PMCID: PMC3299544  PMID: 22419862
indacaterol; onset of action; chronic obstructive pulmonary disease; bronchodilators; once-daily; long-acting β2-agonists
3.  Delivery characteristics and patients’ handling of two single-dose dry-powder inhalers used in COPD 
For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction. The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies. The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD). The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD. Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use. Patients’ preference was assessed after completion of both study periods. Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler. For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively. In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01).
Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities. Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler. These are important factors for optimum dose delivery and successful COPD management.
doi:10.2147/COPD.S18529
PMCID: PMC3133507  PMID: 21760722
Breezhaler; HandiHaler; COPD; use; preference; dose delivery
4.  Asthma that is unresponsive to usual care 
doi:10.1503/cmaj.090089
PMCID: PMC2802604  PMID: 19825927
5.  A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study 
Background
Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) – tiotropium and glycopyrronium. Previous studies have compared glycopyrronium with open-label tiotropium. In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.
Methods
In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily. The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: –50 mL). Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.
Results
657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study. Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: –32, 31 mL). Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0–4 h post-dose versus tiotropium (all p < 0.001). FEV1 area under the curve from 0–4 h (AUC0–4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12. Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant). Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035). Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).
Conclusion
In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.
Trial registration
ClinicalTrial.gov, NCT01613326
doi:10.1186/1471-2466-14-4
PMCID: PMC3907130  PMID: 24438744
COPD; Glycopyrronium; Breezhaler; Tiotropium; Bronchodilator; Long-acting muscarinic antagonist; Blinding
6.  Predicting the need for supplemental oxygen during airline flight in patients with chronic pulmonary disease: A comparison of predictive equations and altitude simulation 
BACKGROUND:
Patients with chronic pulmonary diseases are at increased risk of hypoxemia when travelling by air. Screening guidelines, predictive equations based on ground level measurements and altitude simulation laboratory procedures have been recommended for determining risk but have not been rigorously evaluated and compared.
OBJECTIVES:
To determine the adequacy of screening recommendations that identify patients at risk of hypoxemia at altitude, to evaluate the specificity and sensitivity of published predictive equations, and to analyze other possible predictors of the need for in-flight oxygen.
METHODS:
The charts of 27 consecutive eligible patients referred for hypoxia altitude simulation testing before flight were reviewed. Patients breathed a fraction of inspired oxygen of 0.15 for 20 min. This patient population was compared with the screening recommendations made by six official bodies and compared the partial pressure of arterial oxygen (PaO2) obtained during altitude simulation with the PaO2 predicted by 16 published predictive equations.
RESULTS:
Of the 27 subjects, 25% to 33% who were predicted to maintain adequate oxygenation in flight by the British Thoracic Society, Aerospace Medical Association or American Thoracic Society guidelines became hypoxemic during altitude simulation. The 16 predictive equations were markedly inaccurate in predicting the PaO2 measured during altitude simulation; only one had a positive predictive value of greater than 30%. Regression analysis identified PaO2 at ground level (r=0.50; P=0.009), diffusion capacity (r=0.56; P=0.05) and per cent forced expiratory volume in 1 s (r=0.57; P=0.009) as having predictive value for hypoxia at altitude.
CONCLUSIONS:
Current screening recommendations for determining which patients require formal assessment of oxygen during flight are inadequate. Predictive equations based on sea level variables provide poor estimates of PaO2 measured during altitude simulation.
PMCID: PMC2734438  PMID: 19707606
Altitude; COPD; Flight; Hypoxemia; Hypoxia altitude simulation test; Normobaric challenge; Recommendations
7.  Single maintenance and reliever therapy (SMART) of asthma: a critical appraisal 
Thorax  2010;65(8):747-752.
The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting β agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6–12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7–10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy.
doi:10.1136/thx.2009.128504
PMCID: PMC2975956  PMID: 20581409
Budesonide; formoterol; compliance; asthma control; exacerbation; study design; asthma; asthma guidelines; asthma pharmacology; perception of asthma/breathlessness
8.  The role of omalizumab in the treatment of severe allergic asthma 
BACKGROUND:
A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.
OBJECTIVE:
To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.
METHODS:
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.
RESULTS:
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.
RECOMMENDATIONS:
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
9.  Le rôle de l’omalizumab dans le traitement de l’asthme allergique grave 
CONTEXTE :
Un nouveau traitement anti-immunoglobuline E (anti-IgE) contre l’asthme, l’omalizumab, a été approuvé au Canada.
OBJECTIF :
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.
MÉTHODOLOGIE :
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.
RÉSULTATS :
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.
RECOMMANDATIONS :
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
10.  Bronchodilator Responsiveness and Reported Respiratory Symptoms in an Adult Population 
PLoS ONE  2013;8(3):e58932.
Background
The relationship between patient-reported symptoms and objective measures of lung function is poorly understood.
Aim
To determine the association between responsiveness to bronchodilator and respiratory symptoms in random population samples.
Methods
4669 people aged 40 years and older from 8 sites in Canada completed interviewer-administered respiratory questionnaires and performed spirometry before and after administration of 200 ug of inhaled salbutamol. The effect of anthropometric variables, smoking exposure and doctor-diagnosed asthma (DDA) on bronchodilator responsiveness in forced expiratory volume in 1 second (FEV1) and in forced vital capacity (FVC) were evaluated. Multiple logistic regression was used to test for association between quintiles of increasing changes in FEV1 and in FVC after bronchodilator and several respiratory symptoms.
Results
Determinants of bronchodilator change in FEV1 and FVC included age, DDA, smoking, respiratory drug use and female gender [p<0.005 to p<0.0001 ]. In subjects without doctor-diagnosed asthma or COPD, bronchodilator response in FEV1 was associated with wheezing [p for trend<0.0001], while bronchodilator response for FVC was associated with breathlessness. [p for trend <0.0001].
Conclusions
Bronchodilator responsiveness in FEV1 or FVC are associated with different respiratory symptoms in the community. Both flow and volume bronchodilator responses are useful parameters which together can be predictive of both wheezing and breathlessness in the general population.
doi:10.1371/journal.pone.0058932
PMCID: PMC3598856  PMID: 23554960
11.  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.
BACKGROUND:
Chronic obstructive pulmonary disease (COPD) and asthma are common; however, mortality rates among individuals with these diseases are not well studied in North America.
OBJECTIVE:
To investigate mortality rates and risk factors for premature death among subjects with COPD.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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
12.  Infection with Mycoplasma pneumoniae is not related to asthma control, asthma severity, and location of airway obstruction 
Background
Mycoplasma pneumoniae is an organism that reportedly has a strong relationship to asthma. However, asthma severity and location of airway obstruction have not been compared between asthmatic patients with and without evidence for remote mycoplasma infection.
Objectives
The aim of this research was to study the relationship between previous M. pneumoniae infections in asthmatic patients and presence of any predilection for the involvement of central or peripheral airways, the severity of the disease, and asthma control.
Methods
Sixty-two patients with asthma were assessed by a validated asthma control test (ACT). All patients underwent spirometry and lung volume studies by body plethysmography. The forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC) were measured. An oropharyngeal swab was obtained for polymerase chain reaction analysis to detect the mycoplasma antigen. Moreover, blood samples were obtained to measure the titration of antimycoplasma immunoglobulin M (IgM) and IgG antibodies. The asthmatic patients with a positive IgG for mycoplasma and negative PCR and negative IgM antibody were considered to have remote history of mycoplasma infection. The relationship between the asthma control using ACT score and pulmonary function variables were compared in patients with and without evidence for remote mycoplasma infection.
Results
The incidence of postnasal drip was higher among the patients with asthma who had no evidence for remote mycoplasma infection (61.3% vs 32%, P = 0.035). The median ACT score was 16.5 (11–22) and 20 (13.75–24) in patients with and without remote M. pneumoniae infection, respectively (P > 0.05). In addition, the medians of the predicted values of the pulmonary function test parameters (FEV1, FEV1/FVC, FRC, FRC/TLC, RV/TLC, maximal mean expiratory flow 25%–75%, forced expiratory flow [FEF] 50%, and FEF 75%) and actual values of 5 Hz and 20 Hz resistance were not different between asthmatic patients with and without evidence of mycoplasma infection (P > 0.05).
Conclusions
The present study revealed that the asthma control status and parameters of lung function tests did not differ between asthmatic patients with and without evidence of chronic M. pneumoniae infection. The latter indicates the similar location of airway obstruction and comparable severity of asthma between the two groups.
doi:10.2147/IJGM.S15867
PMCID: PMC3056323  PMID: 21403784
Mycoplasma pneumoniae; asthma; asthma control test; airway; pulmonary function test
13.  Pharmacokinetic comparability of Prolastin®-C to Prolastin® in alpha1-antitrypsin deficiency: a randomized study 
Background
Alpha1-antitrypsin (AAT) deficiency is characterized by low blood levels of alpha1-proteinase inhibitor (alpha1-PI) and may lead to emphysema. Alpha1-PI protects pulmonary tissue from damage caused by the action of proteolytic enzymes. Augmentation therapy with Prolastin® (Alpha1-Proteinase Inhibitor [Human]) to increase the levels of alpha1-PI has been used to treat individuals with AAT deficiency for over 20 years. Modifications to the Prolastin manufacturing process, incorporating additional purification and pathogen-reduction steps, have led to the development of an alpha1-PI product, designated Prolastin®-C (Alpha1-Proteinase inhibitor [Human]). The pharmacokinetic comparability of Prolastin-C to Prolastin was assessed in subjects with AAT deficiency.
Methods
In total, 24 subjects were randomized to receive 60 mg/kg of functionally active Prolastin-C or Prolastin by weekly intravenous infusion for 8 weeks before crossover to the alternate treatment for another 8 weeks. Pharmacokinetic plasma samples were drawn over 7 days following last dose in the first treatment period and over 10 days following the last dose in the second period. The primary end point for pharmacokinetic comparability was area under the plasma concentration versus time curve over 7 days post dose (AUC0-7 days) of alpha1-PI determined by potency (functional activity) assay. The crossover phase was followed by an 8-week open-label treatment phase with Prolastin-C only.
Results
Mean AUC0-7 days was 155.9 versus 152.4 mg*h/mL for Prolastin-C and Prolastin, respectively. The geometric least squares mean ratio of AUC0-7 days for Prolastin-C versus Prolastin had a point estimate of 1.03 and a 90% confidence interval of 0.97-1.09, demonstrating pharmacokinetic equivalence between the 2 products. Adverse events were similar for both treatments and occurred at a rate of 0.117 and 0.078 per infusion for Prolastin-C (double-blind treatment phase only) and Prolastin, respectively (p = 0.744). There were no treatment-emergent viral infections in any subject for human immunodeficiency virus, hepatitis B or C, or parvovirus B19 during the course of the study.
Conclusion
Prolastin-C demonstrated pharmacokinetic equivalence and a comparable safety profile to Prolastin.
Trial Registration
ClinicalTrials.gov Identifier: NCT00295061
doi:10.1186/1472-6904-10-13
PMCID: PMC2958874  PMID: 20920295
14.  Influence of current or former smoking on asthma management and control 
BACKGROUND:
In patients with asthma, smoking has been associated with accelerated decline in pulmonary function, poor disease control and reduced responsiveness to corticosteroids.
OBJECTIVE:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.  A Cohort Study of Traffic-Related Air Pollution and Mortality in Toronto, Ontario, Canada 
Environmental Health Perspectives  2009;117(5):772-777.
Background
Chronic exposure to traffic-related air pollution (TRAP) may contribute to premature mortality, but few studies to date have addressed this topic.
Objectives
In this study we assessed the association between TRAP and mortality in Toronto, Ontario, Canada.
Methods
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 ≤ 2.5 μm (PM2.5) and ozone levels. We assigned predicted pollution exposures to 2,360 subjects from a respiratory clinic, and abstracted health data on these subjects from medical billings, lung function tests, and diagnoses by pulmonologists. We tracked mortality between 1992 and 2002. We used standard and multilevel Cox proportional hazard models to test associations between air pollution and mortality.
Results
After controlling for age, sex, lung function, obesity, smoking, and neighborhood deprivation, we observed a 17% increase in all-cause mortality and a 40% increase in circulatory mortality from an exposure contrast across the interquartile range of 4 ppb NO2. We observed no significant associations with other pollutants.
Conclusions
Exposure to TRAP was significantly associated with increased all-cause and circulatory mortality in this cohort. A high prevalence of cardiopulmonary disease in the cohort probably limits inference of the findings to populations with a substantial proportion of susceptible individuals.
doi:10.1289/ehp.11533
PMCID: PMC2685840  PMID: 19479020
air pollution; GIS; mortality; nitrogen dioxide; traffic air pollution; Toronto
16.  Hot tub lung mimicking classic acute and chronic hypersensitivity pneumonitis: Two case reports 
Pulmonary disease in otherwise healthy patients can occur by secondary exposure to nontuberculous mycobacteria from hot tubs. The pathology of hot tub lung may be related to an infection, a hypersensitivity reaction or both. Previous reports of hot tub lung have highlighted distinct pathological features that have distinguished this entity from classic hypersensitivity pneumonitis. Two cases of hot tub lung in Ontario, which presented at very different time points in their disease course, are reported; one patient presented more fulminantly with a clinical picture resembling subacute hypersensitivity pneumonitis, and the other presented with chronic disease. Both cases exhibited clinical, radiological and pathological findings closely mimicking classic subacute and chronic hypersensitivity pneumonitis.
PMCID: PMC2676409  PMID: 17885696
Hot tub; Hypersensitivity pneumonitis; Nontuberculous mycobacteria
17.  Asthma in Canada: missing the treatment targets 
doi:10.1503/cmaj.080120
PMCID: PMC2276550  PMID: 18390947
18.  Asthma control in Canada remains suboptimal: The Reality of Asthma Control (TRAC) study 
BACKGROUND:
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).
OBJECTIVES:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.  Asthma control in Canada 
Canadian Family Physician  2007;53(4):672-677.
OBJECTIVE
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.
DESIGN
National telephone survey of patients between April and August 2004.
SETTING
Canada.
PARTICIPANTS
Eight hundred ninety-three adults 18 to 54 years old diagnosed with asthma more than 6 months before the survey.
MAIN OUTCOME MEASURES
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.
RESULTS
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.
CONCLUSION
Asthma control and management remained suboptimal in Canada and relatively unchanged since the previous major survey in 1999.
PMCID: PMC1952597  PMID: 17872718
20.  Types, frequency and impact of asthma triggers on patients’ lives: a quantitative study in five European countries 
The Journal of Asthma  2013;51(2):127-135.
Objective:
To identify the types, frequency and impact of asthma triggers and the relationship to asthma control among adults with asthma in Europe.
Methods:
Adults with self-reported physician-diagnosed asthma receiving maintenance asthma treatment and self-reported exposure to known asthma triggers completed an online questionnaire; a subset completed a diary over 3–4 weeks. Information on asthma control (Asthma Control Test™ [ACT]), asthma triggers, frequency of exposure and behaviours in response or to avoid asthma triggers and the perceived impact on daily life was captured. A post-hoc analysis evaluated the impact of high trigger burden on the frequency of severe asthma exacerbations, hospitalisations and days lost at work/study.
Results:
A total of 1202 adults participated and 177 completed the diary. Asthma was uncontrolled for the majority (76%) of participants and most (52%) reported exposure to 6–15 asthma triggers. As trigger burden increased, behavioural changes to manage trigger exposure had a significantly increased impact on daily life (p < 0.0001) and job choice (p = 0.002). Participants reporting a high trigger burden (>16) were more likely to report uncontrolled asthma than those with a low trigger burden (1–5). Participants with a high trigger burden had previously experienced on average two more severe asthma attacks during a lifetime (p < 0.001), two more hospitalisations (p < 0.001) and 3.5 more missed days at work or study in the last year due to their asthma (p < 0.001) than those with a low trigger burden.
Conclusions:
Adults with asthma reporting a high trigger burden (>16 different triggers) experience more severe asthma attacks than those reporting lower trigger burdens.
doi:10.3109/02770903.2013.846369
PMCID: PMC3934435  PMID: 24050523
Asthma control; asthma triggers; behaviour; exacerbation; hospitalisation; questionnaire; trigger burden

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