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Clarus Leung,1 Jean Bourbeau,2 Don D Sin,1 Shawn D Aaron,3 J Mark FitzGerald,4 François Maltais,5 Darcy D Marciniuk,6 Denis O’Donnell,7 Paul Hernandez,8 Kenneth R Chapman,9 Brandie Walker,10 Jeremy D Road,4 Liyun Zheng,1 Carl Zou,1 James C Hogg,1 Wan C Tan1 On behalf of the CanCOLD Collaborative Research Group1Centre for Heart Lung Innovation, St Pauls Hospital, The University of British Columbia, Vancouver, BC, Canada; 2Research Institute McGill University Health Centre, McGill University, Montreal, Quebec, Canada; 3The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada; 4Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, Canada; 5Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Quebec, Canada; 6Respiratory Research Centre, University of Saskatchewan, Saskatoon, Canada; 7Department of Medicine, Queen’s University, Kingston, Canada; 8Department of Medicine, Dalhousie University, Halifax, Canada; 9Toronto General Hospital Research Institute, University of Toronto, Toronto, Canada; 10Department of Medicine, University of Calgary (BW), Alberta, CanadaCorrespondence: Wan C TanCentre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Rm 166, 1081 Burrard Street, Vancouver, B.C, V6Z 1Y6, CanadaTel +1-604-682-2344 ext 62749Fax +1-604-806-9274Email wan.tan@hli.ubc.caPurpose: To determine the spirometric-based prevalence of COPD across different regions in Canada and to evaluate the site heterogeneity of risk factors.Patients and Methods: In this cross-sectional, population-based study, random samples of non-institutionalized adults aged ≥ 40 years were generated by random digit dialling. Participants answered an interviewer-administered questionnaire and performed spirometry before and after bronchodilator administration. COPD was defined as post-bronchodilator FEV1/FVC < 0.70 (fixed ratio, FR) and as FEV1/FVC < 5th percentile (lower limits of normal, LLN). Separate logistic regression models were used to compute the risk (adjusted odds ratio, aOR) for COPD. I2 and Tau2 analyses were used to evaluate heterogeneity.Results: Out of 5176 (95%) participants, 4893 (47% male with mean age 56.6 years (95% confidence interval, 56.0– 57.2)) had spirometry that satisfied ATS criteria. The population prevalence of COPD was 16.2% (95% CI, 14.5– 17.8) by FR and 11.2% (95% CI, 9.7– 12.6) by LLN. Male predominance in prevalence was shown by FR but not by LLN criteria. Patient characteristics associated with an increased risk of COPD included: age (OR 1.56; 95% CI 1.33– 1.84); history of physician-diagnosed asthma (OR 3.30; 95% CI 2.42– 4.49); and childhood hospitalization for respiratory illness (OR 1.81; 95% CI 1.17– 2.80). In terms of smoking-related risk factors, current smoking status had the highest odds ratio (OR 3.49; 95% CI 2.55– 4.80). Variance in prevalence among sites was significantly reduced by adjusting for risk factors in Tau2 analyses. Higher odds of exposure for each risk factor was found in more severe COPD, suggesting that a higher risk could be linked to the development of severe disease.Conclusion: This study reports the population prevalence of COPD in nine urban cities which collectively represent the majority of the Canadian population and demonstrates that heterogeneity in prevalence among sites is substantially explained by variation in associated risk factors for COPD.Keywords: prevalence, heterogeneity, COPD

Background Recently, several proteins of the extracellular matrix have been characterised as active contributors to allergic airway disease. Microfibrillarassociated protein 4 (MFAP4) is an extracellular matrix protein abundant in the lung, whose biological functions remain poorly understood. In the current study we investigated the role of MFAP4 in experimental allergic asthma. Methods MFAP4-deficient mice were subjected to alum/ovalbumin and house dust mite induced models of allergic airway disease. In addition, human healthy and asthmatic primary bronchial smooth muscle cell cultures were used to evaluate MFAP4-dependent airway smooth muscle responses. Results MFAP4 deficiency attenuated classical hallmarks of asthma, such as eosinophilic inflammation, eotaxin production, airway remodelling and hyperresponsiveness. In wild-type mice, serum MFAP4 was increased after disease development and correlated with local eotaxin levels. MFAP4 was expressed in human bronchial smooth muscle cells and its expression was upregulated in asthmatic cells. Regarding the underlying mechanism, we showed that MFAP4 interacted with integrin αvβ5 and promoted asthmatic bronchial smooth muscle cell proliferation and CCL11 release dependent on phosphatidyloinositol-3-kinase but not extracellular signal-regulated kinase pathway. Conclusions MFAP4 promoted the development of asthmatic airway disease in vivo and pro-asthmatic functions of bronchial smooth muscle cells in vitro. Collectively, our results identify MFAP4 as a novel contributor to experimental asthma, acting through modulation of airway smooth muscle cells. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory illness is a leading cause of death worldwide, with rates that will continue to escalate into the foreseeable future. Rural residents have an increased risk of dying from some forms of respiratory disease, although little is known about the healthcare utilization or location of death for persons with advanced respiratory illness in rural settings. The purpose of this study was to examine rural--urban differences in healthcare utilization and location of death for residents of Saskatchewan, Canada, with chronic obstructive pulmonary disease (COPD) or lung cancer in the last 12 months of life. Methods: A retrospective cohort study was undertaken of 1098 patients who died in 2004 with a cause of death recorded as COPD or lung cancer in administrative health data from Saskatchewan Health. Decedents were classified as residents of rural/remote (≤9,999 population size), small urban or urban (≥100 000) locations and analysis conducted using this primary variable of interest. Comparisons were made between the three groups in terms of demographic characteristics, healthcare utilization (physician visits, length of stay, hospitalizations, institutional care, home care, transitions between care settings) and location of death (hospital, long-term care [LTC] or home). Results: The study population was 57% male with a mean age of 77 years (SD=11). Demographic characteristics, underlying cause of death and number of comorbid conditions were similar between urban, small urban and rural/remote groups. After adjustment for area of residence, underlying cause of death (UCOD), age group, sex, marital status, and comorbidity, urban, small urban and rural/remote residents were comparable in terms of the likelihood of: any hospitalizations, having had 5 or more transfers between settings, and dying in hospital. The proportion of home deaths in rural settings was 15.4%, and was comparable to the rate in urban settings (16.3%). Urban residents were more likely to have had 24 or more physician visits in the last year of life compared with small urban (OR=0.52, 95% CI=.37-.74) or rural/remote residents (OR=0.52, 95% CI=.40-.69), while rural/remote residents were more likely to have received any institutional LTC (OR=1.40, 95% CI=1.03-1.90) than the other groups. Hospital as a location of death was more likely for those with a UCOD of cardiovascular disease (OR=1.84, 95% CI=1.24- 2.71), but was less likely for those aged 80-85 years (OR=0.46, 95% CI=.31-.69), those aged more than 85 years (OR=0.28, 95% CI=.19-.42) and those who had never married (OR=0.48, 95% CI=.29-.78). Residents of rural/remote areas were significantly less likely than those in urban or small urban settings to receive any home care (OR=0.74, 95% CI=.56-.97), any home palliative care (OR=0.29, 95% CI=.19-.45) or home physiotherapy services (OR=0.09, 95% CI=.03-.25). Rural/remote residents were, however, much more likely to receive home supportive care (OR=1.60, 95% CI=1.17-2.19) and home meal preparation (OR=2.51, 95% CI=1.44-4.39). Conclusions: While the healthcare needs of persons with respiratory illness in the last year of life were likely to be similar between locations, rural-urban differences were apparent in the number of primary care physician visits and in access to and the nature of home care services provided. Significantly fewer physician visits were made by residents of small urban or rural remote locations compared with those in urban settings, although additional research is needed to determine the reasons for this discrepancy. The likelihood of receiving home care services and professional home care services such as palliative care and physiotherapy was significantly lower for persons in rural/remote locations. The challenges experienced by rural remote regions with supporting patients in the community may have led to the increased likelihood of admission to institutional LTC noted for this group compared with residents of urban and small urban settings. The low home death rates is both urban and rural settings may pose particular hardship for rural families who may need to travel extensively or temporarily relocate to be closer to the hospital where their loved one is dying. Further investigation of issues related to differences in quality of care and unmet health care needs between rural and non-rural settings will strengthen the evidence base to allow equitable care at the end of life [ABSTRACT FROM AUTHOR]

BACKGROUND: The effect that neonatal bacille Calmette-Guérin (BCG) vaccination has on tuberculin skin test (TST) results is not well evaluated in preschool children. METHODS: This was a retrospective cohort study of TST results in aboriginal children in Saskatchewan reserve communities. Records from the centralized provincial tuberculosis program were searched for aboriginal children aged 0 to 4 years during the time period 1991 to 1999. Only the first TST result reported as part of infant and preschool screening programs was considered. Children with active tuberculosis and those evaluated as part of a contact-tracing program were excluded. The BCG-vaccinated and unvaccinated groups were compared using wheal size cut points of 5 mm, 10 mm, and 15 mm. RESULTS: Data from 1,086 children with neonatal BCG vaccination and 1,867 unvaccinated children were analyzed. The rate of TST reactions was higher in vaccinated children at all ages, using a cut point of 5 mm. The rate of TST reactions was no different in vaccinated children >/= 1 year old when using a cut point of 15 mm. When using a cut point of 10 mm, the rate of TST reactions was higher at age 1 year but not different at age 4 years in the vaccinated children. CONCLUSION: The rate of TST reactions in preschool aboriginal children living on a reserve who have received neonatal BCG vaccination is affected by the cut point and age. The BCG vaccination status and age should therefore be considered when interpreting TST reactivity in the clinical assessment of aboriginal children participating in a tuberculosis control program. [ABSTRACT FROM AUTHOR]

We treated a 23-year-old aboriginal woman with drug-resistant pulmonary tuberculosis (TB). She experienced intolerance to her oral anti-TB medications, had subtherapeutic drug levels, and failed to respond to treatment. She then was effectively treated with percutaneous gastrojejunostomy tube (PGJT) administration of drugs. We present our data on the serum drug levels of rifampin, para-aminosalicylic acid, and levofloxacin after PGJT administration, and compare these values to published levels for oral administration of these drugs. In our patient, serum drug levels peaked and began to decline earlier than in the published data for oral administration of the same drugs. [ABSTRACT FROM AUTHOR]

Study Objectives: Validation of test-shortening procedures for the 2-min tidal breathing methacholine challenge method.Design: Retrospective chart review.Setting: Tertiary-care university clinical pulmonary function laboratory.Patients: One thousand subjects aged 10 to 85 years (mean +/- SD, 44.5 +/- 16.0 years), 44.5% male, referred for methacholine challenge.Intervention: Two-minute tidal breathing methacholine challenge was performed, with both physician and technician access to published test-shortening procedures.Measurements and Results: There were 315 positive test results (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)] < or = 8 mg/mL) and 685 negative test results. The subjects with positive test results were less likely to be male (39.1 vs 47.5%; p < 0.02) and had lower FEV(1) (91.8 +/- 14.9% predicted vs 97.2 +/- 13.9% predicted; p < 0.001). The average starting PC(20) was between 0.5 mg/mL and 1.0 mg/mL; the most common PC(20) was 1 mg/mL (67%). There were 431 skipped concentrations in 380 subjects. The mean number of methacholine inhalations was 3.7 +/- 1.1 (3.9 +/- 0.1 for negative test results vs 3.3 +/- 1.2 for positive test results; p < 0.001). Eighteen subjects had a > or = 20% FEV(1) fall on the first inhalation, and 11 subjects had a > or = 20% FEV(1) fall after a skipped concentration. In only one case (0.1%) an FEV(1) fall > or = 40% on the first concentration was reported, compared with no cases after a skipped concentration and seven cases with a > or = 40% FEV(1) fall after a routine doubling dose step-up.Conclusions: The 2-min tidal breathing methacholine test in clinical practice can be safely shortened to an average of less than four inhalations using starting concentrations based on FEV(1), asthma medication, and clinical features, and by occasionally omitting concentrations. [ABSTRACT FROM AUTHOR]

Scotty J Butcher,1 Brendan J Pikaluk,2 Robyn L Chura,1 Mark J Walkner,1 Jonathan P Farthing,2 Darcy D Marciniuk31School of Physical Therapy, University of Saskatchewan, Saskatoon, SK, Canada; 2College of Kinesiology, University of Saskatchewan, Saskatoon, SK, Canada; 3Division of Respiratory, Critical Care and Sleep Medicine, University of Saskatchewan, Saskatoon, SK, CanadaAbstract: High-level activities are typically not performed by patients with chronic obstructive pulmonary disease (COPD), which results in reduced functional performance; however, the physiological parameters that contribute to this reduced performance are unknown. The aim of this study was to determine the relationships between high-level functional performance, leg muscle strength/power, aerobic power, and anaerobic power. Thirteen patients with COPD underwent an incremental maximal cardiopulmonary exercise test, quadriceps isokinetic dynamometry (isometric peak torque and rate of torque development; concentric isokinetic peak torque at 90°/sec, 180°/sec, and 270°/sec; and eccentric peak torque at 90°/sec), a steep ramp anaerobic test (SRAT) (increments of 25 watts every 10 seconds), and three functional measures (timed up and go [TUG], timed stair climb power [SCPT], and 30-second sit-to-stand test [STS]). TUG time correlated strongly (P < 0.05) with all muscle strength variables and with the SRAT. Isometric peak torque was the strongest determinant of TUG time (r = –0.92). SCPT and STS each correlated with all muscle strength variables except concentric at 270°/sec and with the SRAT. The SRAT was the strongest determinant of SCPT (r = 0.91), and eccentric peak torque at 90°/sec was most significantly associated with STS (r = 0.81). Performance on the SRAT (anaerobic power); slower-velocity concentric, eccentric, and isometric contractions; and rate of torque development are reflected in all functional tests, whereas cardiopulmonary exercise test performance (aerobic power) was not associated with any of the functional or muscle tests. High-level functional performance in patients with COPD is associated with physiological parameters that require high levels of muscle force and anaerobic work rates.Keywords: stair climb, sit to stand, timed up and go, steep ramp, isokinetic

W Darlene Reid,1,2 Cristiane Yamabayashi,1 Donna Goodridge,3 Frank Chung,4 Michael A Hunt,1 Darcy D Marciniuk,5 Dina Brooks,6 Yi-Wen Chen,1 Alison Hoens,1,7 Pat Camp1,21Department of Physical Therapy, University of British Columbia, Vancouver, 2Institute of Heart and Lung Health, University of British Columbia, Vancouver, 3College of Nursing, University of Saskatchewan, 4Physiotherapy, Burnaby Hospital, Fraser Health, British Columbia, 5Division of Respirology, Critical Care and Sleep Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, 6Department of Physical Therapy, University of Toronto, Toronto, ON, 7Providence Health Care, Vancouver, BC, CanadaIntroduction: The prescription of physical activity for hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can be complicated by the presence of comorbidities. The current research aimed to synthesize the relevant literature on the benefits of exercise for people with multimorbidities who experience an AECOPD, and ask: What are the parameters and outcomes of exercise in AECOPD and in conditions that are common comorbidities as reported by systematic reviews (SRs)?Methods: An SR was performed using the Cochrane Collaboration protocol. Nine electronic databases were searched up to July 2011. Articles were included if they (1) described participants with AECOPD, chronic obstructive pulmonary disease (COPD), or one of eleven common comorbidities, (2) were an SR, (3) examined aerobic training (AT), resistance training (RT), balance training (BT), or a combination thereof, (4) included at least one outcome of fitness, and (5) compared exercise training versus control/sham.Results: This synthesis examined 58 SRs of exercise training in people with AECOPD, COPD, or eleven chronic conditions commonly associated with COPD. Meta-analyses of endurance (aerobic or exercise capacity, 6-minute walk distance – 6MWD) were shown to significantly improve in most conditions (except osteoarthritis, osteoporosis, and depression), whereas strength was shown to improve in five of the 13 conditions searched: COPD, older adults, heart failure, ischemic heart disease, and diabetes. Several studies of different conditions also reported improvements in quality of life, function, and control or prevention outcomes. Meta-analyses also demonstrate that exercise training decreases the risk of mortality in older adults, and those with COPD or ischemic heart disease. The most common types of training were AT and RT. BT and functional training were commonly applied in older adults. The quality of the SRs for most conditions was moderate to excellent (>65%) as evaluated by AMSTAR scores.Conclusion: In summary, this synthesis showed evidence of significant benefits from exercise training in AECOPD, COPD, and conditions that are common comorbidities. A broader approach to exercise and activity prescription in pulmonary rehabilitation may induce therapeutic benefits to ameliorate clinical sequelae associated with AECOPD and comorbidities such as the inclusion of BT and functional training.Keywords: pulmonary disease, chronic obstructive, comorbidity, exercise, physical fitness

Abstract Asthma is a very common disorder that still causes significant morbidity and mortality. A high percentage of individuals with asthma also experience exercise-induced bronchoconstriction (EIB). This article reviews the current literature and updates the reader on the safety, efficacy, and clinical applications of leukotriene modifiers in the treatment of EIB.

Abstract Background Systemic inflammation is associated with various complications in chronic obstructive pulmonary disease including weight loss, cachexia, osteoporosis, cancer and cardiovascular diseases. Inhaled corticosteroids attenuate airway inflammation, reduce exacerbations, and improve mortality in chronic obstructive pulmonary disease. Whether inhaled corticosteroids by themselves or in combination with a long-acting β2-adrenoceptor agonist repress systemic inflammation in chronic obstructive pulmonary disease is unknown. The Advair Biomarkers in COPD (ABC) study will determine whether the effects of inhaled corticosteroids alone or in combination with a long-acting β2-adrenoceptor agonist reduce systemic inflammation and improve health status in patients with chronic obstructive pulmonary disease. Methods/Design After a 4-week run-in phase during which patients with stable chronic obstructive pulmonary disease will receive inhaled fluticasone (500 micrograms twice daily), followed by a 4-week withdrawal phase during which all inhaled corticosteroids and long acting β2-adrenoceptor agonists will be discontinued, patients will be randomized to receive fluticasone (500 micrograms twice daily), fluticasone/salmeterol combination (500/50 micrograms twice daily), or placebo for four weeks. The study will recruit 250 patients across 11 centers in western Canada. Patients must be 40 years of age or older with at least 10 pack-year smoking history and have chronic obstructive pulmonary disease defined as forced expiratory volume in one second to vital capacity ratio of 0.70 or less and forced expiratory volume in one second that is 80% of predicted or less. Patients will be excluded if they have any known chronic systemic infections, inflammatory conditions, history of previous solid organ transplantation, myocardial infarction, or cerebrovascular accident within the past 3 months prior to study enrolment. The primary end-point is serum C-reactive protein level. Secondary end-points include circulating inflammatory cytokines such as interleukin-6 and interleukin-8 as well as health-related quality of life and lung function. Discussion If inhaled corticosteroids by themselves or in combination with a long-acting β2-adrenoceptor agonist could repress systemic inflammation, they might greatly improve clinical prognosis by reducing various complications in chronic obstructive pulmonary disease.

INTRODUCTION: Respiratory illness is a leading cause of death worldwide, with rates that will continue to escalate into the foreseeable future. Rural residents have an increased risk of dying from some forms of respiratory disease, although little is known about the healthcare utilization or location of death for persons with advanced respiratory illness in rural settings. The purpose of this study was to examine rural-urban differences in healthcare utilization and location of death for residents of Saskatchewan, Canada, with chronic obstructive pulmonary disease (COPD) or lung cancer in the last 12 months of life. METHODS: A retrospective cohort study was undertaken of 1098 patients who died in 2004 with a cause of death recorded as COPD or lung cancer in administrative health data from Saskatchewan Health. Decedents were classified as residents of rural/remote (< or =9,999 population size), small urban (10 000-99 999) or urban (> or =100 000) locations and analysis conducted using this primary variable of interest. Comparisons were made between the three groups in terms of demographic characteristics, healthcare utilization (physician visits, length of stay, hospitalizations, institutional care, home care, transitions between care settings) and location of death (hospital, long-term care [LTC] or home). RESULTS: The study population was 57% male with a mean age of 77 years (SD=11). Demographic characteristics, underlying cause of death and number of comorbid conditions were similar between urban, small urban and rural/remote groups. After adjustment for area of residence, underlying cause of death (UCOD), age group, sex, marital status, and comorbidity, urban, small urban and rural/remote residents were comparable in terms of the likelihood of: any hospitalizations, having had 5 or more transfers between settings, and dying in hospital. The proportion of home deaths in rural settings was 15.4%, and was comparable to the rate in urban settings (16.3%). Urban residents were more likely to have had 24 or more physician visits in the last year of life compared with small urban (OR=0.52, 95% CI=.37-.74) or rural/remote residents (OR=0.52, 95% CI=.40-.69), while rural/remote residents were more likely to have received any institutional LTC (OR=1.40, 95% CI=1.03-1.90) than the other groups. Hospital as a location of death was more likely for those with a UCOD of cardiovascular disease (OR=1.84, 95% CI=1.24-2.71), but was less likely for those aged 80-85 years (OR=0.46, 95% CI=.31-.69), those aged more than 85 years (OR=0.28, 95% CI=.19-.42) and those who had never married (OR=0.48, 95% CI=.29-.78). Residents of rural/remote areas were significantly less likely than those in urban or small urban settings to receive any home care (OR=0.74, 95% CI=.56-.97), any home palliative care (OR=0.29, 95% CI=.19-.45) or home physiotherapy services (OR=0.09, 95% CI=.03-.25). Rural/remote residents were, however, much more likely to receive home supportive care (OR=1.60, 95% CI=1.17-2.19) and home meal preparation (OR=2.51, 95% CI=1.44-4.39). CONCLUSIONS: While the healthcare needs of persons with respiratory illness in the last year of life were likely to be similar between locations, rural-urban differences were apparent in the number of primary care physician visits and in access to and the nature of home care services provided. Significantly fewer physician visits were made by residents of small urban or rural remote locations compared with those in urban settings, although additional research is needed to determine the reasons for this discrepancy. The likelihood of receiving home care services and professional home care services such as palliative care and physiotherapy was significantly lower for persons in rural/remote locations. The challenges experienced by rural remote regions with supporting patients in the community may have led to the increased likelihood of admission to institutional LTC noted for this group compared with residents of urban and small urban settings. The low home death rates is both urban and rural settings may pose particular hardship for rural families who may need to travel extensively or temporarily relocate to be closer to the hospital where their loved one is dying. Further investigation of issues related to differences in quality of care and unmet health care needs between rural and non-rural settings will strengthen the evidence base to allow equitable care at the end of life. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular comorbidities are increasingly being recognised in early stages of chronic obstructive pulmonary disease (COPD) yet complete cardiorespiratory functional assessments of individuals with mild COPD or presenting with COPD risk factors are lacking. This paper reports on the effectiveness of the cardiocirculatory-limb muscles oxygen delivery and utilisation axis in smokers exhibiting no, or mild to moderate degrees of airflow obstruction using standardised cardiopulmonary exercise testing (CPET)., Methods: Post-bronchodilator spirometry was used to classify participants as 'ever smokers without' (n=88), with 'mild' (n=63) or 'mild-moderate' COPD (n=56). All underwent CPET with continuous concurrent monitoring of oxygen uptake (V'O 2 ) and of bioimpedance cardiac output (Qc) enabling computation of arteriovenous differences (a-vO 2 ). Mean values of Qc and a-vO 2 were mapped across set ranges of V'O 2 and Qc isolines to allow for meaningful group comparisons, at same metabolic and circulatory requirements., Results: Peak exercise capacity was significantly reduced in the 'mild-moderate COPD' as compared with the two other groups who showed similar pulmonary function and exercise capacity. Self-reported cardiovascular and skeletal muscle comorbidities were not different between groups, yet disease impact and exercise intolerance scores were three times higher in the 'mild-moderate COPD' compared with the other groups. Mapping of exercise Qc and a-vO 2 also showed a leftward shift of values in this group, indicative of a deficit in peripheral O 2 extraction even for submaximal exercise demands. Concurrent with lung hyperinflation, a distinctive blunting of exercise stroke volume expansion was also observed in this group., Conclusion: Contrary to the traditional view that cardiovascular complications were the hallmark of advanced disease, this study of early COPD spectrum showed a reduced exercise O 2 delivery and utilisation in individuals meeting spirometry criteria for stage II COPD. These findings reinforce the preventive clinical management approach to preserve peripheral muscle circulatory and oxidative capacities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Infections are considered as leading causes of acute exacerbations of chronic obstructive pulmonary disease (COPD). Non-infectious risk factors such as short-term air pollution exposure may play a clinically important role. We sought to estimate the relationship between short-term air pollutant exposure and exacerbations in Canadian adults living with mild to moderate COPD., Methods: In this case-crossover study, exacerbations ('symptom based': ≥48 hours of dyspnoea/sputum volume/purulence; 'event based': 'symptom based' plus requiring antibiotics/corticosteroids or healthcare use) were collected prospectively from 449 participants with spirometry-confirmed COPD within the Canadian Cohort Obstructive Lung Disease. Daily nitrogen dioxide (NO 2 ), fine particulate matter (PM 2.5 ), ground-level ozone (O 3 ), composite of NO 2 and O 3 (O x ), mean temperature and relative humidity estimates were obtained from national databases. Time-stratified sampling of hazard and control periods on day '0' (day-of-event) and Lags ('-1' to '-6') were compared by fitting generalised estimating equation models. All data were dichotomised into 'warm' (May-October) and 'cool' (November-April) seasons. ORs and 95% CIs were estimated per IQR increase in pollutant concentrations., Results: Increased warm season ambient concentration of NO 2 was associated with symptom-based exacerbations on Lag-3 (1.14 (1.01 to 1.29), per IQR), and increased cool season ambient PM 2.5 was associated with symptom-based exacerbations on Lag-1 (1.11 (1.03 to 1.20), per IQR). There was a negative association between warm season ambient O 3 and symptom-based events on Lag-3 (0.73 (0.52 to 1.00), per IQR)., Conclusions: Short-term ambient NO 2 and PM 2.5 exposure were associated with increased odds of exacerbations in Canadians with mild to moderate COPD, further heightening the awareness of non-infectious triggers of COPD exacerbations., Competing Interests: Competing interests: BAR reports grants/contracts from the Canadian Institutes of Health Research (CIHR), Réseau de Recherche en Santé Respiratoire du Québec (RSRQ), Research Institute of the MUHC (RI MUHC), Ministère de l'Économie et de l'Innovation (MEI) Québec, McGill University Health Centre (MUHC) Foundation Grant, Fonds de Recherche Santé Québec (FRSQ), and CHEST Foundation Grant; and payments/honoraria from the Canadian Thoracic Society (CTS), CHEST/ACCP, Respiplus (non-profit), Alberta Kinesiology Association (AKA), and McGill University Continuing Professional Development (CPD). SDA reports payments/honoraria from AstraZeneca, GSK; and participation on Data Safety Monitoring/Advisory Board for AstraZeneca, GSK, and Sanofi. PH reports grants/contracts from Boehringer Ingelheim, Cyclomedica, Grifols, Vertex; consulting fees from Acceleron, AstraZeneca, Boehringer Ingelheim, Covis, GlaxoSmithKline, Janssen, Novartis, Sanofi, Teva, Takeda, Valeo; and leadership/fiduciary role in the Canadian Thoracic Society. FM reports grants/contracts from GlaxoSmithKline, AstraZeneca, Sanofi, Novartis, Boehringer Ingelheim, Grifols; consulting fees from AstraZeneca; payment/honoraria from GlaxoSmithKline, Boehringer Ingelheim, Grifols, Novartis; and stock/stock options from Oxynov. DM reports grants/contracts from AstraZeneca, Boehringer Ingelheim, Canadian Institute of Health Research, GlaxoSmithKline, Grifols, Lung Association—Saskatchewan, Novartis, Sanofi, Saskatchewan Health Research Foundation, Schering-Plough; consulting fees from Alberta Health Services, Canadian Foundation for Healthcare Improvement, Health Canada, Lung Association—Saskatchewan, Ontario Ministry of Health and Long-Term Care, Saskatchewan Health Authority, Yukon Health and Social Services; payment/honoraria from the Lung Association—Saskatchewan, American College of Chest Physicians; leadership/fiduciary role in the CHEST journal, Canadian Thoracic Society, American Thoracic Society and AARC; and is an employee of the University of Saskatchewan. DE O’D reports grants/contracts from AstraZeneca, Lung Health Foundation and Boehringer Ingelheim Canada; and payment/honoraria from GSK and Viajes Pacifico. BLW reports payment/honoraria from AstraZeneca, GSK, Sanofi; and Data Safety Monitoring/Advisory Board participation for AstraZeneca, GSK, and Sanofi. JB reports grants/contracts from the Canadian Institute of Health Research (CIHR), Réseau en santé respiratoire du FRQS, McGill University, McGill University Health Centre Foundation, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GSK, Grifols, Novartis, Sanofil, Trudell Canada Ltd; and payment/honoraria from AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GSK, Pfizer Canada Ltd, and Trudell Canada Ltd., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic obstructive pulmonary disease (COPD) and lung cancer are both detrimental diseases that present great burdens on society. Years of life lost (YLL), premature years of life lost (PYLL), working years lost (WYL), and productivity loss are all effective measures in identifying economic burden of disease., Objective: We propose a population-based study to analyze comprehensive provincial cohorts of Saskatchewan residents with COPD, lung cancer, and combined COPD and lung cancer in order to identify the burden these diseases present., Methods: Saskatchewan residents over the age of 35 years who had COPD, lung cancer, or both, between January 1, 2000, and December 31, 2015, will be identified and used in this study. Data for analysis including age, gender, and date of death, alongside Statistics Canada income estimates, will be used to estimate productivity loss and WYL. Statistics Canada life tables will be used to calculate YLL and PYLL by subtracting the patients' ages at death by their life expectancies, adjusted using sex and age at death. We will link the Saskatchewan cancer registry with Saskatchewan health administrative databases to create three cohorts: (1) COPD; (2) lung cancer; and (3) COPD and lung cancer. Individuals with lung cancer will be identified using ICDO-T (International Classification of Diseases for Oncology-Topography) codes, and those with COPD will be defined and identified as individuals who had at least 1 visit to a physician with a diagnosis of COPD or 1 hospital separation with a diagnosis of COPD. Those without a valid health care coverage for a consecutive 12 months prior to the first diagnostic code will be excluded from the study. Those with a combined diagnosis of COPD and lung cancer will be identified as individuals who were diagnosed with COPD in the 12 months following their lung cancer diagnosis or anytime preceding their lung cancer diagnosis., Results: As of April 2021, we have had access to all relevant data for this study, have received funding (January 2020), and have begun the preliminary analysis of our data set., Conclusions: It is well documented that COPD and lung cancer are both destructive diseases in terms of YLL, PYLL, WYL, and productivity loss; however, no studies have been conducted to analyze a cohort with combined COPD and lung cancer. Understanding the economic burden associated with each of our 3 cohorts is necessary in understanding and thus reducing the societal impact of COPD and lung cancer., International Registered Report Identifier (irrid): RR1-10.2196/31350., (©Erika Dianne Penz, Benjamin John Fenton, Nianping Hu, Darcy Marciniuk. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.03.2022.)

Background: Patient-oriented research affords individuals with opportunities to genuinely contribute to health care research as members of research teams. While checklists and frameworks can support academic researchers' awareness of patient engagement methods, less guidance appears available to support their understanding of how to develop and maintain collaborative relationships with their patient partners. This knowledge is essential as patient partners report that the social atmospheres of research teams significantly impacts the quality of their experiences. This study sought to develop theory regarding how academic researchers support and sustain patient engagement in patient-oriented research., Methods: A six-step, rapid realist review was conducted: (1) research question development, (2) preliminary theory development, (3) search strategy development; (4) study selection and appraisal, (4) data extraction, analysis and synthesis (5) identification of relevant formal theories, and (6) theory refinement with stakeholders. Findings were additionally distilled by collective competence theory., Results: A program theory was developed from 62 international studies which illuminated mechanisms supporting academic researchers to engage patient partners, contexts supporting these mechanisms, and resources that enabled mechanism activation. Interaction between seven contexts (patient-oriented research belief, prior interaction with a healthcare system, prior interaction with a particular academic researcher, educational background of patient partner, prior experience with patient-oriented research, study type, and time lived in a rural-urban setting) and seven mechanisms (deciding to become involved in patient-oriented research, recognizing valuable experiential knowledge, cultural competence, reducing power differentials, respectful team environment, supporting patient partners to feel valued, and readiness to research) resulted in an intermediate outcome (sense of trust). Trust then acted as an eighth mechanism which triggered the final-level outcome (empowered patient-centred lens)., Conclusions: Our theory posits that if patient partners trust they are a member of a supportive team working alongside academic researchers who authentically want to incorporate their input, then they are empowered to draw upon their experiential knowledge of health care systems and contribute as researchers in patient-oriented research. Our theory extends conceptual thinking regarding the importance of trust on patient-oriented research teams, how patient partners' trust is shaped by team interactions, and the role that academic researchers have within those interactions., (© 2021. The Author(s).)

Background: Dyspnea is a common symptom that has many causes, including obstructive airway disorders. We sought to examine previous diagnosis of obstructive airway disorders and other conditions in patients receiving treatment with inhaled medications for shortness of breath in a community setting., Methods: This cross-sectional study included consecutive patients aged 18 years and older receiving treatment for shortness of breath with inhaled medications for a minimum of 6 months. Study participants were recruited through community pharmacies in Edmonton and Saskatoon, Canada, between February 2009 and February 2012. Previous diagnosis of obstructive airway disorders by a primary care provider was assessed by patient self-report and review of health records. We conducted an assessment (as per guidelines from the American Thoracic Society and the European Respiratory Society), including pulmonary function tests; diagnoses were adjudicated by an expert physician panel (2 respirologists and 1 emergency physician). The agreement between diagnoses derived from pulmonary function tests and diagnoses from primary care providers was evaluated., Results: A total of 328 patients (median age 50 yr, 57.3% female) underwent assessment; 134 (40.9%) of patients reported ever having a pulmonary function test performed. After adjudication, 138 (42.1%) were diagnosed with asthma only, 86 (26.2%) with chronic obstructive pulmonary disease only and 11 (3.4%) with both. Some patients (93, 28.4%) had no evidence of obstructive airway disorders and 20 (6.1%) had evidence of other conditions that cause shortness of breath, such as heart failure and pulmonary hypertension. Overall, 62 (18.9%) patients could not be assigned a diagnosis., Interpretation: In a group of community-based patients with shortness of breath being treated with inhalers, less than half ever had pulmonary function tests performed, and a considerable proportion had no evidence of lung disease or other conditions. These findings highlight the need for confirmatory testing, including pulmonary function tests, before prescribing inhalers for patients with presumed obstructive airway disorders., Competing Interests: Competing interests: Ross Tsuyuki has received investigator-initiated funds from Merck, and consulting fees from Emergent BioSolutions and Shoppers Drug Mart. Darcy Marciniuk reports funding from the Canadian Respiratory Research Network, the Canadian Institutes of Health Research (CIHR), the Respiratory Health Network of the Fonds de la recherche en santé du Québec, Almirall, Merck, Nycomed, Pfizer Canada, the Canadian Thoracic Society and Theratechnologies; nonfinancial support from GlaxoSmithKline; grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and the Lung Association of Saskatchewan; personal fees from the Canadian Foundation for Healthcare Improvement, the Chinese Committee of Health and Family Planning, Health Canada, Mylan, the Saskatchewan Ministry of Health, the Saskatchewan Health Authority, and Yukon Health and Social Services; and grants from Canada Health Infoway, CIHR, the Lung Health Institute of Canada, Sanofi, Saskatchewan Health Research Foundation and Schering-Plough. No other competing interests were declared., (Copyright 2020, Joule Inc. or its licensors.)

Background: The patient-oriented research (POR) discourse has been criticized as being fragmented, lacking consistent terminology and having few evaluative studies. Our research team will use rapid realist review methodology to generate broad, process-based program theory regarding how partnering patients with researchers in POR generates an impact within a health care system., Methods: This protocol for a rapid realist review will involve multiple steps, including research question development; preliminary program theory and search strategy development; study selection and appraisal; data extraction, analysis and synthesis; and program theory refinement. We will be guided by the Realist and Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) publication standards for realist synthesis. Unlike traditional reviews, a realist review aims to discover and understand causal processes that exist within a complex environment, asking questions regarding what works for whom, under what circumstances, how and why. Our multidisciplinary team consists of patient partners, health care professionals, a health sciences librarian and health services researchers. Patient partners are full research partners, supporting development of our guiding research question and identifying community partners and stakeholder groups to disseminate our findings. Patient partners will be asked to recommend literature sources, to review and vet our set of search terms, and to review, evaluate and reflect on our initial program theory in light of their personal, lived expertise., Interpretation: We will share the results of our rapid realist review with community partners and stakeholder groups. We will also disseminate our program theory by means of publication in a peer-reviewed journal and presentation at scientific conferences., Competing Interests: Competing interests: None declared., (Copyright 2020, Joule Inc. or its licensors.)

Clinical guidelines have been developed recognizing pulmonary rehabilitation (PR) as a key component in the management of patients with chronic lung disease. The medical director of a PR program is a key player in every program and is a requirement for operation of the program. The medical director must be a licensed physician who has experience in respiratory physiology management. The purpose of this document is to provide an update regarding the clinical, programmatic, legislative, and regulatory issues that impact PR medical directors in North America. It describes the clinical rationale for physician involvement, relevant legislative and regulatory requirements, and resources available that the medical director can utilize to promote evidence-based and cost-effective PR services. All pulmonary rehabilitation (PR) programs must include a medical director. There are many clinical, programmatic, legislative, and regulatory issues that impact the PR medical director. The purpose of this document is to concentrate on the unique roles and responsibilities of the PR medical director.

Background: COPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations., Methods: Data were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18 months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed., Results: A total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score > 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs 5.0 [interquartile range, 2.0-7.0]; P = .01), and they were more likely to have baseline PSQI scores > 5 (50.3% vs 37.3%; P = .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95% CI, 1.01-1.18; P = .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95% CI, 1.00-1.21; P = .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95% CI, 1.09-2.03)., Conclusions: Higher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18 months' prospective follow-up., (Copyright © 2019. Published by Elsevier Inc.)

While there are both ethical and practical imperatives to address health inequity issues related to chronic disease management for persons with social complexity, existing programs often do not appropriately address the needs of these individuals. This leads to low levels of participation in programs, suboptimal chronic disease management, and higher health-care utilization. The aims of this project were to describe the challenges related to availability, accessibility, and acceptability faced by socially complex patients with Chronic Obstructive Pulmonary Disease (COPD) who were eligible, but declined enrollment in a traditional Chronic Disease Management Program (CDMP). Using a qualitative descriptive study approach informed by a health equity lens, interviews with participants, managers, and a focus group with providers were used to gather data addressing the above aims. Qualitative data were analyzed using Braun and Clarke's theoretical thematic analysis approach. The ability of participants to manage chronic disease was profoundly influenced by contextual and personal factors, such as poverty, disability, personal attitudes and beliefs (including shame, mistrust, and hopelessness), and barriers inherent in the organization of the health-care system. The existing chronic disease management program did not adequately address the most critical needs of socially complex patients. Challenges with accessibility and acceptability of chronic disease management and health services played important roles in the ways these socially complex participants managed their chronic illness. The individualistic approach to self-management of chronic illness inherent in conventional CDMP can be poorly aligned with the needs, capacity, and circumstances of many socially complex patients. Innovative models of care that promote incremental and guided approaches to enhancing health and improving self-efficacy need further development and evaluation.