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Background: Patients with chronic obstructive pulmonary disease (COPD) are commonly treated with inhaled corticosteroid/long-acting ß2-agonist combination therapy. While previous studies have investigated the host–microbiome interactions in COPD, the effects of specific steroid formulations on this complex cross-talk remain obscure. Methods: We collected and evaluated data from the Study to Investigate the Differential Effects of Inhaled Symbicort and Advair on Lung Microbiota (DISARM), a randomized controlled trial. Bronchoscopy was performed on COPD patients before and after treatment with salmeterol/fluticasone, formoterol/budesonide or formoterol-only. Bronchial brush samples were processed for microbial 16S rRNA gene sequencing and host mRNA sequencing. Longitudinal changes in the microbiome at a community, phylum and genus level were correlated with changes in host gene expression using a Spearman's rank correlation test. Findings: In COPD patients treated with salmeterol/fluticasone, the expression levels of 676 host genes were significantly correlated to changes in the alpha diversity of the small airways. At a genus level, the expression levels of 122 host genes were significantly related to changes in the relative abundance of Haemophilus. Gene enrichment analyses revealed the enrichment of pathways and biological processes related to innate and adaptive immunity and inflammation. None of these changes were evident in patients treated with formoterol/budesonide or formoterol alone. Interpretation: Changes in the microbiome following salmeterol/fluticasone treatment are related to alterations in the host transcriptome in the small airways of patients with COPD. These data may provide insights into why some COPD patients treated with inhaled corticosteroids may be at an increased risk for airway infection, including pneumonia. Funding: The Canadian Institute of Health Research, the British Columbia Lung Association, and an investigator-initiated grant from AstraZeneca. [ABSTRACT FROM AUTHOR]

Rationale: Automatic prediction algorithms based on routinely collected health data may be able to identify patients at high risk for hospitalizations related to acute exacerbations of chronic obstructive pulmonary disease (COPD).Objectives: To conduct a proof-of-concept study of a population surveillance approach for identifying individuals at high risk of severe COPD exacerbations.Methods: We used British Columbia's administrative health databases (1997-2016) to identify patients with diagnosed COPD. We used data from the previous 6 months to predict the risk of severe exacerbation in the next 2 months after a randomly selected index date. We applied statistical and machine-learning algorithms for risk prediction (logistic regression, random forest, neural network, and gradient boosting). We used calibration plots and receiver operating characteristic curves to evaluate model performance based on a randomly chosen future date at least 1 year later (temporal validation).Results: There were 108,433 patients in the development dataset and 113,786 in the validation dataset; of these, 1,126 and 1,136, respectively, were hospitalized for COPD within their outcome windows. The best prediction algorithm (gradient boosting) had an area under the receiver operating characteristic curve of 0.82 (95% confidence interval, 0.80-0.83), which was significantly higher than the corresponding value for the model with exacerbation history as the only predictor (current standard of care: 0.68). The predicted risk scores were well calibrated in the validation dataset.Conclusions: Imminent COPD-related hospitalizations can be predicted with good accuracy using administrative health data. This model may be used as a means to target high-risk patients for preventive exacerbation therapies. [ABSTRACT FROM AUTHOR]

Background: The economic impact of multimorbidity in severe or difficult-to-treat asthma has not been comprehensively investigated.Aims: To estimate the incremental healthcare costs of coexisting chronic conditions (comorbidities) in patients with severe asthma, compared with non-severe asthma and no asthma.Methods: Using health administrative data in British Columbia, Canada (1996-2016), we identified, based on the intensity of drug use and occurrence of exacerbations, individuals who experienced severe asthma in an incident year. We also constructed matched cohorts of individuals without an asthma diagnosis and those who had mild/dormant or moderate asthma (non-severe asthma) throughout their follow-up. Health service use records during follow-up were categorised into 16 major disease categories based on the International Classification of Diseases. Incremental costs (in 2016 Canadian Dollars, CAD$1=US$0.75=₤0.56=€0.68) were estimated as the adjusted difference in healthcare costs between individuals with severe asthma compared with those with non-severe asthma and non-asthma.Results: Relative to no asthma, incremental costs of severe asthma were $2779 per person-year (95% CI 2514 to 3045), with 54% ($1508) being attributed to comorbidities. Relative to non-severe asthma, severe asthma was associated with incremental costs of $1922 per person-year (95% CI 1670 to 2174), with 52% ($1003) being attributed to comorbidities. In both cases, the most costly comorbidity was respiratory conditions other than asthma ($468 (17%) and $451 (23%), respectively).Conclusions: Comorbidities accounted for more than half of the incremental medical costs in patients with severe asthma. This highlights the importance of considering the burden of multimorbidity in evidence-informed decision making for patients with severe asthma. [ABSTRACT FROM AUTHOR]

Rationale: Lung dysbiosis promotes airway inflammation and decreased local immunity, potentially playing a role in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Objectives: We sought to determine the relationship between sputum microbiome at the time of AECOPD hospitalization and 1-year mortality in a COPD cohort. Methods: We used sputum samples from 102 patients hospitalized because of AECOPD. All subjects were followed for 1 year after discharge. The microbiome profile was assessed through sequencing of 16S rRNA gene. Microbiome analyses were performed according to 1-year mortality status. To investigate the effect of α-diversity measures and taxon features on time to death, we applied Cox proportional hazards regression models and obtained hazard ratios (HRs) associated with these variables. Measurements and Main Results: We observed significantly lower values of α-diversity (richness, Shannon index, evenness, and Faith's Phylogenetic Diversity) among nonsurvivors (n = 19, 18.6%) than survivors (n = 83, 81.4%). β-Diversity analysis also demonstrated significant differences between both groups (adjusted permutational multivariate ANOVA, P = 0.010). The survivors had a higher relative abundance of Veillonella; in contrast, nonsurvivors had a higher abundance of Staphylococcus. The adjusted HRs for 1-year mortality increased significantly with decreasing α-diversity. We also observed lower survival among patients in whom sputum samples were negative for Veillonella (HR, 13.5; 95% confidence interval, 4.2-43.9; P < 0.001) or positive for Staphylococcus (HR, 7.3; 95% confidence interval, 1.6-33.2; P = 0.01). Conclusions: The microbiome profile of sputum in AECOPD is associated with 1-year mortality and may be used to identify subjects with a poor prognosis at the time of hospitalization. [ABSTRACT FROM AUTHOR]

The increased longevity afforded by combination antiretroviral therapy in developed countries has led to an increased concern regarding senescence-related diseases in patients with human immunodeficiency virus (HIV) infection. Previous epidemiologic analyses have demonstrated an increased risk of chronic obstructive pulmonary disease, as well as a significant burden of respiratory symptoms in HIV-infected patients. We performed the St. George's Respiratory Questionnaire (SGRQ) in 199 HIV-positive men, and determined the predominant factors contributing to poor respiratory-related health status. In univariate analyses, worse SGRQ scores were associated with respiratory-related variables such as greater smoking pack-year history ( p=0.028), lower forced expiratory volume in 1 second (FEV1) ( p<0.001), and worse emphysema severity as quantified by computed tomographic imaging ( p=0.017). In addition, HIV-specific variables, such as a history of plasma viral load >100,000 copies/mL ( p=0.043), lower nadir CD4 cell count ( p=0.040), and current CD4 cell count ≤350 cells/μL ( p=0.005), as well as elevated levels of inflammatory markers, specifically plasma interleukin (IL)-6 ( p=0.002) and alpha-1 antitrypsin ( p=0.005) were also associated with worse SGRQ scores. In a multiple regression model, FEV1, current CD4 count ≤350 cells/μL, and IL-6 levels remained significant contributors to reduced respiratory-related health status. HIV disease activity as measured by HIV-related immunosuppression in conjunction with the triggering of key inflammatory pathways may be important determinants of worse respiratory health status among HIV-infected individuals. Limitations of this analysis include the absence of available echocardiograms, diffusion capacity and lung volume testing, and an all-male cohort due to the demographics of the clinic population. [ABSTRACT FROM AUTHOR]

Background: Reduced forced expiratory volume in one second (FEV1) has been linked to non small cell lung cancer (NSCLC). However, it is unclear whether all or only certain histological subtypes of NSCLC are associated with reduced FEV1. Moreover, there is little information on whether gender modifies this relationship. Using a large tissue registry, we sought to determine the relationship between FEV1 and subtypes of NSCLC and determine whether this relationship is modified by gender. Methods: We used data from patients who underwent tumor resection for NSCLC at a teaching hospital in Vancouver and had various pre-operative clinical measurements including FEV1. We divided the cohort into quartiles of predicted FEV1 and using both logistic and linear regression modeling techniques determined whether FEV1 was related to the occurrence of adeno or squamous cell carcinoma in men and women. Results: There were 610 patients in the study (36% females). On average, women were more likely to have adenocarcinoma than were men (72% of all cases of NSCLC in women versus 40% in men; p < 0.001). In women, there was no significant relationship between FEV1 and the risk of any histological subtypes of NSCLC. In men, however, there was an inverse relationship between the risk of adenocarcinoma and FEV1 such that the lowest quartile of FEV1 was 47% less likely to have adenocarcinoma compared with the highest FEV1 quartile (adjusted odds ratio, 0.52; 0.28 to 0.98; p for trend, 0.028). The reverse was observed for squamous cell carcinoma. Conclusion: In individuals undergoing lung resection for NSCLC, the risk of adenocarcinoma and squamous cell carcinoma of the lung varies as a function of FEV1, independent of smoking intensity in men but not in women. Clinical Implications: These data indicate that women are much more susceptible to adenocarcinoma than are men especially when they have normal or near normal lung function. It may thus be useful to conduct periodic surveillance chest radiographs in asymptomatic female smokers (or ex-smokers) to ascertain peripheral nodules or masses before distant metastases occur since adenocarcinomas tend to metastasize earlier in the disease course than squamous cell carcinomas. [ABSTRACT FROM AUTHOR]

Background: Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and the epigenetic age of the airway epithelium and peripheral blood of PLWH., Methods: Airway epithelial brushings from 34 PLWH enrolled in the St. Paul's Hospital HIV Bronchoscopy cohort and peripheral blood from 378 PLWH enrolled in The Strategic Timing of Antiretroviral Treatment (START) study were profiled for DNA methylation. The DNA methylation biomarker of age and healthspan, GrimAge, was calculated in both tissue compartments. We tested the association of GrimAge with COPD in the airway epithelium and airflow obstruction as defined by an FEV 1 /FVC<0.70, and FEV 1 decline over 6 years in blood., Findings: The airway epithelium of PLWH with COPD was associated with greater GrimAge residuals compared to PLWH without COPD (Beta=3.18, 95%CI=1.06-5.31, P=0.005). In blood, FEV 1 /FVC1 decline was inversely correlated with GrimAge residuals in blood (r=-0.13, P=0.012). PLWH who had normal lung function but who subsequently developed an FEV 1 /FVC<0.70 over the course of 6 years had higher GrimAge residuals at baseline (Beta=2.33, 95%CI=0.23-4.44, P=0.031)., Interpretation: GrimAge may reflect lung and systemic epigenetic changes that occur with advanced airflow obstruction and may help to identify PLWH with a higher risk of developing COPD., Funding: Canadian Institutes of Health Research and the British Columbia Lung Association. The START substudy was funded by NIH grants: UM1-AI068641, UM1-AI120197, and RO1HL096453., Competing Interests: Declaration of interests SH reports consulting fees from the non-profit organization, Epigenetic Clock Development Foundation, and royalty income from patents surrounding epigenetic clocks. HK reports consulting fees and payments from AbbVie, Janssen, MSD, ViiV, Gilead, and Intercept, outside of the submitted work. KK reports consulting fees and payments from Allergan and Nuvaira, outside of the submitted work. DS reports payments from AstraZeneca, GSK, and Boehringer Ingelheim, outside of the submitted work. MH reports consulting fees and payments from Gilead, Merck, and ViiV, outside of the submitted work. RMN reports payments from ViiV, Gilead, and Theratechnologies, outside of the submitted work. J Montaner reports grants from Gilead, Merck, ViiV, the Public Health Agency of Canada, and the BC Ministry of Health, outside of the submitted work. JML reports a grant from AstraZeneca, outside of the submitted work. The remaining authors report no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Low body weight is associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, it is not known whether gender modifies this relationship., Methods: We pooled data of 8686 COPD patients from 7 studies with a median length of 36-months of follow up. Using a longitudinal natural cubic spline regression model, we examined the dose-response relationship between body mass index (BMI) and the rate of decline in forced expiratory volume in one second (FEV 1 ) in patients with GOLD 1 and 2 disease, stratified by gender and adjusted for age, smoking status, and cohort effects., Results: There was an inverse linear relationship between BMI and the rate of FEV 1 decline in GOLD Grades 1 and 2, which was modified by gender (p < 0.001). In male patients, an increase of BMI by 1 kg/m 2 reduced FEV 1 decline by 1.05 mL/year (95% CI 0.96, 1.14). However, in female patients, BMI status did not have a clinically meaningful impact on FEV 1 decline: an increase of baseline BMI by 1 kg/m 2 reduced FEV 1 decline by 0.16 ml/year (95% CI 0.11, 0.21). These gender-modified relationships were similar between GOLD 1 and 2 patients, and between current and former smokers., Conclusion: In mild to moderate COPD, higher BMI was associated with a less rapid decline of FEV 1 in male patients whereas this association was minimal in females patients. This gender-specific BMI effect was independent of COPD severity and smoking status.

Background: There is high interest in strategies for improving early detection of chronic obstructive pulmonary disease (COPD). These strategies often rely on opportunistic encounters between patients with undiagnosed COPD and the healthcare system; however, the frequency of these encounters is currently unknown., Methods: We used administrative health data for the province of British Columbia, Canada, from 1996 to 2015. We identified patients with COPD using a validated case definition, and assessed their visits to pharmacists, primary care and specialist physicians in the 5 years prior to the initial diagnosis of COPD. We used generalised linear models to compare the rate of outpatient visits between COPD and non-COPD comparator subjects matched on age, sex and socioeconomic status., Results: We assessed 112 635 COPD and non-COPD pairs (mean 68.6 years, 51.0% male). Patients with COPD interacted with pharmacists most frequently in the 5 years before diagnosis (mean 14.09, IQR 4-17 visits/year), followed by primary care (10.29, IQR 4-13 visits/year) and specialist (8.11, IQR 2-11 visits/year) physicians. In the 2 years prior to diagnosis, 72.1% of patients with COPD had a respiratory-related primary care visit that did not result in a COPD diagnosis. Compared with non-COPD subjects, patients with COPD had higher rates of primary care (rate ratio (RR) 1.40, 95% CI 1.39 to 1.41), specialist (RR 1.35, 95% CI 1.34 to 1.37) and pharmacist (RR 1.62, 95% CI 1.60 to 1.63) encounters., Conclusions: Patients with COPD used higher rates of outpatient services before diagnosis than non-COPD subjects. Case detection technologies implemented in pharmacy or primary care settings have opportunities to diagnose COPD earlier., Competing Interests: Competing interests: DDS has received honoraria for speaking engagements from Boehringer Ingelheim (BI), AstraZeneca (AZ) and Novartis; has served on COPD advisory committees for AZ; Sanofi-Aventis and CSA; and has received research funding from AZ, BI and Merck, outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Inhaled corticosteroids (ICSs) are often prescribed in patients with chronic obstructive pulmonary disease (COPD). Their impact on the risk of lung cancer, a leading cause of mortality in COPD patients, remains uncertain.Population-based linked administrative data between the years 1997 and 2007 from the province of British Columbia, Canada, were used to evaluate the association between lung cancer risk and ICS use in COPD patients. COPD was defined on the basis of receipt of three COPD-related prescriptions in subjects ≥50 years of age. Exposure to ICS was incorporated into multivariable Cox regression models using several time-dependent methods ("ever" exposure, cumulative duration of use, cumulative dose, weighted cumulative duration of use and weighted cumulative dose).There were 39 676 patients who met the inclusion criteria. The mean±sd age of the cohort was 70.7±11.1 years and 53% were female. There were 994 (2.5%) cases of lung cancer during follow-up. In the reference case analysis (time-dependent "ever" exposure), ICS exposure was associated with a 30% reduced risk of lung cancer (HR 0.70 (95% CI 0.61-0.80)). ICS exposure was associated with a decrease in the risk of lung cancer diagnosis over all five methods of quantifying exposure.This population-based study suggests that ICS use reduces the risk of lung cancer in COPD patients., Competing Interests: Conflict of interest: A.J.N. Raymakers has nothing to disclose. Conflict of interest: M. Sadatsafavi has nothing to disclose. Conflict of interest: D.D. Sin reports grants and personal fees for advisory board work, speaking engagements and organising education from AstraZeneca, grants and personal fees for advisory board work and organising meetings from Boehringer Ingelheim, grants from Merck Frosst, and personal fees for advisory board work from Novartis, outside the submitted work. Conflict of interest: J.M. FitzGerald has nothing to disclose. Conflict of interest: C.A. Marra has nothing to disclose. Conflict of interest: L.D. Lynd reports grants from Canadian Institute for Health Research, during the conduct of the study; and grants from AstraZeneca, outside the submitted work., (Copyright ©ERS 2019.)

Background: Most patients with asthma have mild disease. However, the clinical course of mild asthma and risk factors for progression are not well studied., Objective: To examine the long-term trajectories of mild asthma and the effects of early-stage risk factors on the subsequent disease course., Methods: From the administrative health data of British Columbia, Canada, we identified patients aged 14 to 45 years with newly diagnosed mild asthma between January 1997 and December 2012. For each follow-up year, we categorized a patient's asthma severity into mild/dormant, moderate, or severe on the basis of the intensity of asthma medications and occurrence of exacerbations. Ordinal logistic regression was used to estimate the probability of severity or all-cause death in the next year as a function of a patient's severity history in the past 3 years and selected baseline risk factors., Results: The study included 70,829 patients with incident mild asthma (62% women; mean age, 31 years). Over 10 years, 8% of these patients transitioned to moderate or severe asthma. Inappropriate use of rescue medications and older age were the most influential determinants for progression from mild asthma (odds ratios, 1.79; 95% CI, 1.68-1.90; P < .001; 1.24 per 10-year increase in age; 95% CI, 1.22-1.27; P < .001), whereas the presence of allergic rhinitis had no significant effects (odds ratio, 0.95; 95% CI, 0.91-1.00; P = .063)., Conclusions: Mild asthma remains largely stable over time. However, potentially modifiable factors such as inappropriate use of rescue medications are associated with a worsened prognosis., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the impact of care provider's specialty on the medical costs of COPD patients over time., Objective: To compare the long-term medical costs between newly hospitalized COPD patients whose post-discharge care was initiated by a pulmonary specialist versus by a general practitioner., Design: Retrospective matched cohort study., Participants: We identified patients with an incident COPD-related hospitalization from the administrative health database (January 1, 1996, to December 31, 2012) of British Columbia, Canada., Main Measures: Patients were categorized as receiving specialist care or primary care within the first 90 days after discharge from an incident COPD-related hospitalization. Using propensity scores, we matched each patient who initially received specialist care to a patient who received primary care based on demographics, COPD severity, comorbidity, and admission time. A survival-adjusted, multi-part generalized linear model was used to estimate direct medical costs (in 2015 Canadian dollars, [$], including inpatient, outpatient, pharmacy, and community care costs) as overall and as COPD-specific and comorbidity-related costs over the following 5 years., Key Results: The sample included 7710 patients under each group. The initial specialist-care recipients had a modestly higher 5-year survival than the generalist-care recipients (0.564 [95% CI 0.535, 0.634] vs 0.555 [95% CI 0.525, 0.625]; P < .001). Meanwhile, the former incurred $2809 higher all-cause medical costs over 5 years compared to the latter (95% CI $2343, $2913; P < .001), mainly driven by higher medication costs (difference $1782 [95% CI $1658, $1830]; P < .001) particularly related to COPD medications ($1170 [95% CI $1043, $1225]; P < .001). Specialist care recipients also incurred higher costs of COPD-related hospitalization ($1144 [95% CI $650, $1221]; P < .001)., Conclusions: Compared to generalist care, specialist care following COPD hospitalization is slightly more expensive, mainly driven by medication costs especially COPD-specific medications. Future studies should compare differences in health-related quality of life and COPD functional status.

Rationale: Readmissions are common following acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and are partially responsible for increased morbidity and mortality in COPD. Numerous factors have been shown to predict readmission of patients previously admitted to hospital for AECOPD; however, factors related to readmission in patients who are triaged in emergency departments (EDs) and sent directly home are poorly understood. We postulate that patients seen in the ED for AECOPD and directly sent home have a high readmission rate, and we suspect that inadequate management and follow-up contribute to this high readmission rate., Methods: We conducted a 1-year retrospective study of all patients seen in the ED for AECOPD at an inner-city tertiary care hospital; 30- and 90-day readmission rates for COPD and all-cause admissions to the ED and hospital were determined. Patients discharged directly home from the ED were compared with those admitted to hospital for management. Patient, treatment, and system variables that could potentially impact readmission were documented. Multivariate Poisson regression models were used to determine which factors predicted readmissions., Results: The readmission rates in the ED group (n=240) were significantly higher than that in the hospitalized group (n=271): 1) the 90-day ED readmissions (1.29 vs 0.51, p <0.0001) and 30-day ED readmissions (0.54 vs 0.20, p <0.0001) (ED vs hospitalized groups) were significantly higher in the ED group; 2) the time to first readmission was significantly shorter in the ED group than in the hospitalized group (24.1±22 vs 31.8±27.8 days; p <0.05). Cardiovascular comorbidities ( p <0.00001), substance abuse disorder ( p <0.001), and mental illness ( p <0.001) were the strongest predictors of readmission in the ED group. Age ( p <0.01), forced expiratory volume in 1 second ( p <0.001), and cardiovascular comorbidities ( p <0.05) were the best predictors for both 30- and 90-day COPD readmission rates in the ED group. Only 50% of the ED group patients received bronchodilators, oral steroids, and antibiotics inclusively, and only 68% were referred for community follow-up. The need for oral steroids to treat AECOPD predicted future 90-day COPD readmissions in the ED group ( p <0.003)., Conclusion: Patients discharged directly home from EDs have a significantly higher risk of readmission to EDs than those who are hospitalized. One possible reason for this is that COPD management is variable in EDs with <50% receiving appropriate therapy., Competing Interests: Disclosure Doctor SF van Eeden is the GlaxoSmithKline-Canadian Institutes of Health Research Professor in COPD. The authors report no other conflicts of interest in this work.

Background: Patients with chronic obstructive pulmonary disease (COPD) and asthma depend on inhalers for management, but critical errors committed during inhaler use can limit drug effectiveness. Outpatient education in inhaler technique remains inconsistent due to limited resources and inadequate provider knowledge., Objective: To determine whether a simple, two-session inhaler education program can improve physician attitudes toward inhaler teaching in primary care practice., Methods: An inhaler education program with small-group hands-on device training was instituted for family physicians (FP) in British Columbia and Alberta. Sessions were spaced one to three months apart. All critical errors were corrected in the first session. Questionnaires surveying current inhaler teaching practices and attitudes toward inhaler teaching were distributed to physicians before and after the program., Results: Forty-one (60%) of a total 68 participating FPs completed both before and after program questionnaires. Before the program, only 20 (49%) reported providing some form of inhaler teaching in their practices, and only four (10%) felt fully competent to teach patients inhaler technique. After the program, 40 (98%) rated their inhaler teaching as good to excellent. Thirty-four (83%) reported providing inhaler teaching in their practices, either by themselves or by an allied health care professional they had personally trained. All stated they could teach inhaler technique within 5 min. Observation of FPs during the second session by certified respiratory educators found that none made critical errors and all had excellent technique., Conclusion: A physician inhaler education program can improve attitudes toward inhaler teaching and facilitate implementation in clinical practices.

Background: Up-to-date estimates of burden of diseases are required for evidence-based decision-making. The objectives of this study were to determine the excess costs of COPD and its trend from 2001 to 2010 in British Columbia, Canada., Methods: We used British Columbia's administrative health data to construct a cohort of patients with COPD and a matched comparison cohort of subjects without COPD. We followed each patient from the time of first COPD-related health-care event (or equivalent time for the comparison cohort). Direct medical costs (in 2010 Canadian dollars [$]) were calculated based on billing records pertaining to hospital admissions, outpatient services use, medication dispensations, and community care services. We determined the excess medical costs of COPD by calculating the difference in overall medical costs between the COPD and the comparison cohorts., Results: The COPD and comparison cohorts comprised 153,570 and 246,801 people, respectively (for both cohorts, mean age at entry was 66.9 years; 47.2% female patients). The excess costs of COPD during the study period were $5,452 per patient-year. Inpatient, outpatient, medication, and community care costs were responsible for 57%, 16%, 22%, and 5% of the excess costs, respectively. Excess costs increased by $296/person-y (P < .01), with hospital costs demonstrating the largest increase over time ($258/person-y; P < .01)., Conclusions: The direct economic burden of COPD is high and has increased significantly between 2001 and 2010 over and above the increase in the health-care costs of the general population. Further investigation is required to elucidate the underlying reasons for the temporal increase in COPD direct costs.

Background: Our aim was to determine the combined and independent effects of tobacco and marijuana smoking on respiratory symptoms and chronic obstructive pulmonary disease (COPD) in the general population., Method: We surveyed a random sample of 878 people aged 40 years or older living in Vancouver, Canada, about their respiratory history and their history of tobacco and marijuana smoking. We performed spirometric testing before and after administration of 200 microg of salbutamol. We examined the association between tobacco and marijuana smoking and COPD., Results: The prevalence of a history of smoking in this sample was 45.5% (95% confidence interval [CI] 42.2%-48.8%) for marijuana use and 53.1% (95% CI 49.8%-56.4%) for tobacco use. The prevalence of current smoking (in the past 12 months) was 14% for marijuana use and 14% for tobacco use. Compared with nonsmokers, participants who reported smoking only tobacco, but not those who reported smoking only marijuana, experienced more frequent respiratory symptoms (odds ratio [OR] 1.50, 95% CI 1.05-2.14) and were more likely to have COPD (OR 2.74, 95% CI 1.66-4.52). Concurrent use of marijuana and tobacco was associated with increased risk (adjusted for age, asthma and comorbidities) of respiratory symptoms (OR 2.39, 95% CI 1.58-3.62) and COPD (OR 2.90, 95% CI 1.53-5.51) if the lifetime dose of marijuana exceeded 50 marijuana cigarettes. The risks of respiratory symptoms and of COPD were related to a synergistic interaction between marijuana and tobacco., Interpretation: Smoking both tobacco and marijuana synergistically increased the risk of respiratory symptoms and COPD. Smoking only marijuana was not associated with an increased risk of respiratory symptoms or COPD.

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading reason for hospitalization in Canada and a significant financial burden on hospital resources. Identifying factors that influence the time a patient spends in the hospital and readmission rates will allow for better use of scarce hospital resources., Objectives: To determine the factors that influence length of stay (LOS) in the hospital and readmission for patients with AECOPD in an inner-city hospital., Methods: Using the Providence Health Records, a retrospective review of patients admitted to St Paul's Hospital (Vancouver, British Columbia) during the winter of 2006 to 2007 (six months) with a diagnosis of AECOPD, was conducted. Exacerbations were classified according to Anthonisen criteria to determine the severity of exacerbation on admission. Severity of COPD was scored using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. For comparative analysis, severity of disease (GOLD criteria), age, sex and smoking history were matched., Results: Of 109 admissions reviewed, 66 were single admissions (61%) and 43 were readmissions (39%). The number of readmissions ranged from two to nine (mean of 3.3 readmissions). More than 85% of admissions had the severity of COPD equal to or greater than GOLD stage 3. The significant indicators for readmission were GOLD status (P<0.001), number of related comorbidities (OR 1.47, 95% CI 1.10 to 1.97; P<0.009) and marital status (single) (OR 4.18, 95% CI 1.03 to 17.02; P<0.046). The requirement for social work involvement during hospital admission was associated with a prolonged LOS (P<0.05)., Conclusions: The results of the present study show that disease severity (GOLD status) and number of comorbidities are associated with readmission rates of patients with AECOPD. Interestingly, social factors such as marital status and the need for social work intervention are also linked to readmission rates and LOS, respectively, in patients with AECOPD.