Search

The impact of the COVID-19 pandemic on the management of ambulatory care sensitive conditions (ACSCs) remains unknown.To compare observed and expected (projected based on previous years) trends in all-cause mortality and healthcare use for ACSCs in the first year of the pandemic (March 2020 to March 2021).We conducted a population-based study using provincial health administrative data on general adul population (Ontario, Canada).Monthly all-cause mortality, and hospitalizations, emergency department (ED) and outpatient visit rates (per 100,000 people at-risk) for seven combined ACSCs (asthma, chronic obstructive pulmonary disease, angina, congestive heart failure, hypertension, diabetes, and epilepsy) during the first year were compared with similar periods in previous years (2016-2019) by fitting monthly time series autoregressive integrated moving-average models.Compared to previous years, all-cause mortality rates increased at the beginning of the pandemic (observed rate in March to May 2020 of 79.98 vs. projected of 71.24 [66.35-76.50]) and then returned to expected in June 2020-except among immigrants and people with mental health conditions where they remained elevated. Hospitalization and ED visit rates for ACSCs remained lower than projected throughout the first year: observed hospitalization rate of 37.29 versus projected of 52.07 (47.84-56.68); observed ED visit rate of 92.55 versus projected of 134.72 (124.89-145.33). ACSC outpatient visit rates decreased initially (observed rate of 4299.57 vs. projected of 5060.23 [4712.64-5433.46]) and then returned to expected in June 2020.

Background Although guidelines have long recommended objective pulmonary function testing to diagnose asthma and chronic obstructive lung disease (COPD), many primary care patients receive a clinical diagnosis of asthma or COPD without objective testing. This often leads to unnecessary treatment with associated incremental costs and side-effects, and delays actual diagnosis. Research Question What are the barriers and enablers to lung function testing for asthma and/or COPD in primary care? Study Design and Methods We searched the literature for qualitative and quantitative studies reporting barriers and/or enablers to in-office or out-of-office lung function testing for diagnosing asthma and/or COPD, in primary care. Two reviewers independently screened abstracts and full texts; assessed methodological quality using the Mixed Methods Appraisal Tool; and extracted data from included studies. Identified barriers and enablers were categorized using the Theoretical Domains Framework (TDF), applying a pre-established coding manual. Results We identified 7988 unique articles, reviewed 336 full-text articles, and included 18 studies in this systematic review. Of these 18, 12 were quantitative, 3 were qualitative, and 3 used mixed methods. All 18 addressed in-office testing and 11 also addressed out-of-office testing. Barriers and enablers overlapped for asthma and COPD, and in- and out-of-office settings. We identified more reported barriers (e.g. lack of knowledge of the usefulness of spirometry) than enablers (e.g. skills for performing reliable spirometry). Barriers mapped to 9 (of a possible 14) TDF domains (for both in- and out-of-office settings). Enablers mapped to three domains for in-office testing and five domains for out-of-office testing. Interpretation Barriers to objective testing for airways disease in primary care are complex and span many theoretical domains. Correspondingly, a successful intervention must leverage multiple behaviour change techniques. A theory-based, multifaceted intervention to address underuse of diagnostic testing for asthma or COPD should now be developed and tested.

Background Chronic obstructive pulmonary disease (COPD) medications reduce exacerbations and improve quality of life. Despite this, some individuals do not receive medications recommended by practise guidelines. Research question How common is non-receipt of recommended medications among people with COPD and what are factors associated with non-receipt? Study design and methods We conducted a population cohort study in Ontario, Canada, a province with universal health care insurance and medication coverage for those aged 65 and older. Health administrative data were used to identify people 66 years of age or older with physician-diagnosed COPD as of 2018 and group them into lower or higher risk for future COPD exacerbation groups. Proportions of patients in each group who did not receive medications recommended by COPD guidelines were determined. Generalized estimating equation modelling was used to determine associations between patient and physician factors and non-receipt of recommended medications. Results About 54% and 88% of people with COPD receoved sufficient recommended medications in the low and high risk of exacerbation groups, respectively. Longer duration of COPD, higher comorbidity, dementia, and older physician age were associated with non-receipt of recommended medications in both groups. People who had a co-diagnosis of asthma and who received care by a pulmonologist and spirometry were more likely to receive recommended medication . Interpretation COPD medications appear underused by the COPD population and various factors are associated with sub-optimal receipt. Targeting these factors would help improve the care and health of people with COPD.

BACKGROUND: Cystic fibrosis (CF) is characterized by neutrophilic inflammation in the airways. Leukotriene B4 (LTB4) is a neutrophil chemoattractant and has been implicated in CF pathogenesis. Acebilustat, a novel, synthetic, small-molecule leukotriene A4 hydrolase inhibitor, reduces LTB4 production. We report findings from a randomized placebo-controlled trial of acebilustat in adult subjects with mild-to-moderate lung disease.METHODS: Subjects were randomized (1:1:1) to once-daily acebilustat 50 mg, 100 mg or placebo for 48 weeks, concomitantly with their current therapeutic regimen. Subjects were stratified by use of concomitant CF transmembrane conductance regulator (CFTR) modulators, baseline percent predicted forced expiratory volume in 1 second (ppFEV1) 50-75 and >75, and number of pulmonary exacerbations in the past year (1 or >1). Primary endpoints were the change from baseline in ppFEV1 and safety. Secondary endpoints included the rate of pulmonary exacerbations.RESULTS: Overall, 199 subjects were randomized and dosed (acebilustat 50 mg, n=67; acebilustat 100 mg, n=66; placebo, n=66). Baseline demographics and disease profile were well balanced among treatment groups. Acebilustat had no statistically significant effect on the primary endpoint of change in ppFEV1 at week 48 or the secondary endpoint pulmonary exacerbations. There was a trend towards reduced pulmonary exacerbations in subjects receiving acebilustat in pre-specified populations with ppFEV1>75 (35% rate reduction) and those on concomitant CFTR modulator therapy (20% rate reduction). Acebilustat was well tolerated.CONCLUSIONS: Acebilustat did not improve lung function. A trend towards reduced pulmonary exacerbations in subjects with an earlier stage of lung disease suggests a potential effect in this population.

Background: The relationship between symptom burden and physical activity (PA) in chronic obstructive pulmonary disease (COPD) remains poorly understood with limited data on undiagnosed individuals and those with mild to moderate disease. Objective: The primary objective was to evaluate the relationship between symptom burden and moderate-to-vigorous intensity PA (MVPA) in individuals from a random population-based sampling mirroring the population at large. Methods: Baseline participants of the Canadian Cohort Obstructive Lung Disease (n=1558) were selected for this cross-sectional sub-study. Participants with mild COPD (n=406) and moderate COPD (n=331), healthy individuals (n=347), and those at risk of developing COPD (n=474) were included. The Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire was used to estimate MVPA in terms of energy expenditure. High symptom burden was classified using the COPD Assessment Test ([CAT] ≥10). Results: Significant associations were demonstrated between high symptom burden and lower MVPA levels in the overall COPD sample (β=-717.09; 95% confidence interval [CI]=-1079.78, -354.40; p

BackgroundImpaired cough results in airway secretion retention, atelectasis and pneumonia in individuals with Duchenne muscular dystrophy (DMD). Lung volume recruitment (LVR) stacks breaths to inflate the lungs to greater volumes than spontaneous effort. LVR is recommended in DMD clinical care guidelines but is not well studied. We aimed to determine whether twice-daily LVR, compared with standard of care alone, attenuates the decline in FVC at 2 years in boys with DMD.MethodsIn this multicentre, assessor-blinded, randomised controlled trial, boys with DMD, aged 6–16 years with FVC >30% predicted, were randomised to receive conventional treatment or conventional treatment plus manual LVR twice daily for 2 years. The primary outcome was FVC % predicted at 2 years, adjusted for baseline FVC % predicted, age and ambulatory status. Secondary outcomes included change in chest wall distensibility (maximal insufflation capacity minus FVC) and peak cough flow.ResultsSixty-six boys (36 in LVR group, 30 in control) were evaluated (median age (IQR): 11.5 years (9.5–13.5), median baseline FVC (IQR): 85% predicted (73–96)). Adjusted mean difference in FVC between groups at 2 years was 1.9% predicted (95% CI −6.9% to 10.7%; p=0.68) in the direction of treatment benefit. We found no differences in secondary outcomes.ConclusionThere was no difference in decline in FVC % predicted with use of twice-daily LVR for boys with DMD and relatively normal lung function. The burden associated with routine LVR may outweigh the benefit. Benefits of LVR to maintain lung health in boys with worse baseline lung function still need to be clarified.Trial registration numberNCT01999075.

BackgroundInfections 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.MethodsIn 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 (NO2), fine particulate matter (PM2.5), ground-level ozone (O3), composite of NO2and O3(Ox), 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.ResultsIncreased warm season ambient concentration of NO2was associated with symptom-based exacerbations on Lag−3 (1.14 (1.01 to 1.29), per IQR), and increased cool season ambient PM2.5was 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 O3and symptom-based events on Lag−3 (0.73 (0.52 to 1.00), per IQR).ConclusionsShort-term ambient NO2and PM2.5exposure 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.

Tetyana Kendzerska,1– 3 Carl van Walraven,1– 3 Daniel I McIsaac,1,3,4 Marcus Povitz,5,6 Sunita Mulpuru,1,2 Isac Lima,1,3 Robert Talarico,1,3 Shawn D Aaron,1,2 William Reisman,5,7 Andrea S Gershon3,8,9 1Department of Medicine, The Ottawa Hospital Research Institute/The Ottawa Hospital, Ottawa, Ontario, Canada; 2Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 3ICES, Ottawa, Toronto, Ontario, Canada; 4Departments of Anesthesiology & Pain Medicine, University of Ottawa and Ottawa Hospital, Ottawa, Ontario, Canada; 5Department of Medicine at Schulich School of Medicine and Dentistry at Western University, London, Ontario, Canada; 6Cumming School of Medicine, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; 7Department of Medicine, London Health Sciences Centre, London, Ontario, Canada; 8Faculty of Medicine, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; 9Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaCorrespondence: Tetyana KendzerskaOttawa Hospital Research Institute, Division of Respirology, University of Ottawa, The Ottawa Hospital, Civic Campus, 1053 Carling Ave, Ottawa, ON, K1Y 4E9, CanadaEmail tkendzerska@toh.caBackground: There is limited evidence on whether obstructive sleep apnea (OSA) can be accurately identified using health administrative data.Study Design and Methods: We derived and validated a case-ascertainment model to identify OSA using linked provincial health administrative and clinical data from all consecutive adults who underwent a diagnostic sleep study (index date) at two large academic centers (Ontario, Canada) from 2007 to 2017. The presence of moderate/severe OSA (an apnea–hypopnea index≥ 15) was defined using clinical data. Of 39 candidate health administrative variables considered, 32 were tested. We used classification and regression tree (CART) methods to identify the most parsimonious models via cost-complexity pruning. Identified variables were also used to create parsimonious logistic regression models. All individuals with an estimated probability of 0.5 or greater using the predictive models were classified as having OSA.Results: The case-ascertainment models were derived and validated internally through bootstrapping on 5099 individuals from one center (33% moderate/severe OSA) and validated externally on 13,486 adults from the other (45% moderate/severe OSA). On the external cohort, parsimonious models demonstrated c-statistics of 0.75– 0.81, sensitivities of 59– 60%, specificities of 87– 88%, positive predictive values of 79%, negative predictive values of 73%, positive likelihood ratios (+LRs) of 4.5– 5.0 and –LRs of 0.5. Logistic models performed better than CART models (mean integrated calibration indices of 0.02– 0.03 and 0.06– 0.12, respectively). The best model included: sex, age, and hypertension at the index date, as well as an outpatient specialty physician visit for OSA, a repeated sleep study, and a positive airway pressure treatment claim within 1 year since the index date.Interpretation: Among adults who underwent a sleep study, case-ascertainment models for identifying moderate/severe OSA using health administrative data had relatively low sensitivity but high specificity and good discriminative ability. These findings could help study trends and outcomes of OSA individuals using routinely collected health care data.Keywords: obstructive sleep apnea, case-ascertainment modelling, health administrative data

Seasonal respiratory viral infections are associated with exacerbations and morbidity among patients with COPD. The real-world clinical outcomes associated with seasonal viral infections are less well established among hospitalized patients.To estimate the association between seasonal respiratory viral infections, 30-day mortality, and intensive care unit (ICU) admission among hospitalized COPD patients.We conducted an analysis of a national prospective multicenter cohort of COPD patients hospitalized with acute respiratory illness during winter seasons (2011-2015) in Canada. Nasopharyngeal swabs were performed on all patients at the onset of hospital admission for diagnosis of viral infection. Primary outcomes were 30-day mortality and ICU admissions. Secondary outcomes included invasive/non-invasive ventilation use.Among 3931 hospitalized patients with COPD, 28.5% (1122/3931) were diagnosed with seasonal respiratory viral infection. Viral infection was associated with increased admission to ICU (OR 1.5, 95% CI 1.2-1.9) and need for mechanical ventilation (OR 1.9, 95% CI 1.4-2.5), but was not associated with mortality (OR 1.1, 95% CI 0.8-1.4). Patients with respiratory syncytial virus (RSV) were equally likely to require ICU admission (OR 1.09, 95% CI 0.67-1.78), and more likely to need non-invasive ventilation (OR 3.1; 95% CI 1.8-5.1) compared to patients with influenza.Our results suggest COPD patients requiring hospitalization for respiratory symptoms should routinely receive viral testing at admission, especially for RSV and influenza, to inform prognosis, clinical management, and infection control practices during winter seasons. Patients with COPD will be an important target population for newly developed RSV therapeutics.ClinicalTrials.gov ID: NCT01517191.

BackgroundSubjects without a previous history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness (AHR) in association with underlying eosinophilic (type 2 (T2)) inflammation, consistent with undiagnosed asthma. However, the prevalence of undiagnosed asthma in these subjects is unknown.MethodsIn this observational study, inhaled corticosteroid-naïve adults without previously diagnosed lung disease reporting current respiratory symptoms and showing normal pre- and post-bronchodilator spirometry underwent fractional exhaled nitric oxide (FENO) measurement, methacholine challenge testing and induced sputum analysis. AHR was defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20) −1and T2 inflammation was defined as sputum eosinophils >2% and/orFENO>25 ppb.ResultsOut of 132 subjects (mean±sdage 57.6±14.2 years, 52% female), 47 (36% (95% CI 28–44%)) showed AHR: 20/132 (15% (95% CI 9–21%)) with PC20−1and 27/132 (21% (95% CI 14–28%)) with PC204–15.9 mg·mL−1. Of 130 participants for whom sputum eosinophils,FENOor both results were obtained, 45 (35% (95% CI 27–43%)) had T2 inflammation. 14 participants (11% (95% CI 6–16%)) had sputum eosinophils >2% and PC20≥16 mg·mL−1, suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with PC20−1(12/20 (60%)) than in those with PC204–15.9 mg·mL−1(8/27 (30%)) or ≥16 mg·mL−1(25/85 (29%)) (p=0.01).ConclusionsAsthma, underlying T2 airway inflammation and eosinophilic bronchitis may remain undiagnosed in a high proportion of symptomatic subjects in the community who have normal pre- and post-bronchodilator spirometry.

BackgroundIt remains unclear why some symptomatic individuals with asthma or COPD remain undiagnosed. Here, we compare patient and physician characteristics between symptomatic individuals with obstructive lung disease (OLD) who are undiagnosed and individuals with physician-diagnosed OLD.MethodsUsing random-digit dialling and population-based case finding, we recruited 451 participants with symptomatic undiagnosed OLD and 205 symptomatic control participants with physician-diagnosed OLD. Data on symptoms, quality of life and healthcare utilisation were analysed. We surveyed family physicians of participants in both groups to elucidate differences in physician practices that could contribute to undiagnosed OLD.ResultsParticipants with undiagnosed OLD had lower mean pre-bronchodilator forced expiratory volume in 1 s percentage predicted compared with those who were diagnosed (75.2%versus80.8%; OR 0.975, 95% CI 0.963–0.987). They reported greater psychosocial impacts due to symptoms and worse energy and fatigue than those with diagnosed OLD. Undiagnosed OLD was more common in participants whose family physicians were practising for >15 years and in those whose physicians reported that they were likely to prescribe respiratory medications without doing spirometry. Undiagnosed OLD was more common among participants who had never undergone spirometry (OR 10.83, 95% CI 6.18–18.98) or who were never referred to a specialist (OR 5.92, 95% CI 3.58–9.77). Undiagnosed OLD was less common among participants who had required emergency department care (OR 0.44, 95% CI 0.20–0.97).ConclusionsIndividuals with symptomatic undiagnosed OLD have worse pre-bronchodilator lung function and present with greater psychosocial impacts on quality of life compared with their diagnosed counterparts. They were less likely to have received appropriate investigations and specialist referral for their respiratory symptoms.

Background: Low health literacy (HL) is a global challenge. HL is positively correlated with chronic airways disease (CAD) outcomes. Despite the importance of HL in disease management, current HL measurement tools are suboptimal. As part of a multi-stage project to develop a performance-based, disease-specific Vancouver Airways Health Literacy Tool (VAHLT) for patients with CAD, this study assessed the relationships between VAHLT scores and CAD patient characteristics. The primary aim of the study is to provide preliminary evidence of construct validity of the VAHLT. Methods: A cross-sectional study design was applied. Patients were recruited from 6 specialty care clinics to complete the measurement tool. Demographic and clinical data, including quality of life (QOL) and disease control, were collected via validated questionnaires. Subjects also completed spirometry. Inferential analysis was conducted using mean difference testing and correlational methods. Results: 320 patients were recruited, and after imputing missing data, 315 were ultimately analyzed. Participants were predominantly female (60.5%), Caucasian (83.1%), had post high-school education (74.2%), with a mean age of 65.2 (SD = 13.17) years. Age was significantly negatively correlated with HL scores (p = .004); patients with post-high school education had significantly higher HL scores than those with a high school education or less (p < .001). No significant sex or ethnicity related differences in HL scores were observed. For clinical outcomes, no significant differences were found between HL scores and disease severity or measures of QOL and asthma control. Conclusions: We report a CAD-specific HL measurement tool developed with involvement of patients and professionals. Age and education were highly correlated with HL, which emphasizes the importance of addressing these factors in HL interventions among CAD patients. In the next phase, we will evaluate the tool’s responsiveness to interventions.

Background: Transfer of young adults (YAs) with chronic diseases from pediatric- to adult hospital-based care is a major life event for this vulnerable group of patients. Inadequate preparation of the YAs and poorly planned transition of care are associated with subsequent treatment non-adherence, discontinuity of care and poor long-term outcomes. A formalized structured process for HCT has been demonstrated to improve patient experience and optimize subsequent engagement with adult healthcare and is now recommended as standard of care. Implementation of this approach is however suboptimal at a global level and practices vary within institutes and between specialties. We recognized this issue at the Ottawa Hospital (TOH) and sought to explore the impact of differences in approaches to HCT from the YA’s perspective. We assessed and compared patient experience of HCT in specialties with and without a structured HCT program with the aim of gaining insight into gaps in care to facilitate reforming current practices and optimizing care. Methods: YAs aged 18 to 25 years (n=175) who had transitioned into five adult specialties at TOH volunteered for this study. A self-care assessment survey and two feedback surveys were customized from the Got TransitionTM HCT measurement resources. Responses of those YAs attending clinics with (n=93) and without (n=82) a structured HCT program were assessed and compared.Results: YAs who transitioned into clinics with structured HCT reported better medical knowledge and practical skills for independent use of the healthcare system compared to YAs who attended clinics without a formal HCT process. This group reported a greater level of involvement in preparation for HCT by their pediatric health-care providers and better education and provision of practical information by their adult healthcare team compared to the YAs attending clinics without a formal HCT process. Conclusions: Results demonstrate superior health knowledge and healthcare usage skills in YAs attending clinics with structured HCT programs and support the benefit of establishing a structured approach to HCT across all specialties caring for transitioned YAs at TOH. By identifying strengths and gaps in current practices, this study has provided a basis to drive institutional reform to improve quality of care for this vulnerable patient population.

Background Patients admitted to the hospital with COPD are commonly managed with inhaled short-acting bronchodilators, sometimes in lieu of the long-acting bronchodilators they take as outpatients. If held on admission, these long-acting inhalers should be re-initiated upon discharge; however, health-care transitions sometimes result in unintentional discontinuation. Research Question What is the risk of unintentional discontinuation of long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist and inhaled corticosteroid (LABA-ICS) combination medications following hospital discharge in older adults with COPD? Study Design and Methods A retrospective cohort study was conducted by using health administrative data from 2004 to 2016 from Ontario, Canada. Adults with COPD aged ≥ 66 years who had filled prescriptions for a LAMA or LABA-ICS continuously for ≥ 1 year were included. Log-binomial regression models were used to determine risk of medication discontinuation following hospitalization in each medication cohort. Results Of the 27,613 hospitalization discharges included in this study, medications were discontinued 1,466 times. Among 78,953 patients with COPD continuously taking a LAMA or LABA-ICS, those hospitalized had a higher risk of having medications being discontinued than those who remained in the community (adjusted risk ratios of 1.50 [95% CI, 1.34-1.67; P Interpretation In an observational study of highly compliant patients with COPD, hospitalization was associated with an increased risk of long-acting inhaler discontinuation. These Results suggest a likely larger discontinuation problem among less adherent patients and should be confirmed and quantified in a prospective cohort of patients with COPD and average compliance. Quality improvement efforts should focus on safe transitions and patient medication reconciliation following discharge.

Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society. Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy. Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.

The actual burden of COPD and asthma may be much higher than appreciated, since a large proportion of individuals are not diagnosed. Our study objective was to compare health care utilization, burden of symptoms and quality of life in subjects with self-reported respiratory symptoms who were subsequently found to have undiagnosed airflow obstruction compared to those having no airflow obstruction.This cross-sectional case-finding study used data from the Undiagnosed COPD and Asthma Population (UCAP) study. Adult subjects with respiratory symptoms who had no history of diagnosed lung disease were recruited in a two-step case-finding process using random digit-dialling of land lines and cell phones located within a 90-min radius of 16 Canadian study sites. Participants were assessed for COPD, asthma or no airflow obstruction using pre- and post-bronchodilator spirometry based on American Thoracic Society diagnostic criteria.1660 participants were recruited, of these 1615 had adequate spirometry and 331 (20.5%) subjects met spirometry criteria for undiagnosed asthma or COPD. Subjects with undiagnosed asthma or COPD had increased respiratory symptoms as assessed by the COPD Assessment Test (CAT), and higher St. George's Respiratory Questionnaire (SGRQ) scores indicating worse health-related quality of life, compared to subjects with no airflow obstruction. No between-group differences were found in health care utilization or work or school absenteeism.Undiagnosed asthma and COPD are common in Canadian adults experiencing breathing problems and are associated with a greater burden of symptoms and poorer health-related quality of life. These results suggest that patients may benefit from early identification and treatment of undiagnosed asthma and COPD.

Summary Background Accurate prediction of exacerbation risk enables personalised care for patients with chronic obstructive pulmonary disease (COPD). We developed and validated a generalisable model to predict individualised rate and severity of COPD exacerbations. Methods In this risk modelling study, we pooled data from three COPD trials on patients with a history of exacerbations. We developed a mixed-effect model to predict exacerbations over 1 year. Severe exacerbations were those requiring inpatient care. Predictors were history of exacerbations, age, sex, body-mass index, smoking status, domiciliary oxygen therapy, lung function, symptom burden, and current medication use. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE), a multicentre cohort study, was used for external validation. Results The development dataset included 2380 patients, 1373 (58%) of whom were men. Mean age was 64·7 years (SD 8·8). Mean exacerbation rate was 1·42 events per year and 0·29 events per year were severe. When validated against all patients with COPD in ECLIPSE (mean exacerbation rate was 1·20 events per year, 0·27 events per year were severe), the area-under-curve (AUC) was 0·81 (95% CI 0·79–0·83) for at least two exacerbations and 0·77 (95% CI 0·74–0·80) for at least one severe exacerbation. Predicted exacerbation and observed exacerbation rates were similar (1·31 events per year for all exacerbations and 0·25 events per year for severe exacerbations vs 1·20 events per year and 0·27 events per year). In ECLIPSE, in patients with previous exacerbation history (mean exacerbation rate was 1·82 events per year, 0·40 events per year were severe), AUC was 0·73 (95% CI 0·70–0·76) for two or more exacerbations and 0·74 (95% CI 0·70–0·78) for at least one severe exacerbation. Calibration was accurate for severe exacerbations (predicted 0·37 events per year vs observed 0·40 events per year) and all exacerbations (predicted 1·80 events per year vs observed 1·82 events per year). Interpretation This model can be used as a decision tool to personalise COPD treatment and prevent exacerbations. Funding Canadian Institutes of Health Research.

Background Hypogammaglobulinemia (serum IgG levels Research Question To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD. Study Design and Methods Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status. Results The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P Interpretation Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.

Rationale: There is uncertainty on the use of using triple therapy (inhaled corticosteroids/long-acting β-agonist/long-acting muscarinic antagonist) inhaler therapy for patients with chronic obstru...

Background Long-term oxygen therapy improves survival in patients with chronic obstructive pulmonary disease (COPD) and chronic severe daytime hypoxemia. However, the efficacy of oxygen th...

Rationale: There is uncertainty on the optimal first-line therapy for symptomatic chronic obstructive pulmonary disease (COPD). Long-acting β2-receptor agonists (LABAs) and long-acting muscarinic a...

Preventing, treating, and promoting recovery from critical illness due to pulmonary disease are foundational goals of the critical care community and the National Heart, Lung, and Blood Institute. Decades of clinical research in acute respiratory distress syndrome, acute respiratory failure, pneumonia, and sepsis have yielded improvements in supportive care, which have translated into improved patient outcomes. Novel therapeutics have largely failed to translate from promising pre-clinical findings into improved patient outcomes in late-phase clinical trials. Recent advances in personalized medicine, "big data", causal inference using observational data, novel clinical trial designs, pre-clinical disease modeling, and understanding recovery from acute illness promise to transform the methods of pulmonary and critical care clinical research. To assess the current state, research priorities, and future directions for adult pulmonary and critical care research, the NHLBI assembled a multidisciplinary working group of investigators. This working group identified recommendations for future research, including: (1) focusing on understanding the clinical, physiological, and biological underpinnings of heterogeneity in syndromes, diseases, and treatment-response with the goal of developing targeted, personalized interventions; (2) optimizing pre-clinical models by incorporating comorbidities, co-interventions, and organ support; (3) developing and applying novel clinical trial designs; and (4) advancing mechanistic understanding of injury and recovery in order to develop and test interventions targeted at achieving long-term improvements in the lives of patients and families. Specific areas of research are highlighted as especially promising for making advances in pneumonia, acute hypoxemic respiratory failure, and acute respiratory distress syndrome.

Background In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). Research Question We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis. Study Design and Methods Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV1 [PC20] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months. Results Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist. Interpretation In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.

Objective Health literacy (HL) is a person’s ability to practically apply a wide range of cognitive and non-cognitive skills, to make health-related decisions. Currently, no tool applies all HL core domains to capture necessary data to measures HL in adult asthma and COPD patients. We endeavored to develop a comprehensive, function-based tool that adequately and accurately measures HL skills of this patient population. We explored the perspectives of patients related to each core HL domain, with an emphasis on self-management practices. Methods Sixteen focus groups were conducted (n = 93; 40 asthma and 53 COPD) across Canada. Data was analyzed using NVivo12. Results Thirteen subthemes were identified within five HL domains: (a) access: active access; passive access; lack of access; (b) understanding: how to improve understanding; (c) trustworthiness; relevancy and validity of information: pre- and post- application of information; (d) communication: barriers to proper communication; (e) application of information: making health decisions. Conclusions Participants provided valuable insight in terms of disease management topics and corresponding items to include in our HL tool. Practice implications Involvement of patients from initial stage allowed us to develop a tool that will serve as a first ever developed HL tool for asthma and COPD patient group.

Background In the last decade, tuberculosis (TB) incidence among Inuit in the Canadian Arctic has been rising. Our aim was to better understand the transmission dynamics of TB in this remote region of Canada using whole-genome sequencing. Methods Isolates from patients who had culture-positive pulmonary TB in Iqaluit, Nunavut, between 2009 and 2015 underwent whole-genome sequencing (WGS). The number of transmission events between cases within clusters was calculated using a threshold of a ≤3 single nucleotide polymorphism (SNP) difference between isolates and then combined with detailed epidemiological data using a reproducible novel algorithm. Social network analysis of epidemiological data was used to support the WGS data analysis. Results During the study period, 140 Mycobacterium tuberculosis isolates from 135 cases were sequenced. Four clusters were identified, all from Euro-American lineage. One cluster represented 62% of all cases that were sequenced over the entire study period. In this cluster, 2 large chains of transmission were associated with 3 superspreading events in a homeless shelter. One of the superspreading events was linked to a nonsanctioned gambling house that resulted in further transmission. Shelter to nonshelter transmission was also confirmed. An algorithm developed for the determination of transmission events demonstrated very good reproducibility (κ score .98, 95% confidence interval, .97–1.0). Conclusions Our study suggests that socioeconomic factors, namely residing in a homeless shelter and spending time in a gambling house, combined with the superspreading event effect may have been significant factors explaining the rise in cases in this predominantly Inuit Arctic community.

Background Approximately 5% of patients with sarcoidosis have clinically manifest cardiac involvement. Clinical features of Cardiac Sarcoidosis are dependent on the location, extent, and activity of the disease. First line therapy is usually with prednisone and this is recommended based on clinician experience, expert opinion and small observational cohorts. There are no published clinical trials in cardiac sarcoidosis and multiple experts in the field have called for randomized clinical trials to answer important patient care questions. Corticosteroid are associated with multiple adverse effects including hypertension, diabetes, weight gain, osteoporosis, and increased risk of infections. In contrast Methotrexate is generally well tolerated and is increasingly used in other forms of sarcoidosis. Objectives The Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial (CHASM CS-RCT; NCT03593759 ) is a multicenter randomized controlled trial designed to evaluate the optimal initial treatment strategy for patients with active cardiac sarcoidosis. We hypothesize that (1) a low dose prednisone/methotrexate combination will have non-inferior efficacy to standard dose prednisone and that (2) the low dose prednisone/ methotrexate combination will result in significantly better quality of life than standard dose prednisone, as a result of reduced burden of side effects. Methods/design Eligible study subjects will have active clinically manifest cardiac sarcoidosis presenting with one or more of the following clinical findings: advanced conduction system disease, significant sinus node dysfunction, non-sustained or sustained ventricular arrhythmia, left ventricular dysfunction or right ventricular dysfunction. Subjects will be randomized in a 1:1 ratio to prednisone 0.5 mg/kg/day for 6 months (maximum dose 30 mg daily) OR to prednisone 20 mg daily for 1 month, then 10 mg daily for 1 month, then 5 mg daily for one month then stop AND methotrexate 15–20 mg once weekly for 6 months. The primary endpoint is summed perfusion rest score on 6-month PET (blinded core-lab review). The summed perfusion rest score is measure of myocardial fibrosis/scar. The design is non-inferiority with a sample size of 97 per group. Discussion Given the multiorgan system potential adverse side effects of prednisone, proving noninferiority of an alternate regimen would be sufficient to make the alternative compare favorably to standard dose steroids. This is the first ever clinical trial in cardiac sarcoidosis and thus in addition to the listed goals of the trial, we will also establish a multi-center, multinational cardiac sarcoidosis clinical trials network. Such a collaborative infrastructure will enable a new era of high quality data to guide physicians when treating cardiac sarcoidosis patients.

Small studies have suggested that patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality. Our aim was to examine the prevalence of subjective sleep-related complaints and predictors of poor sleep quality in a large community-based COPD cohort. We analyzed cross-sectional data on sleep questionnaire responses from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study, a population-based, prospective longitudinal cohort study across Canada. The cohort comprises a COPD group and two matched non-COPD (never-smokers and ever-smokers) groups. Sleep-related symptoms were assessed using questionnaires including Pittsburgh Sleep Quality Index (PSQI). A total score of PSQI > 5 is indicative of poor sleep quality. Health-related quality of life measures and the presence of mood disturbance were assessed using Short Form-36™ Health Survey (SF-36) multi-item questionnaires and Hospital Anxiety and Depression Scale (HADS), respectively. Predictors of poor sleep quality were analyzed using multivariable logistic regression analysis. Of the 1123 subjects, 263 were healthy controls, 323 at-risk controls, and 537 had COPD (297 had mild, 240 with moderate to severe disease). The mean PSQI score was not significantly different between groups. COPD patients with poor sleep quality had lower diffusion capacity, higher HADS anxiety and depression scores and lower SF-36 mental and physical component summary scores than COPD patients classified as good sleepers. The presence of restless legs and obstructive sleep apnea symptoms, waist circumference, predicted diffusion capacity and HADS anxiety and depression scores were identified as independent predictors of poor sleep quality.

Rationale Despite the high prevalence of obstructive sleep apnea (OSA) and concurrent use of opioid therapy, no large-scale population studies have investigated whether opioid use and pre-existing OSA may interact synergistically to increase the risk of adverse health consequences. To address this knowledge gap, we conducted a retrospective cohort study using provincial health administrative data to evaluate whether the combined presence of opioid use and OSA increases the risk of adverse health consequences, such as mortality, hospitalizations, and emergency department (ED) visits; and if it does, whether this co-occurrence has synergistic clinical relevance. Methods We included all adults who underwent a diagnostic sleep study in Ontario, Canada, between 2013 and 2016. Individuals were considered exposed to opioids if they filled a prescription that overlapped with the date of their sleep study (Opioid+). Individuals with at least a 50% probability of having a diagnosis of moderate to severe OSA (OSA+) were identified using a previously externally validated case-ascertainment model. The primary outcome was all-cause mortality; secondary outcomes were all-cause or ischemic heart disease hospitalizations, all-cause ED visits, and motor vehicle collisions (MVC) requiring hospital or ED visit. We used multivariable Cox regression models to compare hazards between four mutually exclusive groups: (1) Opioid+ OSA+; (2) Opioid+ OSA-; (3) Opioid- OSA+, and (4) OSA- Opioid- (reference for comparison). Relative excess risks due to interaction (RERI) were calculated to test for additive interaction. Results Of 300,663 adults who underwent a sleep study, 15,713 (5.2%) were considered as Opioid+ and 128,351 (42.7%) as OSA+. Over a median of two years, 6,223 (2.1%) died from any cause. Regardless of OSA status, opioid use at the date of the sleep study was associated with an increased hazard for all-cause mortality with the greatest hazard associated with Opioid+ OSA- (adjusted hazard ratio [aHR]: 1.75, 95% CI 1.57–1.94), but not Opioid+ OSA+ (aHR: 1.14, 95% CI 1.02–1.27) as hypothesized. Regardless of OSA status, opioid use at the date of the sleep study was associated with an increased hazard for all secondary outcomes. Opioid+ OSA+ was associated with the greatest hazards of all-cause hospitalizations (aHR 1.55, 95% CI 1.49–1.61) and MVC (aHR of 1.39; 95% CI 1.09–1.77); however, no statistically significant synergistic effects were observed. Conclusions Adults referred for sleep disorder assessment who used opioids had a significantly increased hazard of adverse health outcomes than those who did not, regardless of whether they had a high probability of moderate to severe OSA. The use of opioids and OSA was associated with the greatest hazard of all-cause hospitalizations and MVC requiring hospital or ED visit. The interaction of opioids and OSA did not confer a synergistic risk for poor outcomes.

RATIONALE: Despite its importance as a leading risk factor for chronic obstructive pulmonary disease (COPD), there is a minimal amount of population-level information regarding smoking prevalence a...

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.