Publications by authors named "Shawn Aaron"

202 Publications

Barriers and Enablers to Objective Testing for Asthma and COPD in Primary Care: A Systematic Review Using the Theoretical Domains Framework.

Chest 2021 Nov 2. Epub 2021 Nov 2.

Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Division of Respirology, Department of Medicine, St. Michael's Hospital, Toronto, Ontario, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.chest.2021.10.030DOI Listing
November 2021

An Updated Definition and Severity Classification of COPD Exacerbations: The Rome Proposal.

Am J Respir Crit Care Med 2021 Sep 27. Epub 2021 Sep 27.

Imperial College London, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland.

The current definition of a chronic obstructive pulmonary disease (COPD) exacerbation (ECOPD) is based solely on worsening respiratory symptoms, with severity classified post hoc by the healthcare resource used to treat the event, which may vary among practitioners and healthcare systems. These shortcomings support a need to revise the ECOPD definition and severity classification to one that is useful at time of patient contact. To achieve this, an expert panel used a modified Delphi method of five rounds of questions generated by a thorough review of the literature, supplemented by virtual discussions. For the 80 identified questions, the agreement level was rated using a Likert scale from 0 (strongly disagree) to 9 (strongly agree). Consensus was defined a priori as a median score ≥7 (strong agreement). The proposed definition states: "In a patient with COPD, an exacerbation is an event characterized by dyspnea and/or cough and sputum that worsens over ≤14 days, that may be accompanied by tachypnea and/or tachycardia, often associated with increased local and systemic inflammation caused by airway infection, pollution, or other insult to the airways." Three severity categories (mild, moderate, or severe) were defined using integration of six clinically measurable variables: intensity of dyspnea, oxygen saturation, respiratory rate, heart rate, C-reactive protein, and, if indicated, arterial blood gases. In conclusion, by incorporating measurable clinical and laboratory variables at the time of exacerbation, the Rome proposal for an updated definition of ECOPD could help standardize care and outcomes for clinicians and researchers alike. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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http://dx.doi.org/10.1164/rccm.202108-1819PPDOI Listing
September 2021

Empire-CF study: A phase 2 clinical trial of leukotriene A4 hydrolase inhibitor acebilustat in adult subjects with cystic fibrosis.

J Cyst Fibros 2021 Sep 16. Epub 2021 Sep 16.

Gregory Fleming James Cystic Fibrosis Research Center and Department of Medicine, University of Alabama at Birmingham, 1918 University Blvd, MCLM 804, Birmingham 35294, AL, USA. Electronic address:

Background: Cystic fibrosis (CF) is characterized by neutrophilic inflammation in the airways. Leukotriene B4 (LTB) is a neutrophil chemoattractant and has been implicated in CF pathogenesis. Acebilustat, a novel, synthetic, small-molecule leukotriene A4 hydrolase inhibitor, reduces LTB 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 (ppFEV) 50-75 and >75, and number of pulmonary exacerbations in the past year (1 or >1). Primary endpoints were the change from baseline in ppFEV 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 ppFEV 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 ppFEV>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.
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http://dx.doi.org/10.1016/j.jcf.2021.08.007DOI Listing
September 2021

Moving beyond AUC: decision curve analysis for quantifying net benefit of risk prediction models.

Eur Respir J 2021 10 4;58(5). Epub 2021 Nov 4.

Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada.

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http://dx.doi.org/10.1183/13993003.01186-2021DOI Listing
October 2021

Factors Affecting Health Literacy as Related to Asthma and COPD Management: Learning from Patient and Health Care Professional Viewpoints.

Health Lit Res Pract 2021 Jul 15;5(3):e179-e193. Epub 2021 Jul 15.

Background: Studies have identified health literacy (HL) as an important determinant of asthma and chronic obstructive pulmonary disease (COPD) management. There are, however, limited data on patients' and health care professionals (HCPs') insights about the link between HL and management of asthma and COPD.

Objective: The aim of this study was to elicit patients' and HCPs' perspectives with respect to factors affecting HL in the context of asthma and COPD management.

Methods: A total of 16 semi-structured focus groups (10 in English and 6 in French) with patients with asthma or COPD (n = 93) and 45 interviews with HCPs, researchers, and policymakers were conducted between June 2015 and April 2017. Participants were asked to share their perspectives with respect to five predefined HL domains-accessing, understanding, evaluating, communicating, and using health-related information-in relation to disease self-management practices. Data were analyzed qualitatively, using a content analysis approach.

Key Results: Most patients and HCPs reflected on factors hampering HL in relation to asthma and COPD management. Thoughts such as "not having enough time during medical consultations," "not receiving consistent messages from different health care professionals," and "language or cultural differences" were frequently mentioned by both patients and HCPs.

Conclusions: We identified multiple factors affecting communication between patients and HCPs as it relates to the self-management of their disease. These included inconsistent messages from different providers, limited consultation time, use of technical language, failure to account for cultural differences, and reduced health literacy, especially as it related to written communication. Future interventions that aim to enhance HL skills in the context of asthma and COPD self-management should consider these issues. Plain Language Summary: The current study advances the health literacy (HL) knowledge base by adding patients' and health care professionals' valuable insights on factors that hamper or facilitate HL in relation to asthma and chronic obstructive pulmonary disease (COPD) management. An important insight from this study is that receiving conflicting information from different health care professional's hampers HL in patients with asthma and/or COPD.
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http://dx.doi.org/10.3928/24748307-20210526-01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279022PMC
July 2021

Specialist Care in Individuals with Asthma Who Required Hospitalization: A Retrospective Population-Based Study.

J Allergy Clin Immunol Pract 2021 10 26;9(10):3686-3696. Epub 2021 Jun 26.

Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia.

Background: Patients who are at risk for severe asthma exacerbations should receive specialist care. However, the care pattern for such patients in the real world is unclear.

Objective: To describe the pattern of care among individuals with asthma who required hospitalization, and to identify factors associated with receiving asthma specialist care.

Methods: This was a retrospective population-based study using health administrative data from two Canadian provinces. Individuals aged 14 to 45 years who were newly diagnosed with asthma between 2006 and 2016 and had at least one hospitalization for asthma at or within 5 years after the initial asthma diagnosis were included. First, we calculated frequencies of primary and specialist care around the asthma diagnosis: 1 year before and 2 years after in a 6-month period. Next, among individuals diagnosed with asthma by a primary care physician, we used multivariable Cox regressions to identify factors associated with receiving specialist care.

Results: For 1862 individuals included, we found that most (≥71% per time period) were cared for by primary care physicians 1 year before and 2 years after the asthma diagnosis; the percentage of individuals seen at least once by a specialist for asthma and/or asthma-related respiratory conditions during the first 6 months since the diagnosis did not exceed 40%. Among 1411 of 1862 individuals who were under primary care before the asthma diagnosis (76%), controlling for covariates, living in a rural area or a low-income neighborhood was associated with less likelihood of receiving specialist care.

Conclusions: Despite recommendations, more than half of individuals with asthma who required hospitalization did not receive specialist care during the first 2 years since the diagnosis. Identified factors associated with receiving asthma specialist care suggested that access is an important barrier to receiving recommended care.
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http://dx.doi.org/10.1016/j.jaip.2021.06.018DOI Listing
October 2021

Case-Ascertainment Models to Identify Adults with Obstructive Sleep Apnea Using Health Administrative Data: Internal and External Validation.

Clin Epidemiol 2021 17;13:453-467. Epub 2021 Jun 17.

ICES, Ottawa, Toronto, Ontario, Canada.

Background: 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.
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http://dx.doi.org/10.2147/CLEP.S308852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216743PMC
June 2021

Factors Associated With Nonreceipt of Recommended COPD Medications: A Population Study.

Chest 2021 Nov 16;160(5):1670-1680. Epub 2021 Jun 16.

ICES, Toronto and Ottawa, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; The Hospital for Sick Children Research Institute, Toronto, ON, Canada.

Background: COPD medications reduce exacerbations and improve quality of life. Despite this, some individuals do not receive medications recommended by practice guidelines.

Research Question: How common is nonreceipt of recommended medications among people with COPD, and what factors are associated with nonreceipt?

Study Design And Methods: This population cohort study was conducted in Ontario, Canada, a province with universal health care insurance and medication coverage for those aged ≥ 65 years. Health administrative data were used to identify people aged ≥ 66 years with physician-diagnosed COPD as of 2018 and group them into cohorts of lower or higher risk for future COPD exacerbations. Proportions of patients in each group who did not receive medications recommended by COPD guidelines were determined. Generalized estimating equation modeling was used to determine associations between patient and physician factors and nonreceipt of recommended medications.

Results: About 54% and 88% of people with COPD received 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 nonreceipt of recommended medications in both groups. People who had a co-diagnosis of asthma, who received care by a pulmonologist and who received spirometry were more likely to receive recommended medication.

Interpretation: COPD medications seem underused by the COPD population, and various factors are associated with suboptimal receipt. Targeting these factors would help improve the care and health of people with COPD.
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http://dx.doi.org/10.1016/j.chest.2021.05.067DOI Listing
November 2021

Dyspnoea and symptom burden in mild-moderate COPD: the Canadian Cohort Obstructive Lung Disease Study.

ERJ Open Res 2021 Apr 19;7(2). Epub 2021 Apr 19.

Division of Respiratory Medicine, Dept of Medicine, McGill University Health Centre, Montreal, QC, Canada.

Studies assessing dyspnoea and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) have focussed on patients in clinical settings, not the general population. The aim of this analysis was to compare the prevalence and severity of dyspnoea and impaired HRQoL in individuals with and without COPD from the general population, focussing on mild-moderate COPD. Analysis of the 3-year Canadian Cohort Obstructive Lung Disease (CanCOLD) study included four subgroups: mild COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1); moderate COPD (GOLD 2); non-COPD smokers; and non-COPD never-smokers. The primary outcome was dyspnoea (Medical Research Council (MRC) scale), and the secondary outcome was HRQoL (COPD Assessment Test (CAT) score; Saint George's Respiratory Questionnaire (SGRQ) score). Subgroups were analysed by sex, physician-diagnosed COPD status and exacerbations. 1443 participants (mild COPD (n=397); moderate COPD (n=262(; smokers (n=449) and never-smokers (n=335)) were studied. People with mild COPD were more likely to report more severe dyspnoea (MRC 2 1) than those without COPD (OR (95% CI) 1.42 (1.05-1.91)), and non-COPD never-smokers (OR (95%CI) 1.64 (1.07-2.52)). Among people with mild COPD, more severe dyspnoea was reported in women men (MRC2 1; OR (95% CI) 3.70 (2.23-6.14)); people with, without, physician-diagnosed COPD (MRC2 1; OR (95% CI) 3.27 (1.71-6.23)), and people with without recent exacerbations (MRC2 1; ≥2 0 exacerbations: OR (95% CI) 3.62 (1.02-12.86); MRC ≥3 1; 1 0 exacerbation: OR (95% CI): 9.24 (2.01-42.42)). Similar between-group differences were obtained for CAT and SGRQ scores. Careful assessment of dyspnoea and HRQoL could help identify individuals for earlier diagnosis and treatment.
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http://dx.doi.org/10.1183/23120541.00960-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053913PMC
April 2021

The Prevalence of Chronic Obstructive Pulmonary Disease (COPD) and the Heterogeneity of Risk Factors in the Canadian Population: Results from the Canadian Obstructive Lung Disease (COLD) Study.

Int J Chron Obstruct Pulmon Dis 2021;16:305-320. Epub 2021 Feb 12.

Centre for Heart Lung Innovation, St Pauls Hospital, The University of British Columbia, Vancouver, BC, Canada.

Purpose: 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 FEV/FVC <0.70 (fixed ratio, FR) and as FEV/FVC <5th percentile (lower limits of normal, LLN). Separate logistic regression models were used to compute the risk (adjusted odds ratio, aOR) for COPD. I and Tau 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 Tau 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.
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http://dx.doi.org/10.2147/COPD.S285338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886112PMC
June 2021

Population-based case-finding to identify airflow obstruction in symptomatic adults at high risk for asthma and COPD.

Eur Respir J 2020 11 19;56(5). Epub 2020 Nov 19.

The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada

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http://dx.doi.org/10.1183/13993003.03574-2020DOI Listing
November 2020

Medication Discontinuation in Adults With COPD Discharged From the Hospital: A Population-Based Cohort Study.

Chest 2021 03 2;159(3):975-984. Epub 2020 Oct 2.

The Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Medicine, University of Ottawa, ON, Canada.

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 < .001] and 1.62 [95% CI, 1.39, 1.90; P < .001] for LAMA and LABA-ICS, respectively). Crude rates of discontinuation for people taking LAMAs were 5.2% in the hospitalization group and 3.3% in the community group; for people taking LABA-ICS, these rates were 5.5% in the hospitalization group and 3.1% in the community group.

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.
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http://dx.doi.org/10.1016/j.chest.2020.09.254DOI Listing
March 2021

Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease.

N Engl J Med 2020 09;383(12):1129-1138

From Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, Quebec, QC (Y.L., F.S., S.B., F.M.), Centre Hospitalier Affilié Universitaire de Trois-Rivières, Trois-Rivières, QC (F.C.), Mount Sinai Hospital, McGill University (M.B.), and Montreal Chest Institute, Research Institute of the McGill University Health Centre and McGill University (J.B.), Montreal, Centre Intégré de Santé et de Services Sociaux de Laval, Laval, QC (B.P.), and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa (S.D.A.) - all in Canada; Hospital Pedro Hispano-Unidade Local de Saúde de Matosinhos, Matosinhos (P.S.), and Centro Hospitalar Vila Nova de Gaia-Espinho, Vila Nova de Gaia (M.G.) - both in Portugal; and Hospital Universitario de Getafe, Getafe (A.A.F.), and Hospital Galdakao, Servicio Vasco de Salud-Osakidetza, Bizkaia (C.E.) - both in Spain.

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 therapy for the management of isolated nocturnal hypoxemia is uncertain.

Methods: We designed this double-blind, placebo-controlled, randomized trial to determine, in patients with COPD who have nocturnal arterial oxygen desaturation without qualifying for long-term oxygen therapy, whether nocturnal oxygen provided for a period of 3 to 4 years would decrease mortality or the worsening of disease such that patients meet current specifications for long-term oxygen therapy. Patients with an oxygen saturation of less than 90% for at least 30% of the recording time on nocturnal oximetry were assigned, in a 1:1 ratio, to receive either nocturnal oxygen or ambient air from a sham concentrator (placebo). The primary outcome was a composite of death from any cause or a requirement for long-term oxygen therapy as defined by the Nocturnal Oxygen Therapy Trial (NOTT) criteria in the intention-to-treat population.

Results: Recruitment was stopped prematurely because of recruitment and retention difficulties after 243 patients, of a projected 600, had undergone randomization at 28 centers. At 3 years of follow-up, 39.0% of the patients assigned to nocturnal oxygen (48 of 123) and 42.0% of those assigned to placebo (50 of 119) met the NOTT-defined criteria for long-term oxygen therapy or had died (difference, -3.0 percentage points; 95% confidence interval, -15.1 to 9.1).

Conclusions: Our underpowered trial provides no indication that nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with COPD. (Funded by the Canadian Institutes of Health Research; INOX ClinicalTrials.gov number, NCT01044628.).
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http://dx.doi.org/10.1056/NEJMoa2013219DOI Listing
September 2020

Summary for Clinicians: Clinical Practice Guideline on Pharmacologic Management of Chronic Obstructive Pulmonary Disease.

Ann Am Thorac Soc 2021 01;18(1):11-16

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mount Auburn Hospital/Beth Israel Lahey Health, Cambridge, Massachusetts; and.

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http://dx.doi.org/10.1513/AnnalsATS.202007-880CMEDOI Listing
January 2021

Reply to Mahler : Pharmacotherapy for Chronic Obstructive Pulmonary Disease: Molecules and Delivery Are Equally Important.

Am J Respir Crit Care Med 2020 11;202(10):1482-1483

The Ottawa Hospital Research Institute at the University of Ottawa Ottawa, Ontario, Canada.

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http://dx.doi.org/10.1164/rccm.202006-2375LEDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667900PMC
November 2020

Outcomes and Resource Utilization Among Patients Admitted to the Intensive Care Unit Following Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

J Intensive Care Med 2021 Sep 28;36(9):1091-1097. Epub 2020 Jul 28.

Division of Critical Care, Department of Medicine, 6363University of Ottawa, Ontario, Canada.

Purpose: Chronic obstructive pulmonary disease (COPD) is a common condition, accounting for a significant number of intensive care unit (ICU) admissions. However, little is known about outcomes and costs among ICU patients admitted with acute exacerbations of COPD (AECOPD). We studied predictors of inhospital mortality and costs of ICU admissions for AECOPD.

Methods: Data were obtained from a prospectively maintained registry from 2 ICUs from 2011 to 2016, including adult patients (age ≥ 18) with an ICU discharge diagnosis of AECOPD. The primary outcome was hospital mortality. Secondary outcomes included ICU length of stay, resource utilization, total hospital costs, and cost per survivor.

Results: We included 390 patients, of which 27.2% died in hospital. Independent predictors of inhospital mortality included age (odds ratio [OR]: 1.95, CI: 1.58-2.67) and the presence of clinical frailty (OR: 4.12, CI: 2.26-6.95). The mean total hospital costs were Can$35 059, with a cost per survivor of Can$48 191. Factors associated with increased cost included transfer from an inpatient setting, severity of illness, and previous ICU admission.

Conclusions: Approximately a quarter of patients admitted to ICU with AECOPD died during hospitalization, and these patients accrued significant costs. This study identifies important factors associated with poor outcome in this at-risk population, which has value in risk stratification and patient or family discussions addressing goals of care.
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http://dx.doi.org/10.1177/0885066620944865DOI Listing
September 2021

Effects of CPAP on Blood Pressure and Sympathetic Activity in Patients With Diabetes Mellitus, Chronic Kidney Disease, and Resistant Hypertension.

CJC Open 2020 Jul 27;2(4):258-264. Epub 2020 Mar 27.

Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Background: Patients with obstructive sleep apnea (OSA) have increased sympathetic activity and frequently also have resistant hypertension (HTN). Treatment of OSA with continuous positive airway pressure (CPAP) decreases awake and sleep blood pressure (BP) and sympathetic activity. This study was designed to assess the effect of treatment of OSA with CPAP on sympathetic activity and BP in patients with diabetes mellitus (DM), chronic kidney disease (CKD), and resistant HTN.

Methods: This was a randomized, double-blind, sham-controlled trial. Patients with DM, CKD, and resistant HTN were randomized to treatment with a therapeutic or subtherapeutic CPAP for 6 weeks. They underwent 24-hour ambulatory BP monitoring and assessment of muscle sympathetic nerve activity before and after 6 weeks on treatment.

Results: Treatment with therapeutic CPAP caused significant decreases in awake systolic and diastolic BP from 144 to 136 mm Hg ( 0.004) and from 79 to 74 mm Hg ( 0.004) and in sleep BP from 135 to 119 mm Hg ( 0.045) and from 75 to 65 mm Hg ( 0.015) compared with treatment with subtherapeutic CPAP. In contrast, treatment with therapeutic CPAP did not decrease sympathetic activity as assessed from muscle sympathetic nerve activity.

Conclusions: Decrease in BP by treatment with CPAP in patients with DM, CKD, and OSA indicates the contribution of OSA to severity of HTN in this clinical scenario. Decrease in BP in the absence of changes in sympathetic activity is suggestive that other mechanisms induced by OSA play a larger role in the maintenance of HTN in these patients.
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http://dx.doi.org/10.1016/j.cjco.2020.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365815PMC
July 2020

Triple Therapy versus Dual or Monotherapy with Long-Acting Bronchodilators for Chronic Obstructive Pulmonary Disease. A Systematic Review and Meta-analysis.

Ann Am Thorac Soc 2020 10;17(10):1308-1318

McMaster University, Hamilton, Ontario, Canada.

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 obstructive pulmonary disease (COPD), who complain of dyspnea and/or exercise intolerance. We conducted a systematic review and meta-analyses to estimate the safety and efficacy of using triple therapy compared with long-acting β-agonist/long-acting muscarinic antagonist dual therapy or monotherapy with a single long-acting bronchodilator in patients with stable COPD who complained of dyspnea and/or exercise intolerance. A search of MEDLINE, Embase, and the Cochrane Library databases was conducted for randomized controlled trials pertaining to the clinical question. A systematic approach was used to screen, abstract, and critically appraise the studies. The grading of recommendations assessment, development, and evaluation method was applied to rate the certainty/quality of the evidence. Eleven studies were eligible for inclusion ( = 14,145 patients). Pairwise random-effects meta-analysis revealed an increase in risk of pneumonia (relative risk, 1.47; 95% confidence interval [95% CI], 1.20-1.80;  < 0.001) and decreased risk of acute exacerbations of COPD (AECOPDs) (relative risk, 0.75; 95% CI, 0.68-0.82;  < 0.001) with triple therapy compared with treatment with dual and monotherapy long-acting bronchodilator therapy. No significant difference in dyspnea scores (standardized mean difference, 0.09; 95% CI, -0.02 to 0.19;  = 0.09) or risk of hospitalization (rate ratio, 0.78; 95% CI, 0.58-1.06;  = 0.11) was noted. When subgroup analysis based on inhaler class was performed, no significant difference was noted between the groups in any of the critical outcomes studied. For patients with a history of one or more AECOPDs in the past year, triple therapy resulted in 230 fewer AECOPDs and 16 more cases of pneumonia per 1,000 patients. In patients with COPD who complain of dyspnea and/or exercise intolerance, triple therapy is not superior to maintenance long-acting bronchodilator therapy, except in patients with a history of one or more exacerbations in the past year, in whom the benefits of reduction in AECOPD outweigh the increased risk of pneumonia.
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http://dx.doi.org/10.1513/AnnalsATS.202001-023OCDOI Listing
October 2020

Dual LABA/LAMA Therapy versus LABA or LAMA Monotherapy for Chronic Obstructive Pulmonary Disease. A Systematic Review and Meta-analysis in Support of the American Thoracic Society Clinical Practice Guideline.

Ann Am Thorac Soc 2020 09;17(9):1133-1143

McMaster University, Hamilton, Onatrio, Canada.

There is uncertainty on the optimal first-line therapy for symptomatic chronic obstructive pulmonary disease (COPD). Long-acting β-receptor agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) have long been mainstays of treatment, though it is still not clear if dual therapy with LABA/LAMA is superior to monotherapy for symptomatic COPD. To clarify the evidence landscape, we conducted a systematic review to answer the following question: in patients with COPD who complain of dyspnea and/or exercise intolerance, is LABA/LAMA combination therapy more effective and equally safe compared with LABA or LAMA monotherapy? A search of Medline, EMBASE, and the Cochrane Library databases was conducted by a medical librarian for randomized controlled trials enrolling patients with COPD who complain of dyspnea and/or exercise intolerance that compare LABA/LAMA combination therapy to LABA or LAMA monotherapy. A systematic approach was used to screen, abstract, and critically appraise the emerging study evidence. The Grading of Recommendations Assessment, Development, and Evaluation method was applied to rate the certainty and quality of the evidence. A total of 24 studies were eligible for inclusion ( = 45,441). Pairwise random-effects meta-analysis revealed reductions in hospital admissions (11% reduction;  < 0.01) and acute exacerbations of COPD (20% reduction;  < 0.002), all in favor of LABA/LAMA dual therapy. Although there is reduced dyspnea (0.10 standardized mean difference;  < 0.001) and improved health-related quality of life (-0.13 standardized mean difference;  < 0.001), both values did not meet a clinical meaningful difference threshold. LABA/LAMA combination therapy showed no difference in treatment-emergent adverse effects (risk ratio, 0.99;  = 0.34) when compared with either LAMA or LABA monotherapy. Based on the reviewed evidence, in patients with symptomatic COPD who complain of dyspnea and/or exercise intolerance, dual LABA/LAMA therapy is superior to either LABA or LAMA monotherapy based on the reduced risk of exacerbations and hospitalizations.
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http://dx.doi.org/10.1513/AnnalsATS.201912-915OCDOI Listing
September 2020

Association of Dysanapsis With Chronic Obstructive Pulmonary Disease Among Older Adults.

JAMA 2020 06;323(22):2268-2280

Department of Medicine, Columbia University Medical Center, New York, New York.

Importance: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), yet much of COPD risk remains unexplained.

Objective: To determine whether dysanapsis, a mismatch of airway tree caliber to lung size, assessed by computed tomography (CT), is associated with incident COPD among older adults and lung function decline in COPD.

Design, Setting, And Participants: A retrospective cohort study of 2 community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which involved 2531 participants (6 US sites, 2010-2018) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved 1272 participants (9 Canadian sites, 2010-2018), and a case-control study of COPD: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which involved 2726 participants (12 US sites, 2011-2016).

Exposures: Dysanapsis was quantified on CT as the geometric mean of airway lumen diameters measured at 19 standard anatomic locations divided by the cube root of lung volume (airway to lung ratio).

Main Outcomes And Measures: Primary outcome was COPD defined by postbronchodilator ratio of forced expired volume in the first second to vital capacity (FEV1:FVC) less than 0.70 with respiratory symptoms. Secondary outcome was longitudinal lung function. All analyses were adjusted for demographics and standard COPD risk factors (primary and secondhand tobacco smoke exposures, occupational and environmental pollutants, and asthma).

Results: In the MESA Lung sample (mean [SD] age, 69 years [9 years]; 1334 women [52.7%]), 237 of 2531 participants (9.4%) had prevalent COPD, the mean (SD) airway to lung ratio was 0.033 (0.004), and the mean (SD) FEV1 decline was -33 mL/y (31 mL/y). Of 2294 MESA Lung participants without prevalent COPD, 98 (4.3%) had incident COPD at a median of 6.2 years. Compared with participants in the highest quartile of airway to lung ratio, those in the lowest had a significantly higher COPD incidence (9.8 vs 1.2 cases per 1000 person-years; rate ratio [RR], 8.12; 95% CI, 3.81 to 17.27; rate difference, 8.6 cases per 1000 person-years; 95% CI, 7.1 to 9.2; P < .001) but no significant difference in FEV1 decline (-31 vs -33 mL/y; difference, 2 mL/y; 95% CI, -2 to 5; P = .30). Among CanCOLD participants (mean [SD] age, 67 years [10 years]; 564 women [44.3%]), 113 of 752 (15.0%) had incident COPD at a median of 3.1 years and the mean (SD) FEV1 decline was -36 mL/y (75 mL/y). The COPD incidence in the lowest airway to lung quartile was significantly higher than in the highest quartile (80.6 vs 24.2 cases per 1000 person-years; RR, 3.33; 95% CI, 1.89 to 5.85; rate difference, 56.4 cases per 1000 person-years; 95% CI, 38.0 to 66.8; P<.001), but the FEV1 decline did not differ significantly (-34 vs -36 mL/y; difference, 1 mL/y; 95% CI, -15 to 16; P=.97). Among 1206 SPIROMICS participants (mean [SD] age, 65 years [8 years]; 542 women [44.9%]) with COPD who were followed up for a median 2.1 years, those in the lowest airway to lung ratio quartile had a mean FEV1 decline of -37 mL/y (15 mL/y), which did not differ significantly from the decline in MESA Lung participants (P = .98), whereas those in highest quartile had significantly faster decline than participants in MESA Lung (-55 mL/y [16 mL/y ]; difference, -17 mL/y; 95% CI, -32 to -3; P = .004).

Conclusions And Relevance: Among older adults, dysanapsis was significantly associated with COPD, with lower airway tree caliber relative to lung size associated with greater COPD risk. Dysanapsis appears to be a risk factor associated with COPD.
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http://dx.doi.org/10.1001/jama.2020.6918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284296PMC
June 2020

Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis.

Chest 2020 10 19;158(4):1420-1430. Epub 2020 May 19.

Department of Medicine, University of Maryland, Baltimore, MD.

Background: Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations.

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 < .001); pooled SHR (meta-analysis) was 1.29 (95% CI, 1.06-1.56, P = .01). Among patients with prior COPD admissions (n = 757), the pooled SHR increased to 1.58 (95% CI, 1.20-2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI, 0.86-1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs 0.29 ± 0.83, P < .001.

Interpretation: Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.
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http://dx.doi.org/10.1016/j.chest.2020.04.058DOI Listing
October 2020

Correction to: Assessment of stigma in patients with cystic fibrosis.

BMC Pulm Med 2020 05 20;20(1):145. Epub 2020 May 20.

The Ottawa Hospital, 501 Smyth Road, Ottawa, Ontario, K1H 8 M5, Canada.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12890-020-1176-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238593PMC
May 2020

Population-based case-finding to identify subjects with undiagnosed asthma or COPD.

Eur Respir J 2020 06 18;55(6). Epub 2020 Jun 18.

The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada

Background: ∼5-10% of adults may have undiagnosed airflow obstruction. The objective of this study was to develop a population-based case-finding strategy to assess the prevalence of undiagnosed airflow obstruction (asthma or COPD) amongst adults with respiratory symptoms in Canada.

Methods: Adults without a previous history of asthma, COPD or lung disease were recruited using random digit-dialling and asked if they had symptoms of dyspnoea, cough, sputum or wheeze within the past 6 months. Those who answered affirmatively completed the Asthma Screening Questionnaire (ASQ), COPD-Diagnostic Questionnaire (COPD-DQ) and COPD Assessment Test (CAT). Those with an ASQ score of ≥6 or a COPD-DQ score of ≥20 underwent pre- and post-bronchodilator spirometry to diagnose asthma or COPD.

Results: 12 117 individuals were contacted at home and assessed for study eligibility. Of the 1260 eligible individuals, 910 (72%) enrolled and underwent spirometry. Ultimately, 184 subjects (20% of those enrolled) had obstructive lung disease (73 asthma and 111 COPD). Individuals found to have undiagnosed asthma or COPD had more severe respiratory symptoms and impaired quality of life compared with those without airflow obstruction. The ASQ, COPD-DQ, and CAT had ROC areas for predicting undiagnosed asthma or COPD of 0.49, 0.64 and 0.56, respectively. Four descriptive variables (age, BMI, sex and pack-years smoked) produced better receiver operating characteristic (ROC) values than the questionnaires (ROC area=0.68).

Conclusion: 20% of randomly selected individuals who report respiratory symptoms in Canada have undiagnosed airflow obstruction due to asthma or COPD. Questionnaires could exclude subjects at low risk but lack the ability to accurately find subjects with undiagnosed disease.
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http://dx.doi.org/10.1183/13993003.00024-2020DOI Listing
June 2020

Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis.

Chest 2020 08 13;158(2):479-490. Epub 2020 Apr 13.

Keenan Research Center in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, ON, Canada; Department of Medicine, Division of Respirology, St. Michael's Hospital, Toronto, ON. Electronic address:

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 FEV [PC] > 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.
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http://dx.doi.org/10.1016/j.chest.2020.03.052DOI Listing
August 2020

Molecular Epidemiology of Mycobacterium tuberculosis To Describe the Transmission Dynamics Among Inuit Residing in Iqaluit Nunavut Using Whole-Genome Sequencing.

Clin Infect Dis 2021 06;72(12):2187-2195

Public Health Ontario Laboratory, Public Health Ontario, Toronto, Ontario, Canada.

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.
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http://dx.doi.org/10.1093/cid/ciaa420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204784PMC
June 2021

Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Am J Respir Crit Care Med 2020 05;201(9):e56-e69

: 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.: 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.: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: ) a strong recommendation for the use of long-acting β-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; ) 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; ) 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; ) 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; ) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and ) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.: 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.
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http://dx.doi.org/10.1164/rccm.202003-0625STDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193862PMC
May 2020

Antibiotic Retreatment for Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med 2020 08;202(4):481-482

The Ottawa Hospital Research InstituteUniversity of OttawaOttawa, Ontario, Canada.

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http://dx.doi.org/10.1164/rccm.202004-0896EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427405PMC
August 2020
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