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Heightened arterial stiffness is a marker of cardiovascular risk and is elevated in chronic obstructive pulmonary disease (COPD). Physical activity has been shown to reduce arterial stiffness, and our previous work has shown that arterial stiffness is related to physical activity and exercise tolerance in COPD. The purpose of this study was to evaluate whether baseline physical activity and exercise tolerance influence the cardiovascular benefits associated with standard COPD outpatient pulmonary rehabilitation (PR).A total of 66 patients with COPD were recruited from the G.F. MacDonald Centre for Lung Health, Edmonton, Alberta, prior to entering PR. Another 23 COPD patients not attending the PR program were recruited as time controls (TC). Arterial stiffness (carotid-radial pulse wave velocity, PWV), physical activity (steps taken over three days), and 6-min walk distance (6MWD) were assessed before and after PR, or before and after six weeks of standard care.Thirty-nine PR and 11 TC completed all parts of the study. Following PR, there was no overall change in PWV. However, changes in arterial stiffness with PR were dependent on baseline exercise tolerance, with those patients with a 6MWD350 m showing a significant reduction in PWV following PR (6MWD350 m: 8.2 ± 1.6 to 8.5 ± 1.7 versus 6MWD350 m: 9.2 ± 0.6 to 7.3 ± 2.0 m/s, p 0.05). The PWV response to PR was not influenced by baseline physical activity levels.COPD patients with low exercise tolerance appear to derive the greatest cardiovascular benefits from PR.

COPD is a common disease with substantial associated morbidity and mortality. Patients with COPD usually have a progression of airflow obstruction that is not fully reversible and can lead to a history of progressively worsening breathlessness, affecting daily activities and health-related quality of life.1-3 COPD is the fourth leading cause of death in Canada4 and the third leading cause of death in the United States where it claimed 133,965 lives in 2009.5 In 2011, 12.7 million US adults were estimated to have COPD.6 However, approximately 24 million US adults have evidence of impaired lung function, indicating an underdiagnosis of COPD.7 Although 4% of Canadians aged 35 to 79 years self-reported having been given a diagnosis of COPD, direct measurements of lung function from the Canadian Health Measures Survey indicate that 13% of Canadians have a lung function score indicative of COPD.4 COPD is also costly. In 2009, COPD caused 8 million office visits, 1.5 million ED visits, 715,000 hospitalizations, and 133,965 deaths in the United States.8 In 2010, US costs for COPD were projected to be approximately $49.9 billion, including $29.5 billion in direct health-care expenditures, $8.0 billion in indirect morbidity costs, and $12.4 billion in indirect mortality costs.9 Exacerbations account for most of the morbidity, mortality, and costs associated with COPD. The economic burden associated with moderate and severe exacerbations in Canada has been estimated to be in the range of $646 million to $736 million per annum.10 This value may be an underestimate given that the prevalence of moderate exacerbations is not well documented, COPD is underdiagnosed, and the rate of hospitalization due to COPD is increasing.11 Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory-changing, and often deadly manifestations of a chronic disease. Exacerbations cause frequent hospital admissions, relapses, and readmissions12; contribute to death during hospitalization or shortly thereafter12; reduce quality of life dramatically12,13; consume financial resources12,14; and hasten a progressive decline in pulmonary function, a cardinal feature of COPD. Hospitalization due to exacerbations accounts for > 50% of the cost of managing COPD in North America and Europe.15,16 COPD exacerbation has been defined as an event in the natural course of the disease characterized by a baseline change in the patient’s dyspnea, cough, and/or sputum that is beyond the normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.17,18 Exacerbation in clinical trials has been defined for operational reasons on the basis of whether an increase in treatment beyond regular or urgent care is required in an ED or a hospital. Exacerbation treatment in clinical trials usually is defined by the use of antibiotics, systemic corticosteroids, or both.19 The severity of the exacerbation is then ranked or stratified according to the outcome: mild, when the clinical symptoms are present but no change in treatment or outcome is recorded; moderate, when the event results in a change in medication, such as the use of antibiotics and systemic corticosteroids; or severe, when the event leads to a hospitalization.1 Two-thirds of exacerbations are associated with respiratory tract infections or air pollution, but one-third present without an identifiable cause.17 Exacerbations remain poorly understood in terms of not only cause but also treatment and prevention. Although the management of an acute exacerbation has been the primary focus of clinical trials, the prevention of acute exacerbations has not been a major focus until recently. Most current COPD guidelines focus on the general diagnosis and evaluation of the patient with COPD, the management of stable disease, and the diagnosis and management of acute exacerbations.1,20 Although current COPD guidelines state that prevention of exacerbations is possible, little guidance is provided to the clinician regarding current available therapies for the prevention of COPD exacerbations.1,20 Moreover, new therapies have promise in preventing acute exacerbations of COPD (AECOPD) and would benefit from critical review of their efficacy in the exacerbation prevention management.21-23 The American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) jointly commissioned this evidence-based guideline on the prevention of COPD exacerbations to fill this important void in COPD management. The overall objective of this CHEST and CTS joint evidence-based guideline (AECOPD Guideline) was to create a practical, clinically useful document describing the current state of knowledge regarding the prevention of AECOPD according to major categories of prevention therapies. We accomplished this by using recognized document evaluation tools to assess and choose the most appropriate studies and evidence to extract meaningful data and to grade the level of evidence supporting the recommendations in a balanced and unbiased fashion. The AECOPD Guideline is unique not only for its topic but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD. This guideline is unique because a group of interdisciplinary clinicians who have special expertise in COPD clinical research and care led the development of the guideline process with the assistance of methodologists.

BACKGROUND:COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS:In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS:The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD. CONCLUSIONS:This guideline is unique because it provides an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data regarding the prevention of COPD exacerbations.

Purpose The objective of this systematic review was to assess the clinical efficacy, safety, tolerability, and health-related quality of life outcomes associated with management of moderate-to-severe chronic pain with oxycodone/naloxone and tapentadol, focusing on the effect of these treatments on patients’ daily functioning. Methods Literature from a wide range of sources, including Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials, was searched to identify randomized controlled trials investigating tapentadol or oxycodone/naloxone for the treatment of patients with chronic pain. A network meta-analysis was conducted to determine the relative efficacy and safety profiles of these treatments. Findings Oxycodone/naloxone was significantly better than tapentadol with respect to the Patient Assessment of Constipation Symptoms total score (risk ratio = –3.60; 95% credible interval, −5.36 to −2.11) and revealed a significantly lower risk of dizziness (risk ratio = 0.72; 95% credible interval, 0.42–0.98). Oxycodone/naloxone was directionally favored, although not significantly superior to tapentadol for headache, fatigue, dry mouth, dyspepsia, and withdrawals due to lack of efficacy. For the AE outcomes of constipation, nausea, and vomiting, as well as pain efficacy and all-cause withdrawals from studies, tapentadol was directionally favored without any statistical difference from oxycodone/naloxone. However, the two treatments were not wholly comparable for the evaluation of pain efficacy because of differences in on-study rescue medication and a higher baseline pain severity in the tapentadol studies. Implications Oxycodone/naloxone offers significant improvements in Patient Assessment of Constipation Symptoms total score and dizziness and was directionally favored for fatigue and headache compared with extended-release tapentadol, which may translate to improved patient daily functioning and health-related quality of life.

Curcumin, a yellow pigment extracted from rhizomes of the plant Curcuma longa (turmeric), has been widely used as food additive and also as a herbal medicine throughout Asia. The present study was designed to study the pharmacological, biochemical and neurochemical effects of daily administration of curcumin to rats subjected to chronic unpredictable stress. Curcumin treatment (20 and 40 mg/kg, i.p., 21 days) significantly reversed the chronic unpredictable stress-induced behavioral (increase immobility period), biochemical (increase monoamine oxidase activity) and neurochemical (depletion of brain monoamine levels) alterations. The combination of piperine (2.5 mg/kg, i.p., 21 days), a bioavailability enhancer, with curcumin (20 and 40 mg/kg, i.p., 21 days) showed significant potentiation of its anti-immobility, neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory (MAO-A) effects as compared to curcumin effect per se. This study provided a scientific rationale for the use of curcumin and its co-administration with piperine in the treatment of depressive disorders.