Mohit Bhutani

Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline.

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.

Assessing Exercise Limitation Using Cardiopulmonary Exercise Testing

The cardiopulmonary exercise test (CPET) is an important physiological investigation that can aid clinicians in their evaluation of exercise intolerance and dyspnea. Maximal oxygen consumption (V˙O2max) is the gold-standard measure of aerobic fitness and is determined by the variables that define oxygen delivery in the Fick equation (V˙O2 = cardiac output × arterial-venous O2 content difference). In healthy subjects, of the variables involved in oxygen delivery, it is the limitations of the cardiovascular system that are most responsible for limiting exercise, as ventilation and gas exchange are sufficient to maintain arterial O2 content up to peak exercise. Patients with lung disease can develop a pulmonary limitation to exercise which can contribute to exercise intolerance and dyspnea. In these patients, ventilation may be insufficient for metabolic demand, as demonstrated by an inadequate breathing reserve, expiratory flow limitation, dynamic hyperinflation, and/or retention of arterial CO2. Lung disease patients can also develop gas exchange impairments with exercise as demonstrated by an increased alveolar-to-arterial O2 pressure difference. CPET testing data, when combined with other clinical/investigation studies, can provide the clinician with an objective method to evaluate cardiopulmonary physiology and determination of exercise intolerance.

The effects of dobutamine and dopamine on intrapulmonary shunt and gas exchange in healthy humans

The development of intrapulmonary shunts with increased cardiac output during exercise in healthy humans has been reported in several recent studies, but mechanisms governing their recruitment remain unclear. Dobutamine and dopamine are inotropes commonly used to augment cardiac output; however, both can increase venous admixture/shunt fraction (Qs/Qt). It is possible that, as with exercise, intrapulmonary shunts are recruited with increased cardiac output during dobutamine and/or dopamine infusion that may contribute to the observed increase in Qs/Qt. The purpose of this study was to examine how dobutamine and dopamine affect intrapulmonary shunt and gas exchange. Nine resting healthy subjects received serial infusions of dobutamine and dopamine at incremental doses under normoxic and hyperoxic (inspired O(2) fraction = 1.0) conditions. At each step, alveolar-to-arterial Po(2) difference (A-aDo(2)) and Qs/Qt were calculated from arterial blood gas samples, intrapulmonary shunt was evaluated using contrast echocardiography, and cardiac output was calculated by Doppler echocardiography. Both dobutamine and dopamine increased cardiac output and Qs/Qt. Intrapulmonary shunt developed in most subjects with both drugs and paralleled the increase in Qs/Qt. A-aDo(2) was unchanged due to a concurrent rise in mixed venous oxygen content. Hyperoxia consistently eliminated intrapulmonary shunt. These findings contribute to our present understanding of the mechanisms governing recruitment of these intrapulmonary shunts as well as their impact on gas exchange. In addition, given the deleterious effect on Qs/Qt and the risk of neurological complications with intrapulmonary shunts, these findings could have important implications for use of dobutamine and dopamine in the clinical setting.

Executive Summary: Prevention of Acute Exacerbation of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline

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

Pulmonary rehabilitation in Canada: A report from the Canadian Thoracic Society COPD Clinical Assembly

49.9 billion, including

Do We Know the Minimal Clinically Important Difference (MCID) for COPD Exacerbations

29.5 billion in direct health-care expenditures,

A systematic review of the effectiveness of discharge care bundles for patients with COPD

8.0 billion in indirect morbidity costs, and

Empowering family physicians to impart proper inhaler teaching to patients with chronic obstructive pulmonary disease and asthma.

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

Elevated levels of circulating CD4(+) CRTh2(+) T cells characterize severe asthma.

646 million to

Physical activity and arterial stiffness in chronic obstructive pulmonary disease.

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.