G O L D lobal Initiative for Chronic bstructive ung isease

Global Initiative for Chronic Obstructive Lung Disease In collaboration with: National Heart, Lung, and Blood Institute, NIH and World Health Organization

GOLD Executive Committee R. Pauwels, Belgium – Chair S. Buist, US C. Jenkins, Australia P. Calverley, UK N. Khaltaev, Switzerland B. Celli, US C. Lenfant, US Y. Fukuchi, Japan J. Luna, Guatemala S. Hurd, US W. MacNee, UK L. Grouse, US N. Zhong, China

GOLD Expert Panel R. Pauwels, Belgium Chair N. Anthonisen, Canada C. Jenkins, Australia W. Bailey, US D. Postma, Netherlands P. Barnes, UK K. Rabe, Netherlands S. Buist, US S. Ramsey, US P. Calverley, UK S. Rennard, US T. Clark, UK R. Rodriguez-Roisin, Spain L. Fabbri, Italy N. Siafakas, Greece Y. Fukuchi, Japan S. Sullivan, US J. Hogg, Canada W. Tan, Singapore

GOLD Sponsors ASTA Medica Merck Sharp & Dohme AstraZeneca Mitsubishi-Tokyo Aventis Nikken Chemicals Bayer Novartis Boehringer-Ingelheim Schering-Plough Byk Gulden Yamanouchi Chiesi Zambon GlaxoSmithKline

Facts About COPD COPD is the 4th leading cause of death in the United States (behind heart disease, cancer, and cerebrovascular disease). In 2000, the WHO estimated 2.74 million deaths worldwide from COPD. In 1990, COPD was ranked 12th as a burden of disease; by 2020 it is projected to rank 5th.

Leading Causes of Deaths U.S. 1998 Cause of Death Number 1. Heart Disease 724,269 2. Cancer 538,947 3. Cerebrovascular disease (stroke) 158,060 4. Respiratory Diseases (COPD) 114,381 5. Accidents 94,828 6. Pneumonia and influenza 93,207 7. Diabetes 64,574 8. Suicide 29,264 9. Nephritis 26,295 10. Chronic liver disease 24,936 All other causes of death 469,314

Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 Proportion of 1965 Rate 3.0 Coronary Heart Disease Stroke Other CVD COPD All Other Causes 2.5 2.0 1.5 1.0 0.5 –59% –64% –35% +163% –7% 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998

Age-Adjusted Death Rates for COPD, U.S., 1960-1995 Deaths per 100,000 60 50 40 30 20 10 1960 1965 1970 1975 1980 1985 1990 1995 2000

Facts About COPD Between 1985 and 1995, the number of physician visits for COPD in the United States increased from 9.3 million to 16 million. The number of hospitalizations for COPD in 1995 was estimated to be 500,000. Medical expenditures amounted to an estimated $14.7 billion.

COPD 1990 Prevalence Male/1000 Female/1000 Established Market Economies 6.98 3.79 Formerly Socialist Economies 7.35 3.45 India 4.38 3.44 China 26.20 23.70 Other Asia and Islands 2.89 1.79 Sub-Saharan Africa 4.41 2.49 Latin America and Caribbean 3.36 2.72 Middle Eastern Crescent 2.69 2.83 World 9.34 7.33 *From Murray & Lopez, 1996

Facts About COPD Between 1985 and 1995, the number of physician visits for COPD in the United States increased from 9.3 million to 16 million. The number of hospitalizations for COPD in 1995 was estimated to be 500,000. Medical expenditures amounted to an estimated $14.7 billion.

Physician Office Visits for Chronic and Unspecified Bronchitis, U.S. Number (Millions) 15 10 5 1980 1985 1990 1995 1998 Year Source: National Ambulatory Medical Care Survey, NCHS

Facts About COPD Cigarette smoking is the primary cause of COPD. In the US 47.2 million people (28% of men and 23% of women) smoke. The WHO estimates 1.1 billion smokers worldwide, increasing to 1.6 billion by 2025. In low- and middle-income countries, rates are increasing at an alarming rate.

Facts About COPD In India, it is estimated that 400-550 thousand premature deaths can be attributed annually to use of biomass fuels, placing indoor air pollution as a major risk factor in the country. In Algeria, the prevalence of tuberculosis and acute respiratory infections has decreased since 1965; an increase in COPD and asthma has been observed in the last decade.

G O L D lobal Initiative for Chronic bstructive ung isease

GOLD Objectives Increase awareness of COPD among health professionals, health authorities, and the general public Improve diagnosis, management, and prevention Stimulate research

GOLD Documents Workshop Report: Global Strategy for the Diagnosis, Management, and Prevention of COPD Executive Summary Pocket Guide for health care providers Guide for patients and their families (available late 2001)

GOLD Workshop Report Evidence-based Implementation oriented Diagnosis Management Prevention Outcomes can be evaluated

GOLD Workshop Report Evidence category Sources of evidence A Randomized clinical trials Rich body of data B Randomized clinical trials Limited body of data   C Non randomized trials Observational studies  D Panel judgment consensus  

GOLD Workshop Report: Contents Introduction Definition and classification Burden of COPD Risk factors Pathogenesis, pathology, and pathophysiology Management Future research

Definition of COPD Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.

Burden of COPD Key Points The burden of COPD is underestimated because it is not usually recognized and diagnosed until it is clinically apparent and moderately advanced. Prevalence, morbidity, and mortality vary appreciably across countries but in all countries where data are available, COPD is a significant health problem in both men and women.

Burden of COPD Key Points The global burden of COPD will increase enormously over the foreseeable future as the toll from tobacco use in developing countries becomes apparent.

Burden of COPD Key Points The economic costs of COPD are high and will continue to rise in direct relation to the ever-aging population, the increasing prevalence of the disease, and the cost of new and existing medical and public health interventions.

Direct and Indirect Costs of COPD, 1993 (US $ Billions) Direct Medical Cost: $14.7 Total Indirect Cost: $ 9.2 Mortality related IDC 4.5 Morbidity related IDC 4.7 Total Cost $23.9

Risk Factors for COPD Host Factors Genes (e.g. alpha1-antitrypsin deficiency) Hyperresponsiveness Lung growth Exposure Tobacco smoke Occupational dusts and chemicals Infections Socioeconomic status

NOXIOUS AGENT (tobacco smoke, pollutants, occupational agent) Pathogenesis of COPD NOXIOUS AGENT (tobacco smoke, pollutants, occupational agent) COPD Genetic factors Respiratory infection Other

Causes of Airflow Limitation Irreversible Fibrosis and narrowing of the airways Loss of elastic recoil due to alveolar destruction Destruction of alveolar support that maintains patency of small airways

Causes of Airflow Limitation Reversible Accumulation of inflammatory cells, mucus, and plasma exudate in bronchi Smooth muscle contraction in peripheral and central airways Dynamic hyperinflation during exercise

GOLD Workshop Report Four Components of COPD Management Assess and monitor disease Reduce risk factors Manage stable COPD Education Pharmacologic Non-pharmacologic Manage exacerbations

Objectives of COPD Management Prevent disease progression Relieve symptoms Improve exercise tolerance Improve health status Prevent and treat exacerbations Prevent and treat complications Reduce mortality Minimize side effects from treatment

GOLD Workshop Report Four Components of COPD Management Assess and monitor disease Reduce risk factors Manage stable COPD Education Pharmacologic Non-pharmacologic Manage exacerbations

Assess and Monitor Disease: Key Points Diagnosis of COPD is based on a history of exposure to risk factors and the presence of airflow limitation that is not fully reversible, with or without the presence of symptoms.

Assess and Monitor Disease: Key Points Patients who have chronic cough and sputum production with a history of exposure to risk factors should be tested for airflow limitation, even if they do not have dyspnea.

Assess and Monitor Disease: Key Points For the diagnosis and assessment of COPD, spirometry is the gold standard. Health care workers involved in the diagnosis and management of COPD patients should have access to spirometry.

Assess and Monitor Disease: Key Points Measurement of arterial blood gas tension should be considered in all patients with FEV1 < 40% predicted or clinical signs suggestive of respiratory failure or right heart failure.

indoor/outdoor pollution Diagnosis of COPD EXPOSURE TO RISK FACTORS SYMPTOMS cough tobacco sputum occupation dyspnea indoor/outdoor pollution è SPIROMETRY

Spirometry: Normal and COPD

Factors Determining Severity Of Chronic COPD Severity of symptoms Severity of airflow limitation Frequency and severity of exacerbations Presence of complications of COPD Presence of respiratory insufficiency Comorbidity General health status Number of medications needed to manage the disease

Classification by Severity Stage Characteristics 0: At risk Normal spirometry Chronic symptoms (cough, sputum)  I: Mild FEV1/FVC < 70%; FEV1 ³ 80% predicted With or without symptoms (cough, sputum) II: Moderate FEV1/FVC < 70%; 30% £ FEV1 < 80% predicted (IIA: 50% £ FEV1 < 80% predicted; IIB: 30% £ FEV1 < 50% predicted) With or without chronic symptoms (cough, sputum, dyspnea) III: Severe FEV1/FVC < 70%; FEV1 < 30% predicted or FEV1 < 50%predicted plus respiratory failure or clinical signs of right heart failure

GOLD Workshop Report Four Components of COPD Management Assess and monitor disease Reduce risk factors Manage stable COPD Education Pharmacologic Non-pharmacologic Manage exacerbations

Reduce Risk Factors Key Points Reduction of total personal exposure to tobacco smoke, occupational dusts and chemicals, and indoor and outdoor air pollutants are important goals to prevent the onset and progression of COPD. Smoking cessation is the single most effective-and cost-effective- intervention to reduce the risk of developing COPD and stop its progression (Evidence A).

Reduce Risk Factors Key Points Brief tobacco dependence treatment is effective (Evidence A), and every tobacco user should be offered at least this treatment at every visit to a health care provider. Three types of counseling are especially effective: practical counseling, social support as part of treatment, and social support arranged outside of treatment (Evidence A).

Reduce Risk Factors Key Points Several effective pharmacotherapies for tobacco dependence are available (Evidence A), and at least one of these medications should be added to counseling if necessary, and in the absence of contraindications.

Reduce Risk Factors Key Points Progression of many occupationally-induced respiratory disorders can be reduced or controlled through a variety of strategies aimed at reducing the burden of inhaled particles and gases (Evidence B).

Brief Strategies To Help The Patient Willing To Quit Smoking ASK Systematically identify all tobacco users at every visit. ADVISE Strongly urge all tobacco users to quit. ASSESS Determine willingness to make a quit attempt. ASSIST Aid the patient in quitting. ARRANGE Schedule follow-up contact.

GOLD Workshop Report Four Components of COPD Management Assess and monitor disease Reduce risk factors Manage stable COPD Education Pharmacologic Non-pharmacologic Manage exacerbations

Manage Stable COPD Key Points The overall approach to managing stable COPD should be characterized by a stepwise increase in the treatment, depending on the severity of the disease. For patients with COPD, health education can play a role in improving skills, ability to cope with illness, and health status. It is effective in accomplishing certain goals, including smoking cessation (Evidence A).

Manage Stable COPD Key Points None of the existing medications for COPD has been shown to modify the long-term decline in lung function that is the hallmark of this disease (Evidence A). Therefore, pharmacotherapy for COPD is used to decrease symptoms and/or complications.

Manage Stable COPD Key Points Bronchodilator medications are central to the symptomatic management of COPD (Evidence A). They are given on an as-needed basis or on a regular basis to prevent or reduce symptoms. The principal bronchodilator treatments are Beta2-agonists, anticholinergics, theophylline, and a combination of these drugs (Evidence A).

Bronchodilators in Stable COPD Bronchodilator medications are central to symptom management in COPD. Inhaled therapy is preferred. The choice between Beta2-agonist, anticholinergic, theophylline or combination therapy depends on availability and individual response in terms of symptoms relief and side effects.

Bronchodilators in Stable COPD Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms. Long-acting inhaled bronchodilators are more convenient. Combining bronchodilators may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator.

Manage Stable COPD Key Points Regular treatment with inhaled glucocortico-steroids should only be prescribed for symptomatic COPD patients with a documented spirometric response to glucocorticosteroids or in those with an FEV1 < 50% predicted and repeated exacerbations requiring treatment with antibiotics and/or oral glucocorticosteroids (Evidence B).

Manage Stable COPD Key Points Chronic treatment with systemic glucocortico-steroids should be avoided because of an unfavorable benefit-to-risk ratio (Evidence A). All COPD-patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).

Manage Stable COPD Key Points The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival (Evidence A).

Management of COPD by Severity of Disease Stage 0: At risk Stage 1: Mild COPD Stage 2: Moderate COPD Stage 3: Severe COPD

Management of COPD: All stages Avoidance of noxious agents - smoking cessation - reduction of indoor pollution - reduction of occupational exposure Influenza vaccination

Management of COPD Stage 0: At Risk Characteristics Recommended Treatment Chronic symptoms - cough - sputum No spirometric abnormalities

Management of COPD Stage I: Mild COPD Characteristics Recommended Treatment FEV1/FVC < 70 % FEV1 > 80 % predicted With or without symptoms Short-acting bronchodilator as needed

Management of COPD Stage IIA: Moderate COPD Characteristics Recommended Treatment FEV1/FVC < 70% 50% < FEV1< 80% predicted With or without symptoms Regular treatment with one or more bronchodilators Rehabilitation Inhaled glucocortico-steroids if significant symptoms and lung function response

Management of COPD Stage IIB: Moderate COPD Characteristics Recommended Treatment FEV1/FVC < 70% 30% < FEV1 < 50% predicted With or without symptoms Regular treatment with one or more bronchodilators Rehabilitation Inhaled glucocortico-steroids if significant symptoms and lung function response or if repeated exacerbations

Management of COPD Stage III: Severe COPD Characteristics Recommended Treatment FEV1/FVC < 70% FEV1 < 30% predicted or presence of respiratory failure or right heart failure Regular treatment with one or more bronchodilators Inhaled glucocorticosteroids if significant symptoms and lung function response or if repeated exacerbations Treatment of complications Rehabilitation Long-term oxygen therapy if respiratory failure Consider surgical options

GOLD Workshop Report Four Components of COPD Management Assess and monitor disease Reduce risk factors Manage stable COPD Education Pharmacologic Non-pharmacologic Manage exacerbations

Manage Exacerbations Key Points Exacerbations of respiratory symptoms requiring medical intervention are important clinical events in COPD. The most common causes of an exacerbation are infection of the tracheobronchial tree and air pollution, but the cause of about one-third of severe exacerbations cannot be identified (Evidence B).

Manage Exacerbations Key Points Inhaled bronchodilators (Beta2-agonists and/or anticholinergics), theophylline, and systemic, preferably oral, glucocortico-steroids are effective for the treatment of COPD exacerbations (Evidence A).

Manage Exacerbations Key Points Patients experiencing COPD exacerbations with clinical signs of airway infection (e.g., increased volume and change of color of sputum, and/or fever) may benefit from antibiotic treatment (Evidence B)

Manage Exacerbations Key Points Noninvasive intermittent positive pressure ventilation (NIIPPV) in acute exacerbations improves blood gases and pH, reduces in-hospital mortality, decreases the need for invasive mechanical ventilation and intubation, and decreases the length of hospital stay (Evidence A).

Management of COPD In selecting a treatment plan, the benefits and risks to the individual, and the direct and indirect costs to the individual, his or her family and the community must be considered.

GOLD Website Address http://www.goldcopd.com