1. GOLD MANAGEMENT PLAN FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
Global initiative for chronic
Obstructive
Lung
Disease
GOLD MANAGEMENT PLAN FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

2. WHAT IS COPD?
“COPD is a disease state characterised 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.”
COPD – which encompasses emphysema and chronic bronchitis – is a chronic, slowly progressive disease. It is a condition in which the passage of air to and from the lungs becomes partially obstructed leading to breathing difficulty. Most airflow limitation is due to a combination of mechanical obstruction in the small airways and loss of pulmonary elastic recoil due to emphysema.
Risk factors for COPD include both host/genetic factors (hereditary deficiency of alpha-1 antitrypsin) and environmental exposures. Heavy exposure to occupational dusts and chemicals (vapours, irritants, fumes, and indoor pollution) can lead to COPD, but most cases of the disease occur as a result of smoking.
The prevalence of COPD is highest in countries where cigarette smoking has been, or still is, very common, while the prevalence is lowest in countries where smoking is less common, or total tobacco consumption per individual is low.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

3. WHAT ARE THE CONSEQUENCES OF COPD?
Symptoms of COPD include: production of sputum, chronic cough & dyspnoea (shortness of breath)
Exacerbations are a major cause of disability and often lead to a significant decrease in quality of life
The disease cannot be fully reversed; however disease progression can be slowed by smoking cessation
Symptoms of COPD include production of sputum, chronic cough and dyspnoea (shortness of breath, breathlessness). More severe symptoms are respiratory failure and clinical signs of right heart failure.
Dyspnoea is the characteristic symptom of COPD. It is due to disturbances in lung mechanics and has a complex aetiology that is linked to the process of breathing. Exacerbations are a major cause of disability and often lead to a significant erosion of quality of life. The frequency of exacerbations increases with disease severity and lung function can take several weeks to recover.
COPD cannot be cured or fully reversed, though the disease can be slowed by smoking cessation. The effects of COPD on patients' daily lives extend far beyond the experience of breathlessness and other symptoms. Normal activities may be severely curtailed, family routines affected, independence and confidence lost and social isolation experienced. Furthermore, the economic impact due to missed work will add to the patient's problems. Depression is common especially in advanced disease and contributes to the perceived disability and social isolation.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

4. WHY TACKLE COPD?
COPD is the fourth leading cause of death in the world
An increase in prevalence/mortality is predicted for the future
A unified international effort is required to reverse incidence trends
COPD is a major and growing cause of morbidity and mortality with a heavy burden on both primary and secondary healthcare services. It is currently the fourth leading cause of death in the world and is projected to rank fifth in 2020 as a worldwide burden of disease according to the World Bank and World Health Organisation.
Despite these grim statistics, attention from healthcare communities and governments is inadequate and COPD remains under-diagnosed and under-treated. A unified international effort is urgently required to reverse these prevalence trends.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

5. WHAT IS GOLD?
GOLD is a collaborative project of the US National Heart, Lung and Blood Institute & WHO
“GOLD provides guidelines to achieve a global strategy for the diagnosis, management and prevention of COPD”
An international panel which consists of specialists in the areas of respiratory medicine, epidemiology, socioeconomics, public health & health education
GOLD aims to increase awareness of COPD and decrease morbidity and mortality
A committed international and distinguished group of scientists encouraged the US National Heart, Lung, and Blood Institute and the World Health Organisation to form the Global initiative for chronic Obstructive Lung Disease (GOLD). They reviewed existing COPD guidelines, as well as new information on pathogenic mechanisms of COPD as they developed a consensus document.
The GOLD initiative aims to improve the prevention and management of COPD through a concerted worldwide effort of people involved in all facets of healthcare and healthcare policy, and to encourage a renewed research interest in this extremely prevalent disease. The 'Global strategy for the diagnosis, management and prevention of COPD' is GOLD's consensus workshop report. It provides guidelines for the management of COPD.
Development of the workshop report was supported through educational grants from: AstraZeneca; Aventis; Bayer; Boehringer Ingelheim; Byk Gulden; Glaxo Wellcome; Merck, Sharp & Dohme; Mitsubishi-Tokyo; Nikken Chemicals; Novartis; SmithKline Beecham; Yamanouchi and Zambon.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

6. GOALS OF EFFECTIVE COPD MANAGEMENT
Prevent disease progression
Relieve symptoms
Improve exercise tolerance
Improve health status
Prevent and treat complications
Prevent and treat exacerbations
Reduce mortality
These goals should be reached with minimum side effects from treatment
Lung damage in COPD is largely irreversible and none of the existing medications for COPD have been shown to modify the long-term decline in lung function that is the hallmark of the disease. Most interventions in COPD are, therefore, directed towards relieving symptoms and improving current health. This should improve quality of life, and increase physical and emotional participation in everyday activities of affected patients.
Smoking cessation is the only therapy shown to slow disease progression in terms of loss of lung function over time. The extent to which the management objectives of COPD can be realised varies with each individual. Some treatments will produce benefits in more than one area.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

7. COMPONENTS OF COPD GUIDELINES
Assess and monitor disease
Decrease risk factors
Manage stable COPD
Manage exacerbations
GOLD's consensus workshop report 'Global strategy for the diagnosis, management and prevention of COPD' presents a COPD management plan with four, staged components: to assess and monitor disease, to reduce risk factors, to manage stable COPD and to manage exacerbations.
The workshop report is based on the best-validated current concepts of COPD pathogenesis and the available evidence on the most appropriate management and prevention strategies.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

8. EVIDENCE-BASED APPROACH STATEMENTS SUPPORTED BY DEFINED LEVELS OF EVIDENCE
Evidence category
Sources of evidence
Evidence A
Randomised controlled trials. Rich body of data
Randomised controlled trials. Limited body of data
Evidence B
The four components of COPD management have been developed using an evidence-based approach whereby statements made are supported by defined levels of evidence, A–D.
Evidence A: evidence is from endpoints of well-designed randomised controlled trials that provide a consistent pattern of findings in the population for which the recommendation is made.
Evidence B: evidence is from endpoints of intervention studies that include only a limited number of randomised controlled trials, posthoc or subgroup analysis of randomised controlled trials, or meta-analysis of randomised controlled trials.
Evidence C: evidence is from uncontrolled or non-randomised trials or observational studies.
Evidence D: this category is used only in cases where the provision of some guidance was deemed valuable but the clinical literature addressing the subject was deemed insufficient to justify placement in one of the other categories.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.
Non-randomised trials
Observational studies
Evidence C
Evidence D
Panel consensus

9. ASSESS & MONITOR DISEASE
Diagnosis should be based on:
a history of exposure to risk factors
& presence of airflow limitation that is not fully reversible
presence of symptoms
Spirometry (FEV1; FEV1/VC) for diagnosis & assessment
standardised, (reproducible), (objective tool)
Annual assessment based on symptoms, spirometry and presence of complications
Even patients who do not show a significant FEV1 response to a SAB test may benefit symptomatically from long-term bronchodilator treatment
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.
For the diagnosis and assessment of severity of COPD, spirometry is the gold standard as it is standardised, reproducible and objective. Assessment of severity is based on the level of symptoms, severity of the spirometric abnormality and the presence of complications such as respiratory failure and right heart failure.
All primary and secondary healthcare workers involved in the diagnosis and management of COPD patients should have access to spirometry. The FEV1 (forced expiratory volume within 1 second) measurement derived from this technique is also valuable to measure deterioration of lung function over time and is a predictor of prognosis and mortality. Ideally, FEV1 should be measured on an annual basis.
Bronchodilator reversibility testing is useful at the time of diagnosis. However, even patients who do not show a significant FEV1 response can benefit symptomatically from long-term bronchodilator treatment.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

10. HOW SHOULD COPD BE DIAGNOSED & ASSESSED
HOW SHOULD COPD BE DIAGNOSED & ASSESSED? KEY INDICATORS FOR CONSIDERING A DIAGNOSIS OF COPD
Dyspnoea
Progressive, persistent, worse on exercise, worse during respiratory infections
Chronic cough
Present intermittently / every day, often present throughout the day
Chronic sputum production
In any pattern
A diagnosis of COPD should be considered in any patient who has dyspnoea and/or other symptoms of COPD, plus a history of exposure to risk factors to the disease. The diagnosis is confirmed by a measure of airflow limitation that is largely irreversible.
Dyspnoea is the reason most patients with COPD seek medical attention and is a major cause of disability and anxiety associated with the disease. As lung function deteriorates breathlessness becomes more intrusive. Wheezing and chest tightness are relatively non-specific symptoms and may vary between days and over the course of a single day. An absence of wheezing or chest tightness does not exclude a diagnosis of COPD.
Chronic cough, usually the first symptom of COPD to develop, may initially be intermittent, but later is present every day (often throughout the day) and is seldom entirely nocturnal. In some cases, significant airflow limitation may develop without the presence of a cough. Small quantities of tenacious sputum are commonly produced by COPD patients after coughing bouts. 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 dyspnoea.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.
History of exposure to risk
factors, especially:
Tobacco smoke, occupational dusts & chemicals, smoke from home heating fuels

11. HOW CAN WE REDUCE THE RISK OF DEVELOPING COPD?
Smoking cessation is the single most effective/cost effective intervention
reduce risk of developing disease (A)
stop progression of disease (A)
Treating tobacco dependence is effective
Every smoker should be offered
counselling (A)
smoking cessation medications where appropriate (A)
Smoking cessation is the single most effective – and cost effective – intervention to reduce the risk of developing COPD and stop its progression (Evidence A). Tobacco dependence treatment is effective and every tobacco user should be offered at least brief treatment (Evidence A).
Three types of counselling are especially effective for the smoker: practical counselling, social support as part of treatment and social support arranged outside treatment (Evidence A). Several pharmacotherapies for tobacco dependence are effective (Evidence A), and at least one of these medications should be added to counselling where appropriate, in the absence of contraindications.
For occupationally-induced respiratory disorders, a variety of strategies can reduce the burden of inhaled particles and gases responsible (Evidence B).
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

12. HOW SHOULD COPD BE MANAGED IN PRACTICE?
Stepwise increase in treatment recommended, dependent on
severity of disease, response to treatments
Exercise training programmes (pulmonary rehabilitation)
improve exercise tolerance/symptoms of dyspnoea & fatigue (A)
Health education
Increase self-management skills, ability to cope with illness and health status (patient well-being) (A)
COPD lung damage is irreversible. Pharmacotherapy aims to improve symptoms and/or decrease complications
The overall approach to managing stable COPD should be characterised by a stepwise increase in treatment, depending on an individualised assessment of the severity of the disease and response to various treatments.
All COPD patients benefit from exercise training programmes with respect to improving both exercise tolerance and symptoms of dyspnoea and fatigue (Evidence A).
For patients with COPD, health education can play a role in improving self-management skills, ability to cope with illness and health status. It is effective in accomplishing certain goals, including smoking cessation (Evidence A).
None of the existing medications for COPD have been shown to modify the long-term decline in lung function (Evidence A). Therefore, pharmacotherapy for COPD is used to improve symptoms and/or decrease complications.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

13. HOW SHOULD COPD BE MANAGED IN PRACTICE?
Bronchodilators are central to managing symptoms (A)
beta2-agonists
anticholinergics
theophylline (A)
Choice of bronchodilator depends on:
a patient’s response (symptom relief and side effects)
availability
Long-acting bronchodilators are more convenient for regular therapy than short-acting agents
The long-acting beta2-agonist, salmeterol has been shown to improve health status significantly in doses of 50mcg b.d.1
Similar data for short-acting beta2-agonists are not available
Bronchodilator medications are central to the symptomatic management of COPD (Evidence A). They are given on an as-needed basis for relief of persistent or worsening symptoms, or on a regular basis to prevent or reduce symptoms.
The principal groups of bronchodilators used in treating COPD are beta2-agonists, anticholinergics and theophylline, and a combination of one or more of these drugs (Evidence A). The choice depends on the availability of the medication and the patient's response in terms of symptom relief and side effects. Regular treatment with long-acting bronchodilators is more convenient than short-acting bronchodilators, as efficacy can be sustained with fewer daily doses.
All categories of bronchodilators have been shown to increase exercise capacity in COPD. Notably, the long-acting inhaled beta2-agonist, salmeterol, given twice daily has been shown to improve health status significantly.1 Use of the anticholinergic, ipratropium, inhaled four times daily also improves health status.2 Similar data for short-acting beta2-agonists are not available.
References
1. Jones PW, Bosh TK, Am J Respir Crit Care Med 1997; 155: 1283–9.
2. Mahler DA et al. Chest 1999; 115(4): 957–65.
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

14. MANAGEMENT OF SYMPTOMS IN COPD
Bronchodilators
Central to symptom management
Prescribed to patients as needed
LABs more convenient than SABs
Benefit patient symptomatically
Methylxanthines
(Theophyllines)
(duration <24 hours
Anticholinergics
(duration of 6-9 hours)
Beta2-agonists
Short-acting
Beta2-agonists
(duration of 4-6 hours)
Fenoterol
Salbutamol
Terbutaline
Long-acting
Beta2-agonists
(duration of >12 hours)
Salmeterol
Formoterol
Ipratropium bromide
Oxitropium bromide
Aminophylline (SR)
Theophylline (SR)
Pharmacological therapy is used to prevent and control symptoms, reduce the frequency and severity of exacerbations, improve health status and improve exercise tolerance.
Adverse effects from bronchodilators are less likely and resolve more rapidly after treatment withdrawal with inhaled rather than with oral treatment. When treatment is given by the inhaled route, attention to effective drug delivery and training in inhaler technique is essential.
Short-acting beta2-agonists (SABs) are taken as required when the symptoms occur. Long-acting bronchodilators (LABs) are indicated as regular treatment when SABs alone become inadequate in preventing or reducing symptoms as the disease gets worse. Of the regular inhaled agents, the beta2-agonists have a longer duration of action than anticholinergics.
Theophylline, which is administered orally, is effective in COPD, but due to its toxic potential inhaled bronchodilators are preferred when available.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

15. HOW SHOULD COPD BE MANAGED IN PRACTICE?
Regular inhaled corticosteroids are recommended for:
patients with a response in FEV1 (B)
patients with an FEV1 <50% predicted & repeated exacerbations (B)
A short course of oral corticosteroids (OCS) is a poor predictor of the long-term response to inhaled glucocorticosteroids
Chronic treatment with OCS should be avoided
unfavourable benefit:risk ratio (A)
Regular treatments with inhaled glucocorticosteroids should only be prescribed for symptomatic COPD patients with a documented spirometric response to glucocorticosteroids or for those with an FEV1 of less than 50% predicted and repeated exacerbations requiring treatment with antibiotics and/or oral glucocorticosteroids (Evidence B).
There is mounting evidence that a short course of oral glucocorticoidsteroids is a poor predictor of the long-term response to inhaled glucocorticoidsteroids in COPD.
Chronic treatment with systemic (i.e. oral) glucocorticosteroids should be avoided because of an unfavourable benefit:risk ratio (Evidence A).
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

16. HOW SHOULD COPD EXACERBATIONS BE MANAGED IN PRACTICE?
Characteristics of exacerbations:
important clinical events
causes largely unknown
significant role of infection (B)
Effective treatments:
Inhaled bronchodilators (A)
Oral corticosteroids (A)
Antibiotic treatment for suspected infection (e.g. change of colour of sputum) (B)
Non-invasive positive pressure ventilation (A)
Exacerbations of respiratory symptoms requiring medical intervention are important clinical events in COPD. The causes of many acute COPD exacerbations remain unknown, but infections seem to play a significant role (Evidence B).
Inhaled bronchodilators (beta2-agonists and/or anticholinergics), theophylline and systemic, preferably oral, glucocorticosteroids are effective for the treatment of COPD exacerbations (Evidence A).
Patients experiencing COPD exacerbations with clinical signs of airway infection (e.g. increased volume and change of colour of sputum, and/or fever) may benefit from antibiotic treatment (Evidence B).
Non-invasive positive pressure ventilation 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).
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

17. FUTURE RESEARCH
Much about COPD is still unknown and further research is needed in many areas:
improved early detection/diagnosis
new approaches for interventions
means to identify the “susceptible” smoker
more effective means of managing exacerbations
standardise tracking = future planning
cost & burden analysis
A better understanding of molecular and cellular mechanisms of COPD should lead to many directions for both basic and clinical investigations. There is a need for improved methods for early detection, new approaches for interventions through targeted pharmacotherapy, means to identify the 'susceptible' smoker and more effective means of managing exacerbations.
Standardised methods for tracking trends in COPD prevalence, morbidity and mortality over time need to be developed so that countries can plan for future increases in the need for healthcare services in view of predicted increases in COPD.
Data are also needed on the use, cost and relevant distribution of medical and non-medical resources for COPD. These data are likely to have some impact on health policy and resource allocation decisions. As options for treating COPD grow, more research will be needed to help guide healthcare providers and health budget managers regarding the most efficient and effective ways of managing this disease.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.

18. GOALS OF EFFECTIVE COPD MANAGEMENT
Prevent disease progression
Relieve symptoms
Improve exercise tolerance
Improve health status
Prevent and treat complications
Prevent and treat exacerbations
Reduce mortality
In summary, the GOLD consensus Workshop Report comprises a COPD management plan which includes directives for the diagnosis, assessment, management and prevention of COPD.
In the light of the information presented here, it is worth revisiting the goals of effective COPD management. These goals should be reached with a minimum of side effects from treatment, a particular problem for COPD where comorbidities are common. In selecting a treatment plan, the benefits and risks to the individual and the costs – direct and indirect – to the community must be considered.
Reference
Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO workshop report, 2001.