lobal Initiative for Chronic bstructive ung isease

lobal Initiative for Chronic

bstructive

ung

isease

G

OLD

18/Oct/2005 Dr. David P. Breen 2

GOLD Website Address

http://www.goldcopd.com


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 DeathsU.S. 1998

All other causes of death 469,31410. Chronic liver disease 24,9369. Nephritis 26,2958. Suicide 29,264

7. Diabetes 64,5746. Pneumonia and influenza 93,2075. Accidents 94,8284. Respiratory Diseases (COPD) 114,3813. Cerebrovascular disease (stroke) 158,060

2. Cancer 538,9471.

Cause of Death Number

Heart Disease 724,269


Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998

0

0.5

1.0

1.5

2.0

2.5

3.0Proportion of 1965 Rate

1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998

–59% –64% –35% +163% –7%

CoronaryHeart

Disease

Stroke Other CVD COPD All OtherCauses


Age-Adjusted Death Rates for COPD, U.S., 1960-1998

60Deaths per 100,000

1960 1965 1970 20001975 1980 1985 1990 1995

50

40

30

20

10

0


Facts About COPD: U.S. Between 1985 and 1995, the number of

physician visits for COPD increased from 9.3 to16 million.

The number of hospitalizations for COPD in 2000 was estimated to be 726,000.

Medical expenditures in 2002 were estimated to be $18.0 billion.


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.


Irish Figures

Diseases of the Respiratory system are the cause of one in five deaths in Ireland today

In 1999 , Respiratory disease caused 7100 deaths: 3700 in men and 3400 in women

26% of respiratory deaths were due to COPD =1846 COPD-related deaths

Clear social gradient: Respiratory mortality in the lowest occupational class was 200% higher than the highest occupational class Inhale survey


Clinically apparent disease

Subclinical/undiagnosed disease


COPD and Smoking

95% of COPD is caused by smoking 45% of young Irish adults are current smokers Prevalence of current smokers is higher in

females (46.5% female v 44.2% male) 30% of school-leavers smoke

ECRHS Group


Smoking in IrelandAdults

43% in 1973 29% in 1994 27% now highest in lowest SE groups declining more slowly in women than men

Children and teenagers 1/10 6th class pupils smoke regularly, 15% boys, 5% girls 1/2 6th class pupils have tried smoking smoking increases steadily in teens in both sexes 30-35% of 17 yo Dublin schoolchildren smoke regularly,

equal in both sexes


Lung Function decline


lobal Initiative for Chronic

bstructive

ung

isease

G

OLD

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 fullyreversible. The airflow limitation is usuallyboth progressive and associated with anabnormal inflammatory response of thelungs 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.


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


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, 2002 (US $ Billions)

Direct Medical Cost: $18.0

Total Indirect Cost: $ 14.1– Mortality related IDC 7.3– Morbidity related IDC 6.8

Total Cost $32.1Source: NHLBI, NIH, DHHS


Risk Factors for COPD

Host Factors Genes (e.g. alpha1-antitrypsin deficiency)

HyperresponsivenessLung growth

Exposure Tobacco smokeOccupational dusts and chemicalsInfectionsSocioeconomic status


Pathogenesis of COPD

NOXIOUS AGENT(tobacco smoke, pollutants, occupational agent)

COPD

Genetic factorsRespiratory infectionOther


Noxious particles and gases

Lung inflammationHost factors

COPD pathology

ProteinasesOxidative stress

Anti-proteinasesAnti-oxidants

Repair mechanisms


INFLAMMATION

Small airway diseaseAirway inflammationAirway remodeling

Parenchymal destructionLoss of alveolar attachments

Decrease of elastic recoil

AIRFLOW LIMITATION


ASTHMAASTHMASensitizing agent

COPDCOPDNoxious agent

Asthmatic airway inflammationCD4+ T-lymphocytes

Eosinophils

COPD airway inflammationCD8+ T-lymphocytes

MacrophagesNeutrophils

Airflow limitationCompletelyreversible

Completelyirreversible


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


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

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD Education Pharmacologic Non-pharmacologic

4. 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.



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.



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.



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.


SYMPTOMScough

sputumdyspnea

EXPOSURE TO RISKFACTORS

tobaccooccupation

indoor/outdoor pollution

SPIROMETRY

Diagnosis of COPD


Spirometry: Normal and COPD

0

5

1

4

2

3

Lite

r

1 65432

FVC

FVC

FEV1

FEV1

Normal

COPD

3.9005.200

2.3504.150 80 %

60 %NormalCOPD

FVCFEV1 FVCFEV1/

Seconds


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 SeverityStage Characteristics0: At risk Normal spirometry

Chronic symptoms (cough, sputum)

I: Mild FEV1/FVC < 70%; FEV1 80% predicted With or without chronic symptoms (cough,

sputum)

II: Moderate FEV1/FVC < 70%; 50% FEV1 < 80% predicted With or without chronic symptoms (cough, sputum,

dyspnea) III: Severe FEV1/FVC < 70%; 30% FEV1 < 50% predicted

With or without chronic symptoms (cough, sputum, dyspnea)

IV: Very Severe FEV1/FVC < 70%; FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure








Reduce Risk FactorsKey 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).


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).


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.


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.









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).



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.



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 symptom 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.

Regular treatment with long-acting inhaled bronchodilators is more effective and convenient than treatment with short-acting bronchodilators, but more expensive.

Combining bronchodilators may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator.



Regular treatment with inhaled glucocorticosteroids is appropriate for symptomatic COPD patients with an FEV1 < 50% predicted (Stage III: Severe COPD and Stage IV: Very Severe COPD) and repeated exacerbations e.g. 3 in the last three years (Evidence A).

This treatment has been shown to reduce the frequency of exacerbations and improve health status (Evidence A).



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).



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 I: Mild COPD

Stage II: Moderate COPD

Stage III: Severe COPD

Stage IV: Very Severe COPD


Management of COPD: All stages

Avoidance of risk factors

- smoking cessation - reduction of indoor pollution

- reduction of occupational exposure

Influenza vaccination


Management of COPD Stage 0: At Risk

Characteristics Recommended Treatment

• Chronic symptomscough- sputum

• No spirometric abnormalities


Management of COPD Stage I: Mild COPD


• FEV1/FVC < 70 %

• FEV1 > 80 % predicted• With or without chronic

symptoms

• Short-acting bronchodilator as needed


Management of COPD Stage II: Moderate COPD


• FEV1/FVC < 70%

• 50% < FEV1< 80% predicted• With or without chronic symptoms

• Short-acting broncho-dilator as needed• Regular treatment with

one or more long-acting bronchodilators

• Rehabilitation


Management of COPD Stage III: Severe COPD

Characteristics Recommended Treatment• FEV1/FVC < 70%

• 30% < FEV1 < 50% predicted• With or without chronic symptoms

• Short-acting broncho-dilator as needed• Regular treatment with one or more long-acting bronchodilators• Inhaled glucocortico-steroids if repeated exacerbations• Rehabilitation


Management of COPD Stage IV: Very Severe COPD

Characteristics Recommended Treatment• FEV1/FVC < 70%

• FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure

• Short-acting bronchodilator as needed • Regular treatment with one or more long-acting bronchodilators• Inhaled glucocorticosteroids if repeated exacerbations• Treat complications• Rehabilitation• Long-term oxygen therapy if respiratory failure• Consider surgical options


Old (2001) 0: At Risk I: Mild II: Moderate IIA IIB

III: Severe

New (2003)

0: At Risk I: Mild II: Moderate III: Severe IV: Very Severe

Therapy at Each Stage of COPD

Characteristics Chronic Symptoms Exposure to risk factors Normal spirometry

FEV1/FVC < 70% FEV1 80% With or without symptoms

FEV1/FVC < 70% 50% < FEV1 < 80% With or without symptoms

FEV1/FVC < 70% 30% < FEV1 < 50% With or without symptoms

FEV1/FVC < 70% FEV1 < 30% or FEV1 < 50% predicted plus chronic respiratory failure

Avoidance of risk factor(s); influenza vaccination

Add short-acting bronchodilator when needed

Add regular treatment with one or more long-acting bronchodilatorsAdd rehabilitation

Add inhaled glucocorticosteroids if repeated exacerbations

Add long-term oxygen if chronic respiratory failureConsider surgical treatments









Manage ExacerbationsKey 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).



Inhaled bronchodilators (beta2-agonists and/or anticholinergics), theophylline, and systemic, preferably oral, glucocortico-steroids 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 color of sputum, and/or fever) may benefit from antibiotic treatment (Evidence B).



Noninvasive intermittent positive pressure ventilation (NIPPV) in 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.


Do you know what COPD is? This chronic lung disease is a major cause of illness, yet many people have it and don’t know it.

If you answer these questions, it will help you find out if you could have COPD.

1. Do you cough several times most days? Yes ___ No ___

2. Do you bring up phlegm or mucus most days? Yes ___ No ___

3. Do you get out of breath more easily than others your age? Yes ___ No ___

4. Are you older than 40 years? Yes ___ No ___

5. Are you a current smoker or an ex-smoker? Yes ___ No ___

If you answered yes to three or more of these questions, ask your doctor if you might have COPD and should have a simple breathing test. If COPD is found early, there are steps you can take to prevent further lung damage and make you feel better.

Take time to think about your lungs……Learn about COPD!

Could it be COPD?


GOLD Website Address

http://www.goldcopd.com



Spirometry is the GOLD Standard for the diagnosis of COPD


Smoking Cessation

Pre-contemplator

contemplationAction

Relapse



Pharmacological treatment 1st line treatment

Nicotine replacement Nicotine polacrilex (gum) Transdermal nicotine Nicotine inhaler Nicotine nasal spray Nicotine lozenges Combined modality

Bupropion 2nd line treatment

Clonidine Nortripyline


Management of Stable Disease

Smoking cessation Pharmacological treatment LTOT Pulmonary rehabilitation Surgery


Pharmacological therapy

Medications can reduce or abolish symptoms,increase exercise tolerance,reduce no and severity of symptoms and improve health status

No treatment alters the rate of decline of lung function Inhaled route is preferable – smaller doses and therefore

reduced side effects by inhalation Combining agents have a greater effect on symptoms than

single agents


General principles Patients must be educated in the device Choose right device for patient – MDI v DPI v

Spacer device Spacer good for delivery and reduce oral s/e Compliance is variable – studies show at east 85%

of patients take 70% of the prescribed doses - ? Reflect the constant symptoms

Education is essential for good adherence and proper use

Spirometry essential for diagnosis but not for monitoring


Bronchodilators Β2 agonist Anticholinergic agents Methylxanthines

Mode of action is smooth muscle relaxation – small changes in FEV but decreases in lung volumes resulting in better emptying and less hyperinflation


Β2 agonist Inhaled (short , long acting), oral Mode of action

Increase in c-amp within cells and promote smooth muscle relaxation

?other non bronchodilator effects S/E

Palpitations, PVC Tremor Sleep disturbance Metabolic - hypokalaemia


Anticholinergic drugs Only available via inhaled route

Ipratropium Oxitropium Tiotropium

Inhibit muscarinic receptors Tiotropium remains bound to receptors for up to 36 hours Onset of bronchodilatation in 30 mins S/E

Not associated with significant incidence of prostatism or cardiac S/E Commonest – dry mouth(tiotropium), metallic taste (ipratropium),

closed angle glaucoma


Methylxanthines Oral or I.V prn preparations Non specific PDE inhibitors and increase c-amp Bronchodilatation only occurs at high dose and

narrow therapeutic/toxic window Keep at level of 8-14 ug.dl Can be bd or od drugs S/E

Major – ventricular and atrial rhythm disturbance, convulsions

Minor – headache, nausea, vomiting, diarrhoea and heartburn


Levels increased Levels decreased

Respiratory acidosisCCFLiver cirrhosisErthyromycinciprofloxacin

Cigarette smokeAnti-convulsant drugsrifampicin


Glucocorticoids Inhalation

Beclomethasone Budesonide Triamcinolone Fluticasone Flunisolide

Oral Not indicated in stable – excessive S/E profile


Pharmacology Effect transcription processes – slow action High dose can be absorbed via the pulmonary circulation

S/E Oral – osteoporosis, cataracts, peripheral myopathy Topical/local S/E can be significant Skin bruising

Clinical outcomes If FEV<50% and a number of exacerbations/year rate of

deterioration in health status can be reduced 3 year prospective studies revealed no effect on rate of

decline of FEV1


Combination therapy Combination treatment is a convenient, safe

and improves compliance Initial data show a significant effect on

pulmonary function and a reduction in symptoms

Largest effects in most severe – FEV<50% and a number of exacerbations


Other agents Mucolytic agents – carbocysteine, iodinated

glycerol Little evidence of any effect on lung function Cochrane review – supports a role for

reducing no of exacerbations in chronic bronchitis

N-acetylcysteine – at present prospective study ongoing


Leukotreine receptor antagonist -No data to support role

Maintenance antibiotic –no data to suggest that these drugs are effective in modifying symptoms, exacerbations or lung function

Respiratory stimulants – oral peripheral chemoreceptor stimulant – improves V/Q matching and improves oxygenation – can result in peripheral neuropathy

Vaccination Influenza – can reduce serious illness and death by

50% Pneumococcal – reduces bacteraemia


Alpha1-antitrypsin deficiency

Augmentation therapy Licensed for i.v. use twice a week Expensive No RCT showing benefit Suggestio that rate of decline in those

receiving drug is less than historical controls.





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lobal Initiative for Chronic bstructive ung isease