copd guidelines update and newer therapies

Percent Change in Age-Adjusted Death Stroke Other CVD COPD All Other Causes... COPD - PathogenesisTobacco Smoke Chronic Inflammation* Emphysema Chronic Bronchitis *CD8+ T-lymphocytes Mac

COPD: Guidelines Update and

Newer Therapies

• The Problem

• Pathogenesis

• Key Clinical Concepts

– Life Prolonging vs Symptomatic Therapy

– Spirometry - The Sixth Vital Sign

– Use of clinical practice guidelines

• COPD Exacerbations

• New Horizons

Outline

Percent Change in Age-Adjusted Death

Stroke Other CVD COPD All Other

Causes

COPD in the United States

Age-Adjusted Death Rates* for COPD by State: 1995-1997

Deaths/100,000 Pop Highest 46-61 (11) High 41-45 (13)

Low 36-40 (13) Lowest 19-35 (13)

*Morbidity and Mortality: 2000 Chart Book on Cardiovascular, Lung, and

Blood Diseases May 2000.

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x

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COPD - Pathogenesis

Tobacco Smoke

Chronic Inflammation*

Emphysema Chronic Bronchitis

*CD8+ T-lymphocytes Macrophages

Neutrophils IL-8 and TNF α

Proteinases Oxidative Stress

Host factors

Repair Mechanisms

COPD Therapy Concepts

• Life prolonging vs symptomatic therapies

• Spirometry - the 6th vital sign

• Use of clinical practice

guidelines

Spirometry - The Sixth Vital Sign

60 %

Normal COPD

COPD Practice Guidelines

• European Thoracic Society - 1995

• American Thoracic Society - 1995

• British Thoracic Society - 1997

Consensus and Ev idence-based Guidelines

For com parisons:

Stoller JK New Eng J Med 346:98 8 , 2 002

GOLD Workshop Report

Four Components of COPD

Management - www.goldcopd.com

Education Pharmacologic Non-pharmacologic

Management of COPD Stage 0: At Risk

Characteristics Recommended Treatment

Management of COPD Stage I: Mild COPD

Characteristics Recommended Treatment

Management of COPD Stage II: Moderate COPD

Characteristics Recommended Treatment

•FEV1/FVC < 70%

•50% < FEV1< 80% predicted

•With or without symptoms

•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 symptoms

•Treatment with one or

more long-acting bronchodilators

•Rehabilitation

•Inhaled steroids if repeated exacerbations (>3/year)

glucocortico-Management of COPD Stage IV: Very Severe COPD

Characteristics Recommended Treatment

•FEV1/FVC < 70%

•FEV1 < 30% predicted or

presence of respiratory

failure or right heart failure

•Treatment with one or more acting bronchodilators

long-•Inhaled glucocorticosteroids if repeated exacerbations (>3/year)

Bronchodilator Therapy

• Inhaled therapy (with spacer) preferred

• Long-acting preparations more convenient

• Combined preparations improve effectiveness and

decrease risk of side effects

Effectiveness of BronchodilatorTherapy?

• FEV1 does not always correlate with symptoms

– Concept of “dynamic hyperinflation” in COPD

• Quality of life issues are important

– Chronic fatigue

– Depression

– Physical immobility

– Dyspnea

COPD - Surgical Options

• Giant Bullous Disease

– Consider bullectomy if see normal lung compression

• Lung Volume Reduction Surgery*

– FEV1 (<20% pred) plus diffuse emphysema or Dlco<20% pred = high risk of surgical death

– Upper lobe emphysema and low exercise capacity =

decreased mortality, increased exercise and QOL

COPD Exacerbation

• Worsening dyspnea

• Increased sputum purulence

• Increase in sputum volume

• Severe - all 3 elements

• Moderate - 2 elements

• Mild - 1 element plus:

• URI in past 5 days

Mod ified f rom A nthonisen et al A nn Int Med 1 06:1 96, 1 98 7

COPD Exacerbations

Frequency

(per year)

Number (patients) SGRQ Symptoms Activities Impacts

0-2

Infrequent 32 48.9 53.2 67.7 36.3

3-8

Frequent 38 64.1 77.0 80.9 50.4 Mean = 3 Total =70 0.0005 0.0005 0.001 0.002

Effect on Quality of Life

Seemungal et al A JRCCM 1 57:1 418 , 1 998

Donaldson et al Thorax 57:8 47, 2 002

Effects on Lung Function Decline

Infrequent Frequent

Conclusion:

Frequent exacerbations accelerate decline in lung function

Air Pollution 5%

Unknown

20%

Exacerbation

Acute Inflammation

Pathophy siology - Current Hy pothesis

Chronic Inflammation

Therapy of COPD Exacerbation

Variable ACCP-ACP GOLD

Diagnostic CXR for admissions CXR, EKG, ABG,

sputum culture, lytes, cbc

Bronchodilators Ipratroprium, add B2

agonist No methylxanthine

B2 agonist, add ipratroprium Yes methylxanthine

Delivery system None preferred Not discussed

Antibiotics Yes, in selected (severe)

Duration unclear Yes, with purulence, Rx local sensitivities

Guidelines

http :/w w w goldcop d com

A nn Int Med 1 34:595, 2 001

Therapy of COPD Exacerbation

Variable ACCP-ACP GOLD

Steroids Yes, for up to two

weeks Yes, oral or IV for 10-14 days

Oxygen Yes Yes - target PaO2 60 torr or Sat of

90% with ABG check

Chest PT No Maybe - for atelectasis or sputum

Therapy of COPD Exacerbation

Variable ACCP-ACP GOLD

Other LMWH, fluids, diet

Guidelines

http :/w w w goldcop d com

A nn Int Med 1 34:595, 2 001

COPD Therapy - New Horizons

• Newer anti-inflammatory agents

– Matrix metalloproteinase inhibitors

– Specific phosphodiesterase (PDE4) inhibitors

• 470 patients - stable COPD

• 3 month, randomized, double blind, once daily tiotropium

vs placebo

Conclusions:

Increased FEV1 and FVC

No tachyphylaxis

Decreased rescue albuterol

Decreased wheezing, SOB

Dry mouth in 9.3%

Casaburi et al CHEST 118:1294, 2000

Specific M1 and M3 Muscarinic Blockade

Specific M1 and M3 Muscarinic Blockade

• 1207 patients, double blind, randomized trial,

• qd tiotropium vs bid salmeterol vs placebo

Lung Volumes in Obstructive Disease

RV RV

TLC

FRC

Room to Breathe

Room to Breathe TLC

-800 -600 -400 -200 0 200 400 600

Chronic Obstructive Pulmonary

Disease

• Effective vs symptomatic therapies

• Spirometry is useful and under-utilized

• Clinical pathways are helpful and cost effective

• Role of surgery has been clarified

• Significance of frequent exacerbations

• Several new and promising avenues of therapy on the horizon

Take Home Points