DR PREMKUMAR M.

D ASSISTANT PROFESSOR DEPARTMENT OF MEDICINE

The Problem Pathogenesis Key Clinical Concepts COPD Exacerbations New Horizons

Outline

Life Prolonging vs. Symptomatic Therapy Spirometry - The Sixth Vital Sign Use of clinical practice guidelines

COPD - Pathogenesis
Tobacco Smoke
Host factors

Chronic Inflammation*
Anti-oxidants Anti-proteinases

Oxidative Stress
Repair Mechanisms

Proteinases

Emphysema Chronic Bronchitis

*CD8+ T-lymphocytes Macrophages Neutrophils IL-8 and TNF

 Life

prolonging vs. symptomatic therapies Spirometry - the 6th vital sign Use of clinical practice guidelines

Prolong Life

Symptomatic

Smoking Cessation Oxygen Reduce exacerbations Pulmonary Rehabilitation LVRS (selected patients) Lung Transplantation

MDI Therapy

Theophylline Corticosteroids (inhaled or oral) Combination Preparations

SABA and anticholinergic LABA and corticosteroids

SA beta-2 agonists LA beta-2 agonists SA and LA Anticholinergics

Spirometry - The Sixth Vital Sign Symptoms or >10 pack year smoker Indications:
0 1 2 FEV1 FVC
5.200 3.900

FEV1/ FVC
80 % 60 %

Normal COPD
FEV1

4.150 2.350

Liter

COPD
4 5 1 2 FEV1 FVC

Normal
3 4

FVC 5 6 Seconds

GOLD Workshop Report

Four Components of COPD Management - www.goldcopd.com

1. Assess and monitor disease 2. Reduce risk factors 3. Manage stable COPD

Education Pharmacologic Non-pharmacologic

4. Manage exacerbations

Management of COPD Stage 0: At Risk

Characteristics Treatment Risk factors Chronic symptoms - cough - sputum No spirometric abnormalities Recommended Adjust risk factors Immunizations

Management of COPD Stage I: Mild COPD

Characteristics Treatment FEV1/FVC < 70 % FEV1 > 80 % predicted With or without symptoms Recommended

Short-acting
bronchodilator as needed

Management of COPD Stage II: Moderate COPD

Characteristics Treatment FEV1/FVC < 70% 50% < FEV1< 80% predicted With or without symptoms Recommended Treatment with one or more long-acting bronchodilators Rehabilitation

Management of COPD Stage III: Severe COPD

Characteristics Treatment FEV1/FVC < 70% 30% < FEV1 < 50% predicted With or without symptoms Recommended Treatment with one or more long-acting bronchodilators Rehabilitation Inhaled glucocorticosteroids if repeated exacerbations (>3/year)

Management of COPD Stage IV: Very Severe COPD

Characteristics Treatment FEV1/FVC < 70% FEV1 < 30% predicted or presence of respiratory failure or right heart failure Recommended
Treatment with one or more long-acting bronchodilators Inhaled glucocorticosteroids if repeated exacerbations (>3/year) Treatment of complications Rehabilitation Long-term oxygen therapy if respiratory failure Consider surgical options

Inhaled therapy (with spacer) preferred Long-acting preparations more convenient Combined preparations improve effectiveness and decrease risk of side effects
Ipratroprium-albuterol Fluticasone-salmeterol Budesonide-formoterol

MDI almost always as effective as nebulizers (in equal doses)

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

Giant Bullous Disease

Lung Volume Reduction Surgery*

Consider bullectomy if see normal lung compression

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 FEV1<25% predicted, younger patient 3-5 year mortality 55%
*NETT Research Group. N Eng J Med 348:2059, 2003

Lung Transplantation

COPD Exacerbation
Definition Elements Severity Severe - all 3 elements Moderate - 2 elements Mild - 1 element plus:

Worsening dyspnea Increased sputum purulence Increase in sputum volume

URI in past 5 days Fever without apparent cause Increased wheezing or cough Increase (+20%) of respiratory rate or heart rate

Modified from Anthonisen et al. Ann Int Med 106:196, 1987

COPD Exacerbation
Pathophysiology - Current Hypothesis Chronic Inflammation

Viral Infection
25%

Unknown
20%

Bacterial Infection
50%

Acute Inflammation

Air Pollution
5%

exaberation

Therapy of COPD Exacerbation

Variable
Diagnostic

ACCP-ACP
CXR for admissions

GOLD
CXR, EKG, ABG, sputum culture, lytes, cbc B2 agonist, add ipratroprium. Yes methylxanthine Not discussed

Bronchodilato Ipratroprium, add B2 rs agonist. No methylxanthine Delivery system Antibiotics None preferred

Yes, in selected (severe). Yes, with purulence, Duration unclear Rx local sensitivities
Ann Int Med 134:595, 2001 http:/www.goldcopd.com

Therapy of COPD Exacerbation

Variable ACCP-ACP
Steroids Yes, for up to two weeks Yes

GOLD
Yes, oral or IV for 10-14 days

Oxygen

Yes - target PaO2 60 torr or Sat of 90% with ABG check Maybe - for atelectasis or sputum control

Chest PT

No

Mucokineti No cs
Ann Int Med 134:595, 2001

Not discussed

http:/www.goldcopd.com

Therapy of COPD Exacerbation

Guidelines

Variable Mechanical Ventilation

ACCP-ACP
Yes - use NIPPV in severe exacerbation

GOLD
Yes if 2 of: Severe dyspnea, access. muscle or paradox, pH <7.35 and PCO2 >45, RR>25 LMWH, fluids, diet
http:/www.goldcopd.com

Other
Ann Int Med 134:595, 2001

Newer anti-inflammatory agents

Cilomilast Rofumilast Piklanilast

Matrix metalloproteinase inhibitors Specific phosphodiesterase (PDE4) inhibitors

Anabolic steroids Repair agents Long-acting anti-muscarinic agents

tiotropium Retinoic acid