Central Ohio Pulmonary Disease, Inc.

Michael L. Corriveau, MD, FACP, FCCP

COPD 2006

Definition of COPD
A disease state characterized by airflow limitation that is not fully reversible..

COPD

Normal Damage + Cholinergic tone

Epidemiology of COPD
12.5 million patients with chronic bronchitis
1.6 million patients with emphysema

8 million office visits and 1.5 million ER visits/year

$30 billion/year lost in healthcare/work loss

Fourth leading cause of death in the US

COPD Mortality Rate Increasing

Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998
3 .0 3.0 2 .5 2.5 2 .0 2.0 1 .5 1.5 1 .0 1.0 0 .5 0.5 0 .0 0

Coronary Heart Disease

Stroke

Other CVD

COPD

All Other Causes

59%

64%

35%

+163%

7%

1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
www.goldcopd.com

Youve come a long way, baby.

COPD Patients
Stereotypical pictures of COPD patients

31

Pink Puffer

Blue Bloater

Causes of COPD
Cigarette smoking Alpha-1 antitrypsin deficiency Industrial causes

Alpha 1 Antitrypsin Deficiency

2 3% of patients with emphysema have AAT deficiency 40,000 60,000 Americans have AAT deficiency Cigarette smoking increases the likelihood of symptomatic disease Onset of symptoms earlier than non-AAT deficient patients (mean age at presentation = 46 years) CXR often shows more prominent bullae in the bases

Diagnosis of COPD
History (dyspnea, cough, wheezing)

Spirometry

Value of Spirometry in COPD

Early, accurate diagnosis More sensitive than peak flow or CXR Document change in lung function over time Having a number may benefit the patient Helpful in stratifying the degree of disease

Spirometry in COPD
Normal FEV1 > 80% of predicted value Predicted value varies with age, height and sex Normal FEV1% > 70% Consider spirometry in past and present smokers over age 45, and patients with chronic cough, dyspnea or wheezing

Smoking Cessation and Reduced Decline in FEV1

100

80

60

Symptoms

Quit age 45 Age 55

FEV1 (%)
40 20 Disability

Death

0 20 30 40 50 60 70 80 90

Age (years)
Fletcher C, Peto R. Br Med J. 1977;1:1645-1648.
32

Lung Volumes in Obstructive Disease

TLC IC TLC
VT

Volume

FRC IC
VT

FRC RV

RV

Normal

COPD

Causes of Dyspnea in COPD

narrowed airways (bronchospasm, increased compliance airway secretions, airway thickening, increased cholinergic tone)

hyperinflation

breathing at high volumes

diaphragm flattening

DYSPNEA

Dyspnea

Inactivity

Reduced activity capacity Deconditioning

Management of COPD
Smoking cessation
Pulmonary rehabilitation

Pharmacologic
Supplemental oxygen

Non-invasive ventilation
Surgical remedies

Smoking Cessation Societal Interventions

Restriction of minors access to tobacco products

Restriction of smoking in public places

Restriction on advertisements

Increasing prices through taxation

Smoking Cessation Physician Interventions

Ask about tobacco use at every visit Advise all smokers to quit Assess smokers readiness to quit Assist the patient in quitting Arrange follow up visit

Management of COPD
Smoking cessation
Pulmonary rehabilitation

Pharmacologic
Supplemental oxygen

Non-invasive ventilation
Surgical remedies

Pulmonary Rehabilitation
Pulmonary rehabilitation is a multidisciplinary service for patients with pulmonary disease and their families, provided by an interdisciplinary team of specialists, with the goal of achieving and maintaining the individuals maximum level of independence and functioning in the community.

Components of Pulmonary Rehabilitation

Education Exercise Psychosocial support

Benefits of Pulmonary Rehabilitation

Improved activity capacity Improved quality of life Decrease in hospitalization Return to work

Management of COPD
Smoking cessation
Pulmonary rehabilitation

Pharmacologic
Supplemental oxygen

Non-invasive ventilation
Surgical remedies

Short-Acting Bronchodilators: Albuterol

Stimulates 2-receptors on airway smooth muscle Onset of effect: 1-3 minutes Duration of action: 4-6 hrs Reliever/rescue medication: PRN dosing 2:1 Selectivity
Albuterol = 1,375:

Long-Acting Bronchodilators: Salmeterol

Stimulates 2-receptors on airway smooth muscle Onset of effect: 20-30 minutes Duration of action: 12+ hrs Maintenance medication: 1 inhalation b.i.d. 2:1 Selectivity
Albuterol = 1,375:1 Salmeterol = 85,000:1

Formoterol
Long-acting 2-agonist Dosage: 12 g b.i.d. via dry-powder inhaler Onset of action: 1-3 minutes Duration of action: dose-dependent (12hour duration with higher dose)

Bartow RA, Brogden RN. Drugs. 1998;55:303-322.

Theophylline
Bronchodilation Increase in central respiratory drive Increased cardiac output Increased muco-ciliary clearance Increased fatigue threshold of the diaphragm

Mucokinetic Agents
Guiafenesin SSKI Mucomyst P & PD

Advair now approved by the FDA for use in COPD with chronic bronchitis
Package insert recommendation for initial and follow-up dexa scan Package insert recommendation for periodic eye examinations

Cholinergic Transmission in the Airways by Acetylcholine (ACh)

Pre-ganglionic nerve pre-synaptic Parasympathetic ganglion Nicotinic transmission M1 receptors (facilitate)

Post-ganglionic nerve Pre-synaptic M2 receptors (inhibitory) Neuromuscular junction ACh Post-synaptic M3 receptors (facilitate)

Airway smooth muscle

Tiotropium: Muscarinic Receptor Subtype Selectivity

Dissociation half-life (hours)

M1
Ipratropium Tiotropium 0.11 14.60

M2
0.035 3.600

M3
0.26 34.70

Disse B et al. Life Sci 1999;64 (6/7):457-464

Tiotropium: Improvement in FEV1 Over 3 Months (vs Ipratropium)

Day 1 1.5 Day 8 Day 92

1.4

FEV1 (L)

1.3

1.2

Tiotropium (n=182) Ipratropium (n=93)

1.1 -60

-5

30

60

120

180

240

300

360

Time (minutes)
p<0.05 on all test days

peak and trough

Van Noord JA. Thorax 2000;55:28994

Medical Letter, May 24, 2004 tiotropium

Improved lung function

Decrease symptoms of COPD

Increases quality of life

Decreases number of exacerbations

an important advance in the treatment of COPD

GOLD Stages of COPD

Old 0: At Risk I: Mild IIA II: Moderate IIB III: Severe

New
Characteristics

0: At Risk
Chronic symptoms Exposures to risk factors Normal spirometry

I. Mild
FEV1/FVC<70% FEV1>80% With or without symptoms

II. Moderate
FEV1/FVC<70% 50%>FEV1<80% With or without symptoms

III. Severe
FEV1/FVC<70% 30%>FEV1<50% With or without symptoms

IV. Very severe

FEV1/FVC<70% FEV1<30% or presence of chronic respiratory failure or right heart failure

Avoidance of risk factor(s); influenza vaccination Add short-acting bronchodilator when needed Add regular treatment with one or more long-acting bronchodilators Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Add long-term oxygen if chronic respiratory failure Consider surgical treatments
NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease. April 2001 (Updated 2003).

LA Bronchodilators in COPD
Drugs lung symptoms exercise decrease function tolerance exacerbations ++ ++ +++ + + ++ ? +/+ ++

Salmeterol Formoterol Tiotropium

CHEST 2004; 125:249-259

GOLD Stage 0

prn short-acting bronchodilator tiotropium + SABA tiotropium + salmeterol or formoterol salmeterol or formoterol + SABA salmeterol or formoterol + tiotropium

II

III

IV CHEST 2004; 125:249-259

add inhaled corticosteroid

Choice of Long-Acting Bronchodilator in COPD

Efficacy Compliance Safety Cost

Alpha 1 Antitrypsin Deficiency Treatment

NIH National Registry showed improved survival and decreased rate of decline in patients receiving augmentation therapy AAT levels increased

Trough levels maintained above minimal threshhold

Weekly infusions of 60 mg/kg

Management of COPD
Smoking cessation
Pulmonary rehabilitation

Pharmacologic
Supplemental oxygen

Non-invasive ventilation
Surgical remedies

Indications for O2 Therapy

PaO2 55 mmHg or less PaO2 56 59 mmHg with complication, such as erythrocytosis or cor pulmonale SaO2 88% or less

Management of COPD
Smoking cessation
Pulmonary rehabilitation

Pharmacologic
Supplemental oxygen

Non-invasive ventilation
Surgical remedies

Noninvasive Ventilation
Stable outpatient management Acute exacerbation treated in hospital increases pH reduces PaCO2 reduces breathlessness 1st 4 hours of Rx decreases length of hospital stay reduces intubation rate

Management of COPD
Smoking cessation
Pulmonary rehabilitation

Pharmacologic
Supplemental oxygen

Non-invasive ventilation
Surgical remedies

Volume Reduction Surgery

A procedure in which 20-30% of the most diseased portions of the lung are removed

Reduces lung hyperinflation

Dilates bronchi by increased traction forces

Places diaphragm at better mechanical advantage

Volume Reduction Surgery Outcomes

Improved dyspnea index scores Improved elastic recoil of the lung Decreased residual volume and FRC Decreased PaCO2 Improved FEV1 Improved 6-minute walk distance

Lung Transplantation
Over 1500 lung transplants/year in the United States 4000 candidates awaiting transplant in the US late 2003 Provides significant improvement in both health-related and overall quality of life

Lung transplantation Inclusion Criteria

Life expectancy less than 3 years

Failure of medical therapy

Age less than 60 years

No extrapulmonary organ failures

Lung Transplantation Exclusion Criteria

Coronary artery disease Continuing substance abuse Inadequate psychosocial support Extreme cachexia or obesity Recent malignancy (<3 years) Long term, high dose corticosteroid use

Useful Informational Web Sites for COPD

www.goldcopd.com

www.ats/copd.com
www.nlhep.org