Central Ohio Pulmonary Disease, Inc.

Michael L. Corriveau, MD, FACP, FCCP

COPD2006

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

0

0.5

1.0

1.5

2.0

2.5

3.0

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

0 .0

0 .5

1 .0

1 .5

2 .0

2 .5

3 .0

1965 1965 -- 19981998 1965 1965 -- 19981998 1965 1965 -- 19981998 1965 - 1998 1965 1965 -- 19981998

––59%59% ––64%64% ––35%35% +163%+163% ––7%7%

CoronaryCoronaryHeartHeart

DiseaseDisease

StrokeStroke Other CVDOther CVD COPD All OtherAll OtherCausesCauses

www.goldcopd.com

“You’ve come a long way,

baby.”

COPD Patients

Stereotypical pictures of COPD patients

31

Blue BloaterBlue BloaterPink PufferPink Puffer

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 smokersover age 45, and patients with chroniccough, dyspnea or wheezing

32

0

20

40

60

80

100

20 30 40 50 60 70 80 90

FEV1

(%)

Age (years)

Death

Disability

Symptoms Quit age 45

Age 55

Fletcher C, Peto R. Br Med J. 1977;1:1645-1648.

Smoking Cessation and Reduced Decline in FEV1

Lung Volumes in Obstructive DiseaseLung Volumes in Obstructive Disease

VT

VT

NormalNormal COPDCOPD

RVRV

RVRV

TLCTLC

FRCFRC

ICIC

ICIC

TLCTLC

FRCFRC

Vo

lum

eV

olu

me

Causes of Dyspnea in COPDnarrowed airways (bronchospasm, increased compliance

airway secretions, airway thickening, increased cholinergic tone)

hyperinflation

breathing athigh volumes

diaphragmflattening

DYSPNEA

Dyspnea

Reduced activitycapacity

Deconditioning

Inactivity

Management of COPD

Smoking cessation

Pulmonary rehabilitation

Pharmacologic

Supplemental oxygen

Non-invasive ventilation

Surgical remedies

Smoking CessationSocietal Interventions

Restriction of minors’ access to tobacco products

Restriction of smoking in public places

Restriction on advertisements

Increasing prices through taxation

Smoking CessationPhysician 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 servicefor patients with pulmonary disease and their families,provided by an interdisciplinary team of specialists,with the goal of achieving and maintaining theindividual’s maximum level of independence and functioningin 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 µg b.i.d. via dry-powder inhaler

• Onset of action: 1-3 minutes

• Duration of action: dose-dependent (12-hour 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 inCOPD with chronic bronchitis

Package insert recommendation for initialand follow-up dexa scan

Package insert recommendation for periodiceye examinations

Pre-ganglionic nervepre-synaptic

Parasympatheticganglion

Post-ganglionicnerve

ACh

Airway smooth muscle

Nicotinic transmission

M1 receptors (facilitate)

Pre-synapticM2 receptors (inhibitory)

Post-synapticM3 receptors (facilitate)

Cholinergic Cholinergic Transmission in the Airways Transmission in the Airways by by Acetylcholine Acetylcholine ((AChACh))

Neuromuscularjunction

Tiotropium: Muscarinic Receptor Subtype Tiotropium: Muscarinic Receptor Subtype SelectivitySelectivity

Ipratropium 0.11 0.035 0.26

TiotropiumTiotropium 14.6014.60 3.6003.600 34.7034.70

Dissociation half-life (hours)M1 M2 M3

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

Van Noord JA. Thorax 2000;55:289–94

Tiotropium: Improvement in FEVTiotropium: Improvement in FEV11 Over 3 Over 3 Months (Months (vsvs Ipratropium)Ipratropium)

FE

V1

(L)

1.1

1.2

1.3

1.4

1.5

Time (minutes)

-60 -5 30 60 120 180

Day 1 Day 8 Day 92

240 300 360

Tiotropium (n=182)

Ipratropium (n=93)

p<0.05 on all test days peak and trough

Medical Letter, May 24, 2004tiotropium

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

NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease. April 2001 (Updated 2003).

Old 0: At Risk I: Mild II: ModerateIIA IIB

III: Severe

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

Characteristics •Chronic symptoms•Exposures 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 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 bronchodilatorsAdd rehabilitation

Add inhaled glucocorticosteroids if repeated exacerbations

Add long-term oxygen if chronic respiratory failureConsider surgical treatments

LA Bronchodilators in COPD

CHEST 2004; 125:249-259

Drugs lung symptoms exercise decrease function tolerance exacerbations

Salmeterol ++ + - +/-

Formoterol ++ + - +

Tiotropium +++ ++ ? ++

0

tiotropium+

SABA

add inhaled corticosteroid

salmeterol orformoterol +tiotropium

IV

III

II

I prn short-acting bronchodilator

tiotropium +salmeterol orformoterol

salmeterol orformoterol +

SABA

GOLD Stage

CHEST 2004; 125:249-259

Choice of Long-Acting Bronchodilator in COPD

Efficacy

Compliance

Safety

Cost

Alpha 1 Antitrypsin DeficiencyTreatment

NIH National Registry showed improved survival and decreasedrate 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 hospitalincreases pHreduces PaCO2reduces breathlessness 1st 4 hours of Rxdecreases length of hospital stayreduces 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 diseasedportions of the lung are removed

Reduces lung hyperinflation

Dilates bronchi by increased traction forces

Places diaphragm at better mechanical advantage

Volume Reduction SurgeryOutcomes

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-relatedand overall quality of life

Lung transplantationInclusion Criteria

Life expectancy less than 3 years

Failure of medical therapy

Age less than 60 years

No extrapulmonary organ failures

Lung TransplantationExclusion 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 Sitesfor COPD

www.goldcopd.com

www.ats/copd.com

www.nlhep.org