Chroni c O bstruct ive Pul monar y Disease

Dr Imad Salah Ahmed Hassan MD, MRCP,

MSc
COPD
2007
Definition of COPD

“A disease state characterized by

airflow limitation that is not

fully reversible..”
 COPD

Normal

Damage +
Cholinergic tone
 How common is COPD?
• About 13.9% of the U.S. adult population (25+
years) have been diagnosed with COPD*

– An estimated 15-19% of COPD cases are work-

related**

• 24 million other adults have evidence of troubled

breathing, indicating COPD is under diagnosed by
up to 60%***
*Braman, S. Update on the ATS Guidelines for COPD. Medscape Pulmonary Medicine. 2005;9(1):1.
**CDC programs in Brief– Workplace Health and Safety-Work-related Lung Diseases.
www.cdc.gov/programs/workpl18.htm
***COPD Fact Sheet. Oct 2003. www/lungusa.org
 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
Coronary Stroke Other CVD COPD All Other
2 .5
2.5 Heart Causes
Disease
2.0
2 .0

1.5
1 .5

1.0
1 .0

0 .5
0.5
–59% –64% –35% +163% –7%
0 .0 0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998

www.goldcopd.com
 New Definition
• Chronic obstructive pulmonary disease
(COPD) is a preventable and treatable disease
state characterised by airflow limitation that is
not fully reversible.
• The airflow limitation is usually progressive
and is associated with an abnormal
inflammatory response of the lungs to noxious
particles or gases, primarily caused by cigarette
smoking.
• Although COPD affects the lungs, it also
produces significant systemic consequences.
• ATS/ERS 2004
 Two Major Causes of COPD
• Chronic Bronchitis is characterized by
– Chronic inflammation and excess mucus
production
– Presence of chronic productive cough
*Source: Braman, S. Update on the ATS Guidelines for COPD. Medscape Pulmonary Medicine. 2005;9(1):1.
Emphysema is characterized by
Damage to the small, sac-like units of the lung that deliver
oxygen into the lung and remove the carbon dioxide
*Source: Braman, S. Update on the ATS Guidelines for COPD. Medscape Pulmonary Medicine.
2005;9(1):1.
 COPD Patients
Stereotypical pictures of COPD patients

31

Pink Puffer Blue Bloater

 Primary Symptoms
• Chronic Bronchitis
– Chronic cough
– Shortness of breath
– Increased mucus
– Frequent clearing of throat

• Emphysema
– Chronic cough
– Shortness of breath
– Limited activity level
Causes of COPD

Cigarette smoking

Industrial causes

Alpha-1 antitrypsin deficiency

 What can cause COPD?
• Smoking is the primary risk factor
– Long-term smoking is responsible for 80-90 %
of cases
• Smoker, compared to non-smoker, is 10 times
more likely to die of COPD

• Prolonged exposures to harmful particles

and gases from:
– Second-hand smoke,
– Industrial smoke,
– Chemical gases, vapors, mists & fumes
– Dusts from grains, minerals & other materials
 COPD in the Mining Industry
Studies show:
• An increased number of cases of chronic bronchitis
in coal & gold miners

• Long-term exposures to low levels of silica may lead

to the development of chronic bronchitis &
emphysema

• Chronic exposure to coal dust, particularly high

levels, may lead to severe respiratory impairment
(emphysema)
*Hnizdo & Vallyathan Chronic obstructive pulmonary disease due to occupational exposure to silica dust: a
review of epidemiological and pathological evidence. Occup Environ Med 2003;60:237-243.
 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

 Other Risk Factors for COPD

• History of childhood respiratory

infections

• Genetic makeup

• Increasing age

• Smoke from home cooking and heating fuel

 Pathophysiology of COPD
• Increased mucus production and reduced
mucociliary clearance - cough and
sputum production
• Loss of elastic recoil - airway collapse
• Increase smooth muscle tone
• Pulmonary hyperinflation
• Gas exchange abnormalities - hypoxemia
and/or hypercapnia
Diagnosis of COPD

History (dyspnea, cough, wheezing)

Physical Examination
Radiology
Spirometry
 Key Indicators for COPD Diagnosis
Chronic cough
Chronic sputum production
Dyspnoea that is
Acute bronchitis
History of exposure to risk
factors
Present intermittently or every day
often present throughout the day;
seldom only nocturnal
Present for many years, worst in
winters. Initially mucoid –
becomes purulent with
exacerbation
Progressive (worsens over time)
Persistent (present every day)
Worse on exercise
Worse during respiratory infections
Repeated episodes
Tobacco smoke
occupational dusts and chemical
smoke from home cooking and
heating fuel
Causes of Dyspnea in COPD
narrowed airways (bronchospasm, increased compliance
airway secretions, airway thickening, increased cholinergic tone)

hyperinflation

breathing at diaphragm DYSPNEA

high volumes flattening
 Physical signs

• Large barrel shaped chest

(hyperinflation)
• Prominent accessory
respiratory muscles in neck
and use of accessory
muscle in respiration
• Low, flat diaphragm
• Diminished breath sound
 Dyspnea

Reduced activity
Inactivity
capacity

Deconditioning
 Spirometry

• Diagnosis
• Assessing severity
• Assessing prognosis
• Monitoring
progression
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
• FEV1 – Forced expired volume in the first
second
• FVC – Total volume of air that can be
exhaled from maximal inhalation to
maximal exhalation
• FEV1/FVC% - The ratio of FEV1 to FVC,
expressed as a percentage.
 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
 COPD classification based on spirometry
GOLD 2003
Severity Postbronchodilator Postbronchodilator
FEV1/FVC FEV1% predicted
At risk >0.7 >80
Mild COPD <0.7 >80
Moderate COPD <0.7 50-80

Severe COPD <0.7 30-50

Very severe <0.7 <30
COPD

SPIROMETRY is not to substitute for clinical judgment in the

evaluation of the severity of disease in individual patients.
Lung Volumes in Obstructive Disease

TLC
IC
TLC VT
FRC
Volume

IC

VT
FRC
RV

RV

Normal COPD
 How is COPD Treated?
• COPD can be managed, but not cured

• Treatment is different for each individual and is

based on severity of the symptoms
• Early diagnosis and treatment can
– Slow progress of the disease
– Relieve symptoms
– Improve an individual’s ability to stay active
– Prevent and treat complications
– Improve quality of life
Management of COPD
Smoking cessation

Pulmonary rehabilitation

Pharmacologic

Supplemental oxygen

Non-invasive ventilation

Surgical remedies
 Smoking Cessation and Reduced
Decline in FEV1
100

80

60 Symptoms Quit age 45

FEV1
(%)
40 Disability Age 55

20 Death

0
20 30 40 50 60 70 80 90
Age (years)
Fletcher C, Peto R. Br Med J. 1977;1:1645-1648.
32
 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
individual’s 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
“Bronchodilator medications are central
to the symptomatic management of
COPD”

GOLD Report 2003

 “All guidelines recommend inhaled
bronchodilator as first line therapy. The
ATS suggest initial therapy with an
anticholinergic drug if regular therapy is
needed”
Chest 2000; 117: 23S-28S
“Patients with moderate to severe symptoms of
COPD require combination of bronchodilators”

“Combining bronchodilators with different

mechanisms and durations of actions may
increase the degree of bronchodilation for
equivalent or lesser side effects’’

GOLD Report 2003

Pharmacotherapy for Stable COPD
Bronchodilators Steroids
• Short-acting β2- • Oral – Prednisolone
agonist – Salbutamol • Inhaled - Fluticasone,
• Long-acting β2- Budesonide

agonist - Salmeterol and

Formoterol
• Anticholinergics –
Ipratropium, Tiiotropium
• Methylxanthines -
Theophylline
 What medications are used to
treat symptoms?
• Bronchodilators –
• Relaxes muscles around airways

• Steroids
• Reduces inflammation

• Oxygen therapy
• Helps with shortness of breath
 What medications are used
to prevent complications?
• Annual flu vaccine
– Reduces risk of flu and its complications

• Pneumonia vaccine
– Reduces risk of common cause of pneumonia
 Short-Acting Bronchodilators:
Salbutamol/Albuterol
• Stimulates β2-receptors on airway smooth
muscle
• Onset of effect: 1-3 minutes
• Duration of action: 4-6 hrs
• Reliever/rescue medication: PRN dosing
∀ β2:β1 Selectivity
– Albuterol = 1,375:
 Long-Acting Bronchodilators:
Salmeterol
• Stimulates β2-receptors on airway smooth
muscle
• Onset of effect: 20-30 minutes
• Duration of action: 12+ hrs
• Maintenance medication: 1 inhalation b.i.d.
∀ β2:β1 Selectivity
– Albuterol = 1,375:1
– Salmeterol = 85,000:1
 Formoterol
• Long-acting β2-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
Seretide 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
Nicotinic transmission
Parasympathetic
ganglion M1 receptors (facilitate)

Post-ganglionic
nerve

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

Airway smooth muscle

 Tiotropium: Muscarinic Receptor Subtype
Selectivity

Dissociation half-life (hours)

M1 M2 M3

Ipratropium 0.11 0.035 0.26

Tiotropium 14.60 3.600 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 Day 8 Day 92

1.5

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;55:289–94
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 II: Moderate III: Severe
IIA IIB
New 0: At Risk I. Mild II. Moderate III. Severe IV. Very severe
Characteristics •Chronic symptoms FEV1/FVC<70%
• FEV1/FVC<70%
• •FEV1/FVC<70% •FEV1/FVC<70%
•Exposures to risk
FEV1>80%
• 50%>FEV1<80%
• •30%>FEV1<50% •FEV1<30% or
factors presence of
With or without
• With or without
• •With or without
•Normal spirometry
symptoms symptoms symptoms 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).
 Management based on GOLD

Post-bronchodilator
FEV1
(% predicted)
 LA Bronchodilators in COPD
Drugs lung symptoms exercise decrease
function tolerance exacerbations

Salmeterol ++ + - +/-

Formoterol ++ + - +

Tiotropium +++ ++ ? ++

CHEST 2004; 125:249-259

 GOLD Stage

I prn short-acting bronchodilator

tiotropium salmeterol or
II + formoterol +
SABA SABA
tiotropium + salmeterol or
III salmeterol or formoterol +
formoterol tiotropium

IV
add inhaled corticosteroid

CHEST 2004; 125:249-259

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

New Developments

Statins

ACE Inhibitors

Sildenafil

Osteoporosis
Useful Informational Web Sites
for COPD

www.goldcopd.com

www.ats/copd.com

www.nlhep.org