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 workrelated** • 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 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

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 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

Chronic sputum production

Dyspnoea that is

Acute bronchitis History of exposure to risk factors

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

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

Inactivity

Reduced activity 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 At risk Mild COPD Moderate COPD Severe COPD Very severe COPD Postbronchodilator FEV1/FVC >0.7 <0.7 <0.7 <0.7 <0.7 Postbronchodilator FEV1% predicted >80 >80 50-80 30-50 <30

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 Volume IC
VT VT

FRC

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 40 20 0 20 30 40 50 60 70 80 90

FEV1 (%)

Symptoms Disability Death

Quit age 45 Age 55

Age (years)
Fletcher C, Peto R. Br Med J. 1977;1:1645-1648.
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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 • Short-acting β2agonist – Salbutamol • Long-acting β2agonist - Salmeterol and
Formoterol

Steroids
• Oral – Prednisolone • Inhaled - Fluticasone,
Budesonide

• Anticholinergics – • Methylxanthines Theophylline

Ipratropium, Tiiotropium

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 (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

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 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;55:289–94

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 New
Characteristics

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

I: Mild IIA I. Mild
• • •

II: Moderate IIB III. Severe
• • •

III: Severe IV. Very severe
• •

II. Moderate
• • •

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 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 Salmeterol Formoterol Tiotropium lung symptoms exercise decrease function tolerance exacerbations ++ ++ +++ + + ++ ? +/+ ++

CHEST 2004; 125:249-259

GOLD Stage 0

I

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

II

III 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