Chronic Obstructive Pulmonary Disease (COPD)

Caesar Antonio O. Ligo, M.D. Silliman University Medical School Dumaguete City, Philippines

COPD: Definition
COPD is a preventable and treatable disease
Characterized by airflow limitation
not fully reversible progressive associated with abnormal inflammatory response of the lungs to noxious particles or gases

Some significant extrapulmonary effects may contribute to its severity

NHLBI/WHO Global Initiative for COPD Workshop Report 2006

COPD: Definition
Some significant extrapulmonary effects may contribute to its severity
weight loss (cachexia) skeletal muscle dysfunction cardiovascular disease osteoporosis depression/fatigue cancer

Annals of the American Thoracic Society 2007. vol. 4, no. 7:522-525

COPD
Emphysema
Anatomically defined condition Destruction and enlargement of the lung alveoli

Chronic Bronchitis
Clinically defined condition Chronic cough and sputum production for 3 months for two successive years

Small Airways Disease

Airways less than 2 mm in diameter May be asymptomatic, but lung function is abnormal (FEF25-75% )

COPD
7th leading cause of death in the Philippines Affects 1.69 million Filipinos 2020: will rise from 6th to 3rd most common cause of death worldwide Prevalence: 13.5%*
Only 6.7% had chronic cough Only 2.9% had a doctor diagnosis of COPD
Philippine COPD Prevalence Study: Philippine College of Chest Physicians Council on COPD 2007

COPD: A growing epidemic & the only chronic illness with increasing mortality! 3.0
Proportion of 1965 death rate 2.5
2.0 1.5 +163% COPD

1.0
0.5

-7% all other causes -35% other cardiovascular disease -59% coronary heart disease -64% stroke 1998

Pauwels RA and Rabe KF, Lancet 2004;364: 613-620

0 1965

Underdiagnosis of COPD
Diagnosed COPD 2.4 - 7 million

Estimated Total COPD 16 million

56 - 85%
Undiagnosed/misdiagnosed

US estimates, Stang 2000

COPD: Risk Factors

Cigarette smoking 1964: Major factor for mortality from COPD Dose-response relationship between smoking and reduced pulmonary function (pack-years) >85% of COPD patients with smoking history 15% of smokers develop COPD Airway responsiveness Dutch hypothesis: Asthma and COPD are variations of the same disease, which is modulated by environmental and genetic factors British hypothesis: Asthma and COPD are fundamentally different diseases: Asthma as an allergic phenomenon, COPD from smoking-related inflammation and damage.

COPD: Risk Factors

Respiratory infections
childhood respiratory infections

Occupational exposures
coal mining, gold mining, cadmium exposure, cotton textile dust.

Ambient air pollution

urban vs. rural biogas fuel

Passive (Second-Hand) smoking exposure

COPD: Genetic Considerations

a1 antitrypsin deficiency
1-2% of COPD patients COPD early in onset Protease Inhibitor (PI) locus: encodes a1 antitrypsin
M allele: normal a1 antitrypsin levels S allele: slightly reduced a1 antitrypsin levels Z allele: markedly reduced a1 antitrypsin levels

COPD: Natural History

%FEV1 normal level at age 20 100
Normal

75 50

Early decline

Disability

25
Death

Respiratory Symptoms

Rapid decline

10

20

30

40

50

60

70

80

Age, year
Fletcher-Peto Curve. British Medical Journal 1977.

COPD: Natural History

85

Lung Function (FEV1) over time

Sustained Quitters 27 ml/year

FEV1 (% pred)

80
75 70 65 60 0

Intermittent quitters Continuing Smokers 60 ml/year

10

Years Follow-up
Anthonisen AJRCCM 2002

COPD: Pathophysiology
Persistent reduction in forced expiratory flow rates: most typical finding in COPD Other abnormalities:
Increased residual volume Increased residual volume/total lung capacity Non-uniform distribution of ventilation V/Q mismatching

COPD: Pathophysiology

Airflow obstruction (Airflow Limitation)

Measured by spirometry Reduced FEV1 (< 80% predicted) Reduced FEV1/FVC (< 70% predicted) Non-reversibility to bronchodilator challenge (< 15% improvement in FEV1 values)

Airflow during forced exhalation is the result of the balance between the elastic recoil of the lungs promoting flow and the resistance of the airways limiting flow.

COPD: Spirometry

COPD: Pathophysiology

Hyperinflation
Air-trapping, increased residual volume, residual volume/total lung capacity and total lung capacity Compensates for airway obstruction Flattened diaphragm
Decrease zone of apposition with chest wall Shortened muscle fibers Generation of greater tension Increased work of breathing by inspiratory muscles

COPD: Pathophysiology

Gas exchange
Non-uniform ventilation V/Q mismatching
accounts for hypoxemia in COPD

Minimal shunting

FEV1 < 50% predicted: PaO2 decreases FEV1 < 25% predicted: PaCO2 increases, development of cor pulmonale and right heart failure (pulmonary hypertension)

COPD: Pathophysiology
COPD
Hypoxemia
Tachypnea Airflow obstruction
Ventilatory requirement

Exacerbations

Air trapping Anxiety

Hyperinflation

Deconditioning

Dyspnea

Activity limitation Patientcentered outcomes

Poor health-related quality of life

COPD: Pathology
Large airway
goblet cells increase in number and extent mucous glands enlarge squamous metaplasia occurs
carcinogenesis mucociliary clearance

smooth muscle hypertrophy bronchial hyperreactivity neutrophil influx

COPD: Pathology
Small Airways
Major site of increased airway resistance Cellular changes:
Goblet cell metaplasia Clara cells replaced with mucus-secreting mononuclear inflammatory cells

Smooth muscle hypertrophy Fibrosis of airway walls Proteolytic destruction of elastic fibers Loss of bronchiolar attachments

COPD: Pathology
Lung Parenchyma
Destruction of gas-exchanging airspaces Perforation of walls Obliteration with coalescence of small air spaces into abnormal and much larger spaces Accumulation of macrophages CD8+ cells Types of emphysema:
Centriacinar associated with cigarette smoking, located mostly in the upper lobes and superior segments of the lower lobes (focal) Panacinar associated with a1AT deficiency, located mostly in the lower lobes.

COPD: Pathology
Centriacinar associated with cigarette smoking, located mostly in the upper lobes and superior segments of the lower lobes (focal) Panacinar associated with a1AT deficiency, located mostly in the lower lobes.

COPD: Pathology

COPD: Pathology

COPD: Pathology

COPD: Pathology

COPD: Pathogenesis

Inflammatory cell recruitment

MMP
Serine proteinases

MMP
Cysteine proteinases

Neutrophil

Macrophage
Proteinase inhibitors

ECM degradation; Lung destruction

Emphysema

Repair

COPD: Clinical Presentation

3 most common symptoms
Cough Sputum production Exertional dyspnea

Physical findings
Prolonged expiratory phase Wheezing Signs of hyperinflation Signs of right heart failure

The Changing Faces of COPD

Rick Hodder University of Ottawa Canada

The Changing Faces of COPD

Rick Hodder University of Ottawa Canada

COPD: Laboratory Findings

Airflow Obstruction: Hallmark of COPD Low FEV1 and FEV1/FVC Lung volumes increase (TLC, FRC, RV) DLCO reduced (emphysema) ABGs Elevated hematocrit Right ventricular hypertrophy on EKG Chest x-ray/CT scan Serum level a1AT

When Spirometry Is Unavailable

Spirometry - gold standard for diagnosis & assessment of COPD because most reproducible, standardized & objective way of measuring airflow limitation.

Where there is no access to spirometry, the diagnosis of COPD could be suspected on the basis of history, symptoms and physical signs.
The Asia Pacific COPD Roundtable Group. Respirology (2005) 10, 917

Chest x-ray

Chest x-ray

Chest CT Scan

EKG: Right Ventricular Hypertrophy

RAD > 90o, RV1 + SV5 = 10mm, R/S V5 or V6 < 1.

Diagnosis of COPD
If > 40 yrs. old

SYMPTOMS cough sputum shortness of breath

EXPOSURE TO RISK FACTORS tobacco occupation indoor/outdoor pollution

SPIROMETRY
A post-bronchodilator FEV1/FVC < 0.70 confirms the presence of airflow limitation that is not fully reversible

Differential Diagnosis: COPD and Asthma

COPD
Onset in mid-life Symptoms slowly progressive Long smoking history Dyspnea during exercise Largely irreversible airflow limitation

Asthma
Onset early in life (childhood) Symptoms vary from day to day Symptoms at night/early morning Allergy, rhinitis, eczema Family history of asthma Largely reversible airflow limitation

COPD: Treatment
Influence natural history of COPD (improve mortality rate)
Smoking cessation Oxygen therapy in chronic hypoxemia

Other therapies
Improve symptoms Decrease severity and frequency of exacerbations

Surgery
LVRS Lung transplant

Procaterol

Indacaterol
Roflumilast

Mechanisms of Bronchodilator Benefit in COPD

Bronchodilation

Reduced hyperinflation

Reduced breathlessness with exertion

Increased activity, exercise endurance

Reduced fatigue

Improved sleep quality

Fewer COPD exacerbations

Reduced breathlessness Improved quality of life

Asthma Therapy is Different from COPD Therapy

Asthma
(Sensitizing agents)

COPD
(Noxious agents)

Asthmatic inflammation CD4+ T-lymphocytes Eosinophils

COPD inflammation CD8+ T-lymphocytes Macrophages, neutrophils

Often Completely Reversible (Corticosteroid-sensitive)

Airflow Obstruction

Frequently Not fully reversible (Corticosteroid-insensitive)

2006 Therapy at Each Stage of COPD

IV: Very Severe

III: Severe
I: Mild FEV1/FVC < 70%

FEV1/FVC < 70% FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure

II: Moderate
FEV1/FVC < 70%

FEV1/FVC < 70%

FEV1 > 80% predicted

50% < FEV1 < 80%

predicted

30% < FEV1 < 50% predicted

Active reduction 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

Thank you.

Even for just listening.