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MBBS project, Zhongshan Hospital
Chronic Obstructive Pulmonary Disease
Jing ZHANG (张静), MD, PhD
Department of Pulmonary Medicine Zhongshan Hospital
Fudan University
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MBBS project, Zhongshan Hospital
OUTLINE
• Definition of COPD
• Epidemiology
• Etiology and risk factors
• Pathophysiology mechanisms
• Clinical manifestation
• How to make the diagnosis and assess the severity of disease
• Management of stable COPD and AECOPD
• Prevention
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MBBS project, Zhongshan Hospital
GOLD
• Global Initiative for Chronic Obstructive Lung Disease
• Global Strategy for Diagnosis, Management and Prevention of COPD
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MBBS project, Zhongshan Hospital
Definition
• COPD is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients.
• Its pulmonary component is characterized by airflow limitation that is not fully reversible.
• The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.
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Epidemiology
• COPD is a leading cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing.
1990
1
2
6 3
10
9
7
14
Ischemic heart disease
Cerebrovascular disease
COPD Lower respiratory infection
Lung cancer
Road traffic accidents
Tuberculosis
Stomach cancer
2020
1
2
3 4
5
6
7
8
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MBBS project, Zhongshan Hospital
The mortality of COPD is increasing!
0
0.5
1.0
1.5
2.0
2.5
3.0
Proportion of 1965 Rate
0.0
0.5
1.0
1.5
2.0
2.5
3.0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
–59% –64% –35% +163% –7%
Coronary Heart
Disease
Stroke Other CVD COPD All Other Causes
Source: NHLBI/NIH/DHHS
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MBBS project, Zhongshan Hospital
Prevalence of COPD in China --BOLD study
• Overall prevalence: 8.2%
• > 43 million
Nanshan Zhong et al. Am J Respir Crit Care Med 2007, 176: 753-760
12.1
4.9
7.8
12.7
5.4
8.8
12.4
5.1
8.2
0
2
4
6
8
10
12
14
Male Female Total
pre
va
len
ce
of
CO
PD
(%)
Urban Rural Total
*
#
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MBBS project, Zhongshan Hospital
In China
• COPD
—the third leading cause of death in rural and the fourth in urban in 2008
—the second leading cause of DALYs lost in 2001
• Incidence and mortality is increasing
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WORLD COPD DAY November 14, 2007
Raising COPD Awareness Worldwide
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Risk factors for COPD
Nutrition
Infections
Socio-economic
status
Aging Populations
Genetic Susceptibility
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Large airway
Mucous gland enlargement
Goblet cell hyperplasia
Impaired muco-ciliary clearance
Cough Sputum
Small airway
Excess mucous & edema
Fibrosis
Destruction of elastic fibers
CHRONIC INFLAMMATION in COPD
Small airway narrowing & collapse
Airflow obstruction
Air trapping
Hyper-inflation
Alveolar space
ECM destruction
Emphysema
Progressive Dyspnea
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COPD and Co-Morbidities —Spilled Inflammation
COPD patients are at increased risk for: • Myocardial infarction, angina
• Osteoporosis
• Respiratory infection
• Depression
• Diabetes
• Lung cancer
COPD has significant extrapulmonary (systemic)
effects including: • Weight loss
• Nutritional abnormalities
• Skeletal muscle dysfunction
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Physical findings
• In early stages of COPD, patients may have an entirely normal physical examination
• Increased forced expiratory time
• Expiratory wheezing
• Signs for emphysema--a barrel chest and enlarged lung volumes with poor diaphragmatic excursion
• Advanced stage--use of accessory muscles of respiration, cyanosis, systemic wasting (weight loss)
• Signs of overt right heart failure--patients with advanced disease
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A group of heterogeneity diseases
"blue bloaters" chronic bronchitis fluid retention cyanosis
"pink puffers― lack of cyanosis use of accessory muscles pursed-lip breathing a dramatic decrease in breath sounds
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Forced expiratory flow rates ↓
FEV1 ↓
FEV1/FVC ↓
Residual volume ↑
RV/TLC ↑
Airflow obstruction
Air trapping
Hyper-inflation
TLC ↑
• Non-uniform ventilation • V/Q mismatching • Destruction of gas-exchanging airspace and
decreased diffusing capacity
PaO2 ↓ +/- PaCO2 ↑
• Pulmonary hypertension • Cor pulmonale • Right ventricular failure
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Lab investigations
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Spirometry
• Objective indices for airflow limitation
• Reproducibility
• Important for diagnosis, assessment of the
severity of the disease, disease progression
monitoring, assessment of prognosis, and
response to therapy
• Indices for airflow obstruction:
(1)FEV1% predicted
(2)FEV1/FVC
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Spirometry (Cont’d)
• FEV1/FVC%
— sensitive, capable of detection for mild airflow
obstruction
• FEV1% predicted
— good indicator for moderate-severe airflow obstruction
• Airflow obstruction is confirmed by post-
bronchodilator FEV1/FVC<0.7
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Chest X-ray
• Objective
— To rule out alternative diagnosis such as tuberculosis
and fibrosis, and identify complications
• In early stage of COPD
— Usually no abnormalities
• In late stage of COPD
— Always non-specific
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Advanced Emphysema
• Large volume lungs
• Thin heart shadow
• Flattened hemidiaphragms
• Attenuated vascular markings in the upper lobe
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Emphysema with bullae
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Cor pulmonale
• Bilateral
enlarged
pulmonary
arteries
• Cardiomegaly
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Chest computed tomography (CT)
Not routinely recommended
However,
• HRCT scanning is sensitive and specific for the detection of emphysema and bullae.
• Necessary before surgical procedure such as lung volume reduction
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Lung density in CT scan
• Lung density is related to emphysema
• To detect the size and distribution of bullae
• To quantitate emphysema: Emphysema index
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• To analyse:
—Thickness of airway wall
—Diameter of airway
• Part of or even the entire airway
Evaluating abnormality of airway by CT scan
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Arterial blood gas measurement
• Perform in patients with FEV1<50% predicted or
with clinical signs suggestive of respiratory
failure or right heart failure
• Mild or moderate hypoxemia →hypoxemia get
worse with hypercapnia
• Criteria for respiratory failure:
— PaO2<60 mmHg with or without PaCO2>50 mmHg
while breathing air at sea level
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Diagnosis and DDx
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Assess and Monitor COPD
• A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors for the disease
• The diagnosis should be confirmed by spirometry. A post-bronchodilator FEV1/FVC < 0.70 confirms the presence of airflow limitation that is not fully reversible
• Comorbidities are common in COPD and should be actively identified
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SYMPTOMS
cough
sputum
shortness of breath
EXPOSURE TO RISK FACTORS
tobacco
occupation
indoor/outdoor pollution
SPIROMETRY
Diagnosis of COPD
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Diagnosis of COPD
Spirometry is the gold standard for COPD diagnosis
Reproducible, objective and can be standardized
—FEV1/FVC<0.7
—FEV1: post-bronchodilator value, which indicates irreversible airflow
—COPD is confirmed by post–bronchodilator FEV1/FVC < 0.7
—Must be interpreted with clinical history—risk factors, symptom, physical examination, lab reports, etc
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Differential Diagnosis: COPD and Asthma
COPD ASTHMA
• Onset in mid-life
• Symptoms slowly
progressive
• Long smoking history
• Dyspnea during exercise
• Largely irreversible
airflow limitation
• Onset early in life (often childhood)
• Symptoms vary from day to day
• Symptoms at night/early morning
• Allergy, rhinitis, and/or eczema also present
• Family history of asthma
• Largely reversible airflow limitation
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Classification of COPD Severity—GOLD 2009
Stage I: Mild FEV1/FVC < 0.70
FEV1 > 80% predicted Stage II: Moderate FEV1/FVC < 0.70 50% < FEV1 < 80% predicted Stage III: Severe FEV1/FVC < 0.70 30% < FEV1 < 50% predicted Stage IV: Very Severe FEV1/FVC < 0.70 FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure
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BODE index
• B:Body mass index
• O:Obstructive index (FEV1%)
• D:Dyspnea(MMRC dyspnea scale)
• E:Exercise Capacity
(6 Minute Walk Test, 6MWT)
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Points
0
1
2
3
FEV1%
≥65
50-64
36-49
≤35
6MWT(m)
≥350
250-349
150-249
≤149
MMRC
0-1
2
3
4
BMI
>21
≤21
BODE index for COPD
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• Relieve symptoms
• Prevent disease progression
• Improve exercise tolerance
• Improve health status
• Prevent and treat complications
• Prevent and treat exacerbations
• Reduce mortality
GOALS of COPD MANAGEMENT VARYING EMPHASIS WITH DIFFERING SEVERITY
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Manage Stable COPD: Key Points
• The overall approach to managing stable COPD should be individualized to address symptoms and improve quality of life.
• For patients with COPD, health education plays an important role in smoking cessation (Evidence A) and can also play a role in improving skills, ability to cope with illness and health status.
• None of the existing medications for COPD have been shown to modify the long-term decline in lung function that is the hallmark of this disease (Evidence A). Therefore, pharmacotherapy for COPD is used to decrease symptoms and/or complications.
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Bronchodilators
• Bronchodilator medications are central to the symptomatic management of COPD (Evidence A). They are given on an as-needed basis or on a regular basis to prevent or reduce symptoms and exacerbations.
• The principal bronchodilator treatments are ß2- agonists, anticholinergics, and methylxanthines used singly or in combination (Evidence A).
• Regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting bronchodilators (Evidence A).
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Glucocorticosteroids
• The addition of regular treatment with inhaled glucocorticosteroids to bronchodilator treatment is appropriate for symptomatic COPD patients with an FEV1 < 50% predicted (Stage III: Severe COPD and Stage IV: Very Severe COPD) and repeated exacerbations (Evidence A).
• An inhaled glucocorticosteroid combined with a long-acting ß2-agonist is more effective than the individual components (Evidence A).
• Chronic treatment with systemic glucocorticosteroids should be avoided because of an unfavorable benefit-to-risk ratio (Evidence A).
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Vaccines
• In COPD patients influenza vaccines can reduce serious illness (Evidence A).
— Should be used in All Stages of Disease Severity
• Pneumococcal polysaccharide vaccine is recommended for COPD patients 65 years and older and for COPD patients younger than age 65 with an FEV1 < 40% predicted (Evidence B).
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Other Pharmacologic Treatments
• Antibiotics: Only used to treat infectious exacerbations of COPD
• Antioxidant agents: No effect of n-acetylcysteine on frequency of exacerbations, except in patients not treated with inhaled glucocorticosteroids
• Mucolytic agents, Antitussives, Vasodilators: Not recommended in stable COPD
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Non-Pharmacologic Treatments
• Rehabilitation: All COPD patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).
• Oxygen Therapy: The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival (Evidence A).
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IV: Very Severe III: Severe II: Moderate I: Mild
Therapy at Each Stage of COPD
FEV1/FVC < 70% FEV1 > 80% predicted
FEV1/FVC < 70% 50% < FEV1 < 80% predicted
FEV1/FVC < 70% 30% < FEV1 <
50% predicted
FEV1/FVC < 70% FEV1 < 30%
predicted or FEV1 < 50%
predicted plus chronic respiratory failure
Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if repeated exacerbations
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add long term oxygen if chronic respiratory failure. Consider surgical
treatments
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MBBS project, Zhongshan Hospital
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MBBS project, Zhongshan Hospital
Management COPD Exacerbations
• An exacerbation of COPD is defined as: — “An event in the natural course of the disease
characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.”
• The most common causes of an exacerbation are infection of the tracheobronchial tree and air pollution, but the cause of about one-third of severe exacerbations cannot be identified (Evidence B).
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MBBS project, Zhongshan Hospital
Medications
• Patients experiencing COPD exacerbations with clinical signs of airway infection (e.g., increased sputum purulence) may benefit from antibiotic treatment (Evidence B).
• Inhaled bronchodilators (particularly inhaled ß2-agonists with or without anticholinergics) and oral glucocortico-steroids are effective treatments for exacerbations of COPD (Evidence A).
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MBBS project, Zhongshan Hospital
Noninvasive ventilation
• Noninvasive mechanical ventilation in exacerbations — improves respiratory acidosis,
— increases pH,
—decreases the need for endotracheal intubation,
— reduces PaCO2, respiratory rate, severity of breathlessness, the length of hospital stay, and mortality (Evidence A).
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MBBS project, Zhongshan Hospital
NEJM 2004;350:2692
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MBBS project, Zhongshan Hospital
NEJM 2004;350:2692
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FE
V1 (
Pe
rcen
tag
e o
f V
alu
e a
t A
ge 2
5)
Age (years)
100
0
75
50
25
100 25 50 75
Never smoked
or not susceptible
to smoke
Stopped at 50 years
Stopped at 65 years
GOLD 0+1b
GOLD 2
GOLD 3
GOLD 4 Disability
Death
Smoked regularly and susceptible to effects of smoking
Smoking cessation is the single most effective — and cost effective — intervention in most people to reduce the risk of developing COPD and stop its progression
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Smoking Cessation: Improvement in Postbronchodilator FEV1 Decline
Anthonisen et al. JAMA. 1994;272(19):1497-1505; Kanner et al. Am J Med. 1999;106(4):410-416.
Follow up (y)
Po
stb
ron
ch
od
ilato
r F
EV
1 L
2.4
2.5
2.6
2.7
2.8
2.9
Screen 2 1 2 3 4 5
Sustained Quitters
Continuous Smokers
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Smoking Cessation: Improvement in FEV1
Scanlon et al. Am J Respir Crit Care Med. 2000;161:381-390.
Annual Visits (AV)
72
74
76
78
80
82
Baseline AV 1 AV 2 AV 3 AV 4 AV 5
Pre
dic
ted
FE
V1
(%)
Sustained Quitters
Continuous Smokers
134
37 23
152
54 208
146
2335
2059
1818
1652
2682
840
507 541 599
673
124
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MBBS project, Zhongshan Hospital
Brief Strategies to Help the Patient Willing to Quit Smoking
• ASK
— Systematically identify all tobacco users at every visit.
• ADVISE
— Strongly urge all tobacco users to quit.
• ASSESS
— Determine willingness to make a quit attempt.
• ASSIST
— Aid the patient in quitting.
• ARRANGE
— Schedule follow-up contact.
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MBBS project, Zhongshan Hospital
Smoking Cessation
• Counseling delivered by physicians and other health professionals significantly increases quit rates over self-initiated strategies.
• Even a brief (3-minute) period of counseling to urge a smoker to quit results in smoking cessation rates of 5-10%.
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MBBS project, Zhongshan Hospital
Pharmacotherapy for quit smoking
• Nicotine Replacement Therapy (NRT)
— Transdermal patch, gum, nasal spray, inhaler,
• Bupropion Sustained Release (Zyban®)
• Varenicline (Champix®)
• Current recommendations from the U.S. Surgeon General are that all smokers considering quitting be offered pharmacotherapy, in the absence of any contraindication to treatment.
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MBBS project, Zhongshan Hospital
Summary
• COPD is a leading cause of morbidity and mortality worldwide and in China, and its disease burden is increasing.
• COPD is preventable and treatable.
• Abnormal and chronic airway inflammation--the underlying mechanism
• Irreversible airflow limitation--core pathophysiology
• COPD is a disease of both pulmonary and extra pulmonary manifestations.
• Spirometry -- golden standard for the diagnosis
• 4 stage of the disease – stepwise management of the stable patients
• Inhalation therapy, LTOT and NIV
• Tobacco control is the major prevention of COPD—pharmaceutical and non-pharmaceutical intervention
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MBBS project, Zhongshan Hospital
Questions
• Please describe the definition and the key points of the diagnosis of COPD.
• Please describe staging of COPD and the management for each stage of the stable disease.
• How to evaluate the acute exacerbation of COPD and make the treatment plan?
• Please list the main methods to help the patients to quit smoking.
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MBBS project, Zhongshan Hospital
Further readings
• John J. Reilly, Jr., Edwin K. Silverman, Steven D. Shapiro. 254 Chronic obstructive pulmonary disease. In: 17th Harrison’s Principle of Internal Medicine. PP 1635-1651.
• GOLD guideline 2010. Available at: http://www.goldcopd.com.
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Total
lung
capacity
Tidal volume
Inspiratory reserve
volume
Expiratory reserve
volume
Residual volume
Inspiratory
capacity
Vital
capacity
Lung Volume and Subdivisions
functional residual
capacity
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Spirometric Indicies
• FEV1 - Forced expiratory volume in one second:
The volume of air expired in the first second of the blow
• FVC - Forced vital capacity:
The total volume of air that can be forcibly exhaled in one breath
• FEV1/FVC ratio:
The fraction of air exhaled in the first second relative to the total volume exhaled
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Obstructive Disease Decrease in expiratory flow rates
Volu
me, lit
ers
Time, seconds
5
4
3
2
1
1 2 3 4 5 6
FEV1 = 1.8L
FVC = 3.2L
FEV1/FVC = 0.56 ↓
Normal
Obstructive