Chronic Obstructive Pulmonary Disease Jing ZHANG (张静), MD, PhD [email protected] Department of Pulmonary Medicine Zhongshan Hospital Fudan University 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 MBBS project, Zhongshan Hospital

GOLD • Global Initiative for Chronic Obstructive Lung Disease

• Global Strategy for Diagnosis, Management and Prevention of COPD

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. MBBS project, Zhongshan Hospital

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

2020

Ischemic heart disease Cerebrovascular disease

1 2

1 2

COPD

6

3

Lower respiratory infection Lung cancer Road traffic accidents Tuberculosis Stomach cancer

3 10 9 7 14

4 5 6 7 8

The mortality of COPD is increasing! Proportion of 1965 Rate 3.0 3.0 2.5 2.5

Coronary Heart Disease

Stroke

Other CVD

COPD

All Other Causes

–59%

–64%

–35%

+163%

–7%

2.0 2.0 1.5 1.5 1.0 1.0 0.5 0.5 0.0 0

1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 Source: NHLBI/NIH/DHHS MBBS project, Zhongshan Hospital

Prevalence of COPD in China --BOLD study • Overall prevalence: 8.2% • > 43 million prevalence of COPD(%)

Urban 14

12.1

12.7

Rural

Total

12.4

12 10

8.8 7.8

8 6

4.9

5.4

5.1

8.2

#

4

2 0

Male

Female

*

Total

Nanshan Zhong et al. Am J Respir Crit Care Med 2007, 176: 753-760 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

MBBS project, Zhongshan Hospital

WORLD COPD DAY November 14, 2007

Raising COPD Awareness Worldwide

Risk factors for COPD Nutrition Infections

Socio-economic status

Aging Populations

Genetic Susceptibility MBBS project, Zhongshan Hospital

CHRONIC INFLAMMATION in COPD Large airway Mucous gland enlargement Goblet cell hyperplasia Impaired muco-ciliary clearance

Cough Sputum

Small airway

Alveolar space

Excess mucous & edema Fibrosis Destruction of elastic fibers

ECM destruction Emphysema

Small airway narrowing & collapse

Airflow obstruction

Air trapping

Hyperinflation

Progressive Dyspnea

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 MBBS project, Zhongshan Hospital

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 MBBS project, Zhongshan Hospital

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

MBBS project, Zhongshan Hospital

Forced expiratory flow rates ↓ FEV1 ↓ FEV1/FVC ↓

Airflow obstruction

Residual volume ↑ RV/TLC ↑

Air trapping

TLC ↑

Hyperinflation

• Non-uniform ventilation • V/Q mismatching • Destruction of gas-exchanging airspace and decreased diffusing capacity

PaO2 ↓ +/- PaCO2 ↑ • Pulmonary hypertension • Cor pulmonale • Right ventricular failure

Lab investigations

MBBS project, Zhongshan Hospital

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 MBBS project, Zhongshan Hospital

Spirometry (Cont’d) •

FEV1／FVC% —

•

FEV1% predicted —

•

sensitive, capable of detection for mild airflow obstruction good indicator for moderate-severe airflow obstruction

Airflow obstruction is confirmed by postbronchodilator FEV1／FVC＜0.7

MBBS project, Zhongshan Hospital

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

MBBS project, Zhongshan Hospital

Advanced Emphysema • Large volume lungs • Thin heart shadow • Flattened hemidiaphragms • Attenuated vascular markings in the upper lobe MBBS project, Zhongshan Hospital

Emphysema with bullae

MBBS project, Zhongshan Hospital

Cor pulmonale • Bilateral enlarged pulmonary arteries • Cardiomegaly

MBBS project, Zhongshan Hospital

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

MBBS project, Zhongshan Hospital

MBBS project, Zhongshan Hospital

MBBS project, Zhongshan Hospital

Lung density in CT scan • Lung density is related to emphysema • To detect the size and distribution of bullae • To quantitate emphysema: Emphysema index MBBS project, Zhongshan Hospital

Evaluating abnormality of airway by CT scan • To analyse: — Thickness of airway wall — Diameter of airway • Part of or even the entire airway

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

MBBS project, Zhongshan Hospital

Diagnosis and DDx

MBBS project, Zhongshan Hospital

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 MBBS project, Zhongshan Hospital

Diagnosis of COPD SYMPTOMS cough sputum shortness of breath

EXPOSURE TO RISK FACTORS tobacco occupation indoor/outdoor pollution

 SPIROMETRY

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 MBBS project, Zhongshan Hospital

Differential Diagnosis: COPD and Asthma COPD

ASTHMA

• Onset in mid-life

• Onset early in life (often

•

Symptoms slowly progressive

• Symptoms vary from day to day • Symptoms at night/early

•

Long smoking history

•

Dyspnea during exercise also present

• Largely irreversible airflow limitation

childhood)

morning

• Allergy, rhinitis, and/or eczema • Family history of asthma • Largely reversible airflow limitation

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

MBBS project, Zhongshan Hospital

BODE index • B：Body mass index • O：Obstructive index （FEV1%） • D：Dyspnea（MMRC dyspnea scale） • E：Exercise Capacity （6 Minute Walk Test, 6MWT）

MBBS project, Zhongshan Hospital

BODE index for COPD 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

MBBS project, Zhongshan Hospital

GOALS of COPD MANAGEMENT VARYING EMPHASIS WITH DIFFERING SEVERITY

• • • • • • •

Relieve symptoms Prevent disease progression Improve exercise tolerance Improve health status Prevent and treat complications Prevent and treat exacerbations Reduce mortality

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. MBBS project, Zhongshan Hospital

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 ß2agonists, 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).

MBBS project, Zhongshan Hospital

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 longacting ß2-agonist is more effective than the individual components (Evidence A). • Chronic treatment with systemic glucocorticosteroids should be avoided because of an unfavorable benefitto-risk ratio (Evidence A). MBBS project, Zhongshan Hospital

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).

MBBS project, Zhongshan Hospital

Other Pharmacologic Treatments • Antibiotics: Only used to treat infectious exacerbations of COPD • Antioxidant agents: No effect of nacetylcysteine on frequency of exacerbations, except in patients not treated with inhaled glucocorticosteroids • Mucolytic agents, Antitussives, Vasodilators: Not recommended in stable COPD

MBBS project, Zhongshan Hospital

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).

MBBS project, Zhongshan Hospital

Therapy at Each Stage of COPD I: Mild

II: Moderate

III: Severe

IV: Very Severe

 FEV1/FVC < 70%

 FEV1/FVC < 70%  FEV1 > 80% predicted

 FEV1/FVC < 70%  50% < FEV1 < 80% predicted

 FEV1/FVC < 70%  30% < FEV1 < 50% predicted

Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed)

 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

Add long term

oxygen if chronic respiratory failure. Consider surgical treatments

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). 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).

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). MBBS project, Zhongshan Hospital

NEJM 2004;350:2692 MBBS project, Zhongshan Hospital

NEJM 2004;350:2692 MBBS project, Zhongshan Hospital

FEV1 (Percentage of Value at Age 25)

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 Never smoked or not susceptible to smoke

100 GOLD 0+1b 75 GOLD 2

Stopped at 50 years

50 GOLD 3 25

GOLD 4

Smoked regularly and susceptible to effects of smoking

Stopped at 65 years

Disability Death

0 25

50

75 Age (years)

100

Smoking Cessation: Improvement in Postbronchodilator FEV1 Decline Postbronchodilator FEV1 L

Sustained Quitters Continuous Smokers

2.9

2.8 2.7

2.6 2.5 2.4 Screen 2

1

2

3

4

5

Follow up (y) Anthonisen et al. JAMA. 1994;272(19):1497-1505; Kanner et al. Am J Med. 1999;106(4):410-416.

Smoking Cessation: Improvement in FEV1

Predicted FEV1 (%)

82

840

673

599

146

80

541 507

54

208

152

78

37

2682 2335

76

23

134 2059

74

1818

Sustained Quitters

1652

Continuous Smokers

72 Baseline

AV 1

124

AV 2 AV 3 Annual Visits (AV)

Scanlon et al. Am J Respir Crit Care Med. 2000;161:381-390.

AV 4

AV 5

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. 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%. 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. 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 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.

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.

MBBS project, Zhongshan Hospital

Thank you！

Questions are welcome  [email protected] MBBS project, Zhongshan Hospital

Lung Volume and Subdivisions Inspiratory reserve volume

Total lung capacity

Inspiratory capacity

Tidal volume Expiratory reserve volume

Vital capacity

functional residual capacity Residual volume

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

Obstructive Disease Decrease in expiratory flow rates Normal

Volume, liters

5 4 3

FEV1 = 1.8L

2

FVC = 3.2L

1

FEV1/FVC = 0.56 ↓

1

2

3

4

5

Time, seconds

6

Obstructive