Chronic Obstructive Pulmonary Diseasefdjpkc.fudan.edu.cn/_upload/article/files/69/b3/a... · •Epidemiology •Etiology and risk factors •Pathophysiology mechanisms ... • Lung

MBBS project, Zhongshan Hospital

Chronic Obstructive Pulmonary Disease

Jing ZHANG (张静), MD, PhD

[email protected]

Department of Pulmonary Medicine Zhongshan Hospital

Fudan University


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


GOLD

• Global Initiative for Chronic Obstructive Lung Disease

• Global Strategy for Diagnosis, Management and Prevention of COPD


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.

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


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


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

*

#


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

WORLD COPD DAY November 14, 2007

Raising COPD Awareness Worldwide


Risk factors for COPD

Nutrition

Infections

Socio-economic

status

Aging Populations

Genetic Susceptibility

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


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


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


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

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


Lab investigations


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


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


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


Advanced Emphysema

• Large volume lungs

• Thin heart shadow

• Flattened hemidiaphragms

• Attenuated vascular markings in the upper lobe


Emphysema with bullae


Cor pulmonale

• Bilateral

enlarged

pulmonary

arteries

• Cardiomegaly


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




Lung density in CT scan

• Lung density is related to emphysema

• To detect the size and distribution of bullae

• To quantitate emphysema: Emphysema index

• To analyse:

—Thickness of airway wall

—Diameter of airway

• Part of or even the entire airway

Evaluating abnormality of airway by CT scan


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


Diagnosis and DDx


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

SYMPTOMS

cough

sputum

shortness of breath

EXPOSURE TO RISK FACTORS

tobacco

occupation

indoor/outdoor pollution

SPIROMETRY

Diagnosis of COPD


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

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


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


BODE index

• B：Body mass index

• O：Obstructive index （FEV1%）

• D：Dyspnea（MMRC dyspnea scale）

• E：Exercise Capacity

（6 Minute Walk Test, 6MWT）


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

• 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


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.


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).


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).


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).


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


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).

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



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).


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).


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).


NEJM 2004;350:2692


NEJM 2004;350:2692

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

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

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


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.


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%.


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.


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


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.


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.


Thank you！

Questions are welcome [email protected]

Total

lung

capacity

Tidal volume

Inspiratory reserve

volume

Expiratory reserve

volume

Residual volume

Inspiratory

capacity

Vital

capacity

Lung Volume and Subdivisions

functional residual

capacity

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

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

Documents

Chronic Obstructive Pulmonary Diseasefdjpkc.fudan.edu.cn/_upload/article/files/69/b3/a... · •Epidemiology •Etiology and risk factors •Pathophysiology mechanisms ... • Lung