CHRO NIC O BSTRU CTI VE

PUL MONARY D ISEASE

Jiang sheng-hua
 Leading Causes of Deaths
U.S. 1998
Cause of Death Number

1. Heart Disease 724,269

2. Cancer
3. Cerebrovascular disease (stroke)
4. 538,947
Respiratory Diseases (COPD)
5. 158,060
Accidents
6. 114,381 and influenza
Pneumonia
7. 94,828
Diabetes 64,574
8. 93,207
Suicide
9. Nephritis
10. 29,264
Chronic liver disease
26,295
All other causes of death
24,936
 Facts About COPD

COPD is the 4th leading cause of death in the

United States (behind heart disease, cancer,
and cerebrovascular disease).

In 2000, the WHO estimated 2.74 million

deaths worldwide from COPD.

In 1990, COPD was ranked 12th as a burden of

disease; by 2020 it is projected to rank 5th.
 Percent Change in Age-Adjusted
Death Rates, U.S., 1965-1998
Proportion of 1965 Rate
3.0
Coronary Stroke Other CVD COPD All Other
2.5 Heart Causes
Disease
2.0

1.5

1.0

0.5
–59% –64% –35% +163% –7%
0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
 Facts About COPD
■ Between 1985 and 1995, the number of
physician visits for COPD in the United
States increased from 9.3 million to
16 million.
■ The number of hospitalizations for COPD
in 1995 was estimated to be 500,000.
Medical expenditures amounted to an
estimated $14.7 billion.
 Facts About COPD
 Cigarette smoking is the primary cause of
COPD.
 In the US 47.2 million people (28% of
men and 23% of women) smoke.
 The WHO estimates 1.1 billion smokers
worldwide, increasing to 1.6 billion by
2025. In low- and middle-income
countries, rates are increasing at an
alarming rate.
 Age-Adjusted Death Rates
for COPD, U.S., 1960-1995
Deaths per 100,000
60

50

40

30

20

10

0
1960 1965 1970 1975 1980 1985 1990 1995 2000
It is unusual for a person to have clinically
apparent COPD without a history of smoking
for at least 20 pack years, and most patients
have at least 40 pack years of exposure.
A pack year is the equivalent of smoking 20
cigarettes per day for a year
 COPD 是可以治疗
和预防的疾病
Definition of COPD （ 1 ）
COPD 是一种具有气流受限特征的可以预防和治疗的
疾病，气流受限不完全可逆、呈进行性发展，与肺部
对香烟烟雾等有害气体或有害颗粒的异常炎症反应有
关

ＣＯＰＤ不仅影响肺，也可以引起显著的全身反应。

Global initiative for Chronic Obstructive

Lung Disease ， GOLD 2006
 Definition of COPD(2)

FEV1/FVC%

支气管扩张药用后
Airflow FEV1/FVC <70% 证实存在
limitation 气道受限不完全可逆
 pathologic processes
Patients with COPD have varying
degrees of three pathologic processes,
each associated with smoking: chronic
bronchitis, small airways obstruction, and
emphysema.
 Pathobiology
Chronic Bronchitis
Peripheral Airway Disease
Emphysema
Reduction in Maximum Expiratory Flow
Chronic bronchitis is a clinical diagnosis,
defined as the presence of chronic cough and
sputum production for at least 3 months of the
year for at least 2 consecutive years in the
absence of any other disease.
The anatomic basis of chronic bronchitis is
hypertrophy and hyperplasia of the mucus-
secreting glands normally found in the
epithelium of larger airways.
 These cells increase in size and number; as a
consequence, they are found in smaller
diameter airways
than in nonsmokers
chronic bronchitis may
contribute to the progression
of airways obstruction.
 Peripheral Airway Disease
the most striking increase in the resistance to
airflow occurs in peripheral airways or
bronchioles.
The degree of abnormality in these airways is
correlated with lung function.
The mechanisms involved in these changes are
unknown.
 Emphysema
the enlargement of air spaces distal to the
conducting airways
There are two important types of emphysema,
centrilobular and panacinar. Centrilobular
emphysema primarily involves the respiratory
bronchioles , Panacinar emphysema involves
the entire distal lung unit
 病理学（ Pathology)

小叶中央型肺气肿
centrilobular

正常肺组织 全小叶型肺气肿
α1-antitrypsin (AAT) deficiency
severe panacinar emphysema associated with
α1-antitrypsin (AAT) deficiency.
AAT is an acute phase serum protein that is
secreted by the liver and that binds to and
neutralizes neutrophil elastase; it is the most
abundant antiprotease in the lung periphery.
but it is not clear
Reduction in Maximum Expiratory
Flow
Reduced expiratory flow is the hallmark of
COPD
the lung's elastic recoil is reduced by
emphysema, and airways resistance is
increased. Maximum expiratory flow is
reduced, and even less effort than normal
causes limitation of flow.
Tests of maximum expiratory flow, such as the
flow-volume curve and the FEV1, are of
clinical value because they reflect major
pathologic processes in COPD and are
relatively insensitive to a patient's effort and
cooperation beyond a threshold minimum
effort.
 Clinical Manifestations
Lung Function
Dyspnea
 Lung Function
The decrease in maximum expiratory flow that
characterizes COPD is most easily identified
in terms of a reduction in FEV1 that is larger
than the reduction in vital capacity, measured
in the same forced expiratory maneuver and
termed the forced vital capacity (FVC)
lower ratios indicate airways obstruction
<70%
Both the FEV1 and the FVC may increase
after treatment with an inhaled bronchodilator,
but the FEV1 does not attain normal values in
COPD, whereas it can return to normal in
patients with asthma
Hyperinflation of the lungs, which is often
manifested as an increase in total lung
capacity, is characteristic of COPD and
reflects loss of lung recoil and limitation of
expiratory flow.
Residual volume often is increased even in
mild cases of COPD.
Functional residual capacityis routinely
increased in moderate and severe COPD.
Arterial hypoxemia with or without carbon
dioxide retention is common in severe COPD.
Hypoxemia generally precedes carbon dioxide
retention, rarely occurs in patients with an
FEV1 in excess of 40% of the predicted
normal value, and is common when the FEV1
is less than 30% of the predicted value. Gas
exchange abnormalities in COPD are due to
abnormally large differences in ventilation-
perfusion ratios among units in the lung.
 Dyspnea
Dyspnea is the major cause of disability in
COPD.

It arises from a sense of increased muscle

effort to breathe in relation to the level of
ventilation achieved
Normal subjects, even at the most strenuous levels of
exercise, use only 60 to 70% of their maximum
voluntary ventilation and never experience dyspnea
comparable to that of diseased patients.
Patients with obstructive airways disease usually
characterize dyspnea as difficulty in inspiring because
airways obstruction changes the shape of the chest
wall and puts the inspiratory muscles at a mechanical
disadvantage.
Expiratory flow limitation does not permit
adequate expiration at normal lung volumes,
so patients breathe at increased lung volumes
This hyperinflation renders inspiratory
muscles relatively ineffective, so that greater
inspiratory effort is required to achieve the
needed ventilation,
The degree of dyspnea in patients with COPD
generally correlates inversely with the FEV1,
but patients with similar degrees of airways
obstruction may complain of different degrees
of dyspnea. Careful assessment of dyspnea is a
useful way to follow the progress of patients
with COPD.
 Diagnosis
Diagnosis of COPD is based on a history of
exposure to risk factors and the presence of
airflow limitation that is not fully reversible, with
or without the presence of symptoms.
Patients who have chronic cough and
sputum production with a history of
exposure to risk factors should be tested
for airflow limitation, even if they do not
have dyspnea.
 Diagnosis of COPD
EXPOSURE TO RISK
SYMPTOMS FACTORS
cough tobacco
sputum occupation
dyspnea indoor/outdoor pollution
➨

SPIROMETRY
 History
COPD is insidious .
Dyspnea typically does not occur until the
FEV1 is about 50% of normal, when the
disease has usually been present for decades.
Patients with COPD often have a history of
chronic bronchitis that has antedated the onset
of dyspnea
first experienced during episodes of acute
bronchitis.
Eventually, dyspnea becomes consistent
being present at rest
Wheezing is also common in COPD, usually
with exertion, but may occur at rest in severe
disease
Patients with COPD have periodic exacerbations,
marked by increased dyspnea, wheezing, cough, and
sputum production..
Exacerbations usually occur in the winter, often with
upper respiratory infections, and are more common in
patients with symptomatic chronic bronchitis and in
those with severe obstruction.
Exacerbations of COPD are the most common cause
of hospitalization and result in substantial morbidity.
Some patients with COPD lose weight and
muscle mass especially in the presence of
severe emphysema. Weight loss is an ominous
prognostic sign in COPD
 Physical Examination
the physical examination is usually normal. In
severe disease, signs are often apparent
The breathing rate is increased, often to more
than 20 breaths per minute at rest in patients
with hypoxemia or carbon dioxide retention.
 Physical signs
the appearance of a barrel chest with increased
anteroposterior diameter,
relatively low-lying diaphragms, and faint
heart sounds. Patients with severe disease use
the strap muscles of the
neck during inspiration..
Breath sounds are often diminished, and both
crackles and wheezes may be heard.
Hypoxemic patients may be cyanotic
In advanced disease, secondary pulmonary
hypertension ,leads to right-sided heart failure
 Spirometry
Spirometry, the measurement of the FEV1 and
FVC, is the “gold standard” for diagnosis of
COPD and is easy to perform in the office
setting Airways obstruction (FEV1/FVC <
0.70) in a person with at least 20 pack years of
tobacco exposure is a presumptive diagnosis of
COPD.
 Spirometry: Normal and COPD

0
FEV1 FVC FEV1/ FVC
Normal 4.150 5.200 80 %
1 COPD 2.350 3.900 60 %

2
FEV1
Liter

3
COPD
4 FVC
FEV1

5 Normal
FVC
1 2 3 4 5 6 Seconds
 Classification by Severity
Stage Characteristics
0: At risk Normal spirometry
Chronic symptoms (cough, sputum)
I: Mild FEV1/FVC < 70%; FEV1 ≥ 80% predicted
With or without symptoms (cough, sputum)
II: Moderate FEV1/FVC < 70%; 30% ≤ FEV1 < 80% predicted
(IIA: 50% ≤ FEV1 < 80% predicted;
IIB: 30% ≤ FEV1 < 50% predicted)
With or without chronic symptoms (cough, sputum,
dyspnea)
III: Severe FEV1/FVC < 70%; FEV1 < 30% predicted or FEV1
< 50%predicted plus respiratory failure or clinical
signs of right heart failure
 Radiologic Studies
Routine chest radiographs are insensitive for
detecting COPD
In advanced cases, patients develop hyperinflation
with flattened diaphragms, increased retrosternal air
space, and an apparently small, vertical heart ( Fig.
88-4 ). Increased or decreased lung markings and
thin-walled bullae may be seen. Signs of pulmonary
hypertension, including fullness of the main
pulmonary arteries, are occasionally observed.
 Computed tomographic (CT)
Computed tomographic (CT) scans are of
considerable value in assessing the presence,
distribution, and extent of emphysema. There
are no standard grading systems.
Emphysematous spaces are seen as “holes” in
the lung
 Serial Evaluation
Patients thought to have COPD should undergo full
pulmonary function testing at least once Testing
should also include repeated spirometry at yearly
intervals and when the patient is acutely ill. If the
FEV1 is less than 40% of the predicted normal value,
arterial blood gas analysis is advisable Annual chest
radiographs should be performed only if the patient is
a candidate for cancer surgery. Finally, the degree of
dyspnea should be documented carefully, as should
dietary intake, weight loss, and occurrence of
exacerbations.
 Differential Diagnosis
The most difficult disease to differentiate from
COPD is asthma
Asthma typically begins early in life with
episodes of dyspnea and wheezing of rapid
onset and that reverse rapidly and completely.
However, patients with asthma can develop
chronic airways obstruction that reverses little
with therapy,
In these instances, the difference between
asthma and COPD can become a matter of
semantics.
Fortunately, the therapies for asthma and
COPD are similar enough so that diagnostic
uncertainties between these two entities should
have little impact on management of the
patient.
Management of COPD
 Management of COPD (1)
The goals of COPD management include:
• Relieve symptoms
• Prevent disease progression
• Improve exercise tolerance
• Improve health status
• Prevent and treat complications
• Prevent and treat exacerbations
• Reduce mortality
• Prevent or minimize side effects from treatment.
Cessation of cigarette smoking should be included
as a goal throughout the management program.
Management of COPD (2)
These goals can be achieved
through implementation of a COPD
management program with four
components:
1. Assess and Monitor
Disease
2. Reduce Risk Factors
3. Manage Stable COPD
4. Manage Exacerbations
GOLD Workshop Report
Four Components of COPD
Management
• Assess and monitor
disease

• Reduce risk factors

• Manage stable COPD

● Education
● Pharmacologic
● Non-pharmacologic

• Manage exacerbations
 Reduce Risk Factors
Key Points
• Reduction of total personal exposure to
tobacco smoke, occupational dusts and
chemicals, and indoor and outdoor air
pollutants are important goals to prevent the
onset and progression of COPD.

• Smoking cessation is the single most

effective-and cost-effective- intervention to
reduce the risk of developing COPD and stop
its progression (Evidence A).
Reduce Risk Factors
Key Points
 Brief tobacco dependence treatment is
effective (Evidence A), and every tobacco
user should be offered at least this treatment
at every visit to a health care provider.

 Three types of counseling are especially

effective: practical counseling, social support
as part of treatment, and social support
arranged outside of treatment (Evidence A).
Reduce Risk Factors
Key Points
 Several effective
pharmacotherapies for tobacco
dependence are available
(Evidence A), and at least one of
these medications should be added
to counseling if necessary, and in
the absence of contraindications.
Reduce Risk Factors
Key Points
 Progression of many
occupationally-induced respiratory
disorders can be reduced or
controlled through a variety of
strategies aimed at reducing the
burden of inhaled particles and
gases (Evidence B).
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.

Stable COPD
 Manage Stable COPD
Key Points
The overall approach to managing stable COPD
should be characterized by a stepwise increase in the
treatment, depending on the severity of the disease.

For patients with COPD, health education can play a

role in improving skills, ability to cope with illness,
and health status. It is effective in accomplishing
certain goals, including smoking cessation (Evidence
A).
Smoking cessation is the only treatment that
has been shown to alter the course of
COPD.[1] Smoking cessation when the FEV1
exceeds 50% of the predicted normal value
either averts or greatly delays the onset of
symptomatic disease. It is probably never too
late for patients with COPD to stop smoking.
Inhaled bronchodilators afford symptomatic relief in
COPD and should be prescribed for all patients who
find them helpful
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.

The principal bronchodilator treatments are Beta2-

agonists, anticholinergics, theophylline, and a
combination of these drugs (Evidence A).
Short-acting β2-agonists have rapid onset of
action and are useful as rescue agents on a
discretionary basis.
Albuterol is the prototypical short-acting β2-
agonist; the normal dose is 200 μg (two puffs
from a metered-dose inhaler).
Ipratropium bromide is an inhaled
anticholinergic drug that is as effective as β2-
agonists in COPD.
Because it has a slower onset of action, it is usually
given on a schedule of three or four times a day at a
dose of 36 μg (two puffs from a metered-dose
inhaler).
Higher doses of these drugs are of benefit in some
patients, and many use both; a combination inhaler is
available. Longer acting β2 agents, such as salmeterol
(50 μg) and formoterol (12 μg), have durations of
action up to 12 hours
Theophylline is less effective, although some
patients receive symptomatic benefit when
theophylline is added to inhaled agents, and a
trial of theophylline is reasonable in patients
with severe dyspnea.
Serum levels should be measured, and a target
of about 10 μg/mL is usually achieved with a
dose of approximately 300 mg twice a day.
Inhaled steroids do not change the long-term rate of
decline in lung function in COPD, but inhaled steroid
therapy may produce a small (about 200 mL) one-
time increase in FEV1.
Of greater importance is evidence that inhaled
steroids reduce the frequency and severity of
exacerbations and reduce mortality in COPD.[3]
Patients with severe disease and multiple
exacerbations should be given inhaled steroids in
relatively high doses,
The combined use of a long-acting β-agonist
with an inhaled steroid produces better control
of symptoms without increased side effects
compared with either used alone .
COPD patients benefit from pulmonary
rehabilitation. The major component of
rehabilitation programs is exercise training.
Regular exercise improves exercise tolerance
and quality of life in patients with COPD. In
addition, rehabilitation programs teach coping
skills and self-reliance, and they tend to reduce
anxiety and depression.
 home 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).
stable patients with arterial Po2 below 60 mm
Hg. Acceptable blood gas levels (Po2 of 65 to
80 mm Hg) can usually be achieved with
oxygen flows of 2 L/min delivered by nasal
cannula.
in such patients during sleep or exercise :

some patients who are not hypoxemic

during the day exhibit hypoxemia while
asleep,
many patients with severe COPD develop
significant hypoxemia with exercise
 Surgical approaches
Surgical approaches to COPD include lung
transplantation and lung volume reduction
surgery
Lung transplantation is falling out of favor
because it is not clear that it prolongs useful
life. Lung volume reduction surgery involves
removal of substantial amounts of
emphysematous lung as identified by CT scan
正常
异常
 Influenza vaccine
Influenza vaccine should be administered
annually to all patients with COPD to prevent
exacerbations. Pneumococcal vaccination is
also recommended because pneumococcal
pneumonia is devastating in these patients
 Management of COPD:
All stages
Avoidance of noxious agents

- smoking cessation
- reduction of indoor pollution
- reduction of occupational exposure

Influenza vaccination
 Management of COPD
Stage 0: At Risk
Characteristics Recommended
Treatment
• Chronic symptoms
- cough
- sputum
• No spirometric
abnormalities
 Management of COPD
Stage I: Mild COPD
Characteristics Recommended
Treatment
• FEV1/FVC < 70 % • Short-acting
• FEV1 > 80 % bronchodilator as
predicted needed
• With or without
symptoms
 Management of COPD
Stage IIA: Moderate COPD
Characteristics Recommended
Treatment
•FEV1/FVC < 70% •Regular treatment
with one or more
•50% < FEV1< 80%
bronchodilators
predicted
•Rehabilitation
•With or without
•Inhaled glucocortico-
symptoms
steroids if significant
symptoms and lung
function response
 Management of COPD
Stage IIB: Moderate COPD
Characteristics Recommended
Treatment
•FEV1/FVC < 70% Regular treatment
with one or more
•30% < FEV1 < 50%
bronchodilators
predicted
•Rehabilitation
•With or without symptoms
•Inhaled
glucocortico-steroids
if significant
symptoms and lung
function response or
if repeated
 Management of COPD
Stage III: Severe COPD
Characteristics Recommended
Treatment •Regular treatment with one or
•FEV1/FVC < 70%
more bronchodilators
•FEV1 < 30% predicted •Inhaled glucocorticosteroids if
or presence of significant symptoms and lung
function response or if repeated
respiratory failure or exacerbations
right heart failure •Treatment of complications
•Rehabilitation
•Long-term oxygen therapy if
respiratory failure
•Consider surgical options
Manage ExacerbationsKey Points
Exacerbations of respiratory symptoms
requiring medical intervention are important
clinical events in 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).
 Manage Exacerbations
Key Points

Inhaled bronchodilators (Beta2-agonists

and/or anticholinergics), theophylline, and
systemic, preferably oral, glucocortico-
steroids are effective for the treatment of
COPD exacerbations (Evidence A).
 Manage Exacerbations
Key Points
Patients experiencing COPD
exacerbations with clinical signs of
airway infection (e.g., increased volume
and change of color of sputum, and/or
fever) may benefit from antibiotic
treatment (Evidence B)
Sputum smear and culture are not usually
helpful, and empirical treatment is the rule. In
low-risk patients, inexpensive antibiotics such
as amoxicillin and trimethoprim-
sulfamethoxazole may be used for 10 days, but
bacterial resistance to these agents is common.
In severe exacerbations, systemic steroid
therapy has been shown to result in a relatively
rapid recovery, and the equivalent of 40 mg of
prednisone per day for 10 to 14 days is
justifiable. It is reasonable to give compliant
patients with COPD a supply of antibiotics and
steroids so they self-treat exacerbations.
In severe exacerbations seen in the hospital or
emergency department, other diagnoses must
be considered. Exacerbations of COPD must
be distinguished from pneumonia ,
pneumothorax and pulmonary embolism
Pneumonia and pneumothorax usually can be
diagnosed by the chest radiograph. In patients
with signs and symptoms typical of
pneumonia, especially substantial fevers or
elevated white blood cell counts, empirical
treatment of pneumonia is appropriate until it
can be excluded.
Pulmonary embolism can be difficult to
diagnose in patients with COPD, and spiral CT
angiography should be used if embolic disease
is suspected
Exacerbations of COPD are often
accompanied by hypoxemia, which can
precipitate heart failure angina an acute
coronary syndrome or hypoxic death in
susceptible individuals. Hypoxemia may also
cause an acute worsening of pulmonary
hypertension or systemic hypertension It is
essential to measure the arterial Po2 and to
treat hypoxemia with oxygen.
Severe exacerbations of COPD require hospitalization
and should be treated with bronchodilator therapy,
intravenous antibiotics, and steroids. Arterial blood
gases should be measured and oxygen therapy
instituted. In COPD, uncontrolled high-flow oxygen
carries the risk of precipitating carbon dioxide
narcosis, and the initial goals should be to maintain
arterial Po2 at levels of about 60 mm Hg In patients
who can be discharged from the emergency
department, a 10-day course of 40 mg of prednisone
per day improves symptoms and reduces the relapse
rate