Pathophysiology

Airway Obstruction
In the COPD patient, routine pulmonary function tests depict the
characteristic pattern of volume-dependent airway obstruction.
Spirometry typically reveals a reduction in the FEV1/FVC ratio and
an even greater relative decline in FEV, which may decrease
between 25% and 75% of vital capacity (Table 1). As airflow
obstruction worsens, a normal volume of gas can no longer be
exhaled in the time available, and vital capacity declines.
Measurement of lung volume consistently reveals an increased
residual volume (RV) and a normal-to-increased functional residual
capacity (FRC). The RV may be 2 to 4 times higher than normal,
because as the expiratory airflow slows, gas becomes trapped in
airways that close prematurely. The FRC may become increased by
2 mechanisms: dynamic hyperinflation and activation of inspiratory
muscles during exhalation. Hyperinflation flattens the diaphragm,
which increases the work of breathing, diminishes the capacity for
exercise, and increases dyspnea. Hyperinflation becomes worse
with exercise, causing dynamic hyperinflation, which adds to the
load of inspiratory muscles.

As a result of these processes, tidal breathing may take place at

lung volumes as high as 1 to 2 L above normal levels. In the patient
who has significant airflow obstruction, an increased FRC provides
the benefits of an enlarged airway diameter -- which provides
greater radial support and thus less airway resistance -- and an
increased driving pressure (ie, elastic recoil) required for exhalation.
The cost to the patient of an increased FRC is the greater work of
breathing incurred at the higher lung volume.

Abnormalities in Gas Exchange

It has long been recognized that the pattern of gas exchange
abnormalities in COPD may differ greatly among patients with
airflow obstruction of identical severity. Early in the course of
disease, when expiratory flow is only slightly reduced, mild
hypoxemia may be the only blood gas abnormality. However, in
advanced stages of COPD, 2 distinct patterns emerge (Table 2).

Table 2. Clinical Findings in Emphysema and Chronic

Bronchitis

Emphysema Chronic Bronchitis

(Pink Puffer) (Blue Bloater)

Dominant symptom Dyspnea Productive cough

Thin build; hyperinflated, Stocky build, wheezy,
Signs
quiet chest right heart failure
Normal or hyperinflation,
Normal or only increased
Chest radiograph decreased markings,
markings
bullae
Arterial blood gas
PaO2 Slightly reduced Markedly reduced
PaCO2 Normal Increased
Spirometry Decreased FEV1 Decreased FEV1
Normal or slightly
Total lung capacity Increased
increased
DLCO Decreased Normal
Pulse oximetry:
Rest Normal Decreased
Exercise Severe desaturation May improve
Hematrocit Normal Increased

DLCO = diffusing capacity of the lung for carbon monoxide; FEV1 =

forced expiratory volume in 1 second; Pao2 = partial pressure of
arterial oxygen; PaCO2 = partial pressure of arterial carbon dioxide

Two clinical patterns. Patients with the type A pattern have

dyspnea and only mild-to-moderate hypoxemia (partial pressure of
arterial oxygen[PaO2] is usually > 65 mm Hg). In addition, these
patients maintain normal or even slightly reduced partial pressure of
arterial carbon dioxide (PaCO2). These patients are sometimes
referred to as pink puffers -- they tend to be thin, to experience
hyperinflation at total lung capacity, and to be free of signs of right
heart failure. The pink puffer usually has emphysema.

Patients with the type B pattern are characterized by marked

hypoxemia and peripheral edema resulting from right heart failure.
These patients, sometimes called blue bloaters, typically exhibit
cough and sputum production. They have frequent respiratory tract
infections, experience chronic carbon dioxide retention (PaCO2 > 45
mm Hg), and have recurrent episodes of cor pulmonale. Type B
patients may have pathologic evidence of severe emphysema, as
well as inflammation of large and small airways and possible defects
in ventilatory control. These patients usually meet the criteria for
chronic bronchitis.

Many patients have features of both clinical types, giving rise to

either mixed or intermediate clinical presentations.

Differing effects on the cardiovascular system. The 2 clinical

types also have very different consequences for the cardiovascular
system. In the type B patient, both alveolar hypoxia and acidosis
(secondary to chronic hypercapnia) stimulate pulmonary arterial
vasoconstriction, and hypoxemia stimulates erythrocytosis.
Increased pulmonary vascular resistance, increased pulmonary
blood volume, and possibly increased blood viscosity from
secondary erythrocytosis all contribute to pulmonary arterial
hypertension.[37] In response to long-term pulmonary hypertension,
cor pulmonale generally develops: The right ventricle becomes
hypertrophic, and increases in cardiac output are achieved by
abnormally high filling pressure in the right ventricle. Additional
hemodynamic loads may cause the right ventricle to fail, with the
consequent development of systemic venous hypertension, which is
manifested by jugular venous distention, peripheral edema, passive
hepatic congestion, and sometimes ascites. It should be noted that,
in the absence of left heart failure, pleural effusion is not a
manifestation of cor pulmonale. In type B patients,
echocardiographic evaluation of right heart function and estimation
of pulmonary artery systolic pressure are useful in quantifying the
degree of pulmonary hypertension.[37]

The emphysematous lung destruction characteristic of type A

patients leads to a restricted vascular bed because of the loss of
pulmonary capillaries from the destroyed alveolar walls. This
condition is reflected in the reduced diffusing capacity of the lung for
carbon monoxide (DLCO) observed in type A (but not type B)
patients.[38] However, because PaO2 levels are only mildly depressed
in type A patients, pulmonary vasoconstriction is minimal and
secondary erythrocytosis does not develop. Cardiac output may be
slightly reduced. As a result, pulmonary hypertension in type A
patients is milder than that in type B patients, and cor pulmonale
develops infrequently, usually only in the terminal phase of the
illness.

Differing degrees of oxygen saturation on exertion. Differences

in gas exchange during exercise also distinguish the 2 clinical types.
Type A patients develop oxygen desaturation during exercise,
whereas type B patients may exhibit increases in oxygen saturation
during exercise.

Differential Diagnosis
The differential diagnosis of an older cigarette smoker presenting
with chronic dyspnea or cough and sputum production is wide.

Dyspnea in these patients can be caused by ischemic heart

disease; congestive heart failure; valvular heart disease; anemia;
and other types of lung disease, such as interstitial lung disease,
lung cancer, asthma, pleural effusion, pulmonary embolism, and
pulmonary hypertension.
Cough and sputum in the patients can be the result of postnasal
drip, asthma, gastroesophageal reflux, lung cancer, and such
chronic pulmonary infections as atypical mycobacterial infection and
bronchiectasis.

Patients who are known to have COPD and who present emergently
because of increased dyspnea or an alteration of their normal cough
and sputum may be experiencing an exacerbation of COPD.
However, they must also be evaluated for ischemic heart disease,
congestive heart failure, pneumonia, pneumothorax, pulmonary
embolism, and lung cancer.

Diagnosis
Common presenting symptoms of COPD are productive cough or
shortness of breath occurring; typically, the patient will be 50 years
or older and will have smoked at least a pack of cigarettes a day for
20 years.

Patient History
The presentation of COPD varies, depending on whether the patient
has dominant emphysema or chronic bronchitis, and most patients
have some degree of overlap (Table 2). The patient with
emphysema presents with dyspnea on exertion -- a condition that
has been slowly increasing for years and that is fairly constant from
day to day. In contrast, the patient with chronic bronchitis usually
presents with a cough that often occurs in the morning and that
produces mucoid phlegm. The volume of phlegm is usually less
than 2 tablespoons. If the volume of phlegm is more than 2
tablespoons, bronchiectasis should be suspected.

Both types of patients are subject to exacerbations, which are

usually associated with increased cough with purulent sputum, and
increased dyspnea. Hemoptysis can occur during these episodes.
Patients who have chronic bronchitis develop peripheral edema
much earlier in their illness than those who have emphysema.

Physical Examination
Early in the evolution of both types of COPD, the physical
examination may be normal. Later in the disease, the patient who
has emphysema tends to be thin, with a quiet, hyperinflated chest
(pink puffers). In contrast, the patient who has chronic bronchitis
tends to be stocky to obese and plethoric as a result of
erythrocytosis. In addition, the chronic bronchitis patient usually
presents with a noisy, wheezy chest and signs of right heart failure,
such as neck vein distention and edema (blue bloaters) (Table 2).
As the disease progresses, both patients prefer to sit upright with
arms extended and weight supported on the palms. On expiration,
patients may tend to purse the lips; on inspiration, a paradoxical
indrawing of the lower intercostal interspaces may be noted.
Cyanosis may be present, often associated with an enlarged, tender
liver. Asterixis is sometimes seen in association with severe
hypercapnia.

Systemic effects of COPD are also seen.[39] Possibly as a

consequence of systemic inflammation, it is not uncommon to find
COPD associated with nutritional abnormalities and weight loss,
skeletal muscle dysfunction (contributing to exercise limitations),
coronary artery disease, low serum testosterone levels (in males),
and osteoporosis.

Diagnostic Studies
Spirometry is a useful test in screening for COPD and should be
performed in all smokers with respiratory symptoms and in all
smokers older than 45 years.[40] Diagnosis of COPD by the history
and physical examination alone is sometimes incorrect. For this
reason, laboratory studies should be performed to confirm the
diagnosis, determine a likely prognosis, and detect potential
complications (eg, pneumothorax) and comorbid conditions (eg,
lung cancer).[41]

COPD is usually diagnosed on the basis of pulmonary function

testing, although radiographic studies and other tests are
sometimes helpful. There are significant differences in the findings
of pulmonary function testing in patients who primarily have
emphysema as compared with those who have chronic bronchitis
(Table 2).

Pulmonary function tests. In COPD patients, pulmonary function

tests are used to confirm the obstructive abnormality, quantify the
severity of the defect, assess the reversibility of the airflow
obstruction in response to therapy,[42] and monitor the course of the
disease. Spirometry is the test of choice for determining the
presence of airflow obstruction. A low FEV1/FVC ratio and a
decreased expiratory flow rate confirm airway obstruction, but the
best way to measure the severity of the obstruction is the FEV1.
Other useful tests include lung volumes, diffusing capacity, arterial
blood gases, and rest and exercise pulse oximetry.

Spirometry. Spirometry is the most useful test for screening airflow

obstruction of any type.[40] The results are presented as the absolute
value and the percentage predicted on the basis of the patient's
gender, age, and height. The earliest abnormality may be a
reduction in the forced expiratory flow (FEF) during the mid-portion
of the expiratory maneuver (FEF25% -75%). The next abnormality
to develop may be a reduced FEV1 and FEV1/ FVC ratio. It is the
reduction in this ratio that identifies the abnormality as an
obstructive defect. As the disease worsens, FVC is also reduced.
Repeated spirometry after inhalation of a beta-agonist, an
anticholinergic, or a combination of both bronchodilator agents can
detect reversible airflow obstruction, although the degree of
reversibility can vary from day to day.[42] The severity of COPD can
be determined from the FEV1/FVC ratio; the FEV1 compared with the
predicted value for a person of that gender, age, and height; and the
clinical findings (Table 1).[1]

Lung volume. Measurement of lung volume detects increases in the

RV and FRC, and these measurements can indicate hyperinflation.
Total lung capacity is usually increased in emphysema and tends to
be normal in chronic bronchitis.

Diffusion capacity. The diffusion capacity for carbon monoxide is

useful as an indicator of the presence of emphysema. One of the
physiologic consequences of emphysema is loss of alveolar-
capillary surface area, and this loss is detected by a reduction in the
lung's diffusion capacity.

Arterial blood gases. Arterial blood gases should be measured in all

patients with advanced COPD. Emphysema patients will maintain a
resting PaO2 only mildly to moderately decreased and will have a
normal PaCO2 until they are in end-stage COPD. In contrast, chronic
bronchitis patients develop severe hypoxemia and daytime
hypercapnia much earlier in the illness, necessitating careful titration
of supplemental oxygen.

Pulse oximetry. Pulse oximetry performed when the patient is at rest

and during exercise is recommended for all patients with severe
COPD. Most patients with severe emphysema (diffusion capacity <
55% of normal) have significant oxygen desaturation during
exercise and require oxygen supplementation during exercise to
maintain oxygen saturation at a level greater than 88%.

Chest Radiography
The chest radiograph may be normal, even in severe cases (Table
2). Radiographic findings that suggest the presence of emphysema
include arterial deficiency in the peripheral lung, hyperinflation of the
lung, and visible bullae.
In chronic bronchitis, the chest radiograph is usually normal (Table
2), but abnormal findings may include thickening of the bronchial
wall of a perihilar bronchus as viewed end-on, as well as increased
bronchovascular lung markings, which account for the so-called
"dirty chest" of chronic bronchitis. Chest radiography is also useful
to exclude other lung diseases, suggest the presence of associated
congestive heart failure, and detect lung masses or pulmonary
nodules.

Computed Tomography of the Chest

Computed tomography (CT) is much more sensitive than chest
radiography for the diagnosis of emphysema; however, CT should
be done only when the diagnosis is uncertain.[43] Patients who have
a normal chest radiograph and normal lung function or only an
isolated decrease in diffusing capacity can have extensive
emphysema, as detected by high-resolution CT.

Other Tests
The hematocrit is often elevated in patients who have a PaO2 less
than 55 mm Hg or in patients who have nocturnal desaturation.
Elevated hematocrit is most common in chronic bronchitis patients.

Sputum examination is indicated only in the setting of suspected

infection, and even then only when the results will alter therapy.[44]

Measurement of the alpha1-antitrypsin level is indicated when a

patient presents with COPD before age 50 years, has a
predominance of basilar emphysema on a chest radiograph, or has
a family history of COPD before age 50 years.[24]

Many COPD patients have nocturnal worsening of oxygen

desaturation, sometimes associated with obstructive sleep
apnea.[45] Nocturnal monitoring of pulse oximetry allows detection of
the desaturation and titration of nocturnal oxygen therapy. Formal
polysomnography (sleep study) should be performed in patients with
a history of snoring and excessive daytime somnolence.[45]

Echocardiography is useful to detect complicating pulmonary

hypertension in patients with severe COPD, although right heart
catheterization may be necessary for confirmation and
measurement of the extent of elevation of pulmonary artery
pressure.[36]

Bone density should be measured because of the common finding

of osteoporosis in COPD patients and the frequent need for steroid
therapy.