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Chronic Obstructive Pulmonary Disease

(COPD)
Updated: Oct 09, 2024
Author: Zab Mosenifar, MD, FACP, FCCP; Chief Editor: John J Oppenheimer, MD more...

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What are the medications for Chronic Obstructive Pulmonary Disease (COPD)? What are the treatment options for C

OVERVIEW

Practice Essentials
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, causing 3.23 million deaths
in 2019. Tobacco smoking accounts for over 70% of COPD cases in high-income countries. In low- and middle-income
countries, tobacco smoking accounts for only 30–40% of COPD cases, and household air pollution is a major risk factor.
[1]

Patients typically have symptoms of chronic bronchitis and emphysema, but the classic triad also includes asthma or a
combination of the above (see the image below).

Venn diagram of chronic obstructive pulmonary disease (COPD). Chronic obstructive lung disease is a disorder in which subsets of patients may
have dominant features of chronic bronchitis, emphysema, or asthma. The result is airflow obstruction that is not fully reversible.

Chronic bronchitis is defined clinically as the presence of a chronic productive cough for 3 months during each of 2
consecutive years (other causes of cough being excluded).

Emphysema is defined pathologically as an abnormal, permanent enlargement of the air spaces distal to the terminal
bronchioles, accompanied by destruction of their walls and without obvious fibrosis.

The 2022 International Classification of Diseases (ICD)-10 diagnosis code for COPD, unspecified is J44.9.
Signs and symptoms

Patients typically present with a combination of signs and symptoms of chronic bronchitis, emphysema, and reactive
airway disease. Symptoms include the following:

Cough, usually worse in the mornings and productive of a small amount of colorless sputum
Breathlessness: The most significant symptom, but usually does not occur until the sixth decade of life
Wheezing: May occur in some patients, particularly during exertion and exacerbations

While the sensitivity of physical examination in detecting mild-to-moderate COPD is relatively poor, the physical signs are
quite specific and sensitive for severe disease. Findings in severe disease include the following:

Tachypnea and respiratory distress with simple activities

Use of accessory respiratory muscles and paradoxical indrawing of lower intercostal spaces (Hoover sign)
Cyanosis
Elevated jugular venous pulse (JVP)
Peripheral edema

Thoracic examination reveals the following:

Hyperinflation (barrel chest)

Wheezing – Frequently heard on forced and unforced expiration
Diffusely decreased breath sounds
Hyperresonance on percussion
Prolonged expiration
Coarse crackles beginning with inspiration in some cases

Certain characteristics allow differentiation between disease that is predominantly chronic bronchitis and that which is
predominantly emphysema. Chronic bronchitis characteristics include the following:

Patients may be obese

Frequent cough and expectoration are typical
Use of accessory muscles of respiration is common
Coarse rhonchi and wheezing may be heard on auscultation
Patients may have signs of right heart failure (ie, cor pulmonale), such as edema and cyanosis

Emphysema characteristics include the following:

Patients may be very thin with a barrel chest

Patients typically have little or no cough or expectoration
Breathing may be assisted by pursed lips and use of accessory respiratory muscles; patients may adopt the tripod
sitting position
The chest may be hyperresonant, and wheezing may be heard
Heart sounds are very distant

See Clinical Presentation for more detail.

Diagnosis

The formal diagnosis of COPD is made with spirometry; when the ratio of forced expiratory volume in 1 second over
forced vital capacity (FEV1/FVC) is less than 70% of that predicted for a matched control, it is diagnostic for a significant
obstructive defect. Criteria for assessing the severity of airflow obstruction (based on the percent predicted
postbronchodilator FEV1) are as follows:

Stage I (mild): FEV1 80% or greater of predicted

Stage II (moderate): FEV1 50-79% of predicted
Stage III (severe): FEV1 30-49% of predicted
Stage IV (very severe): FEV1 less than 30% of predicted or FEV1 less than 50% and chronic respiratory failure

Arterial blood gas (ABG) findings are as follows:

 ABGs provide the best clues as to acuteness and severity of disease exacerbation
Patients with mild COPD have mild to moderate hypoxemia without hypercapnia
As the disease progresses, hypoxemia worsens and hypercapnia may develop, with the latter commonly being
observed as the FEV1 falls below 1 L/s or 30% of the predicted value
pH usually is near normal; a pH below 7.3 generally indicates acute respiratory compromise
Chronic respiratory acidosis leads to compensatory metabolic alkalosis

In patients with emphysema, frontal and lateral chest radiographs reveal the following:

Flattening of the diaphragm

Increased retrosternal air space
A long, narrow heart shadow
Rapidly tapering vascular shadows accompanied by hyperlucency of the lungs
Radiographs in patients with chronic bronchitis show increased bronchovascular markings and cardiomegaly

Advantages of high-resolution CT include the following:

Greater sensitivity than standard chest radiography

High specificity for diagnosing emphysema (outlined bullae are not always visible on a radiograph)
May provide an adjunctive means of diagnosing various forms of COPD (eg, lower lobe disease may suggest
alpha1-antitrypsin (AAT) deficiency
May help the clinician determine whether surgical intervention would benefit the patient

Other tests are as follows:

Hematocrit – Patients with polycythemia (hematocrit greater than 52% in men or 47% in women) should be
evaluated for hypoxemia at rest, with exertion, or during sleep

Serum potassium – Diuretics, beta-adrenergic agonists, and theophylline act to lower potassium levels

Measure AAT in all patients younger than 40 years, in those with a family history of emphysema at an early age, or
with emphysematous changes in a nonsmoker (also see Alpha1-Antitrypsin Deficiency).

Sputum evaluation will show a transformation from mucoid in stable chronic bronchitis to purulent in acute
exacerbations

Pulse oximetry, combined with clinical observation, provides instant feedback on a patient's status

Electrocardiography can help establish that hypoxia is not resulting in cardiac ischemia and that the underlying
cause of respiratory difficulty is not cardiac in nature

The distance walked in 6 minutes (6MWD) is a good predictor of all-cause and respiratory mortality in patients with
moderate COPD [2, 3] ; patients with COPD who desaturate during the 6MWD have a higher mortality rate than do
those who do not desaturate

Two-dimensional echocardiography can screen for pulmonary hypertension

Right-sided heart catheterization can confirm pulmonary artery hypertension and gauge the response to
vasodilators

See Workup for more detail.

Management

Smoking cessation continues to be the most important therapeutic intervention for COPD. Risk factor reduction (eg,
influenza vaccine) is appropriate for all stages of COPD. Approaches to management by stage include the following:

Stage I (mild obstruction): Short-acting bronchodilator as needed

Stage II (moderate obstruction): Short-acting bronchodilator as needed; long-acting bronchodilator(s);

cardiopulmonary rehabilitation
 Stage III (severe obstruction): Short-acting bronchodilator as needed; long-acting bronchodilator(s);
cardiopulmonary rehabilitation; inhaled glucocorticoids if repeated exacerbations

Stage IV (very severe obstruction or moderate obstruction with evidence of chronic respiratory failure): Short-acting
bronchodilator as needed; long-acting bronchodilator(s); cardiopulmonary rehabilitation; inhaled glucocorticoids if
repeated exacerbation; long-term oxygen therapy (if criteria met); consider surgical options such as lung volume
reduction surgery (LVRS) and lung transplantation

Agents used include the following:

Short-acting beta2 -agonist bronchodilators (eg, albuterol, metaproterenol, levalbuterol, pirbuterol)

Long-acting beta2 -agonist bronchodilators (eg, salmeterol, formoterol, arformoterol, indacaterol, vilanterol)

Respiratory anticholinergics (eg, ipratropium, tiotropium, aclidinium, revefenacin)

Xanthine derivatives (ie, theophylline)

Phosphodiesterase-4 Inhibitors (ie, roflumilast)

Inhaled corticosteroids (eg, fluticasone, budesonide): Peripheral blood eosinophil counts may help stratify the
likelihood of efficacy.

Oral corticosteroids (eg, prednisone)

Beta2 -agonist and anticholinergic combinations (eg, ipratropium and albuterol, umeclidinium bromide/vilanterol
inhaled)

Beta2 -agonist and corticosteroid combinations (eg, budesonide/formoterol, fluticasone and salmeterol,
vilanterol/fluticasone inhaled)

Pulmonary rehabilitation programs are typically multidisciplinary approaches that emphasize the following:

Patient and family education

Smoking cessation
Medical management (including oxygen and immunization)
Respiratory and chest physiotherapy
Physical therapy with bronchopulmonary hygiene, exercise, and vocational rehabilitation
Psychosocial support

Indications for admission for acute exacerbations include the following:

Failure of outpatient treatment

Marked increase in dyspnea
Altered mental status
Increase in hypoxemia or hypercapnia
Inability to tolerate oral medications such as antibiotics or steroids

See Treatment and Medication for more detail.

Background
In Western Europe, Badham (1808) and Laennec (1827) made the classic descriptions of chronic bronchitis and
emphysema in the early 19th century. A British medical textbook of the 1860s described the familiar clinical picture of
chronic bronchitis as an advanced disease with repeated bronchial infections that ended in right-sided heart failure.
Overall, this malady caused more than 5% of all deaths in the Middle Ages and earlier. The condition was most common
among the poor; therefore, it was attributed to "bad" living.

Developments in the 20th century included the widespread use of spirometry (see Workup), recognition of airflow
obstruction as a key factor in determining disability, and the improvement of pathologic methods to assess emphysema.
Participants in the Ciba symposium of 1958 proposed definitions of chronic bronchitis and emphysema, incorporating
the concept of airflow obstruction.

Chronic bronchitis is defined clinically as the presence of a chronic productive cough for 3 months during each of 2
consecutive years (other causes of cough being excluded). Emphysema, on the other hand, is defined pathologically as
an abnormal, permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of
their walls and without obvious fibrosis.

Airflow limitation in emphysema is due to loss of elastic recoil and decrease in airway tethering, whereas chronic
bronchitis leads to narrowing of airway caliber and increase in airway resistance. Although some patients predominantly
display signs of one of these diseases or the other, most fall somewhere in between the spectrum of these two
conditions.

Oral and inhaled medications are used for patients with stable COPD to reduce dyspnea, improve exercise tolerance, and
prevent complications. Most of the medications used in COPD treatment are directed at the potentially reversible
mechanisms of airflow limitation. (See Medication.)

Pathophysiology
Pathologic changes in chronic obstructive pulmonary disease (COPD) occur in the large (central) airways, the small
(peripheral) bronchioles, and the lung parenchyma. Most cases of COPD are the result of exposure to noxious stimuli,
most often cigarette smoke. The normal inflammatory response is amplified in persons prone to COPD development. The
pathogenic mechanisms are not clear but are most likely diverse. Increased numbers of activated polymorphonuclear
leukocytes and macrophages release elastases in a manner that cannot be counteracted effectively by antiproteases,
resulting in lung destruction.

The primary offender has been found to be human leukocyte elastase, with synergistic roles suggested for proteinase-3
and macrophage-derived matrix metalloproteinases (MMPs), cysteine proteinases, and a plasminogen activator.
Additionally, increased oxidative stress caused by free radicals in cigarette smoke, the oxidants released by phagocytes,
and polymorphonuclear leukocytes all may lead to apoptosis or necrosis of exposed cells. Accelerated aging and
autoimmune mechanisms have also been proposed as having roles in the pathogenesis of COPD. [4, 5]

Cigarette smoke causes neutrophil influx, which is required for the secretion of MMPs; this suggests, therefore, that
neutrophils and macrophages are required for the development of emphysema.

Studies have also shown that in addition to macrophages, T lymphocytes, particularly CD8+, play an important role in the
pathogenesis of smoking-induced airflow limitation.

To support the inflammation hypothesis further, a stepwise increase in alveolar inflammation has been found in surgical
specimens from patients without COPD versus patients with mild or severe emphysema. Indeed, mounting evidence
supports the concept that dysregulation of apoptosis and defective clearance of apoptotic cells by macrophages play a
prominent role in airway inflammation, particularly in emphysema. [6] Azithromycin (Zithromax) has been shown to
improve this macrophage clearance function, providing a possible future treatment modality. [7]

In patients with stable COPD without known cardiovascular disease, there is a high prevalence of microalbuminuria,
which is associated with hypoxemia independent of other risk factors. [8]

Chronic bronchitis

Mucous gland hyperplasia (as seen in the images below) is the histologic hallmark of chronic bronchitis. Airway
structural changes include atrophy, focal squamous metaplasia, ciliary abnormalities, variable amounts of airway smooth
muscle hyperplasia, inflammation, and bronchial wall thickening.
Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells.

Histopathology of chronic bronchitis showing hyperplasia of mucous glands and infiltration of the airway wall with inflammatory cells (high-powered
view).

Damage to the endothelium impairs the mucociliary response that clears bacteria and mucus. Inflammation and
secretions provide the obstructive component of chronic bronchitis. Neutrophilia develops in the airway lumen, and
neutrophilic infiltrates accumulate in the submucosa. The respiratory bronchioles display a mononuclear inflammatory
process, lumen occlusion by mucus plugging, goblet cell metaplasia, smooth muscle hyperplasia, and distortion due to
fibrosis. These changes, combined with loss of supporting alveolar attachments, cause airflow limitation by allowing
airway walls to deform and narrow the airway lumen.

In contrast to emphysema, chronic bronchitis is associated with a relatively undamaged pulmonary capillary bed. The
body responds by decreasing ventilation and increasing cardiac output. This V/Q mismatch results in rapid circulation in
a poorly ventilated lung, leading to hypoxemia and polycythemia. Eventually, hypercapnia and respiratory acidosis
develop, leading to pulmonary artery vasoconstriction and cor pulmonale. With the ensuing hypoxemia, polycythemia,
and increased CO2 retention, these patients have signs of right heart failure and are known as "blue bloaters."

Emphysema

Emphysema is a pathologic diagnosis defined by permanent enlargement of airspaces distal to the terminal bronchioles.
This leads to a dramatic decline in the alveolar surface area available for gas exchange. Furthermore, loss of alveoli
leads to airflow limitation by 2 mechanisms. First, loss of the alveolar walls results in a decrease in elastic recoil, which
leads to airflow limitation. Second, loss of the alveolar supporting structure leads to airway narrowing, which further
limits airflow.

Emphysema has 3 morphologic patterns:

Centriacinar
Panacinar
 Distal acinar, or paraseptal

Centriacinar emphysema is characterized by focal destruction limited to the respiratory bronchioles and the central
portions of the acini. This form of emphysema is associated with cigarette smoking and is typically most severe in the
upper lobes.

Panacinar emphysema involves the entire alveolus distal to the terminal bronchiole. The panacinar type is typically most
severe in the lower lung zones and generally develops in patients with homozygous alpha1-antitrypsin (AAT) deficiency.

Distal acinar emphysema, or paraseptal emphysema, is the least common form and involves distal airway structures,
alveolar ducts, and sacs. This form of emphysema is localized to fibrous septa or to the pleura and leads to formation of
bullae (as seen in the images below). The apical bullae may cause pneumothorax. Paraseptal emphysema is not
associated with airflow obstruction.

Gross pathology of advanced emphysema. Large bullae are present on the surface of the lung.

Gross pathology of a patient with emphysema showing bullae on the surface.

The gradual destruction of alveolar septae (shown in the image below) and of the pulmonary capillary bed in emphysema
leads to a decreased ability to oxygenate blood. The body compensates with lowered cardiac output and
hyperventilation. This V/Q mismatch results in relatively limited blood flow through a fairly well oxygenated lung with
normal blood gases and pressures in the lung, in contrast to the situation in chronic bronchitis. Because of low cardiac
output, the rest of the body also suffers from tissue hypoxia and pulmonary cachexia. Eventually, these patients develop
muscle wasting and weight loss and are identified as "pink puffers."
At high magnification, loss of alveolar walls and dilatation of airspaces in emphysema can be seen.

Emphysematous destruction and small airway inflammation

Emphysematous destruction and small airway inflammation often are found in combination in individual patients, leading
to the spectrum that is known as COPD. When emphysema is moderate or severe, loss of elastic recoil, rather than
bronchiolar disease, is the dominant mechanism of airflow limitation. By contrast, when emphysema is mild, bronchiolar
abnormalities are most responsible for the majority of the deficit in lung function. Although airflow obstruction in
emphysema is often irreversible, bronchoconstriction due to inflammation accounts for some reversibility. Airflow
limitation is not the only pathophysiologic mechanism by which symptoms occur.

Dynamic hyperinflation

Lung volumes, particularly dynamic hyperinflation, have also been shown to play a crucial role in the development of
dyspnea perceived during exercise. In fact, the improvement in exercise capacity brought about by several treatment
modalities, including bronchodilators, oxygen therapy, lung volume reduction surgery (LVRS), and maneuvers learned in
pulmonary rehabilitation, is more likely due to delaying dynamic hyperinflation rather than improving the degree of airflow
obstruction. [9, 10, 11, 12, 13, 14, 15, 16] Additionally, hyperinflation (defined as the ratio of inspiratory capacity to total lung
capacity [IC/TLC]) has been shown to predict survival better than forced expiratory volume in 1 second (FEV1). [6]

Etiology
Cigarette smoking

The primary cause of COPD is exposure to tobacco smoke. Overall, tobacco smoking accounts for as much as 90% of
COPD risk.

Cigarette smoking induces macrophages to release neutrophil chemotactic factors and elastases, which lead to tissue
destruction. Clinically significant COPD develops in 15% of cigarette smokers, although this number is believed to be an
underestimate. Age of initiation of smoking, total pack-years, and current smoking status predict COPD mortality.

People who smoke have an increased annual decline in FEV1: the physiologic normal decline in FEV1 is estimated to be
20-30 ml/y, but the rate of decline in COPD patients is generally 60 ml/y or greater.

Secondhand smoke, or environmental tobacco smoke, increases the risk of respiratory infections, augments asthma
symptoms, and causes a measurable reduction in pulmonary function.

A study by Nagelmann et al concluded that lung function deviation and lung structural changes are present in people who
smoke cigarettes before the clinical signs of airway obstruction reveal them. [17] These changes can be detected by body
plethysmography and diffusing capacity measurement with routine spirometry.

Airway hyperresponsiveness

Airway hyperresponsiveness (ie, Dutch hypothesis) stipulates that patients who have nonspecific airway hyperreactivity
and who smoke are at increased risk of developing COPD with an accelerated decline in lung function. Nonspecific
airway hyperreactivity is inversely related to FEV1 and may predict a decline in lung function.

The data regarding the possible role of airway hyperresponsiveness as a risk factor for the development of COPD in
people who smoke are unclear. It is important to note, however, that 60% demonstrate bronchial hyperresponsiveness.
[18] Moreover, bronchial hyperreactivity may result from airway inflammation observed with the development of smoking-

related chronic bronchitis. This may contribute to airway remodeling, leading to a more fixed obstruction, as is seen in
persons with COPD.

Environmental factors

COPD does occur in individuals who have never smoked. [19] Although the role of air pollution in the etiology of COPD is
unclear, the effect is small when compared with that of cigarette smoking. In developing countries, the use of biomass
fuels with indoor cooking and heating is likely to be a major contributor to the worldwide prevalence of COPD. Long-term
exposure to traffic-related air pollution may be a factor in COPD in patients with diabetes and asthma. [20]

Alpha1-antitrypsin deficiency

Alpha1-antitrypsin (AAT) is a glycoprotein member of the serine protease inhibitor family that is synthesized in the liver
and is secreted into the bloodstream. The main purpose of this 394-amino-acid, single-chain protein is to neutralize
neutrophil elastase in the lung interstitium and to protect the lung parenchyma from elastolytic breakdown. Severe AAT
deficiency predisposes to unopposed elastolysis with the clinical sequela of an early onset of panacinar emphysema. To
see complete information on Alpha1-Antitrypsin Deficiency, please go to the main article by clicking here.

AAT deficiency is the only known genetic risk factor for developing COPD and accounts for less than 1% of all cases in
the United States. Severe AAT deficiency leads to premature emphysema at an average age of 53 years for nonsmokers
and 40 years for smokers.

Nearly 24 variants of the AAT molecule have been identified, and all are inherited as codominant alleles. The most
common M allele (PiM) may be found in 90% of people, and homozygous (PiMM) phenotypes produce serum levels
within the reference range. The homozygous PiZZ state is the most common deficiency state and accounts for 95% of
people in the severely deficient category.

Intravenous drug use

Emphysema occurs in approximately 2% of persons who use intravenous (IV) drugs. This is attributed to pulmonary
vascular damage that results from the insoluble filler (eg, cornstarch, cotton fibers, cellulose, talc) contained in
methadone or methylphenidate.

The bullous cysts found in association with IV use of cocaine or heroin occur predominantly in the upper lobes. In
contrast, methadone and methylphenidate injections are associated with basilar and panacinar emphysema.

Immunodeficiency syndromes

Human immunodeficiency virus (HIV) infection has been found to be an independent risk factor for COPD, even after
controlling for confounding variables such as smoking, IV drug use, race, and age. [21]

Apical and cortical bullous lung damage occurs in patients who have autoimmune deficiency syndrome and
Pneumocystis carinii infection. Reversible pneumatoceles are observed in 10-20% of patients with this infection.

Vasculitis syndrome

Hypocomplementemic vasculitis urticaria syndrome (HVUS) may be associated with obstructive lung disease. Other
manifestations include angioedema, nondeforming arthritis, sinusitis, conjunctivitis, and pericarditis.

Connective tissue disorders

Cutis laxa is a disorder of elastin that is characterized most prominently by the appearance of premature aging. The
disease usually is congenital, with various forms of inheritance (ie, dominant, recessive). Precocious emphysema has
been described in association with cutis laxa as early as the neonatal period or infancy. The pathogenesis of this disorder
includes a defect in the synthesis of elastin or tropoelastin.
Marfan syndrome is an autosomal dominant inherited disease of type I collagen characterized by abnormal length of the
extremities, subluxation of the lenses, and cardiovascular abnormality. Pulmonary abnormalities, including emphysema,
have been described in approximately 10% of patients.

Ehlers-Danlos syndrome refers to a group of inherited connective tissue disorders with manifestations that include
hyperextensibility of the skin and joints, easy bruisability, and pseudotumors; it has also been associated with a higher
prevalence of COPD.

Salla disease

Salla disease is an autosomal recessive storage disorder described in Scandinavia; the disease is characterized by
intralysosomal accumulation of sialic acid in various tissues. The most important clinical manifestations are severe
intellectual disability, ataxia, and nystagmus. Precocious emphysema has been described and likely is secondary to
impaired inhibitory activity of serum trypsin.

Epidemiology
The National Health Interview Survey reports the prevalence of emphysema at 18 cases per 1000 persons and chronic
bronchitis at 34 cases per 1000 persons. [22] While the rate of emphysema has stayed largely unchanged since 2000, the
rate of chronic bronchitis has decreased. Another study estimates a prevalence of 10.1% in the United States. [23]
However, the exact prevalence of COPD in the United States is believed to be underestimated. This is largely due to the
fact that it is an underdiagnosed (and undertreated) disease, because most patients do not present for medical care until
the disease is in a late stage.

The exact prevalence of COPD worldwide is largely unknown, but estimates have varied from 7-19%. The Burden of
Obstructive Lung Disease (BOLD) study found a global prevalence of 10.1%. [24] Men were found to have a pooled
prevalence of 11.8% and women 8.5%. The numbers vary in different regions of the world. Cape Town, South Africa, has
the highest prevalence, affecting 22.2% of men and 16.7% of women.

Hannover, Germany, on the other hand, has the lowest prevalence, of 8.6% for men and 3.7% for women. The differences
can be explained in part by site and sex differences in the prevalence of smoking. As noted above, these reports are
widely believed to be underestimates because COPD is known to be underdiagnosed and undertreated. Additionally, the
prevalence in women is believed to be increasing.

Although current rates of COPD in men are higher than the rates in women, the rates in women have been increasing.
COPD occurs predominantly in individuals older than age 40 years.

Severe, early onset disease likely represents a distinct genotype and is more commonly seen in females, African
Americans, and those with a maternal family history of COPD. [25]

A study by Mintz et al estimated the prevalence of unidentified COPD. [26] Using the Lung Function Questionnaire (LFQ)
and spirometry results, the study determined that approximately 1 in 5 patients (21%) aged 30 years or older with a
history of smoking for 10 years or longer seen in a primary care center is likely to have COPD.

Prognosis
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, causing 3.23 million deaths
in 2019. [1] In terms of COPD as the underlying cause of death, absolute mortality rates for US patients aged 25 years or
older (2005) were 77.3 deaths per 100,000 males and 56.0 deaths per 100,000 females, or 64.3 persons per 100,000
overall. Internationally, overall mortality rates from COPD vary markedly, from more than 400 deaths per 100,000 males
aged 65-74 years in Romania to fewer than 100 deaths per 100,000 population in Japan.

The FEV1 was used to predict outcome in COPD until other factors were identified to play a role in determining the
outcome of COPD patients. These discoveries resulted in the creation of the multidimensional BODE index (body mass
index, obstruction [FEV1], dyspnea [modified Medical Research Council dyspnea scale], and exercise capacity [6MWD]).
[27] This index was developed to assess an individual’s risk of death or hospitalization.
Prognosis is based on a point system, with all 4 factors used to determine the score, as follows:

Body mass index: greater than 21 = 0 points; less than 21 = 1 point

FEV1 (postbronchodilator percent predicted): greater than 65% = 0 points; 50-64% = 1 point; 36-49% = 2 points; less
than 35% = 3 points
Modified Medical Research Council (MMRC) dyspnea scale: MMRC 0 = dyspneic on strenuous exercise (0 points);
MMRC 1 = dyspneic on walking a slight hill (0 points); MMRC 2 = dyspneic on walking level ground, must stop
occasionally due to breathlessness (1 point); MMRC 3 = dyspneic after walking 100 yards or a few minutes (2
points); MMRC 4 = cannot leave house; dyspneic doing activities of daily living (3 points)
Six-minute walking distance: greater than 350 meters = 0 points; 250-349 meters = 1 point; 150-249 meters = 2
points; less than 149 meters = 3 points

The approximate 4-year survival based on the point system above is as follows:

0-2 points = 80%

3-4 points = 67%
5-6 points = 57%
7-10 points = 18%

The use of a clinical scoring system reinforces that determinants of prognosis in COPD remain multifactorial. Waschki et
al argued that objective assessments of physical activity, including 6-minute walk test results, are best able to predict
mortality. [28] However, additional socioeconomic factors also likely play a role in COPD prognosis; for example, a
retrospective cohort study highlighted the increased risk of COPD-related mortality in patients who reside in isolated rural
areas. [29]

A study by Sundh et al determined that the Clinical COPD Questionnaire (CCQ), which estimates quality of life in patients
with COPD, is effective. [30] The CCQ identified that heart disease, depression, and underweight status are independently
associated with lower health-related quality of life in patients with COPD.

In a multicenter, prospective, observational study of 201 consecutive patients with moderate-to-severe COPD, Martinez-
Garcia et al reported that in addition to smoking, pulmonary hypertension, and declining lung function (known risk factors
for mortality in patients with COPD), bronchiectasis (which is common in patients with moderate-to-severe COPD) is
independently associated with increased risk of all-cause mortality. [31]

In this study, those who had bronchiectasis were found to be 2.5 times more likely to die than those who did
not. Bronchiectasis remained an independent factor after adjustment for dyspnea, partial pressure of oxygen, body mass
index, presence of potentially pathogenic microorganisms in sputum, presence of daily sputum production, number of
severe exacerbations and peripheral albumin, and ultrasensitive C-reactive protein concentrations. [31]

Patient Education
It is important to educate the patient with COPD about the disease and to encourage his or her active participation in
therapy. The 2 most essential points for the patient to understand are as follows:

The dangers of smoking and the improvement in quality of life attainable with smoking cessation
The need to seek medical care early during an exacerbation and to not wait until they are in distress

For patient education resources, visit the Lung Disease and Respiratory Health Center. Also, see the patient education
articles Chronic Obstructive Pulmonary Disease (COPD), Smoking (Cigarette), Asthma, and Emphysema.

Clinical Presentation