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Chronic obstructive pulmonary disease:

Diagnosis and staging
AUTHORS:
MeiLan King Han, MD, MS
Mark T Dransfield, MD
Fernando J Martinez, MD, MS
SECTION EDITOR:
James K Stoller, MD, MS
DEPUTY EDITOR:
Paul Dieffenbach, MD
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Oct 2023.
This topic last updated: Oct 13, 2023.
INTRODUCTIONChronic obstructive pulmonary disease (COPD) is
a common respiratory condition characterized by cough, dyspnea,
and airflow limitation [1]. Approximately 10 percent of individuals
aged 40 years or older have COPD, although the prevalence varies
between countries and increases with age [1-3]. COPD is
consistently ranked among the top causes of death in the United
States, killing more than 120,000 individuals each year [4,5]; prior to
the COVID-19 (coronavirus disease 2019) pandemic, it was the third
leading cause worldwide [6]. As a consequence of its high
prevalence and chronicity, COPD causes high resource utilization
with frequent clinician office visits, multiple hospitalizations due to
acute exacerbations, and the need for chronic therapy [7].
Establishing a correct diagnosis of COPD is important because
appropriate management can decrease symptoms (especially
dyspnea), reduce the frequency and severity of exacerbations,
improve health status, improve exercise capacity, and prolong
survival [8]. Many health conditions in older adults can result in
dyspnea or cough, so respiratory symptoms should not be attributed
to COPD without appropriate evaluation and diagnosis.

The definition, clinical manifestations, diagnostic evaluation, and

staging of COPD are discussed here. The risk factors, natural
history, prognosis, and treatment of COPD are discussed separately.

●(See "Chronic obstructive pulmonary disease: Risk

factors and risk reduction".)
 ●(See "Chronic obstructive pulmonary disease:
Prognostic factors and comorbid conditions".)
●(See "Stable COPD: Overview of management".)
●(See "COPD exacerbations: Clinical manifestations and
evaluation".)
●(See "COPD exacerbations: Management".)

DEFINITIONSCOPD should be understood in the context of other

closely related common respiratory conditions (emphysema, chronic
bronchitis, and chronic obstructive asthma) that represent an
overlapping spectrum of airway diseases.
COPD — The Global Initiative for Chronic Obstructive Lung Disease
(GOLD), a project initiated by the National Heart, Lung, and Blood
Institute (NHLBI) and the World Health Organization (WHO), defines
COPD as a "heterogeneous lung condition characterized by chronic
respiratory symptoms (dyspnea, cough, expectoration,
exacerbations) due to abnormalities of the airway (bronchitis,
bronchiolitis) and/or alveoli (emphysema) that cause persistent,
often progressive, airflow obstruction" [1,9].
In practice, the diagnosis of COPD requires all of the following
(see 'Diagnosis' below):
●The presence of pulmonary symptoms (dyspnea, cough,
or sputum production)
●The appropriate clinical context (most notably but not
exclusively tobacco exposure) (table 1)
●Evidence of airflow limitation
Chronic bronchitis — Chronic bronchitis is defined as a chronic
productive cough over a defined period, classically for at least three
months in each of two successive years, in a patient in whom other
causes of chronic cough (eg, bronchiectasis) have been excluded
[1]. It may precede or follow development of airflow limitation
[1,10,11]. This definition has been used in many studies, despite the
arbitrarily selected symptom duration. By age 35 to 40 years,
cigarette smokers may develop chronic bronchitis and start to have
intermittent exacerbations of their symptoms even in the absence of
airflow obstruction [12].
Emphysema — Emphysema describes enlargement of the airspaces
distal to the terminal bronchioles that is accompanied by
destruction of the airspace walls, a pathologic finding frequently
seen in patients with COPD [13]. This finding manifests clinically
with decreased breath sounds and evidence of hyperinflation of the
lungs on examination or imaging; it is frequently associated with
dyspnea. Emphysema is classically not accompanied by
macroscopic fibrosis. While emphysema can exist in individuals who
do not have airflow limitation, it is more common among patients
who have moderate or severe airflow obstruction [1,14-16].
The various subtypes of emphysema (eg, proximal acinar, panacinar,
distal acinar) are described below. (See 'Pathology' below.)
Airflow limitation — Airflow limitation is physiologically defined as
an abnormally reduced ability to exhale efficiently. The severity and
presence of airflow limitation are determined by evaluating the
forced expiratory volume in one second (FEV1) and the ratio of the
FEV1 to the total forced expiratory volume (aka, forced vital
capacity [FVC]). (See 'Spirometry' below and "Office spirometry",
section on 'Interpretation'.)

Airflow limitation may be fixed or may change in response to

exogenous factors (eg, environmental exposure, temperature, and
medications). Asthma is defined by significant variability in airflow
obstruction, whereas COPD is characterized by obstruction that is
not fully reversible with medication.

Asthma — The Global Initiative for Asthma (GINA) gives the

following definition of asthma: "Asthma is a chronic inflammatory
disorder of the airways that leads to recurrent episodes of wheezing,
breathlessness, chest tightness, and coughing. These episodes are
associated with widespread, but variable, airflow obstruction that is
often reversible either spontaneously or with treatment" [1]. The
episodic nature of the symptoms and reversibility of airflow
obstruction are clinical features that help distinguish asthma from
COPD. However, adults with longstanding asthma may develop
persistent airflow limitation. Distinguishing these patients from
those with COPD is difficult, particularly in the context of additional
COPD risk factors (table 1).
Interrelationships among these conditions — Chronic bronchitis
and emphysema were previously incorporated into the definition of
COPD [17,18], and their clinical features overlap those of patients
with asthma and COPD. This has caused considerable confusion
regarding appropriate classification of patients with respiratory
symptoms and COPD risk factors. Important points about these
interrelationships include:
●COPD – Patients with emphysema or chronic bronchitis
and persistent postbronchodilator airflow limitation meet
the definition of COPD. Chronic bronchitis, emphysema,
and postbronchodilator airflow limitation commonly occur
together [19].
●Asthma – Patients with asthma who only have inducible
airway obstruction or whose airflow limitation is
completely reversible with bronchodilator therapy are not
considered to have COPD.
●Asthma and COPD – Patients with asthma whose airflow
limitation does not remit completely and who have other
appropriate clinical risk factors (eg, older age, exposure
history) are considered to have both asthma and COPD.
The etiology and pathogenesis of COPD in such patients
may be different from that of other COPD patients (table
2). While descriptors "asthma and COPD overlap (ACO)"
and "COPD-A" have been proposed to identify patients
with airway disease who have features of both asthma
and COPD, the topic remains controversial. No single,
universally accepted definition has emerged. Central to
most of the proposed definitions are age >40 years,
history of asthma at a younger age, persistent
postbronchodilator airflow obstruction, and evidence of
partial bronchodilator reversibility. (See "Asthma and
COPD overlap (ACO)".)
Further study of this relationship will be needed to
determine with certainty how treatment algorithms
should be tailored to these patients [20,21]. An evolving
literature suggests differential responses to inhaled
glucocorticoids in patients with or without increased
circulating eosinophils [22,23]. Peripheral eosinophilia is
recommended by GOLD and our authors for use clinically
to guide pharmacotherapy in all patients with COPD.
(See "Stable COPD: Follow-up pharmacologic
management", section on 'Blood eosinophils, inhaled
corticosteroids, and exacerbations'.)
Subgroups of COPD patients with eosinophilia may
experience clinical improvement with biologic
medications shown to have benefit in asthma.
(See "Stable COPD: Follow-up pharmacologic
management", section on 'Future
directions' and "Management of refractory chronic
obstructive pulmonary disease", section on 'Frequent
exacerbations despite azithromycin or roflumilast'.)
●Pre-COPD – Patients with chronic bronchitis or
emphysema without irreversible airway obstruction
do not have COPD but are at high risk for developing the
disease [24,25]. The term "pre-COPD" is used to identify
such individuals who have either respiratory symptoms,
radiographic abnormalities consistent with COPD, or
early lung function changes in the context of COPD risk
 factors but do not have airway obstruction as defined by
FEV1/FVC <0.7. There is not full consensus on the defining
features of pre-COPD, but diagnostic criteria have been
proposed (table 3) [1,26,27].
Epidemiologic studies suggest that nearly 50 percent of
current and former smokers without airway obstruction
have respiratory symptoms, which correlate with reduced
exercise capacity, radiographic emphysema and wall
thickening, and lung function at the lower end of the
normal range [15,16]. While many of these patients are
treated off-label with bronchodilators or inhaled
glucocorticoids, one large trial failed to show
improvement in respiratory symptoms or quality of life
with dual long-acting bronchodilator therapy (indacaterol-
glycopyrrolate) versus placebo in this population [28].
Hence, existing evidence does not support inhaled
bronchodilator therapies for symptomatic patients
without airway limitation. Additional study is needed to
determine appropriate preventative and maintenance
therapies for this population.
●Other airway diseases – Patients with airflow limitation
due to diseases that have a known etiology or a specific
pathology (eg, cystic fibrosis, bronchiectasis, obliterative
bronchiolitis) are not considered to have COPD. However,
these exclusions are loosely defined [29].
PATHOLOGYHistology is not obtained from patients with COPD as
part of the diagnostic work-up. The predominant pathologic changes
of COPD are found in the airways, but changes are also seen in the
lung parenchyma and pulmonary vasculature. In a given individual,
the pattern of pathologic changes depends on features of the
underlying disease (eg, chronic bronchitis, emphysema, alpha-1
antitrypsin deficiency), genetic susceptibility, and disease severity
[1]. While radiographic methods do not have the resolution of
histology, high-resolution computed tomography (HRCT) can assess
lung parenchyma [30], airways [31], and pulmonary vasculature [32].
(See 'Additional testing' below.)

Pathologic features of COPD (by compartment) include:

●Airways – In the airways, COPD results in chronic

inflammation, increased numbers of goblet cells, mucus
gland hyperplasia, fibrosis, as well as narrowing in and
loss of small airways. In addition, airway collapse
frequently occurs due to the loss of tethering caused by
emphysematous destruction of alveolar walls [14]. Among
patients with chronic bronchitis who have mucus
hypersecretion, an increased number of goblet cells and
enlarged submucosal glands are typically seen.
Chronic airway inflammation in chronic bronchitis and
emphysema is frequently characterized by the presence
of CD8+ T-lymphocytes, neutrophils, and CD68+
monocytes/macrophages (picture 1) [33-37]. In
comparison, the bronchial inflammation of asthma is
more often characterized by the presence of CD4+ T-
lymphocytes, eosinophils, and increased interleukin (IL)-4
and IL-5 [38-40]. These findings are not diagnostic,
however, as there can be significant overlap between
these inflammatory airway phenotypes in individual
patients.
●Lung parenchyma – Emphysema affects the structures
distal to the terminal bronchiole, consisting of the
respiratory bronchiole, alveolar ducts, alveolar sacs, and
alveoli, known collectively as the acinus. These
structures in combination with their associated
capillaries and interstitium form the lung parenchyma.
The part of the acinus that is affected by permanent
dilation or destruction determines the subtype of
emphysema.
•Proximal acinar (also known as centrilobular)
emphysema refers to abnormal dilation or destruction
of the respiratory bronchiole, the central portion of the
acinus. It is commonly associated with cigarette
smoking and is the most common emphysema subtype
seen in patients with COPD. Centrilobular emphysema
is also seen in coal workers’ pneumoconiosis.
•Panacinar emphysema refers to enlargement or
destruction of all parts of the acinus. Diffuse panacinar
emphysema is a characteristic of alpha-1 antitrypsin
deficiency, although it can be seen in combination
with proximal acinar emphysema in other patients with
COPD. (See "Clinical manifestations, diagnosis, and
natural history of alpha-1 antitrypsin deficiency".)
•In distal acinar (also known as paraseptal)
emphysema, the alveolar ducts are predominantly
affected. Distal acinar emphysema may occur alone or
in combination with proximal acinar and panacinar
emphysema. When it occurs alone, extensive
subpleural paraseptal emphysema may be associated
 with spontaneous pneumothorax, but it is otherwise of
little clinical significance. (See "Pneumothorax in
adults: Epidemiology and etiology".)
●Pulmonary vasculature – Changes in the pulmonary
vasculature in COPD include intimal hyperplasia and
smooth muscle hypertrophy/hyperplasia, which are
thought to be due to chronic hypoxic vasoconstriction of
the small pulmonary arteries [41].
CLINICAL PRESENTATION
Symptoms and pattern of onset — The three cardinal symptoms of
COPD are dyspnea, chronic cough, and sputum production; the most
common early symptom is exertional dyspnea. Less common
symptoms include wheezing and chest tightness (table 4A).
However, any of these symptoms may develop independently and
with variable intensity.
There are various ways in which patients with COPD present [42]:
●Patients who have an extremely sedentary lifestyle but
few complaints – These patients require careful
questioning to elicit a history that is suggestive of COPD.
Some patients unknowingly avoid exertional dyspnea by
shifting their expectations and limiting their activity.
They may be unaware of the extent of their limitations or
that their limitations are due to respiratory symptoms,
although they may complain of fatigue.
●Patients who present with progressive dyspnea and
chronic cough – For these patients, dyspnea may initially
be noticed only during exertion. However, it eventually
becomes noticeable with progressively less exertion or
even at rest. The chronic cough is characterized by the
insidious onset of sputum production, which occurs in the
morning initially but may progress to occur throughout
the day. The daily sputum volume rarely exceeds 60
milliliters. The sputum is usually mucoid but becomes
more purulent during exacerbations.
●Patients who present with intermittent pulmonary
symptoms and signs – These patients have minimal
symptoms at baseline but episodically develop some of
the following: cough, purulent sputum, wheezing, fatigue,
and dyspnea. Typically, the interval between
exacerbations decreases as the severity of the COPD
increases. This symptom complex can be a diagnostic
challenge due to overlap with other common chronic
diseases. For example, the combination of intermittent
 wheezing and dyspnea may lead to an incorrect diagnosis
of asthma. Conversely, other illnesses with similar
episodic manifestations (eg, heart failure, bronchiectasis,
bronchiolitis) are often incorrectly diagnosed as a COPD
exacerbation (table 5). (See "COPD exacerbations:
Management".)
Approximately 62 percent of patients with moderate to severe COPD
report variability in symptoms (eg, dyspnea, cough, sputum,
wheezing, or chest tightness) over the course of the day or week to
week; morning is typically the worst time of day [43].

Patients with COPD may experience weight gain (due to activity

limitations), weight loss (possibly due to dyspnea while eating or
increased metabolic work of breathing), limitation of activity
(including sexual), cough, syncope, or feelings of depression or
anxiety. Weight loss generally reflects more advanced disease and
is associated with a worse prognosis.

Comorbid diseases that may accompany COPD include lung cancer,

bronchiectasis, cardiovascular disease, osteoporosis, metabolic
syndrome, skeletal muscle weakness, anxiety, depression, and
cognitive dysfunction. Patients may also report a family history of
COPD or other chronic respiratory illness [1,44-49].
Risk factors, including smoking and inhalational exposures — For
patients presenting with respiratory symptoms, it is critical to
assess for the genetic, developmental, and environmental risk
factors that can predispose to the development of COPD (table 4A)
[1,26,50]. The increasing recognition of these varying risk factors
beyond smoking alone have led to a proposed taxonomy of COPD
"etiotypes" (table 2). Understanding the predominant etiology of
disease in a given patient may allow for more targeted risk
reduction. A more complete discussion of COPD risk factors and risk
reduction can be found elsewhere. (See "Chronic obstructive
pulmonary disease: Risk factors and risk reduction".)
The most common risk factor for COPD is cigarette smoking. Other
exposures including passive smoke and biomass fuel use also play
significant roles worldwide [1,51,52].
●Smoking history – The amount and duration of smoking
contribute to disease severity [1,53-55]. Thus, a key step
in the evaluation of patients with suspected COPD is to
ascertain the number of pack-years smoked (packs of
cigarettes per day multiplied by the number of years). A
smoking history should include the age of starting and
the age of quitting, as patients may underestimate the
 number of years they smoked. With enough smoking,
almost all smokers will develop measurably reduced lung
function [8]. While studies have shown an overall "dose-
response curve" for smoking and lung function, some
individuals develop severe disease with fewer pack-years
and others have minimal to no symptoms despite many
pack-years [8].
The exact threshold for the duration/intensity of cigarette
smoking that will result in COPD varies from one
individual to another. In the absence of an additional
genetic/environmental/occupational predisposition,
smoking less than 10 to 15 pack-years of cigarettes is
unlikely to result in COPD.
●History of fume and dust exposure – The
environmental/occupational history may disclose other
important risk factors for COPD, such as exposure to
fumes or organic or inorganic dusts, including household
biomass smoke. These exposures help to explain the
significant minority of patients with COPD who never
smoked [53,56,57].
●Other risk factors – Certain pulmonary and systemic
infections are known to cause permanent structural
changes in the lung that predispose to COPD. In
particular, childhood pneumonias, tuberculosis infection,
and human immunodeficiency virus (HIV) are associated
with high risk for later development of COPD [50].
Similarly, premature birth and early-life asthma may
affect the development of the lung and increase the risk
of COPD. A history of asthma is also important to elicit
because poorly controlled asthma in adulthood may
progress to fixed airflow limitation and COPD [56,58]. A
strong family history of COPD or other chronic respiratory
illnesses, particularly early in life, may suggest a genetic
predisposition to COPD.
Physical examination — The findings on physical examination of
the chest vary with COPD severity (table 4A-B). (See 'Assessment of
severity and staging' below.)
●Mild disease – In mild disease, the physical examination
may be normal. Subtle clues include prolonged expiratory
time and faint end-expiratory wheezes on forced
exhalation.
●Moderate to severe disease – As the severity of the
airway obstruction increases, physical examination may
reveal hyperinflation (eg, increased resonance to
 percussion), decreased breath sounds, wheezes, crackles
at the lung bases, and/or distant heart sounds [59].
Features of severe disease include an increased
anteroposterior diameter of the chest ("barrel-shaped"
chest) and a depressed diaphragm with limited movement
based on chest percussion.
●End-stage disease and chronic respiratory failure –
Patients with end-stage COPD may adopt positions that
relieve dyspnea, such as leaning forward with arms
outstretched and weight supported on the palms or
elbows. This posture may be evident during the
examination or may be suggested by the presence of
callouses or swollen bursae on the extensor surfaces of
forearms. Other physical examination findings include
use of the accessory respiratory muscles of the neck and
shoulder girdle, expiration through pursed lips,
paradoxical retraction of the lower interspaces during
inspiration (ie, Hoover sign) [60,61], cyanosis, asterixis
due to severe hypercapnia, and an enlarged, tender liver
due to right heart failure. Neck vein distention may also
be observed because of increased intrathoracic pressure,
especially during expiration.
●Adjunctive signs – Yellow stains on the fingers due to
nicotine and tar from burning tobacco are a clue to
ongoing and heavy cigarette smoking [62]. Clubbing of
the digits is not typical in COPD (even with associated
hypoxemia). Its presence suggests comorbidities such as
lung cancer, interstitial lung disease, or bronchiectasis.
DIAGNOSTIC EVALUATION
Whom to evaluate — Further diagnostic evaluation for COPD is
appropriate in adults who report dyspnea, chronic cough, or chronic
sputum production, or who have had a gradual decline in activity
level, particularly if they have risk factors for COPD (eg, cigarette
smoking, indoor biomass smoke) (table 4A) [1,54]. Adults without
any symptoms should not undergo further testing for COPD.
Some patients with significant symptomatic COPD fail to report
these symptoms to physicians. We agree with the Global Initiative
for Chronic Obstructive Lung Disease (GOLD) in advocating for
active case finding among at risk individuals [1]. The CAPTURE
questionnaire (Chronic obstructive pulmonary disease Assessment
in Primary care To identify Undiagnosed Respiratory disease
and Exacerbation risk) is a well-validated tool that can help identify
occultly symptomatic patients who would likely benefit from therapy
for COPD and would therefore be candidates for diagnostic
evaluation using spirometry (table 6) [63,64]. Notably, in one large
trial of its use as a screening tool for clinically significant COPD in a
primary care population, the CAPTURE questionnaire exhibited a
sensitivity 48 percent, specificity 89 percent, positive predictive
value 10 percent, and number needed to screen of 82 [65].
Based both on the post hoc analysis of results from the CAPTURE
screening trial [65] and the increased emphasis on symptoms rather
than airflow limitation as a driver of therapeutic strategies [1], use
of CAPTURE without peak flow measurements may identify patients
appropriate for further evaluation and therapy. Patients with a
questionnaire score of 0 to 2 are at lower risk, whereas those with
scores 3 to 6 should undergo spirometric evaluation.
Current guidelines do not support population-based screening of
asymptomatic adults for COPD with spirometry [66,67], as
asymptomatic mild airflow obstruction does not require treatment
[54,67]. Asymptomatic and nonsmoking individuals with mild airflow
obstruction but no history of asthma do not have the same
progressive decline in lung function that is observed among
individuals who have a similar degree of airflow obstruction and are
symptomatic or continue to smoke [68].
How to evaluate — Patients at risk for COPD should be evaluated
with spirometry; we also typically obtain laboratory testing for
dyspnea (eg, complete blood count, thyroid-stimulating hormone, N-
terminal pro hormone brain natriuretic peptide [BNP]) and a chest
radiograph to assess for other cardiac and pulmonary conditions.
Spirometry — Spirometry is required to establish the diagnosis of
COPD. When evaluating a patient for possible COPD, we perform
spirometry before and after bronchodilator administration to
determine whether airflow limitation is present and whether it is
partially or fully reversible. Airflow limitation that is irreversible or
only partially reversible with bronchodilator treatment is a defining
physiologic feature of COPD. (See "Office spirometry", section on
'Post-bronchodilator spirometry'.)
The most important values measured during spirometry are the
forced expiratory volume in one second (FEV1) and the forced vital
capacity (FVC). The postbronchodilator ratio of FEV1/FVC determines
whether nonreversible airflow limitation is present [1]; the
postbronchodilator percent predicted value for FEV1 determines the
severity of airflow limitation (algorithm 1). The ratio of FEV1/FVC is
not used to determine severity of airflow limitation because FVC
often decreases with increasing obstruction due to air trapping or
premature termination of exhalation.
●Threshold for airflow limitation – The ideal threshold for
establishing airflow limitation in the diagnosis of COPD
has not been empirically determined. We agree with the
GOLD recommendations, which support the simple and
well-established use of postbronchodilator FEV1/FVC <0.7
as the threshold for airflow limitation [1].
However, the FEV1/FVC ratio decreases with age, so use
of the fifth percentile lower limit of normal (LLN) of the
FEV1/FVC ratio (or, equivalently, a z-score of -1.645) rather
than the absolute value of <0.7 has been advocated by
some as a dividing point for the diagnosis of COPD and
other obstructive lung diseases [69-73]. In practice, the
adverse consequences of overdiagnosis of COPD in the
elderly by use of a fixed ratio are somewhat mitigated by
checking spirometry only in patients with symptoms and
risk factors for COPD, but underdiagnosis of younger
persons with abnormal airflow for age remains a concern.
(See "Office spirometry", section on 'Ratio of
FEV1/FVC' and "Selecting reference values for
pulmonary function tests", section on 'Spirometry'.)
One large study pooling data from nearly 25,000 adults in
population-based cohorts found that a fixed threshold of
0.7 was nearly optimal for determining persons at
increased risk for COPD hospitalization or death,
performing slightly better than LLN [74]. However, an
analysis of current and former smokers with airflow
limitation based on GOLD criteria but normal lung
function based on LLN found that these patients had
normal measures of multiple other respiratory-related
phenotypes, including CT-measured emphysema and gas
trapping [75].
●Alternatives to FEV1/FVC – The forced expiratory volume
in six seconds (FEV6), obtained by stopping the expiratory
effort after six seconds rather than at cessation of
airflow, is an acceptable surrogate for the FVC [76-80].
The advantages of the FEV1/FEV6 include less frustration
by the patient and technician trying to achieve an end-of-
test plateau, less chance of syncope, shorter testing
time, and better repeatability, without loss of sensitivity
or specificity. If used, the LLN for FEV1/FEV6 from the
Third National Health and Nutrition Examination Survey
(NHANES III) is a reasonable threshold to diagnose
airflow limitation. Global Lung Function Initiative (GLI)
spirometry equations do not include FEV6 reference
 values, so this method cannot be used with spirometry
software that relies on these equations. (See "Office
spirometry", section on 'Forced expiratory volume in six
seconds' and "Office spirometry", section on 'Ratio of
FEV1/FVC'.)
By definition, patients with significant smoking exposure, abnormal
prebronchodilator FEV1/FVC, but normal postbronchodilator FEV1/FVC
do not meet current criteria for COPD; however, they are at high risk
for developing COPD. Such patients comprised 6 percent of former
or current heavy smokers in one cohort. Compared with smokers
without prebronchodilator obstruction, these patients had a higher
likelihood of progression to COPD (hazard ratio [HR] 6.2, 95% CI 4.6-
8.3), with 61 percent (versus 14 percent) progressing to COPD within
five years [81]. We reassess this group of patients with repeat
spirometry after one year, or earlier if they have worsening
symptoms.
Additional testing — In the setting of chronic respiratory symptoms
and appropriate risk factors, spirometry is the only testing required
for the diagnosis of COPD. Additional testing is directed at ruling out
alternative diagnoses.
●Laboratory studies – For patients with dyspnea, we
obtain laboratory studies as part of a broad evaluation for
potential etiologies. This often includes a complete blood
count for assessment of anemia, an assessment of
electrolytes and kidney function, a thyroid-stimulating
hormone level, and a plasma BNP or N-terminal pro-BNP
(NT-proBNP) concentration as a component of the
evaluation of suspected heart failure (HF).
(See "Approach to the patient with dyspnea", section on
'Initial testing in chronic dyspnea'.)
●Chest radiograph – For patients with suspected COPD,
we typically obtain a chest radiograph to evaluate for
alternative parenchymal processes and assess pulmonary
comorbidities. Plain chest radiographs have a poor
sensitivity for detecting COPD. As an example, only about
half of patients with COPD of moderate severity are
identified as having COPD by a plain chest radiograph (ie,
sensitivity of 50 percent).
Radiographic features suggestive of COPD (usually seen
in advanced disease) include:
•Rapidly tapering vascular shadows, increased
radiolucency of the lung, a flat diaphragm, and a long,
narrow heart shadow on a frontal radiograph (image 1).
 •A flat diaphragmatic contour and an increased
retrosternal airspace on a lateral radiograph (image 2).
These findings are due to hyperinflation.
•Bullae, defined as radiolucent areas larger than one
centimeter in diameter and surrounded by arcuate
hairline shadows. They are due to locally severe
disease and may or may not be accompanied by
widespread emphysema (image 3).
•When advanced COPD leads to pulmonary
hypertension and cor pulmonale, prominent hilar
vascular shadows and encroachment of the heart
shadow on the retrosternal space may be seen [82,83].
The cardiac enlargement may become evident only by
comparison with previous chest radiographs.
(See "Treatment and prognosis of pulmonary arterial
hypertension in adults (group 1)".)
●Computed tomography, for alternative diagnoses or if
spirometry is not available – There are settings where
thoracic CT is routinely available and accessible,
whereas spirometric testing can be challenging to obtain.
CT has greater sensitivity and specificity than standard
chest radiography for the detection of emphysema. This
is particularly true with high-resolution computed
tomography (HRCT; ie, collimation of 1 to 2 mm) [84-88].
Expiratory scans, particularly when used in conjunction
with the inspiratory scans, can help to assess
nonemphysematous air trapping as a surrogate measure
for small airway abnormalities [89] (see "High resolution
computed tomography of the lungs").
In the absence of other findings, CT-detected
emphysema, air trapping, and airway remodelling
involving a significant portion of the lungs is highly
suggestive of COPD, and some have advocated for these
findings as an alternative diagnostic pathway [50].
Because spirometry has a larger role in disease staging,
is more cost-effective, and avoids unnecessary radiation
exposure, we do not favor this approach unless
spirometry cannot be obtained.
CT scanning may also be performed when symptoms or
the physical examination suggest a potential
complication of COPD (eg, pneumonia, pneumothorax,
giant bullae), an alternate diagnosis (eg, thromboembolic
disease) is suspected, or lung cancer screening is
indicated [1]. (See "Evaluation and medical management
of giant bullae", section on 'Evaluation' and "Clinical
presentation, evaluation, and diagnosis of the
nonpregnant adult with suspected acute pulmonary
embolism" and "Screening for lung cancer", section on
'Low-dose chest CT'.)
Certain CT scan features can anatomically characterize
the emphysema as centriacinar (centrilobular),
panacinar, or paraseptal, although this is usually not
necessary for clinical management [87,90]:
•Centriacinar emphysema occurs preferentially in the
upper lobes and produces holes in the center of
secondary pulmonary lobules. The walls of
emphysematous spaces are usually imperceptible, but
central vessels may be visible (image 4). In contrast,
the walls of cysts in pulmonary Langerhans
histiocytosis, another cystic lung disease of cigarette
smokers, are thicker (image 5).
(See 'Pathology' above.)
•Panacinar emphysema more commonly involves the
lung bases and involves the entire secondary
pulmonary lobule (image 6). Panacinar emphysema can
cause a generalized paucity of vascular structures.
Among patients with alpha-1 antitrypsin deficiency,
panacinar emphysema is the more common pattern.
(See "Clinical manifestations, diagnosis, and natural
history of alpha-1 antitrypsin deficiency", section on
'Clinical manifestations'.)
•Paraseptal (distal acinar) emphysema produces small,
subpleural collections of gas located in the periphery
of the secondary pulmonary lobule (image 7). It is
considered to be the precursor of bullae (image 8).
(See 'Pathology' above.)
Newer CT scanners with higher resolution and new
analytical methods can resolve airway dimensions,
although the clinical significance of these measures is
undefined [87,91-93]. Similarly, high-resolution scans can
detect pruning of the distal vascular tree, which arises
from destruction of alveoli and their associated capillary
beds due to emphysema [32]. Quantitative parameters
based on lung density, airway wall thickening, airway
dilation, and vascular pruning have all been established
to gauge severity of emphysema, airway disease, and
pulmonary vascular pathology, respectively, but they
 have been used primarily as research tools and are not
yet widely available.
DIAGNOSISThe presence of symptoms compatible with COPD (eg,
dyspnea at rest or on exertion, cough with or without sputum
production, progressive limitation of activity) is suggestive of the
diagnosis, especially if there is a history of exposure to triggers of
COPD (eg, tobacco smoke, occupational dust, indoor biomass
smoke), a family history of chronic lung disease, or presence of
associated comorbidities (table 1).
The diagnosis of COPD is confirmed by the following [1,94]:
●Spirometry demonstrating airflow limitation (ie, a forced
expiratory volume in one second/forced vital capacity
[FEV1/FVC] ratio less than 0.7 or below the lower limit of
normal [LLN]) that is incompletely reversible after the
administration of an inhaled bronchodilator (table 4A-B).
(See 'Spirometry' above.)
●Absence of an alternative explanation for the symptoms
and airflow limitation (table 5) [1]. The differential
diagnosis of COPD is discussed below. (See 'Differential
diagnosis' below and "Approach to the patient with
dyspnea".)
DIFFERENTIAL DIAGNOSISAmong patients who present in mid
or later life with dyspnea, cough, and sputum production, the
differential diagnosis is broad (eg, heart failure, COPD, interstitial
lung disease, thromboembolic disease) (table 5). Typically,
persistent airflow limitation on pulmonary function testing and
absence of radiographic features of heart failure or interstitial lung
disease direct the clinician to a narrower differential, which
includes COPD, chronic obstructive asthma, bronchiectasis,
tuberculosis, constrictive bronchiolitis, and diffuse panbronchiolitis
[1]. Importantly, these conditions are not mutually exclusive and
commonly occur together. For example, patients with asthma may
develop COPD, and patients with COPD may have concurrent
bronchiectasis.
●Chronic obstructive asthma – Older patients with a
lifetime history of asthma may develop chronic airway
remodeling including fixed airway obstruction. For
patients without risk factors for COPD, chronic
obstructive asthma is the presumed diagnosis in these
cases. In patients with risk factors for COPD, however, a
clear distinction between chronic obstructive asthma and
COPD is not possible. As an example, a patient who has
suffered from atopic asthma since childhood and smoked
cigarettes for 15 years in their twenties and thirties could
present in their fifties with a combination of asthma and
COPD. Recognizing the coexistence of these diseases is
essential in devising a treatment plan that reflects both
underlying disease processes. (See 'Interrelationships
among these conditions' above and "Asthma in
adolescents and adults: Evaluation and
diagnosis" and "Asthma and COPD overlap (ACO)".)
●Chronic bronchitis with normal spirometry – A small
portion of cigarette smokers have a chronic productive
cough for three months in each of two successive years
but do not have airflow limitation on pulmonary function
tests. They are not considered to have COPD, although
they may develop COPD if they continue to smoke.
(See 'Interrelationships among these conditions' above.)
●Central airway obstruction – Central airway obstruction
can be caused by numerous benign and malignant
processes and can mimic COPD with a slowly progressive
dyspnea on exertion followed by dyspnea with minimal
activity (table 7). Monophonic wheezing or stridor may be
present. Symptoms are minimally improved by inhaled
bronchodilator, if at all. A high index of suspicion is
needed as conventional chest radiographs are rarely
diagnostic. Though insensitive, flow-volume loops can
show the characteristic changes of central airway
obstruction, frequently before abnormalities in the
spirometric volumes are noted (figure 1 and figure 2)
[95]. A high-resolution computed tomography (HRCT)
scan with three-dimensional reconstruction can be
helpful. The gold standard for diagnosis is direct
visualization. (See "Clinical presentation, diagnostic
evaluation, and management of malignant central airway
obstruction in adults", section on 'Diagnostic evaluation
and initial management' and "Presentation and
diagnostic evaluation of non-life-threatening and
nonmalignant subglottic and tracheal stenosis in adults",
section on 'Initial diagnostic testing'.)
●Bronchiectasis – Bronchiectasis, a condition of
abnormal widening of the bronchi that is associated with
chronic or recurrent infection, shares many clinical
features with COPD, including inflamed and easily
collapsible airways, obstruction to airflow, and
exacerbations characterized by increased dyspnea and
sputum production. Bronchiectasis is suspected on the
basis of prominent symptoms of cough and daily
mucopurulent sputum production. The diagnosis is
usually established clinically based on the characteristic
cough and sputum production and the presence of
bronchial wall thickening and luminal dilatation on chest
CT scans. (See "Clinical manifestations and diagnosis of
bronchiectasis in adults".)
●Heart failure – Heart failure is a common cause of
dyspnea among middle-aged and older patients and some
patients experience chest tightness and wheezing with
fluid overload due to heart failure. Occasionally, airflow
limitation is noted, although a restrictive pattern is more
common. Heart failure is usually differentiated by the
presence of fine basilar crackles, radiographic evidence
of an increased heart size, and pulmonary edema. The
brain natriuretic peptide (BNP) is typically increased in
heart failure but can also be increased during right heart
strain from cor pulmonale. (See "Heart failure: Clinical
manifestations and diagnosis in adults".)
●Tuberculosis – In an area endemic for tuberculosis, the
overall prevalence of airflow obstruction was 31 percent
among those with a past history of tuberculosis
compared with 14 percent among those without [96,97].
This association was unchanged after adjustment for
respiratory disease in childhood, smoking, and exposure
to dust and smoke. Thus, tuberculosis is both a risk
factor for COPD and a potential comorbidity [1].
(See "Clinical manifestations and complications of
pulmonary tuberculosis".)
●Constrictive bronchiolitis – Constrictive bronchiolitis,
also known as bronchiolitis obliterans, is characterized
by submucosal and peribronchiolar fibrosis that causes
concentric narrowing of the bronchiolar lumen.
Constrictive bronchiolitis is most commonly seen
following inhalation injury, transplantation (eg, bone
marrow, lung), or in the context of rheumatoid lung or
inflammatory bowel disease (table 8). Symptoms include
progressive onset of cough and dyspnea associated with
hypoxemia at rest or with exercise. Crackles may be
present. Pulmonary function tests show a progressive
and irreversible airflow limitation. Findings on inspiratory
CT scan include centrilobular bronchial wall thickening,
bronchiolar dilation, tree-in-bud pattern, and a mosaic
ground-glass attenuation pattern. (See "Overview of
 bronchiolar disorders in adults", section on 'Bronchiolitis
obliterans'.)
●Diffuse panbronchiolitis – Diffuse panbronchiolitis is
predominantly seen in male nonsmokers of East Asian
descent. Almost all have chronic sinusitis. On pulmonary
function testing, an obstructive defect is common,
although a mixed obstructive-restrictive pattern may also
be seen. Chest radiographs and HRCT scans show diffuse
centrilobular nodular and linear opacities corresponding
to thickened and dilated bronchiolar walls with
intraluminal mucous plugs. (See "Diffuse
panbronchiolitis", section on 'Diagnosis'.)
●Lymphangioleiomyomatosis –
Lymphangioleiomyomatosis (LAM) is seen primarily in
young females of childbearing age. Pulmonary function
testing frequently reveals mild airflow obstruction,
although a mixed obstructive-restrictive pattern may be
seen. CT scans typically demonstrate small, thin-walled
cysts that can at times be confused with emphysema.
However, the airspaces in emphysema are not actually
cysts but are caused by the destruction of alveolar walls
and permanent enlargement of distal airspaces, so the
"walls" are typically inapparent. (See 'Diagnosis' above
and "Sporadic lymphangioleiomyomatosis: Epidemiology
and pathogenesis" and "Diagnostic approach to the
adult with cystic lung disease".)
POST-DIAGNOSTIC WORK-UPFollowing a diagnosis of COPD,
additional testing may be appropriate to assess disease severity and
guide optimal initial therapeutic management.
Etiologic evaluation, including alpha-1 antitrypsin testing — If not
performed prior to establishing the diagnosis, a new diagnosis of
COPD should prompt a search for underlying etiologic factors. For
many patients, the etiology is long-term cigarette smoking.
However, it is important to review with the patient whether
underlying asthma, workplace exposures, indoor use of biomass
fuel, a prior history of tuberculosis, or familial predisposition is
contributory because mitigation of ongoing exposures may reduce
disease progression (table 2). (See 'Risk factors, including smoking
and inhalational exposures' above and "Chronic obstructive
pulmonary disease: Risk factors and risk reduction".)
It is appropriate to test all patients with COPD for alpha-1 antitrypsin
(AAT) deficiency by obtaining an AAT serum level and AAT
genotyping (algorithm 2) [1,98,99]. (See "Clinical manifestations,
diagnosis, and natural history of alpha-1 antitrypsin deficiency",
section on 'Evaluation and diagnosis'.)
Exercise capacity — Objectively measured exercise impairment is
a strong signal of overall health status and a predictor of prognosis
in COPD [100,101]. For patients with COPD, we perform a formal six-
minute walk test with ambulatory oximetry measurement. This
allows for assessment of exercise capacity as well as a
determination of gas exchange during exercise. Patients with
exertional hypoxemia should have further assessment of their gas
exchange. (See 'Assessing gas exchange, in select
patients' below.)
Timed walking tests can assess pulmonary disability and may
uncover previously unrecognized severe disease in patients with
reduced dyspnea perception or sedentarism. Exercise testing is also
standard part of preprogram evaluation for pulmonary rehabilitation,
which is recommended for COPD patients with dyspnea or a history
of exacerbations. (See "Evaluation of pulmonary disability", section
on 'Exercise tests' and "Pulmonary rehabilitation", section on
'Preprogram evaluation'.)
Lung volumes, for those with impaired vital capacity — When a
reduced forced vital capacity (FVC) is present on postbronchodilator
spirometry, we perform lung volume measurement by body
plethysmography to determine whether the reduction in FVC is due
to air trapping, hyperinflation, or a concomitant restrictive
ventilatory defect. Body plethysmography is strongly preferred for
lung volume measurement when available because gas dilution
methods may be insensitive for the detection of air trapping.
Decreased inspiratory capacity (IC) and vital capacity, accompanied
by an increased total lung capacity (TLC), functional residual
capacity (FRC), and residual volume (RV), are indicative of
hyperinflation. An increased FRC or RV with a normal TLC is
indicative of air trapping without hyperinflation. Restrictive deficits
will present with a reduced TLC, and restrictive interstitial lung
diseases will demonstrate reductions in TLC, FRC, and RV.
(See "Overview of pulmonary function testing in adults", section on
'Lung volumes' and "Dynamic hyperinflation in patients with
COPD".)
Assessing gas exchange, in select patients — We perform
additional assessment of gas exchange in patients with COPD with
moderate to severe airflow limitation (forced expiratory volume in
one second [FEV1] ≤50 percent predicted or z-score ≤-2.5), marginal
resting oxygen saturation [O2Sat] (O2Sat ≤92 percent), exertional
hypoxemia (O2Sat <90 percent), or severe dyspnea (modified Medical
Research Council [mMRC] score ≥2).
 ●Diffusing capacity for carbon monoxide (DLCO) –
Although DLCO decreases in proportion to the severity of
emphysema in most patients with COPD, it cannot be
used to detect mild emphysema because it is neither a
sensitive nor a specific test. However, reductions in
DLCO are associated with increased symptoms,
worsened health status, and increased risk of death
independently of airflow obstruction and other clinical
findings [102-104]. DLCO reductions out of proportion to
airflow limitation may suggest concomitant restrictive
lung disease or pulmonary hypertension, which require
further work-up. (See "Clinical features and diagnosis of
pulmonary hypertension of unclear etiology in adults".)
●Arterial blood gas – A resting arterial blood gas
demonstrating arterial oxygen tension (PaO2) ≤55 mmHg
(7.33 kPa) is an indication for continuous supplemental
oxygen. Similarly, the presence of chronic respiratory
acidosis (figure 3 and figure 4) should lead to evaluation
for sleep-disordered breathing and possible nocturnal
noninvasive ventilation. (See "Long-term supplemental
oxygen therapy" and "Nocturnal ventilatory support in
COPD".)
●CT imaging – While chest CT imaging is not
recommended for all patients, we agree with the global
initiative for obstructive lung disease recommendations,
which suggest CT imaging in the following
circumstances: patients with persistent exacerbations;
symptoms out of proportion to disease severity on lung
function testing; FEV1 less than 45 percent predicted
with significant hyperinflation (as consideration for
endobronchial valve placement); those meeting criteria
for lung volume reduction surgery; and patients meeting
criteria for lung cancer screening [1].
ASSESSMENT OF SEVERITY AND STAGINGSeveral different
strategies have been devised to categorize patients for the purposes
of disease management and prognosis. While historical approaches
generally weighed spirometric values more strongly, it has been
increasingly recognized that other aspects of disease, such as the
severity of symptoms, risk of exacerbations, and the presence of
comorbidities, are important to the patient's experience and to
disease prognosis [1,105].
GOLD classification systems — While the Global Initiative for
Chronic Obstructive Lung Disease (GOLD) strategy recommends
COPD diagnosis using symptoms accompanied by a forced
expiratory volume in one second (FEV1)/ forced vital capacity (FVC)
ratio <0.7, the severity of obstruction is determined by the
FEV1 percent predicted. The GOLD system uses four grades:
●GOLD 1 (mild disease): FEV1 ≥80 percent predicted
●GOLD 2 (moderate disease): FEV1 between 50 and 80
percent predicted
●GOLD 3 (severe disease): FEV1 between 30 and 50
percent predicted
●GOLD 4 (very severe disease): FEV1 <30 percent
predicted
This spirometric severity grading system is important due to its
simplicity and subsequent use in many clinical trials and
observational studies; however, its prognostic capacity for mortality
is modest [106].
Other groups have suggested potential spirometry-derived
alternatives to the GOLD Grade system. For example, the STaging of
Airflow obstruction by Ratio (STAR) severity classification scheme
was derived using approximately the 25th, 50th, and 75th percentile of
the FEV1/FVC ratios from the COPDGene cohort study and validated
using COPDGene and a second independent cohort [107]. Like GOLD,
this classification divides patients with COPD into 4 stages: STAR
stage 1 is defined by an FEV1/FVC ratio between 0.6 and 0.7; STAR
stage 2 by an FEV1/FVC ratio between 0.5 and 0.6; STAR stage 3 by
an FEV1/FVC ratio between 0.4 and 0.5; and STAR stage 4 by an
FEV1/FVC ratio <0.4.
The GOLD and STAR systems provided similar discrimination for
mortality and successfully separated patients in the studied
observational cohorts by dyspnea, respiratory quality of life, and
imaging assessments of disease [107]. A potential advantage of the
STAR system is that it does not rely on predicted lung size based on
age, height, or race/ethnicity. It does, however, depend on obtaining
good-quality spirometry (eg, expiratory plateau in the last second of
expiration or expiratory time ≥15 seconds) [108]. STAR requires
further validation in population-based cohorts before it can be
widely adopted.
While GOLD grade relates to spirometric severity of disease, GOLD
recommends a different system, the ABE assessment tool, for use in
determining initial therapy. The GOLD ABE assessment tool uses an
individual’s symptoms (ie, modified Medical Research Council
[mMRC] dyspnea scale or COPD Assessment Test) and exacerbation
history to guide pharmacotherapy (algorithm 3) [1]. The
multidimensional GOLD "ABE" evaluation is discussed in more detail
separately in the context of initial management of COPD.
(See "Stable COPD: Initial pharmacologic management".)
We agree with the GOLD strategy to monitor postbronchodilator
spirometry yearly to track decline in FEV1, which may identify
patients whose disease is progressing more quickly than usual.
Follow-up spirometric assessment may also be helpful in therapeutic
decision making when considering multiple potential causes of
worsening dyspnea. Finally, spirometric values remain an essential
component of decision making for lung volume reduction and lung
transplantation. (See "Management of refractory chronic
obstructive pulmonary disease", section on 'Lung Volume Reduction,
in select patients with dyspnea' and "Management of refractory
chronic obstructive pulmonary disease", section on 'Lung
transplantation'.)
BODE index — The BODE index is another system for assessment
of COPD severity and prognosis. It is calculated based on weight
(body mass index [BMI]), airflow limitation (FEV1), dyspnea (mMRC
dyspnea score), and exercise capacity (six-minute walk distance)
(calculator 1), and it has been used to assess an individual’s risk of
death. This index provides better prognostic information than the
FEV1 alone and can be used to assess therapeutic response to
medications, pulmonary rehabilitation therapy, and other
interventions [100,101,107,109]. (See "Chronic obstructive
pulmonary disease: Prognostic factors and comorbid conditions",
section on 'BODE index'.)
COPD Foundation system — The COPD Foundation has introduced a
system that includes seven severity domains, each of which has
therapeutic implications (figure 5) [54,94]. These domains are based
upon assessment of spirometry, regular symptoms, number of
exacerbations in the past year, oxygenation, emphysema on CT scan
or air trapping on lung volumes, presence of chronic bronchitis, and
comorbidities. Within the spirometry domain, the COPD Foundation
uses five grades:
●SG 0: Normal spirometry
●SG 1: Mild, postbronchodilator FEV1/forced vital capacity
(FVC) ratio <0.7, FEV1 ≥60 percent predicted
●SG 2: Moderate, postbronchodilator FEV1/FVC ratio <0.7,
FEV1 between 30 and 60 percent predicted
●SG 3: Severe, postbronchodilator FEV1/FVC ratio <0.7,
FEV1 <30 percent predicted
●SG U: Undefined, postbronchodilator FEV1/FVC ratio >0.7,
FEV1 <80 percent predicted
An advantage of this staging system is that it simplifies the
interpretation of spirometry; any spirometric finding results in a
classification, which is not the case in the GOLD system.

While FEV1 is used to gauge severity, the FEV1/FVC ratio is not used
for this purpose because measurement of FVC becomes less reliable
as the disease progresses (the long exhalations are difficult for the
patients), thus making the ratio less accurate unless high-quality
spirometry is ensured (algorithm 1). (See "Chronic obstructive
pulmonary disease: Prognostic factors and comorbid conditions",
section on 'Forced expiratory volume in one second' and "Office
spirometry", section on 'Interpretation'.)
SOCIETY GUIDELINE LINKSLinks to society and government-
sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links:
Chronic obstructive pulmonary disease".)
INFORMATION FOR PATIENTSUpToDate offers two types of
patient education materials, “The Basics” and “Beyond the Basics.”
The Basics patient education pieces are written in plain language,
at the 5th to 6th grade reading level, and they answer the four or five
key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who
prefer short, easy-to-read materials. Beyond the Basics patient
education pieces are longer, more sophisticated, and more detailed.
These articles are written at the 10th to 12th grade reading level and
are best for patients who want in-depth information and are
comfortable with some medical jargon.

Here are the patient education articles that are relevant to this
topic. We encourage you to print or e-mail these topics to your
patients. (You can also locate patient education articles on a variety
of subjects by searching on “patient info” and the keyword(s) of
interest.)

●Basics topics (see "Patient education: Chronic

obstructive pulmonary disease (COPD) (The
Basics)" and "Patient education: Chronic bronchitis (The
Basics)" and "Patient education: Medicines for chronic
obstructive pulmonary disease (COPD) (The Basics)")
●Beyond the Basics topics (see "Patient education:
Chronic obstructive pulmonary disease (COPD) (Beyond
the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definitions – The Global Initiative for Chronic
Obstructive Lung Disease (GOLD) defines COPD as
follows: "COPD is a heterogeneous lung condition
characterized by chronic respiratory symptoms due to
abnormalities of the airway and/or alveoli that cause
persistent, often progressive, airflow obstruction."
(See 'Definitions' above.)
Substantial overlap exists between COPD and the other
disorders that may cause airflow limitation (eg,
emphysema, chronic bronchitis, asthma, bronchiectasis,
bronchiolitis) as illustrated in the figure (figure 6).
(See 'Interrelationships among these conditions' above.)
●Clinical features – Common presentations of COPD
include patients with few complaints but an extremely
sedentary lifestyle; patients with chronic, daily
respiratory symptoms (eg, dyspnea on exertion, cough);
and patients with recurrent acute exacerbations (eg,
wheezing, cough, dyspnea, fatigue). Patients should be
asked about current smoking and the number of pack-
years smoked (packs of cigarettes per day multiplied by
the number of years); other inhalational exposures;
tuberculosis, HIV, and childhood pulmonary infections; a
history of asthma; and a family history of lung diseases.
The physical examination of the chest varies with the
severity of the COPD but is often normal in mild disease
(table 4A-B). (See 'Clinical Presentation' above.)
Diagnostic evaluation – The diagnosis of COPD should be
considered and spirometry performed pre- and
postbronchodilator administration in all patients who
report any combination of dyspnea, chronic cough, or
chronic sputum production, especially if there is a history
of exposure to triggers of COPD (eg, tobacco smoke,
occupational dust, indoor biomass smoke), a family
history of chronic lung disease, or presence of associated
comorbidities (table 1). For individuals with risk factors,
use of the CAPTURE (Chronic obstructive pulmonary
disease Assessment in Primary care To
identify Undiagnosed Respiratory disease
and Exacerbation risk) questionnaire and peak flow
measurement to assess unreported symptoms and
potential air flow limitation may identify additional
symptomatic patients appropriate for further evaluation.
•Spirometry pre- and postbronchodilator – COPD is
confirmed when a patient with compatible symptoms
 is found to have irreversible airflow limitation (ie, a
postbronchodilator forced expiratory volume in one
second [FEV1]/forced vital capacity [FVC] ratio less
than 0.7 [or below the lower limit of normal (LLN)]) and
no alternative explanation for the symptoms and
airflow obstruction. (See 'Spirometry' above
and 'Diagnosis' above.)
•Additional testing – In the evaluation of patients with
COPD, laboratory studies and chest radiography are
typically performed to exclude alternative diagnoses,
evaluate for comorbidities, or assess a change in
symptoms that suggests a complication of COPD.
Chest CT is performed to evaluate abnormalities seen
on the conventional chest radiograph, to exclude
certain complications of COPD (eg, thromboembolic
disease, lung cancer), or when a patient is being
considered for lung volume reduction surgery,
endobronchial valves, or lung transplantation.
(See 'Additional testing' above.)
●Differential diagnosis – Among patients who present in
mid- or later-life with dyspnea, cough, and sputum
production, the differential diagnosis is broad (eg, heart
failure, COPD, interstitial lung disease, thromboembolic
disease) (table 5). (See 'Differential diagnosis' above.)
●Post-diagnostic work-up – Following a diagnosis of
COPD, additional testing may be appropriate to assess
disease severity and guide optimal initial therapeutic
management.
•Etiologic evaluation, including alpha-1 antitrypsin
testing – If not performed prior to establishing the
diagnosis, a new diagnosis of COPD should prompt a
search for underlying etiologic factors (table 2). It is
appropriate to test all patients with COPD for alpha-1
antitrypsin (AAT) deficiency by obtaining an AAT
serum level and AAT genotyping (algorithm 2).
•Exercise capacity – For patients with COPD, we
perform a formal six-minute walk test with ambulatory
oximetry measurement. This allows for assessment of
exercise capacity as well as a determination of gas
exchange during exercise.
•Other studies – Assessment of lung volumes and gas
exchange are appropriate for patients with evidence of
more severe disease. (See 'Lung volumes, for those
 with impaired vital capacity' above and 'Assessing
gas exchange, in select patients' above.)
●Assessment of severity and staging
•The original GOLD staging system was based solely
on postbronchodilator FEV1. Although well-recognized
and commonly used, it has been criticized for
underestimating the importance of the severity of
symptoms, risk of exacerbations, and presence of
comorbidities in predicting outcome.
(See 'Assessment of severity and staging' above.)
•The revised GOLD "ABE" strategy uses a combination
of an individual's symptoms and history of
exacerbations and hospitalizations due to
exacerbations to stratify symptoms and exacerbation
risk and guide therapy (algorithm 3). (See 'GOLD
classification systems' above.)
•Other multidimensional staging systems include the
BODE index (calculator 1) and the COPD Foundation
system (figure 5). (See 'BODE index' above
and 'COPD Foundation system' above.)
ACKNOWLEDGMENTThe editorial staff at UpToDate acknowledge
Stephen Rennard, MD, who contributed to earlier versions of this
topic review.
Use of UpToDate is subject to the Terms of Use.

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Topic 1455 Version 67.0

GRAPHICS
Key indicators for considering a diagnosis of COPD
Symptoms

Dyspnea

Cough

Sputum

Risk factors

Smoking

Biomass fuel exposure

Asthma

Childhood infections

Prematurity

Family history

Comorbidities

Heart disease

Metabolic syndrome

Osteoporosis

Sleep apnea
 Depression

Lung cancer

Skin wrinkling
Consider the diagnosis of COPD and perform spirometry if any of these indicators are
present. These indicators are not diagnostic by themselves, but the presence of
multiple key indicators increases the probability of a diagnosis of COPD. Spirometry
is needed to establish a diagnosis of COPD.
Graphic 50637 Version 3.0
Classification of COPD by etiology ("etiotype")
COPD etiotype Description

COPD due to genetic factors (COPD-G) Alpha-1 antitrypsin deficiency

Combined effect of multiple common variants

COPD due to abnormal lung development (COPD-D) Impaired lung maturation, most commonly due to premature birth

COPD due to environmental exposures

Cigarette smoking COPD (COPD-C) Cigarette smoking or vaping

Passive exposure to tobacco smoke

Biomass and pollution exposure (COPD-P) Exposure to biomass combustion

Ambient air pollution, including wildfire smoke
Occupational hazard exposures

COPD due to infections (COPD-I) Early childhood infections; bronchiectasis

HIV-associated COPD; tuberculosis-associated COPD

COPD and asthma (COPD-A) Abnormal lung development associated with childhood asthma; c

COPD of unknown cause (COPD-U) Patients without currently known risk factors

A proposed taxonomy for COPD based on etiology. Individually, some patients may
have multiple causal factors.
COPD: chronic obstructive pulmonary disease; HIV: human immunodeficiency virus.
Reference:

1. Celli B, Fabbri L, Criner G, et al. Definition and nomenclature of chronic obstructive pulmonary

disease: Time for its revision. Am J Respir Crit Care Med 2022; 206:1317.
Graphic 140745 Version 1.0
Proposed diagnostic criteria for pre-COPD
Potential manifestations of pre-COPD
 Symptoms Chronic bronchitis
Dyspnea
Intermittent wheeze and sputum production

Pulmonary function DLCO <80% predicted

FEV1 decline >40 mL/year
Preserved ratio impaired spirometry (PRISM)

Imaging Emphysema on CT (>5% or visual dx)

Vascular remodeling or pruning
Airway thickening

A diagnosis of pre-COPD should be considered in patients with risk factors for COPD
who have any of the above characteristics without airflow limitation (FEV1/FVC >0.7).
COPD: chronic obstructive pulmonary disease; DLCO: diffusing capacity of carbon
monoxide; FEV1: forced expiratory volume in one second; CT: computed
tomography; FVC: forced vital capacity.
Adapted from:

1. Celli B, Fabbri L, Criner G, et al. Definition and nomenclature of chronic obstructive pulmonary

disease: Time for its revision. Am J Respir Crit Care Med 2022; 206:1317.

2. Han MK, Agusti A, Celli BR, et al. From GOLD 0 to Pre-COPD. Am J Respir Crit Care Med 2021;

203:414.
Graphic 140744 Version 1.0
Leukocyte infiltration in COPD

Photomicrograph showing leukocyte infiltration in a small airway of a smoker with

severe COPD (A); and that of smoker with a mild COPD (B). Immunostaining with
monoclonal antibody anti-CD45. Leukocytes are stained in red. Original
magnification: X400.
Reproduced with permission from: Turato G, Zuin R Miniati M et al. Airway inflammation in severe
chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema.
Am J Respir Crit Care Med 2002;166:105. Copyright © 2002 American Thoracic Society.
Graphic 69029 Version 3.0
Diagnosis of chronic obstructive pulmonary disease:
Clinical features
History

Risk factors
 Family history
 Smoking history
  Age at initiation
 Average amount smoked per day since initiation
 Date when stopped smoking or a current smoker
 Environmental history
 The chronologically taken environmental history may disclose important risk factors for COPD
 History of childhood pulmonary infections, HIV, or tuberculosis
 Asthma

Symptoms
 Dyspnea
 Ask about the amount of effort required to induce uncomfortable breathing. Many individuals will deny symptoms o
 Cough
 Cough with or without sputum production should be an indication for spirometric testing. The presence of chronic co
 Wheezing
 Wheezing or squeaky noises occurring during breathing indicate the presence of airflow obstruction
 Acute chest illnesses
 Inquire about occurrence and frequency of episodes of increased cough and sputum with wheezing, dyspnea, or feve

Physical examination

Physical findings are generally present only with severe disease

Chest
 The presence of emphysema (only when severe) is indicated by: overdistention of the lungs in the stable state (chest
decreased intensity of breath and heart sounds, and prolonged expiratory phase
 Evidence of airflow obstruction: wheezes during auscultation on slow or forced breathing and prolongation of forced
 Frequently observed with severe disease (characteristic, but not diagnostic): pursed-lip breathing, use of accessory re

Other
 Unusual positions to relieve dyspnea at rest
 Digital clubbing is NOT typical in COPD (even with associated hypoxemia) and suggests other diagnoses (eg, lung c
 Mild dependent edema may be seen in the absence of right heart failure

COPD: chronic obstructive pulmonary disease.

Graphic 53303 Version 7.0
Differential diagnosis of COPD
Diagnosis

COPD Onset in
 deficien

Symptom

Long sm

Dyspnea

Largely

Asthma Onset ea

Symptom

Symptom

Allergy,

Family h

Largely

Central airway obstruction (eg, bronchogenic or metastatic cancer, lymphadenopathy, scarring from Monoph
endotracheal tube)
Variable

Chest ra

Airway

Heart failure Fine bas

Chest ra

Pulmona
be seen

Bronchiectasis Large vo

Commo

Coarse c

Chest ra

Tuberculosis Onset al

Chest ra

Positive

High loc
 Obliterative bronchiolitis Onset in

May hav

HRCT o

Diffuse panbronchiolitis Most pa

Highest

Almost

Chest ra
HRCT: high-resolution computed tomography; PPD: purified protein derivative;
IGRA: interferon gamma release assay.

* These features tend to be characteristic of the respective diseases, but do not

occur in every case. For example, a person who has never smoked may develop
COPD (especially in the developing world, where other risk factors may be more
important than cigarette smoking); asthma may develop in adult and even elderly
patients.
Adapted with permission from the Global Initiative for Chronic Obstructive Pulmonary Disease.
Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary
disease: Revised 2011. Global Initiative for Chronic Obstructive Lung Disease (GOLD),
www.goldcopd.org (Accessed on August 10, 2012).
Graphic 51974 Version 5.0
Diagnosis of chronic obstructive pulmonary disease: PFTs
and chest radiograph
Spirometry

Spirometry is the essential test to confirm the diagnosis and establish the staging of COPD. If values are abnormal, a po
partially reversible with bronchodilator is suggestive of COPD rather than asthma. A postbronchodilator ratio of FEV 1/F

In the presence of a low FEV1/FVC, the percent of predicted FEV1 is used to determine the severity of airflow limitation
 GOLD 1: Mild (FEV1 ≥80% predicted)
 GOLD 2: Moderate (50% predicted ≤FEV1 <80% predicted)
 GOLD 3: Severe (30% predicted ≤FEV1 <50% predicted)
 GOLD 4: Very severe (FEV1 <30% predicted)

Lung volumes

Body plethysmography to assess lung volumes is not necessary except in patients with a low FVC on spirometry (<80%

Diffusing capacity for carbon monoxide

Measurement of DLCO can help establish the presence of emphysema, but is not necessary for the routine diagnosis of

Chest radiography
 Evidence of hyperinflation (eg, enlarged lungs, flattened diaphragm, increased AP diameter) and loss of parenchyma (e
emphysema. Radiography is frequently obtained to exclude other lung disease.

Arterial blood gases (ABGs)

Mild and moderate airflow obstruction – ABG usually not needed.

Moderately severe airflow obstruction – ABG is optional, but oximetry should be done. ABGs are obtained if oxygen s

Severe and very severe airflow obstruction – ABGs are essential to assess for hypercapnia.
PFTs: pulmonary function tests; COPD: chronic obstructive pulmonary disease; FEV 1:
forced expiratory volume in 1 second; FVC: forced vital capacity; LLN: lower limit of
normal; GOLD: Global Initiative for Chronic Obstructive Lung Disease; DLCO:
diffusing capacity for carbon monoxide; ABG: arterial blood gas.
Graphic 61983 Version 6.0
CAPTURE questionnaire for identifying patients with
undiagnosed COPD
Instructions: For each question, place an X in the box with the answer that is best for you. There are no right or wrong ans

Please answer each question

1. Have you ever lived or worked in a place with dirty or polluted air, smoke, second-hand smoke, or dust?

2. Does your breathing change with seasons, weather, or air quality?

3. Does your breathing make it difficult to do things such as carry heavy loads, shovel dirt or snow, jog, play tennis, or swim?

4. Compared to others your age, do you tire easily?

Please answer the question

5. In the past 12 months, how many times did you miss work, school, or other activities due to a cold, bronchitis, or pneumoni

The final score is a summation of patient responses to each of the five items,
yielding a questionnaire score ranging from 0 ("no" to all 5 questions) to 6 ("yes" to
all questions and at least two respiratory events during the past year).
CAPTURE: Chronic obstructive pulmonary disease Assessment in Primary care To
identify Undiagnosed Respiratory disease and Exacerbation risk; COPD: chronic
obstructive pulmonary disease.
Reprinted with permission of the American Thoracic Society. Copyright © 2019 American Thoracic
Society. From: Martinez FJ, Mannino D, Leidy NK, et al. A New Approach for Identifying Patients
with Undiagnosed Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2017;
195:748-756. The American Journal of Respiratory and Critical Care Medicine is an official journal
of the American Thoracic Society.
Graphic 121674 Version 2.0
 Classification and grading of ventilatory impairments based
on spirometry [1,2]

FEV1: forced expiratory volume in one second; FVC: forced vital capacity; LLN: lower
limit of normal, the 5th percentile.
* Low refers to levels below the 5th percentile, or a z-score <–1.645; absolute
values are not used due to changes in spirometry with age and other factors.
¶ A reduced FVC does not prove a restrictive process. Confirmation of restriction
requires evaluation of lung volumes in a pulmonary function laboratory (ie, total lung
capacity z-score <–1.645 or below fifth percentile).
Δ A reduced FVC with normal FEV1/FVC and lung-volumes is a "nonspecific" pattern
that may be followed over time. One-third of patients with nonspecific patterns
develop obstructive or restrictive disease in the next three years.
◊ Many patients with reduced FEV1/FVC and low FVC have simple obstruction with
air-trapping or failure to complete exhalation.
§ The severity of obstructive and mixed obstructive/restrictive ventilatory
impairments are physiologically graded by decrement in FEV 1. Patients with
restriction should have restrictive impairment confirmed and graded based on total
lung capacity, but may be monitored by changes in FEV1. FEV1 may also be used as
an alternative method to grade severity of confirmed restriction when only
spirometry or % predicted values are available.
¥ Z-score is the preferred method for grading severity based on 2022 European
Respiratory Society/American Thoracic Society (ERS/ATS) guidelines because it
reduces bias due to age, sex, and other factors. Some spirometry software continues
to report percent predicted, so we also include categorization based on this reporting
method. The percent predicted severity classification has been adapted from earlier
guidelines and modernized by reducing the number of distinct categories.
References:

1. Stanojevic S, Kaminsky DA, Miller MR, et al. ERS/ATS technical standard on interpretive

strategies for routine lung function tests. Eur Respir J 2022; 60:2101499.

2. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur

Respir J 2005; 26:948.

Graphic 139645 Version 3.0
Panacinar emphysema in alpha-1 antitrypsin deficiency

Chest radiograph shows marked hyperexpansion with paucity of vascular structures

at the bases and redistribution of vascular flow to the lesser involved upper lobes.
These findings are typical of severe panacinar emphysema.
Courtesy of Paul Stark, MD.
Graphic 65594 Version 4.0
Chest x-ray emphysema
The posteroanterior (A) and lateral (B) chest x-rays of a 71-year-old female with
emphysema show increased lung volumes with flattened hemidiaphragms on the
lateral examination (arrow) and increase in the retrosternal space (arrowhead). The
normal retrosternal airspace is less than 2.5 cm. A prominent pulmonary artery on
the posteroanterior view (dashed arrow) reflects secondary pulmonary hypertension.
Graphic 87221 Version 2.0
Chest radiograph of a giant bilateral bullae in young
smoker

Chest radiograph shows large bilateral collections of gas devoid of any vascular
structures with a sharp edge concave laterally, which is a differentiating feature from
pneumothorax. The functioning lung is retracted to the bases.
Courtesy of Paul Stark, MD.
Graphic 82207 Version 4.0
Centrilobular emphysema pulmonary hypertension

Axial CT images confirm the presence of centrilobular (centriacinar) emphysema (A)

and pulmonary hypertension (B). The lung parenchyma shows lucent spaces of
parenchymal destruction interspersed among normal lung tissue best appreciated in
the right upper lobe (A). The main pulmonary artery (arrow) measures 3.8 cm
(normal <2.9 cm). The pulmonary artery and aorta should be about the same size
and in this case the main pulmonary artery is larger than the companion ascending
aorta.
CT: computed tomography.
Graphic 82308 Version 3.0
Pulmonary Langerhans cell histiocytosis

High-resolution CT with thin section shows the cysts in pulmonary Langerhans cell
histiocytosis (PLCH), which vary markedly in size and may be larger than 10 mm.
The cysts are bizarre in shape, often closely related to pulmonary arteries, and
mimic bronchiectasis. Few nodules are present in this case.
CT: computed tomography.
Courtesy of Talmadge E King Jr, MD.
Graphic 72698 Version 5.0
Panlobular emphysema

HRCT shows a paucity of vascular structures in both lower lobes, most evident in the
anterior-basal segment of the right lower lobe.
HRCT: high-resolution computed tomography.
Courtesy of Paul Stark, MD.
Graphic 57950 Version 4.0
Paraseptal emphysema
Several subpleural emphysematous spaces are present in the periphery of the left
upper lobe (arrows) in a patient with accompanying severe centrilobular
emphysema.
Courtesy of Paul Stark, MD.
Graphic 53689 Version 2.0
Paraseptal emphysema with bullae

Paraseptal emphysema in the periphery of both upper lobes and in the left lower lobe
on a background of centrilobular emphysema. Several large subpleural bullae are
visible in both lungs and are the result of paraseptal emphysema.
Courtesy of Paul Stark, MD.
Graphic 60307 Version 2.0
Conditions associated with central airway obstruction
Malignant Nonmalignant

Primary endoluminal malignancy Benign airway tumors

 Bronchogenic  Squamous cell papilloma
 Adenoid cystic  Hamartoma
 Mucoepidermoid Lymphadenopathy
 Carcinoid  Sarcoidosis
 Plasmacytoma  Infectious (ie, tuberculosis)
Metastatic carcinoma to the airway Vascular
 Bronchogenic  Vascular ring
 Renal cell  Vascular aneurysm
 Breast Cartilage
 Thyroid  Relapsing polychondritis
 Colon Granulation tissue
 Sarcoma  Endotracheal tubes
 Melanoma  Tracheostomy tubes
Laryngeal and nasopharyngeal carcinoma  Airway stents
Esophageal carcinoma  Foreign bodies
Mediastinal tumors  Surgical anastomosis (eg, post resectio
 Thymic carcinoma  Granulomatosis with polyangiitis (We
 Thyroid carcinoma  Rhinoscleroma (klebsiella infection)
 Germ cell tumors (eg, teratoma) Pseudotumor
Lymphadenopathy  Endobronchial pseudotumor
 Associated with any of the above malignancies Hyperdynamic

 Lymphoma  Tracheomalacia
 Bronchomalacia
Webs
 Idiopathic progressive subglottic steno
 Tuberculosis
 Sarcoidosis
Other
 Goiter
 Mucus plug
 Vocal cord paralysis
 Airway hematoma
 Burn/smoke injury
 Epiglottitis
 Blood clot
 Amyloid
Modified with permission from: Ernst A, Feller-Kopman D, Becker HD, Mehta AC. Central airway
obstruction. Am J Respir Crit Care Med 2004; 169:1278. Copyright © 2004 American Thoracic
Society.
Graphic 55320 Version 5.0
Flow-volume loops in upper airway obstruction

The configuration of the flow-volume loop can help distinguish the site of airway
narrowing. The airways are divided into intrathoracic and extrathoracic components
by the thoracic inlet.
(A) Normal flow-volume loop: the expiratory portion of the flow-volume curve is
characterized by a rapid rise to the peak flow rate, followed by a nearly linear fall in
flow. The inspiratory curve is a relatively symmetrical, saddle-shaped curve.
(B) Dynamic (or variable, nonfixed) extrathoracic obstruction: flow limitation and
flattening are noted on the inspiratory limb of the loop.
(C) Dynamic (or variable, nonfixed) intrathoracic obstruction: flow limitation and
flattening are noted on the expiratory limb of the loop.
(D) Fixed upper airway obstruction (can be intrathoracic or extrathoracic): flow
limitation and flattening are noted in both the inspiratory and expiratory limbs of the
flow-volume loop.
(E) Peripheral or lower airways obstruction: expiratory limb demonstrates concave
upward, also called "scooped-out" or "coved" pattern.
TLC: total lung capacity; RV: residual volume.
Adapted from: Stoller JK. Spirometry: a key diagnostic test in pulmonary medicine. Cleve Clin J
Med 1992; 59:75.
Graphic 76811 Version 7.0
Flow-volume loop and degree of upper airway narrowing

Volume (as liters [L] from total lung capacity [TLC]) is plotted against inspiratory and
expiratory flows. The blue line (C) is the control effort; the number on each curve
refers to the orifice diameter in mm. Lesions must narrow the tracheal lumen to less
than 8 mm before abnormalities can be detected by spirometry.
TLC: total lung capacity; RV: residual volume.
Redrawn from Miller RD, Hyatt RE. Obstructing lesions of the larynx and trachea: clinical and
physiologic characteristics. Mayo Clin Proc 1969; 44:145.
Graphic 73686 Version 4.0
Conditions associated with the histologic finding of
constrictive bronchiolitis
Inhalation of dusts or toxins

Mineral dusts - asbestos, silica, iron oxide, aluminum oxide, talc, mica, and coal

Toxins - NO2, sulfur dioxide, ammonia, chlorine, and phosgene

Drug reaction

Infection - viral, mycoplasma

Connective tissue disease, especially rheumatoid arthritis

Chronic rejection in heart-lung, lung, and bone marrow transplant recipients

Hypersensitivity reactions

Ulcerative colitis

Idiopathic
NO2: nitrogen dioxide.
Adapted from Myers JL, Colby TV, Clin Chest Med 1993; 14:611.
Graphic 58035 Version 2.0
Our approach to diagnosis of alpha-1 antitrypsin (AAT)
deficiency

COPD: chronic obstructive pulmonary disease; ANCA: antineutrophil cytoplasmic

antibody; PCR: polymerase chain reaction; IEF: isoelectric focusing (assesses protein
migration).
* It is preferable to obtain simultaneous measurement of AAT level and targeted
genotyping. Targeted genotyping uses PCR to identify specific common pathogenic
AAT variants (eg, F, I, S, and Z) and the normal M allele, although panels vary
among laboratories. Sequential testing of genotype first followed by serum level is an
alternative. Refer to UpToDate content on the diagnosis of AAT deficiency.
¶ Interpretation of a specific abnormal result should be based upon the reference
range reported by the laboratory. A reasonable threshold for differentiating normal
Pi*MM (normal genotype) from other genotypes with one or more deficient alleles is
20 micromol/L (100 mg/dL).
Δ IEF is an alternative, but gene sequencing is typically preferred.
◊ Depending on the specific variant, heterozygotes may have a serum AAT level that
is reduced or within the normal range. As AAT is an acute phase reactant, a mildly
low AAT level can increase into the normal range during acute illness. However, a
severely low AAt level would not increase into the normal range.
§ Targeted genotyping, in combination with a low serum AAT level, is acceptable for
diagnosis of AAT deficiency. There is no need to confirm genotype result with
alternative test, such as IEF, if result is clear and consistent with AAT level.
¥ AAT levels can be low in the absence of AAT deficiency (eg, variation in the assay
or improper storage of specimen). If unexplained, obtain specialty consultation, as
appropriate.
Graphic 104220 Version 5.0
Compensation to chronic respiratory acidosis

95% significance bands for plasma pH and H+ and HCO3– concentrations in chronic
hypercapnia. Because of the compensatory rise in the plasma HCO 3– concentration,
there is much less change in H+ concentration and pH than in acute hypercapnia.
Schwartz WB, Brackett NC Jr, Cohen JJ. J Clin Invest 1965; 44:291. By copyright permission of the
American Society for Clinical Investigation.
Graphic 63315 Version 4.0
Expected compensation ranges for simple acid-base
disorders

Reproduced with permission from: Harrington JT, Cohen JJ, Kassirer JP. Mixed acid-base
disturbances. In: Acid/Base, Cohen JJ, Kassirer JP (Eds), Little, Brown, Boston: 1982. Copyright ©
1982 Lippincott Williams & Wilkins. www.lww.com.
Graphic 79833 Version 9.0
New diagnosis of COPD

COPD: chronic obstructive pulmonary disease; COVID-19: coronavirus disease 2019;

GOLD: Global Initiative for Chronic Obstructive Lung Disease; CAT: COPD
Assessment Test; SABA: short-acting beta-agonist; SAMA: short-acting muscarinic
antagonist; LAMA: long-acting muscarinic antagonist (anticholinergic); LABA: long-
acting beta-agonist; mMRC: Modified Medical Research Council; FEV 1: forced
expiratory volume in one second; FVC: forced vital capacity.
* COPD is diagnosed based on the presence of chronic respiratory symptoms
(dyspnea, cough, sputum production) accompanied by airflow limitation. All patients
with COPD defined by GOLD have airflow limitation based on a reduced FEV 1/FVC
ratio <0.70. The severity of airflow limitation is determined by the reduction in FEV 1.
¶ An exacerbation of COPD is characterized by increased dyspnea and/or cough and
sputum that worsens in less than 14 days, may be accompanied by tachypnea or
tachycardia, and is often caused by infection, environmental irritation, or other insult
to the airways. "Moderate exacerbations" are typically defined as those which require
treatment with systemic glucocorticoids. More objective severity classifications have
been proposed but are difficult to establish via patient history. Please refer to
UpToDate content on "COPD exacerbations: Clinical manifestations and evaluation"
for additional information.

Δ CAT: http://www.catestonline.org (Accessed on January 12, 2023).

◊ For those prescribed a LABA alone, SAMA-SABA combination therapy is likely to be
most potent but will have some of the same side effects as LAMA. For those
prescribed a LAMA, SAMA should generally not be used concomitantly, so SABA alone
is preferred.

§ Occasional patients with only minimal intermittent symptoms are appropriate for
only as-needed rescue therapy rather than treatment with long-acting
bronchodilators.
Graphic 54300 Version 13.0
COPD Foundation guide to assessment of COPD severity

COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in one
second; FVC: forced vital capacity; SG: spirometry grade; PaO 2: arterial tension of
oxygen; CT: computed tomography.
Reprinted with permission from the COPD Foundation. Slight modifications were made.
(Thomashow B, Crapo J, Yawn B, et al. The COPD Foundation Pocket Consultant Guide. Chronic
Obstructive Pulmonary Diseases: Journal of the COPD Foundation. 2014; 1(1): 83-87). Copyright
© 2014 Informa Plc.
Graphic 95124 Version 1.0
Chronic obstructive pulmonary disease

This nonproportional Venn diagram shows subsets of patients with chronic bronchitis,
emphysema, and asthma (black circles). The subsets defined as COPD are shaded
gray. Subset areas are not proportional to actual relative subset sizes. Asthma is, by
definition, associated with reversible airflow obstruction; in variant asthma, special
maneuvers may be necessary to make the obstruction evident. Patients with asthma
whose airflow obstruction is completely reversible (subset 9) are not considered to
have COPD. In many cases it is virtually impossible to differentiate patients with
asthma whose airflow obstruction does not remit completely from persons with
chronic bronchitis and emphysema who have partially reversible airflow obstruction
with airway hyperreactivity. Thus, patients with unremitting asthma are classified as
having COPD (subsets 6, 7 and 8). Chronic bronchitis and emphysema with airflow
obstruction usually occur together (subset 5), and some patients may have asthma
associated with these two disorders (subset 8). Individuals with asthma exposed to
chronic irritation, as from cigarette smoke, may develop chronic productive cough, a
feature of chronic bronchitis (subset 6). Such patients are often referred to in the
United States as having asthmatic bronchitis or the asthmatic form of COPD. Persons
with chronic bronchitis or emphysema without airflow obstruction (subsets 1, 2 and
11) are not classified as having COPD. In order to emphasize that cough and sputum
are abnormal, individuals with these symptoms and normal lung function were
classified as GOLD Stage 0, at risk, in the original GOLD classification [1]. This stage
was deleted in the 2006 revision because of uncertainties about whether it is
progressive [2]. Patients with airway obstruction due to diseases with known etiology
or specific pathology, such as cystic fibrosis or obliterative bronchiolitis (subset 10),
are not generally included in the definition of COPD.
1. Data from: Global initiative for chronic obstructive lung disease (GOLD). Workshop report:
Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary
disease: Update 2005.
2. Data from: Global initiative for chronic obstructive lung disease (GOLD). Workshop report:
Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary
disease: Update 2006.
Graphic 66708 Version 1.0