Global Strategy for the Diagnosis, Management, and
Prevention of Chronic Obstructive Pulmonary Disease
GOLD Executive Summary
Jørgen Vestbo1,2, Suzanne S. Hurd3, Alvar G. Agustı ´4, Paul W. Jones5, Claus Vogelmeier6,
Antonio Anzueto7, Peter J. Barnes8, Leonardo M. Fabbri9, Fernando J. Martinez10,
Masaharu Nishimura11, Robert A. Stockley12, Don D. Sin13, and Roberto Rodriguez-Roisin4
1Manchester Academic Health Sciences Centre, South Manchester University Hospital NHS Foundation Trust, Manchester, United Kingdom;
2Odense University Hospital and University of Southern Denmark, Odense, Denmark;3Global Initiative for Chronic Obstructive Lung Disease,
Vancouver, Washington;4Hospital Clı ´nic, Universitat de Barcelona, Barcelona, Spain;5St George’s Hospital Medical School, London, United
Kingdom;6University of Gießen and Marburg School of Medicine, Marburg Germany;7University of Texas Health Science Center, San Antonio,
Texas;8National Heart and Lung Institute, London, United Kingdom;9University of Modena and Reggio Emilia, Modena, Italy;10University of
Michigan School of Medicine, Ann Arbor, Michigan;11Hokkaido University School of Medicine, Sapporo, Japan;12University Hospitals Birmingham,
Birmingham, United Kingdom; and13St Paul’s Hospital, Vancouver, Canada
Chronic obstructive pulmonary disease (COPD) is a global health
problem, and since 2001, the Global Initiative for Chronic Obstruc-
tive Lung Disease (GOLD) has published its strategy document for
the diagnosis and management of COPD. This executive summary
document that has implemented someof thevast knowledge about
COPD accumulated over the last years. Today, GOLD recommends
airflow limitation, (3) history of exacerbations, and (4) comorbidities.
COPD into four categories—A, B, C, and D. Nonpharmacologic and
pharmacologic management of COPD match this assessment in an
bations. Identification and treatment of comorbidities must have high
priority, and a separate section in the document addresses manage-
The revised document also contains a new section on exacerbations of
local guidelines on the management of COPD.
Keywords: COPD; clinical assessment; COPD management; exacerba-
Summary of New Recommendations
Levels of Evidence
1. Definition and Overview
Burden of COPD
Factors That Influence Disease Development and
Pathology, Pathogenesis, and Pathophysiology
2. Diagnosis and Assessment
Assessment of Disease
3. Therapeutic Options
4. Management of Stable COPD
Identify and Reduce Exposures
Treatment of Stable COPD
Monitoring and Follow-up
5. Management of Exacerbations
Hospital Discharge and Follow-up
Home Management of Exacerbations
Prevention of COPD Exacerbations
6. COPD and Comorbidities
Anxiety and Depression
Metabolic Syndrome and Diabetes
Chronic obstructive pulmonary disease (COPD) is a major public
Author Contributions: All authors have contributed to this report; J.V. wrote the first draft.
Correspondence and requests for reprints should be addressed to Jørgen Vestbo,
D.M.Sc., Manchester Academic Sciences Health Centre, Respiratory Research
Group, University of Manchester, University Hospital South Manchester, Southmoor
Road, Manchester M23 9LT, UK. E-mail: email@example.com
This article has an online supplement, which is accessible from this issue’s table of
contents at www.atsjournals.org
Am J Respir Crit Care Med
Copyright ª 2013 by the American Thoracic Society
Originally Published in Press as DOI: 10.1164/rccm.201204-0596PP on August 9, 2012
Internet address: www.atsjournals.org
Vol 187, Iss. 4, pp 347–365, Feb 15, 2013
in terms of burden of disease and third in terms of mortality. Al-
though COPD has received increasing attention from the medical
community in recent years, it is still relatively unknown or ignored
by the public as well as public health and government officials.
In 1998, the Global Initiative for Chronic Obstructive Lung
Disease (GOLD) was formed to bring more attention to the
management and prevention of COPD. Among the important
objectives of GOLD are to increase awareness of COPD and to
help the millions of people who suffer from this disease and die
prematurely from it or its complications. In 2001, the GOLD pro-
gram released a consensus report, Global Strategy for the Diag-
nosis, Management, and Prevention of COPD; this document
was revised in 2006, and now we present the 2011 version.
The GOLD document is a global document and for that reason
make the same guidelines for developing countries as for, for ex-
ample, Europe and North America.A strategy documentprovides
advice on diagnosis and management that can be implemented in
national guidelines. It can be expanded for rich countries and re-
stricted for poorer ones. It provides guidance on principles and
drug classes to be applied, and national guidelines can therefore
build on the assessment and management principles suggested
by GOLD—and then modify it to fit their country’s needs.
Based on multiple scientific and clinical achievements in the
10 years since the 2001 GOLD report was published, this revised
edition provides a new paradigm for treatment of stable COPD.
This major revision builds on the strengths from the original rec-
ommendations and incorporates new knowledge to make three
important new recommendations:
1. One of the strengths was the treatment objectives. These
have stood the test of time, but are now organized into
two groups: objectives that are directed toward immedi-
ately relieving and reducing the impact of symptoms, and
objectives that reduce the risk of adverse health events
in the future. This emphasizes the need for clinicians to
maintain a focus on both the short-term and long-term
impact of COPD on their patients.
2. A second strength of the original strategy was the simple,
intuitive system for classifying COPD severity. This was
based on the FEV1and was called a staging system because
it was believed, at the time, that the majority of patients
followed a path of disease progression that tracked the
severity of the airflow limitation. Much is now known about
the characteristics of patients in the different GOLD
stages—for example, their level of risk of exacerbations,
hospitalization, and death. However at an individual patient
level, the FEV1is an unreliable marker of the severity of
breathlessness, exercise limitation, and health status impair-
ment. This report retains the GOLD classification system of
airflow limitation because it is a predictor of future adverse
events, but the term “stage” is now replaced by “grade.”
3. At the time of the original report, improvement in both
symptoms and health status was a GOLD treatment objec-
tive, but symptom assessment did not have a direct relation
to the choice of management, and health status measure-
ment was a complex process largely confined to clinical
studies. Now, there are simple and reliable questionnaires
designed for use in routine daily clinical practice. These have
been validated in many languages, which has enabled the
development of a new assessment system that integrates
patient symptoms and their risk for serious adverse health
events in the future. In turn, this new assessment system has
led to the construction of a new approach to management—
one that matches assessment to treatment objectives. The
new management approach can be used in any clinical
setting anywhere in the world and moves COPD treatment
toward individualized medicine—matching the patient’s
therapy more closely to his or her needs. Whereas recom-
mendations on treatment are evidence based, a novel assess-
ment system will have to be consensus based, with the aim
that future studies will test the value of this system.
Summary of New Recommendations
A summary of the new issues presented in this report follows:
1. This document has been considerably shortened in length
by limiting section 1 to the essential background data on
COPD. Readers who wish to access more comprehensive
information are referred to a variety of excellent text-
books that have appeared in the last decade.
2. Section 2 includes information on diagnosis and assess-
ment of COPD. The definition of COPD has not been
significantly modified but has been reworded for clarity.
3. Assessment of COPD is based on the patient’s level of
symptoms, exacerbation history, the severity of the spiro-
metric abnormality, and the identification of comorbid-
ities. Whereas spirometry was previously used to support
a diagnosis of COPD, spirometry is now required to make
a confident diagnosis of COPD.
4. Airflow limitation as determined by spirometry is divided
into four grades (GOLD 1, mild; GOLD 2, moderate;
GOLD 3, severe; and GOLD 4, very severe) using the
fixed ratio, post-bronchodilator FEV1/FVC , 0.7, to de-
fine airflow limitation. It is recognized that the use of the
fixed ratio (FEV1/FVC) may lead to more frequent diag-
noses of COPD in older adults with mild COPD as the
normal process of aging affects lung volumes and flows,
and may lead to underdiagnosis in adults younger than 45
years. The concept of staging has been abandoned be-
cause a staging system based on FEV1alone was inade-
quate and the evidence for an alternative staging system
does not exist. The most severe spirometric grade, GOLD
4, does not include reference to respiratory failure as this
seemed to be an arbitrary inclusion.
5. A new section (section 3) on therapeutic approaches has
been added. This includes descriptive information on both
pharmacologic and nonpharmacologic therapies, and iden-
tifying any adverse effects.
MENT OF STABLE COPD (section 4); MANAGEMENT OF EXACER-
BATIONS (section 5); and COPD AND COMORBIDITIES (section
6), covering both management of comorbidities in patients with
COPD and of COPD in patients with comorbidities.
7. In section 4, MANAGEMENT OF STABLE COPD, recommen-
ded approaches to both pharmacologic and nonpharma-
cologic treatment of COPD are presented. In previous
GOLD documents, recommendations for management
of COPD were based solely on spirometric category.
However, there is considerable evidence that the level
of FEV1is a poor descriptor of disease status, and for
this reason, the management of stable COPD based on
a strategy considering both disease impact (determined
mainly by symptom burden and activity limitation) and
future risk of disease progression (especially of exacer-
bations) is recommended.
8. Section 5, MANAGEMENT OF EXACERBATIONS, presents
a revised definition of a COPD exacerbation.
348AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINEVOL 1872013
9. Section 6, COMORBIDITIES AND COPD, focuses on cardiovas-
cular diseases, osteoporosis, anxiety and depression, lung
cancer, infections, and metabolic syndrome and diabetes.
Levels of Evidence
Levels of evidence are assigned to management recommenda-
Evidence levels are enclosed in parentheses after the relevant
statement, for example, “(Evidence A).” Levels of evidence used
in this document have not changed with respect to previous re-
leases and are listed in the original document (www.goldcopd.org).
1. DEFINITION AND OVERVIEW
d COPD, a common preventable and treatable disease, is
characterized by persistent airflow limitation that is usually
progressive and associated with an enhanced chronic in-
flammatory response in the airways and the lung to nox-
ious particles or gases. Exacerbations and comorbidities
contribute to the overall severity in individual patients.
d COPD is a leading cause of morbidity and mortality
worldwide and results in an economic and social bur-
den that is both substantial and increasing.
d Inhaled cigarette smoke and other noxious particles such
as smoke from biomass fuels cause lung inflammation,
a normal response that appears to be modified in pa-
tients who develop COPD. This chronic inflammatory
response may induce parenchymal tissue destruction
(resulting in emphysema) and disrupt normal repair and
defense mechanisms (resulting in small airway fibrosis).
These pathological changes lead to air trapping and pro-
gressive airflow limitation, and in turn to breathlessness
and other characteristic symptoms of COPD.
COPD, a common preventable and treatable disease, is charac-
terized by persistent airflow limitation that is usually progressive
and associated with an enhanced chronic inflammatory response
in the airways and the lung to noxious particles or gases. Exac-
erbations and comorbidities contribute to the overall severity in
The chronic airflow limitation characteristic of COPD is
caused by a mixture of small airways disease (obstructive bron-
chiolitis) and parenchymal destruction (emphysema), the relative
contributions of which vary from person to person. Chronic in-
flammation causes structural changes and narrowing of the small
airways. Destruction of the lung parenchyma, also by inflamma-
tory processes, leads to the loss of alveolar attachments to the
small airways and decreases lung elastic recoil; in turn, these
changes diminish the ability of the airways to remain open during
expiration. Airflow limitation is best measured by spirometry, as
Burden of COPD
COPD prevalence, morbidity, and mortality vary across countries
cumulative exposures over decades. Often, the prevalence of
COPD is directly related to the prevalence of tobacco smoking,
although in many countries, outdoor, occupational, and indoor
air pollution—the latter resulting from the burning of wood and
other biomass fuels—are major COPD risk factors (1). The pre-
valence and burden of COPD are projected to increase in the
coming decades due to continued exposure to COPD risk fac-
tors and the aging of the world’s population.
Prevalence. Existing COPDprevalence data showremarkable
variation due to differences in survey methods, diagnostic crite-
ria, and analytic approaches (2). Despite the complexities and
the widespread underrecognition and underdiagnosis of COPD
(3), data from the Latin American Project for the Investigation
of Obstructive Lung Disease (PLATINO) and the Burden of
Obstructive Lung Diseases program (BOLD) have documented
more severe disease than previously found and a substantial
prevalence (3–11%) of COPD among never-smokers (4).
Morbidity. Morbidity measures traditionally include physician
visits, emergency department visits, and hospitalizations. Morbid-
ity due to COPD increases with age (5–7) and may be affected by
other comorbid chronic conditions (e.g., cardiovascular disease,
musculoskeletal impairment, or diabetes mellitus) that are fre-
quent in patients with COPD and may impact on the patient’s
health status, as well as interfere with COPD management.
Mortality. Underrecognition and underdiagnosis of COPD still
affectthe accuracyof mortality data(8, 9) withCOPD often listed
as a contributory cause of death or omitted from the death cer-
tificate entirely (10). The Global Burden of Disease Study pro-
jected that COPD, which ranked sixth as a cause of death in 1990,
will become the third leading cause of death worldwide by 2020;
a newer projection estimated COPD will be the fourth leading
cause of death in 2030 (11). This increased mortality is mainly
driven by the expanding epidemic of smoking, reduced morta-
lity from other common causes of death, and aging of the world
Economic and social burden. COPD is associated with signifi-
cant economic burden. There is a direct relationship between the
changes as the disease progresses. For example, hospitalization
and ambulatory oxygen costs soar as COPD severity increases.
than the impact of COPD on workplace and home productivity. In
1990, COPD was the 12th leading cause of disability-adjusted life
years (DALYs) lost in the world, responsible for 2.1% of the total.
According to the projections, COPD will be the seventh leading
cause of DALYs lost worldwide in 2030 (11).
Factors That Influence Disease Development
Although cigarette smoking is the best-studied COPD risk factor,
there is consistent epidemiological evidence that nonsmokers may
also develop chronic airflow limitation (5–7, 12). Besides, among
people with the same smoking history, not all will develop COPD,
for reasons that are still unclear but likely involve differences in
genetic backgrounds and other exposures.
Across the world, cigarette smoking is the most commonly en-
countered risk factor for COPD. Cigarette smokers have a higher
prevalence of respiratory symptoms and lung function abnormal-
mortality rate than nonsmokers (13). Other types of tobacco (e.g.,
pipe, cigar, water pipe ) and marijuana (15) are also risk fac-
tors for COPD (16, 17). Passive exposure to cigarette smoke (also
known as environmental tobacco smoke) may also contribute to
respiratory symptoms (18) and COPD (19) by increasing the
lung’s total burden of inhaled particles and gases (20, 21). Smok-
ing during pregnancy may also pose a risk for the fetus, by af-
fecting lung growth and development in utero and possibly the
priming of the immune system (22, 23).
GOLD Executive Summary 349
Occupational exposures, including organic and inorganic dusts
and chemical agents and fumes, are an underappreciated risk fac-
tor for COPD (24–26). Wood, animal dung, crop residues, and
coal, typically burned in open fires or poorly functioning stoves,
may lead to very high levels of indoor air pollution. Evidence
continues to grow that indoor pollution from biomass cooking
and heating in poorly ventilated dwellings is an important risk
factor for COPD (27–33). Almost 3 billion people worldwide use
biomass and coal as their main source of energy for cooking,
heating, and other household needs, so the population at risk
worldwide is very large (30, 34).
COPD, such as genetics, lung development abnormalities, accel-
erated aging, bronchial hyperreactivity, and socioeconomic sta-
tus, among others, are listed in recent reviews and in the full
Pathology, Pathogenesis, and Pathophysiology1
Inhaled particles (from cigarette smoke or other sources) cause
lung inflammation, a normal response that appears to be modi-
fied in individuals who develop COPD. This chronic inflam-
matory response may induce parenchymal tissue destruction
(resulting inemphysema), anddisrupt normal repairand defense
mechanisms (resulting in small airway fibrosis), which in turn
lead to air trapping and progressive airflow limitation.
Pathology. Chronic inflammatory changes with increased num-
bers of inflammatory cell types, and structural changes resulting
from repeated injury and repair, are found in the airways, lung
parenchyma, and pulmonary vasculature of patients with COPD
(35). In general, these changes increase with disease severity and
persist despite smoking cessation.
Pathogenesis. The above-mentioned pathological changes ap-
pears to be an enhancement of the normal, physiological, inflam-
matory response of the respiratory tract to chronic irritants. The
understood but may be genetically determined. Lung inflamma-
tion persists after smoking cessation through unknown mech-
anisms, although autoantigens and persistent microorganisms
may play a role (36). Patients can clearly develop COPD with-
out smoking, but the nature of the inflammatory response in these
patients is unknown.
Pathophysiology. AIRFLOW LIMITATION AND GAS TRAPPING. In-
FEV1. Parenchymal destruction due to emphysema also contrib-
utes to airflow limitation due to reduced elastic recoil (37). In
combination, both progressively lead to gas trapping during expi-
ration, resulting in hyperinflation.
GAS EXCHANGE ABNORMALITIES. Gas exchange abnormalities
anisms in COPD. The main one is ventilation–perfusion (VA/Q)
Reduced ventilatory drive may lead to carbon dioxide reten-
tion, particularly when combined with reduced ventilation.
MUCUS HYPERSECRETION. Mucus hypersecretion, resulting in
a chronic productive cough, is a feature of chronic bronchitis and
is not necessarily associated with airflow limitation. Conversely,
not all patients with COPD have symptomatic mucus hyperse-
cretion. When present, it is due to an increased number
of goblet cells and enlarged submucosal glands in response to
chronic airway irritation.
PULMONARY HYPERTENSION. Pulmonaryhypertensionmayde-
velop late in the course of COPD. It can be due to hypoxic vaso-
constriction of small pulmonary arteries, eventually resulting in
structural changes that include intimal hyperplasia and later
smooth muscle hypertrophy/hyperplasia, and/or loss of pulmo-
nary capillary bed due to emphysema (39). In pulmonary
vessels, an inflammatory response similar to that seen in the air-
ways (and evidence of endothelial dysfunction) has been identi-
fied. Severe pulmonary hypertension may lead to right ventricular
hypertrophy and eventually to right-side cardiac failure.
EXACERBATIONS. Exacerbations of respiratory symptoms of-
unknown factors. During exacerbations, there is a flare-up of in-
flammation, increased hyperinflation and gas trapping, reduced
expiratory flow, and increased dyspnea (40). There is also wor-
sening of VA/Q abnormalities, which can result in hypoxemia
and hypercapnia (41). Other medical conditions (pneumonia,
thromboembolism, and acute cardiac failure) may mimic or ag-
gravate an exacerbation of COPD.
COMORBIDITIES. It is increasingly recognized that many pa-
tients with COPD have comorbidities and that these have a major
impact on their quality of life and survival (42). The precise
pathobiology of this association is under investigation but may
involve mechanical as well as biological or genetic mechanisms.
For instance, airflow limitation and hyperinflation affect cardiac
function and gas exchange (43).
2. DIAGNOSIS AND ASSESSMENT
d A clinical diagnosis of COPD should be considered in
any patient who has dyspnea, chronic cough and/or
sputum production, and a history of exposure to risk
factors for the disease.
d Spirometry is required to make the diagnosis in this
clinical context; the presence of a post-bronchodilator
FEV1/FVC less than 0.70 confirms the presence of per-
sistent airflow limitation and thus of COPD.
d The goals of COPD assessment are to determine: (1)
the impact of the disease on the patient’s health status,
(2) the severity of airflow limitation, and (3) the risk
of future exacerbations, in order to guide therapy.
The risk of future exacerbations is estimated by the
severity of airflow limitation and the history of previous
d Comorbidities, including cardiovascular disease, skele-
tal muscle dysfunction, metabolic syndrome, osteopo-
rosis, depression, and lung cancer, occur frequently in
patients with COPD. Comorbidities should be actively
looked for, and treated appropriately if present.
A clinical diagnosis of COPD should be considered in any patient
who has dyspnea, chronic cough and/or sputum production, and
a history of exposure to risk factors for the disease. Spirometry is
required to make the diagnosis in this clinical context; the pres-
ence of a post-bronchodilator FEV1/FVC less than 0.70 confirms
the presence of persistent airflow limitation and thus of COPD.
The spirometric criterion for airflow limitation remains
a post-bronchodilator fixed ratio of FEV1/FVC less than 0.70.
This criterion is simple, independent of reference values, and
has been used in numerous clinical trials forming the evidence
base from which most of our treatment recommendations are
drawn. Diagnostic simplicity and consistency are key for the busy
nonspecialist clinician. Although post-bronchodilator spirometry
1Illustrations of many of the topics covered in this section can be found in the
Teaching Slide Set on the GOLD website: http://www.goldcopd.org.
350AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINEVOL 1872013
is required for the diagnosis and assessment of severity of COPD,
the degree of reversibility of airflow limitation (e.g., measuring
FEV1before and after bronchodilator or corticosteroids) is no
Symptoms. The characteristic symptoms of COPD are chronic
and progressive dyspnea, cough, and sputum production. Chro-
nic cough and sputum production may precede the development
of airflow limitation by many years. Individuals, particularly
those exposed to COPD risk factors, who present with these
symptoms should be examined to search for an underlying
cause(s) and appropriate interventions taken. Conversely, signif-
icant airflow limitation may develop without chronic cough and
Medical history. A detailed medical history of a new patient
known or thought to have COPD should assess:
d Exposure to risk factors
d Past medical history
d Family history of COPD or other chronic respiratory
d Pattern of symptom development
d History of exacerbations or previous hospitalizations for
d Presence of comorbidities
d Impact of the disease on the patient’s life
d Social and family support available to the patient
d Possibilities for reducing risk factors, especially smoking
Physicalexamination. Although an important part of patient
care, a physical examination is rarely diagnostic in COPD.
Physical signs of airflow limitation are usually not present un-
til significant impairment of lung function has occurred (44,
45), and their detection has a relatively low sensitivity and
Spirometry. Spirometry is the most reproducible and objec-
tive measurement of airflow limitation available. Peak expira-
tory flow measurement alone cannot be reliably used as the
only diagnostic test, despite its good sensitivity, because of
its weak specificity (46). Good-quality spirometric measure-
ment is possible in any health care setting, and all health care
workers who care for patients with COPD should have access
Assessment of Disease
The goals of COPD assessment are to determine: (1) the impact
of the disease on the patient’s health status, (2) the severity of
airflow limitation, and (3) the risk of future events (such as ex-
acerbations, hospital admissions, or death), to, eventually, guide
therapy. To achieve these goals, COPD assessment must con-
sider the following aspects of the disease separately:
d Current level of patient’s symptoms
d Severity of airflow limitation
d Exacerbation risk
d Presence of comorbidities
Assessment of symptoms. There are several validated ques-
tionnaires to assess symptoms in patients with COPD that can
be used to distinguish patients with less severe symptoms from
patients with more severe symptoms. GOLD primarily recom-
mends the use of the Modified British Medical Research Council
Test (CAT), the latter having a broader coverage of the impact of
COPD on the patient’s daily life and well-being. Other symptoms
scales can be used where available, for example, the Clinical
COPD Questionnaire, and future GOLD updates are likely to
expand in this area.
Assessment of airflow limitation severity. Table 1 shows the
classification of airflow limitation severity in COPD. Specific spi-
rometric cut points are used for purposes of simplicity. Spirom-
etry should be performed after the administration of an adequate
dose of a short-acting inhaled bronchodilator to minimize vari-
ability. Worsening airflow limitation is associated with an increas-
ing prevalence of exacerbations (see below) and risk of death.
Assessment of exacerbation risk. An exacerbation of COPD is
defined as an acute event characterized by a worsening of the
patient’s respiratory symptoms that is beyond normal day-to-
day variations and leads to a change in medication (47–49). The
rate at which exacerbations occur varies greatly between pa-
tients (50). The best predictor of having frequent exacerbations
(two or more exacerbations per year) is a history of previous
treated events (51). Severity of exacerbations is usually clas-
sified as mild when exacerbations of respiratory symptoms re-
quire change of inhaled treatment by the patient, moderate
when exacerbations of respiratory symptoms require medical
intervention including a short course of antibiotic and/or oral
steroids, and severe when exacerbations of respiratory symp-
toms require hospitalization.
Assessment of comorbidities. Comorbidities occur frequently
in COPD and include cardiovascular disease, skeletal muscle
dysfunction, metabolic syndrome, osteoporosis, depression, and
for other concomitant diseases; this is particularly striking for
COPD and lung cancer (52–55).
Combined COPD assessment. Figure 1 illustrates the pro-
posed combined assessment of COPD. The MRC or CAT
scale is recommended for assessing symptoms, with an mMRC
grade greater than or equal to 2 or a CAT score greater than or
equal to 10 indicating a high level of symptoms. These cutoffs
should be used as indicators; the primary aim is to separate
patients with a significant symptom burden from those with
less symptoms. There are two methods of assessing exacerba-
tion risk. One is a population-based method using the GOLD
spirometric classification (Table 1), with GOLD 3 or GOLD 4
categories indicating high risk. The other is based on the indi-
vidual patient’s history of exacerbations (51, 56), with two or
more exacerbations in the preceding year indicating high risk.
Given the significance of an exacerbation leading to hospital
admission (57), hospitalization will often be an indicator of
high risk as well. If there is a discrepancy between the risk
category as assessed by spirometric classification and that de-
rived from exacerbation history, the assessment pointing to the
highest risk should be used.
To use Figure 1, first assess symptoms and determine if the
patient belongs to the left side of the box—less symptoms (as indi-
cated by mMRC grade 0–1 or CAT , 10)—or the right side—more
symptoms (as indicated by mMRC > 2 or CAT > 10). Next, assess
the risk of exacerbations to determine if the patient belongs to the
TABLE 1. GRADING OF SEVERITY OF AIRFLOW LIMITATION IN
COPD (BASED ON POST-BRONCHODILATOR FEV1)
In patients with FEV1/FVC , 0.70:
FEV1> 80% predicted
50% < FEV1, 80% predicted
30% < FEV1, 50% predicted
FEV1, 30% predicted
Definition of abbreviation: COPD ¼ chronic obstructive pulmonary disease;
GOLD ¼ Global Initiative for Chronic Obstructive Lung Disease.
GOLD Executive Summary 351
lower part of the box—low risk—or the upper part of the box—high
risk. This can be done by either of two methods: (1) use spirometry
to determine the GOLD grade of airflow limitation (GOLD 1 and 2
indicate low risk, whereas GOLD 3 and 4 indicate high risk); or (2)
assess the number of exacerbations the patient has had within the
previous 12 months (zero or one indicates low risk, whereas two or
more exacerbations indicates high risk). In some patients, these two
ways of assessing risk of exacerbations will not lead to the same
level of risk; in this case, the risk should be determined by the
method indicating high risk.
The groups can be summarized as follows:
Patient group A—low risk, less symptoms
GOLD 1–2 (mild or moderate airflow limitation)
and 0–1 exacerbation per year and mMRC grade 0–1 or CAT
score , 10
Patient group B—low risk, more symptoms
GOLD 1–2 (mild or moderate airflow limitation)
and 0–1 exacerbation per year and mMRC grade > 2 or
CAT score > 10
Patient group C—high risk, less symptoms
GOLD 3–4 (severe or very severe airflow limitation)
and/or > 2 exacerbations per year and/or > 1 hospitalized
exacerbation per year and mMRC grade 0–1 or CAT score , 10
Patient group D—high risk, more symptoms
GOLD 3–4 (severe or very severe airflow limitation)
and/or > 2 exacerbations per year / > 1 hospitalized exac-
erbation per year and mMRC grade > 2 or CAT score > 10
This approach, combined with an assessment of potential
comorbidities, reflects the complexity of COPD better than
the unidimensional analysis of airflow limitation previously used
for staging the disease and forms the basis of the guide to indi-
vidualized management provided in section 4.
Additional investigations. Thefollowingadditionalinvestigations
IMAGING. A chest X-ray is not useful to establish a diagnosis
in COPD, but it is valuable in excluding alternative diagnoses
and establishing the presence of significant comorbidities.
LUNG VOLUMES AND DIFFUSING CAPACITY. Patients with
COPD exhibit gas trapping (a rise in residual volume) from
early in the disease, and as airflow limitation worsens, static hy-
perinflation (an increase in total lung capacity) occurs. These
changes can be documented by body plethysmography, or less
accurately by helium dilution lung volume measurement. Dif-
fusing capacity can be assessed by the uptake of carbon mon-
oxide using the single-breath method. These measurements
help characterize the severity of COPD but are not essential
to patient management.
OXIMETRY AND ARTERIAL BLOOD GAS MEASUREMENT. Pulse
oximetry can be used to evaluate a patient’s oxygen saturation
and need for supplemental oxygen therapy. Pulse oximetry
should be used to assess all stable patients with FEV1less than
35% predicted or with clinical signs suggestive of respiratory
failure or right heart failure. If peripheral saturation is less than
92%, arterial blood gases should be assessed (58).
a1-ANTITRYPSIN DEFICIENCY SCREENING. The World Health
Organization recommends that patients with COPD from areas
with a particularly high prevalence of a1-antitrypsin deficiency
should be screened for this genetic disorder (59). The typical
patient tends to present at a younger age (,45 yr) with lower
lobe emphysema. A serum concentration of a1-antitrypsin be-
low 15 to 20% of the normal value is highly suggestive of ho-
mozygous a1-antitrypsin deficiency.
EXERCISE TESTING. Objectively measured exercise impair-
ment, assessed by a reduction in self-paced walking distance
(60) or during incremental exercise testing in a laboratory
(61), is a powerful indicator of health status impairment and
predictor of prognosis (62). Monitoring of physical activity
may be more relevant regarding prognosis than evaluating
exercise capacity (63).
COMPOSITE SCORES. Several variables, including age, dyspnea,
FEV1, body mass index, exercise tolerance assessed by walking
distance or peak oxygen consumption, and/or arterial hypoxemia,
identify patients at increased risk for mortality (64–66).
In some patients with chronic asthma, a clear distinction from
COPD is not possible using current imaging and physiological
testing techniques, and it is assumed that asthma and COPD co-
exist in these patients. In these cases, current management will
include use of antiinflammatory drugs, and other treatments
need to be individualized. Other potential diagnoses are usually
easier to distinguish from COPD (Table 2).
3. THERAPEUTIC OPTIONS
d In patients who continue to smoke, smoking cessation
is a key therapeutic measure. Pharmacotherapy and
nicotine replacement reliably increase long-term smok-
ing abstinence rates.
d Appropriate pharmacologic therapy can reduce COPD
symptoms, reduce the frequency and severity of exacer-
bations, and improve health status and exercise tolerance.
d To date, none of the existing medications for COPD
has been shown conclusively to modify the long-term
decline in lung function.
d Each pharmacological treatment regimen needs to be patient
comorbidities, drug availability, and the patient’s response.
d Influenza and pneumococcal vaccination should be of-
fered to every patient with COPD; they appear to be
more effective in older patients and those with more
severe disease or cardiac comorbidity.
d All patients who get short of breath when walking on their
own pace on level ground should be offered rehabilitation;
it can improve symptoms, quality of life, and physical and
emotional participation in everyday activities.
All text of this section can be found in the online supplement.
Figure 1. Combined COPD assessment. When assessing risk, choose the
highest risk according to GOLD spirometric grade or exacerbation history.
352AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINEVOL 1872013
4. MANAGEMENT OF STABLE COPD
d Identification and reduction of exposure to risk factors
are important in the prevention and treatment of COPD.
All individuals who smoke should be encouraged to quit.
d The level of FEV1is an inadequate descriptor of the
impact of the disease on patients, and for this reason,
individualized assessment of symptoms and future risk
of exacerbation should also be incorporated into the
management strategy for stable COPD.
d Regular physical activity is recommended for all patients
d All patients with COPD with breathlessness when walk-
ing at their own pace on level ground benefit from reha-
bilitation and maintenance of physical activity, improving
their exercise tolerance and quality of life, and reducing
symptoms of dyspnea and fatigue.
d Pharmacologic therapy is used to reduce symptoms,
reduce frequency and severity of exacerbations, and
improve health status and exercise tolerance. Existing
medications for COPD have not been conclusively
shown to modify the long-term decline in lung function
that is the hallmark of this disease.
d For both b2-agonists and anticholinergics, long-acting
formulations are preferred over short-acting formula-
tions. Based on efficacy and side effects, inhaled bron-
chodilators are preferred over oral bronchodilators.
d Long-term treatment with inhaled corticosteroids added
to long-acting bronchodilators is recommended for pa-
tients at high risk of exacerbations.
d Long-term monotherapy with oral or inhaled cortico-
steroids is not recommended in COPD.
d The phospodiesterase-4 inhibitor roflumilast may be
useful to reduce exacerbations for patients with FEV1
less than 50% predicted, chronic bronchitis, and fre-
d Influenza vaccines can reduce the risk of serious illness
(such as hospitalization due to lower respiratory tract
infections) and death in patients with COPD.
d The routine use of antibiotics is not indicated in patients
with clinically stable COPD, other than for treating infec-
tious exacerbations ofCOPDandother bacterialinfections.
Once COPD has been diagnosed, effective management should
be based on an individualized assessment of the disease having
two goals in mind:
1. Reduce current symptoms
2. Reduce the risk of future events (Table 3)
These goals should be reached with minimal side effects from
treatment, a particular challenge in patients with COPD because
they commonly have comorbidities that also need to be carefully
identified and treated.
Identify and Reduce Exposures
Identification and reduction of exposure to risk factors are im-
portant in the treatment (and prevention) of COPD. Since
cigarette smoking is the most commonly encountered and easily
identifiable risk factor, smoking cessation should be encouraged
for all individuals who smoke. Reduction of total personal expo-
sure to occupationaldusts,fumes,and gases and to indoor and out-
door air pollutants may be more difficult but should be attempted.
Treatment of Stable COPD
In previous versions of the GOLD report, COPD treatment rec-
ommendations were based on spirometry only. This is in keeping
with the fact that most of the clinical trial evidence about treat-
ment efficacy in COPD is oriented around baseline FEV1. How-
ever, FEV1alone is a poor descriptor of disease status, and for
this reason, the treatment strategy for stable COPD should con-
sider also an individual patient’s symptoms and future risk of
exacerbations as illustrated in Figure 1.
Physical activity. Regular physical activity is recommended for
all patients with COPD.
Rehabilitation. Although more information is needed on cri-
all patientswith COPD appear to benefit from rehabilitation and
maintenance of physical activity, improving their exercise toler-
ance and experiencing decreased dyspnea and fatigue (67) (Ev-
depend on local policies, availability, and affordability.
Nonpharmacologic management of COPD according to the
individualized assessment of symptoms and exacerbation risk
(Figure 1) is shown in Table 4.
Theclasses ofmedications commonlyused in treating COPD are
shown in Table E1 in the online supplement, and a detailed de-
the online supplement. The choice within each class depends on
the availability of medication and the patient’s response. A pro-
posed model for initial pharmacological management of COPD
according to the individualized assessment of symptoms and
exacerbation risk (Figure 1) is shown in Table 5.
Group A. Group A patients have few symptoms and a low risk
of exacerbations. Specific evidence for the effectiveness of phar-
macologic treatments is not available for patients with FEV1
greater than 80% predicted (GOLD 1). However, for all group
A patients, a short-acting bronchodilator is recommended as
first choice based on its effect on lung function and breathless-
ness. Second choice is a combination of short-acting broncho-
dilators or the introduction of a long-acting bronchodilator. The
evidence for this step-up is weak; few studies of the combination
exist (68, 69), and most trials of therapy with long-acting bron-
chodilators have been performed in patients with more severe
airflow limitation (70, 71).
Group B. Group B patients have more significant symptoms
but still a low risk of exacerbations. Long-acting bronchodilators
are superior to short-acting bronchodilators (taken as needed)
and are therefore recommended (70, 71). There is no evidence
to recommend one class of long-acting bronchodilators over
another for initial treatment. In the individual patient, the
choice should depend on the patient’s perception of symptom
relief. For patients with severe breathlessness, the second choice
is a combination of long-acting bronchodilators (72, 73). Only
short-term studies of this treatment option have been reported,
and patients on a combination of long-acting bronchodilators
should be carefully followed and their treatment effect evaluated.
GOLD Executive Summary353
Alternative choices include short-acting bronchodilators and the-
ophylline, the latter of which can be used if inhaled bronchodi-
lators are unavailable or unaffordable.
Group C. Group C patients have few symptoms but a high risk
of exacerbations. As first choice, a long-acting anticholinergic
or a combination of inhaled corticosteroid/long-acting b2-
agonist is recommended (71, 74–79). Unfortunately, there is only
one study directly comparing these treatments, which makes
differentiation difficult (80). Both long-acting anticholinergic
and long-acting b2-agonist reduce the risk of exacerbations
(70, 71), and although good long-term studies are lacking, this
principle of combination treatment seems sound (although in
many countries expensive). The recommendation for a combi-
nation of inhaled corticosteroid/long-acting anticholinergic is
not evidence based. A phosphodiesterase-4 inhibitor may be
considered if the patient has chronic bronchitis (81, 82). Alter-
native choices include short-acting bronchodilators and theoph-
ylline if long-acting inhaled bronchodilators are unavailable or
Group D. Group D patients have many symptoms and a high
riskof exacerbations. The rationale for the first choice of therapy
is the same as that for patients in group C, as reduction of
exacerbation risk seems most important. As second choice, a
combination of all three classes of drugs (inhaled corticosteroid/
long-acting b2-agonist/long-acting anticholinergic) is recommen-
ded (83), although there are conflicting findings concerning this
treatment (84); support for it mainly comes from short-term stud-
ies (85). It is also possible to add a phosphodiesterase-4 inhibitor
to the treatment chosen as first choice, provided the patient has
chronic bronchitis (81). A phosphodiesterase-4 inhibitor is effec-
tive when added to a long-acting bronchodilator (82), whereas
evidence of its benefit when added to inhaled corticosteroid comes
from less valid secondary analyses. Alternative choices include
short-acting bronchodilators, and theophylline or carbocysteine
(86) can be used if long-acting inhaled bronchodilators are un-
available or unaffordable.
d For both b2-agonists and anticholinergics, long-acting for-
mulations are preferred over short-acting formulations
d The combined use of short- or long-acting b2-agonists and
anticholinergics may be considered if symptoms are not
improved with single agents (Evidence B).
d Based on efficacy and side effects, inhaled bronchodilators
are preferred over oral bronchodilators (Evidence A).
d Based on evidence of relatively low efficacy and more side
effects, treatment with theophylline is not recommended
unless other long-term treatment bronchodilators are un-
available or unaffordable (Evidence B).
Corticosteroids and phosphodiesterase-4 inhibitors—recom-
d There is no evidence to recommend a short-term therapeu-
tic trial with oral corticosteroids in patients with COPD to
identify those who will respond to inhaled corticosteroids or
d Long-term treatment with inhaled corticosteroids is recom-
mended for patients with FEV1less than 50% of predicted
and/or frequent exacerbations that are not adequately con-
trolled by long-acting bronchodilators (Evidence A).
d Long-term monotherapy with oral corticosteroids is not
recommended in COPD (Evidence A).
d Long-term monotherapy with inhaled corticosteroids is
not recommended in COPD because it is less effective
than the combination of inhaled corticosteroids with
long-acting b2-agonists (Evidence A).
d The phosphodiesterase-4 inhibitor roflumilast may also be
used to reduce exacerbations for patients with chronic
bronchitis, FEV1less than 50% of predicted, and frequent
exacerbations that are not adequately controlled by long-
acting bronchodilators (Evidence B).
Monitoring and Follow-up
Routine follow-up is essential in COPD. The frequency of follow-
up visits and type of examinations needs to be individualized. In
general, the following aspects need to be considered:
TABLE 3. GOALS FOR TREATMENT OF STABLE COPD
d Relieve symptoms
d Improve exercise tolerance
d Improve health status
d Prevent disease progression
d Prevent exacerbations
d Reduce mortality
Definition of abbreviation: COPD ¼ chronic obstructive pulmonary disease.
TABLE 2. COPD AND ITS DIFFERENTIAL DIAGNOSES
Diagnosis Suggestive Features
COPD Onset in midlife
Symptoms slowly progressive
History of tobacco smoking or exposure
to other types of smoke
Onset early in life (often childhood)
Symptoms vary widely from day to day
Symptoms worse at night/early morning
Allergy, rhinitis, and/or eczema also present
Family history of asthma
Chest X-ray shows dilated heart, pulmonary
Pulmonary function tests indicate volume
restriction, not airflow limitation
Large volumes of purulent sputum
Commonly associated with bacterial infection
Chest X-ray/CT shows bronchial dilation,
bronchial wall thickening
Onset all ages
Chest X-ray shows lung infiltrate
High local prevalence of tuberculosis
Onset at younger age, nonsmokers
May have history of rheumatoid arthritis
or acute fume exposure
Seen after lung or bone marrow transplantation
CT on expiration shows hypodense areas
Predominantly seen in patients of Asian
Most patients are male and nonsmokers
Almost all have chronic sinusitis
Chest X-ray and HRCT show diffuse small
opacities and hyperinflation
Congestive heart failure
Definition of abbreviations: CT ¼ computer tomography; HRCT ¼ high-resolution
These features tend to be characteristic of the respective diseases, but are not
mandatory. For example, a person who has never smoked may develop COPD
(especially in the developing world where other risk factors may be more impor-
tant than cigarette smoking); asthma may develop in adult and even in elderly
354AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINEVOL 1872013
Symptoms. At each visit, inquire about changes in symptoms
since the last visit, including cough and sputum, breathless-
ness, fatigue, activity limitation, and sleep disturbances. Ques-
tionnaires such as the CAT (87) can be performed every 2 to
3 months; trends and changes are more valuable than single
and smoke exposure; strongly encourage participation in pro-
grams to reduce and eliminate wherever possible exposure to
COPD risk factors.
Lung function. It may worsen over time, even with the best
etry performed at least once a year to identify patients whose
lung function is declining quickly.
Pharmacotherapy and other medical treatment. To adjust ther-
apy appropriately as the disease progresses, each follow-up visit
should include a discussion of the current therapeutic regimen.
Dosages of various medications, adherence to the regimen,
inhaler technique, effectiveness of the current regime at con-
trolling symptoms, and side effects of treatment should be mon-
itored. Treatment modifications should be recommended as
appropriate with a focus on avoiding unnecessary polypharmacy.
Exacerbation history. Evaluate the frequency, severity, and
likely causes of any exacerbations (88). Specific inquiry into
unscheduled visits to providers, telephone calls for assistance,
and use of urgent or emergency care facilities is important. Se-
verity of exacerbations can be estimated by the increased need
for bronchodilator medication or corticosteroids, by the need for
antibiotic treatment, or by documenting hospitalizations.
Comorbidities. Identification and manage them in line with lo-
cal treatment guidance (see section 6).
in patients with COPD due to smoking, poor general health status,
age, obesity, and COPD severity (89). Postoperative pulmonary
complications include lung infections, atelectasis, and/or increased
airflow limitation, which all potentially result in acute respiratory
failure (90–93). The surgical site is the most important predictor of
postoperative pulmonary complications and risk increases as the
incision approaches the diaphragm (92). Epidural or spinal anes-
thesia appears to have a lower risk than general anesthesia. To
prevent postoperative pulmonary complications, patients with
COPD should be optimally treated before surgery. Surgery
should be postponed if an exacerbation is present.
identified by careful history, physical examination, chest radiogra-
phy, and a complete battery of pulmonary function tests, including
spirometry with bronchodilator response, static lung volumes, dif-
fusing capacity, and arterial blood gases at rest (94, 95). The risk of
postoperative complications is particularly high in patients with
decreased predicted postoperative pulmonary function (FEV1or
DLCO, 30–40% predicted). These patients should undergo fur-
ther lung function assessment, for example, tests of regional dis-
tribution of perfusion and exercise capacity (94, 95). Poor exercise
capacity (peak VO2, 10 ml/kg/min or 35% predicted) identifies
a group of patients at very high risk. The final decision to pursue
surgery should be made after discussion with the surgeon, pulmo-
nary specialist, primary clinician, and the patient.
5. MANAGEMENT OF EXACERBATIONS
d An exacerbation of COPD is an acute event character-
ized by a worsening of the patient’s respiratory symp-
toms that is beyond normal day-to-day variations and
leads to a change in medication.
d Exacerbations of COPD can be precipitated by several
factors. The most common causes appear to be viral
upper respiratory tract infections and infection of the
d The diagnosis of an exacerbation relies exclusively on
the clinical presentation of the patient complaining of
an acute change of symptoms (baseline dyspnea, cough,
and/or sputum production) that is beyond normal day-
d The goal of treatment in COPD exacerbations is to min-
imize the impact of the current exacerbation and to pre-
vent the development of subsequent exacerbations.
d Short-acting inhaled b2-agonists with or without short-
acting anticholinergics are usually the preferred bron-
chodilators for treatment of an exacerbation.
d Systemic corticosteroids and antibiotics can shorten re-
covery time, improve lung function (FEV1) and arterial
hypoxemia (PaO2), and reduce the risk of early relapse,
treatment failure, and length of hospital stay.
d COPD exacerbations can often be prevented. Smok-
ing cessation, influenza and pneumococcal vaccina-
tion, knowledge of current therapy including inhaler
technique, and appropriate treatment are all interven-
tions that reduce the number of exacerbations and
An exacerbation of COPD is an acute event characterized by
a worsening of the patient’s respiratory symptoms that is be-
yond normal day-to-day variations and leads to a change in
Exacerbations of COPD are important events in the course of
the disease because they:
d Negatively affect a patient’s quality of life (88, 96)
d Have effects on symptoms and lung function that take
several weeks to recover (97)
d Accelerate the rate of decline of lung function (98, 99)
d Are associated with significant mortality, particularly in
those requiring hospitalization
d Have high socioeconomic costs (100)
In-hospital mortality of patients admitted for a hypercapnic
exacerbation with acidosis is approximately 10% (101). Mortality
TABLE 4. NONPHARMACOLOGIC MANAGEMENT OF COPD
Patient GroupEssential RecommendedDepending on Local Guidelines
ASmoking cessation (can include pharmacologic treatment) Physical activityFlu vaccination
B–D Smoking cessation (can include pharmacologic treatment)
Definition of abbreviation: COPD ¼ chronic obstructive pulmonary disease.
GOLD Executive Summary355
reaches 40% at 1 year after discharge in those needing mechan-
ical ventilator support, and all-cause mortality 3 years after
hospitalization is as high as 49% (100–104). Prevention, early
detection, and prompt treatment of exacerbations are vital to
reduce the burden of COPD (105).
Exacerbations of COPD can be precipitated by several fac-
tors. The most common causes appear to be respiratory tract
infections (viral or bacterial) (106–112). Air pollution can also
precipitate exacerbations of COPD (113–115). However, the
cause of about one-third of severe exacerbations of COPD can-
not be identified. Some patients appear particularly prone to
developing exacerbations of COPD, whereas others do not.
Those reporting two or more exacerbations of COPD per year
are often defined as “frequent exacerbators” (51, 56), a pheno-
type that appears stable over time. Severity of exacerbations is
usually classified as mild when exacerbations of respiratory
symptoms require change of inhaled treatment by the patient,
moderate when exacerbations of respiratory symptoms require
medical intervention including a short course of antibiotic and/
or oral steroids, and severe when exacerbations of respiratory
symptoms require hospitalization.
In addition to infections and exposure to pollutants, exacer-
bations of respiratory symptoms (especially dyspnea) in patients
with COPD may be due to different mechanisms that may
overlap in the same patients. Conditions that may mimic
and/or aggravate exacerbations, including pneumonia, pulmo-
nary embolism, congestive heart failure, cardiac arrhythmia,
pneumothorax, and pleural effusion, need to be considered
in the differential diagnosis and treated if present (47, 90,
97, 116). Interruption of maintenance therapy has also been
shown to lead to exacerbations.
Currently, the diagnosis of an exacerbation relies exclusively on
the clinical presentation of the patient complaining of an acute
change of symptoms (baseline dyspnea, cough, and/or sputum
production) that is beyond normal day-to-day variation. In the
future, a biomarker or panel of biomarkers that allows a more
precise etiologic diagnosis would be desirable.
The assessment of an exacerbation is based on the patient’s
medical history and clinical signs of severity and some labora-
tory tests, if available. The following tests may be considered to
assess the severity of an exacerbation:
d Pulse oximetry for tracking and/or adjusting supplemental
oxygen therapy. The measurement of arterial blood gases
is required if the coexistence of acute or acute-on-chronic
respiratory failure is suspected (PaO2, 8.0 kPa [60 mm Hg]
with or without PaCO2. 6.7 kPa [50 mm Hg] breathing
ambient air). Assessment of the acid–base status is neces-
sary before initiating mechanical ventilation (90, 117).
d Chest radiographs are useful in excluding alternative
d An ECG may aid in the diagnosis of coexisting cardiac
d Whole-blood count may identify polycythemia (hemato-
crit . 55%), anemia, or leukocytosis.
d The presence of purulent sputum during an exacerbation
can be sufficient indication for starting empirical antibiotic
treatment (118). Haemophilus influenzae, Streptococcus
pneumoniae, and Moraxella catarrhalis are the most common
bacterial pathogens involved in an exacerbation (108); in
GOLD 3 and GOLD 4 patients, Pseudomonas aeruginosa
d Biochemical test abnormalities, including electrolyte dis-
turbances and hyperglycemia, can be associated with exac-
erbations. However, these abnormalities can also be due
to associated comorbidities.
Spirometry is not recommended during an exacerbation be-
cause it can be difficult to perform and measurements are not
are to minimize the impact of the current exacerbation and prevent
the development of subsequent exacerbations (119). Depending on
the severity of an exacerbation and/or the severity of the underly-
ing disease, an exacerbation can be managed in an outpatient or
inpatient setting. More than 80% of exacerbations can be managed
on an outpatient basis (51, 79, 120) with pharmacologic therapies
including bronchodilators, corticosteroids, and antibiotics.
Table 6 shows the indications for hospital assessment and po-
tential admission of a patient with a COPD exacerbation. When
a patient comes to the emergency department, the first actions are
to provide controlled oxygen therapy and to determine whether
the exacerbation is life threatening (Table 7). If so, the patient
should be admitted to the intensive care unit (ICU) immediately.
Otherwise, the patient may be managed in the emergency depart-
ment or hospital. In addition to pharmacologic therapy, hospital
management of exacerbations includes respiratory support (oxy-
gen therapy, ventilation).
Pharmacologic treatment. The three classes of medications
most commonly used for exacerbations of COPD are broncho-
dilators, corticosteroids, and antibiotics.
SHORT-ACTING BRONCHODILATORS. Although there are no
controlled trials, short-acting inhaled b2-agonists with or without
short-acting anticholinergics are usually the preferred bronchodi-
lators for treatment of an exacerbation (90, 121) (Evidence C). A
systematic review of the route of delivery of short-acting bron-
chodilators found no significant differences in FEV1 between
metered-dose inhalers (with or without a spacer device) and neb-
ulizers (122), although the latter can be more convenient for
sicker or frail patients. Intravenous methylxanthines (theophyl-
line or aminophylline) are only to be used in selected cases when
there is insufficient response to short-acting bronchodilators
(123–127) (Evidence B). Side effects of methylxanthines are sig-
nificant, and their beneficial effects in terms of lung function and
clinical endpoints are modest and inconsistent (128, 129).
CORTICOSTEROIDS. Data from studies in secondary health
shorten recovery time, improve lung function (FEV1) and arterial
hypoxemia (PaO2) (130–133) (Evidence A), and reduce the risk of
early relapse, treatment failure, and length of hospital stay (130,
132, 134). A dose of 30–40 mg prednisolone per day for 10–14
days is recommended (Evidence D). Therapy with oral prednis-
olone is preferable (135). Nebulized budesonide alone may be an
alternative (although more expensive) to oral corticosteroids in
the treatment of exacerbations (131, 136, 137).
ANTIBIOTICS. There is evidence supporting the use of anti-
biotics in exacerbations when patients have clinical signs of a
bacterial infection, for example, increase in sputum purulence
(118). A systematic review of the very few available placebo-
controlled studies has shown that antibiotics reduce the risk of
short-term mortality by 77%, treatment failure by 53%, and
sputum purulence by 44%. This review supports antibiotics
356 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINEVOL 187 2013
for only moderately or severely ill patients with COPD exacer-
bations with increased cough and sputum purulence (138, 139).
Procalcitonin III, a marker that is specific for bacterial infec-
tions, may be of value in the decision to use antibiotics (140),
but this test is expensive and thus not widely established. A
study in patients with COPD with exacerbations requiring me-
chanical ventilation (invasive or noninvasive) indicated that not
giving antibiotics was associated with increased mortality and
a greater incidence of secondary nosocomial pneumonia (141). In
summary, antibiotics should be given to patients with exacerba-
tions of COPD who have three cardinal symptoms—increase in
dyspnea, sputum volume, and sputum purulence (Evidence B);
patients who have two of the cardinal symptoms, if increased
purulence of sputum is one of the two symptoms (Evidence C);
or require mechanical ventilation (invasive or noninvasive) (Ev-
idence B) (142). The recommended length of antibiotic therapy
is usually 5–10 days (Evidence D). The choice of the antibiotic
should be based on the local bacterial resistance pattern.
ADJUNCT THERAPIES. Depending on the clinical condition of
the patient, an appropriate fluid balance with special attention
to the administration of diuretics, anticoagulants, treatment of
comorbidities, and nutritional aspects should be considered.
At all times, health care providers should strongly enforce strin-
gent measures against active cigarette smoking.
Respiratory support. OXYGEN THERAPY. Controlled oxygen
should be titrated to improve the patient’s hypoxemia with a
target saturation of 88–92% (143). Once oxygen is started, arte-
rial blood gases should be checked 30 to 60 minutes later to
ensure satisfactory oxygenation without carbon dioxide retention
or acidosis. Venturi masks (high-flow devices) offer more accurate
and controlled delivery of oxygen than do nasal prongs but are less
likely to be tolerated by the patient (90).
VENTILATORY SUPPORT. Some patients need immediate ad-
mission to an ICU (Table 8). Admission of patients with severe
exacerbations to intermediate or special respiratory care units
may be appropriate if personnel, skills, and equipment exist to
identify and manage acute respiratory failure successfully.
Ventilatory support in an exacerbation can be provided by
either noninvasive (by nasal or facial mask) or invasive (by oro-
tracheal tube or tracheostomy) ventilation. Respiratory stimu-
lants are not recommended for acute respiratory failure (121).
NONINVASIVE MECHANICAL VENTILATION. Noninvasive mech-
anical ventilation (NIV) has been studied in several randomized,
controlled trials in acute respiratory failure, consistently pro-
viding success rates of 80 to 85% (144–147). NIV improves
respiratory acidosis (increases pH and decreases PaCO2) and
decreases respiratory rate, severity of breathlessness, compli-
cations such as ventilator-associated pneumonia, and length
of hospital stay (Evidence A). More importantly, mortality
and intubation rates are reduced by this intervention (145,
148–150) (Evidence A). Table 9 summarizes the indications
for NIV (90, 144, 146, 151, 152).
INVASIVE MECHANICAL VENTILATION. The indications for ini-
tiating invasive mechanical ventilation during an exacerbation
are shown in Table 10, and include failure of an initial trial of
NIV (153). As experience is being gained with the generalized
clinical use of NIV in COPD, several indications for invasive
mechanical ventilation are being successfully treated with NIV,
and in all but a few situations, there is nothing to be lost by
a trial of noninvasive ventilation (153).
TABLE 5. INITIAL PHARMACOLOGIC MANAGEMENT OF COPD*
Patient Group Recommended First Choice Alternative ChoiceOther Possible Treatments†
A Short-acting anticholinergic prn
Short-acting b2-agonist prn
Short-acting anticholinergic and
B Long-acting anticholinergic
Long-acting anticholinergic and
CInhaled corticosteroid and
and long-acting b2-agonist
D Inhaled corticosteroid and
Inhaled corticosteroid, long-acting b2-agonist,
and long-acting anticholinergic
Inhaled corticosteroid, long-acting b2-agonist,
and phosphodiesterase-4 inhibitor
Long-acting anticholinergic and
Long-acting anticholinergic and
Definition of abbreviation: COPD ¼ chronic obstructive pulmonary disease.
*Medications in each cell are mentioned in alphabetical order and therefore not necessarily in order of preference.
yMedications in this column can be used alone or in combination with other options in the First and Alternative Choice columns.
GOLD Executive Summary357
The use of invasive ventilation in patients with very severe
event, the patient’s wishes, and availability of intensive care
facilities. When possible, a clear statement of the patient’s
own treatment wishes—an advance directive or “living will”—
makes these difficult decisions much easier to resolve. Major
hazards include the risk of ventilator-acquired pneumonia
(especially when multiresistant organisms are prevalent), baro-
trauma, and failure to wean to spontaneous ventilation.
Contrary to some opinions, acute mortality among patients
with COPD with respiratory failure is lower than mortality
among patients ventilated for non-COPD causes (154). Despite
this, there is evidence that patients who might otherwise survive
may be denied admission to intensive care for intubation be-
cause of unwarranted prognostic pessimism (155).
Hospital Discharge and Follow-up
Insufficient clinical data exist to establish the optimal duration of
hospitalization in individual patients with an exacerbation of
COPD (156–158), although units with more respiratory consul-
tants and better-organized care have lower mortality and reduced
length of hospital stay after admission for an exacerbation (159).
In the hospital prior to discharge, patients should start long-
acting bronchodilators, either anticholinergics and/or b2-agonists
with or without inhaled corticosteroids. Hospitalization offers
a unique window of opportunity to reinforce smoking cessation
measures if necessary. Table 11 provides a checklist of items to
assess at time of discharge and Table 12 shows items to assess at
follow-up 4 to 6 weeks after discharge from the hospital.
Home visits by a community nurse may permit earlier dis-
charge of patients hospitalized with an exacerbation without
increasing readmission rates (90, 160–163). Use of a written
action plan increases appropriate therapeutic interventions for
an exacerbation, an effect that does not decrease health care
resource use (164) (Evidence B) but may shorten recovery time
For patients who are hypoxemic during an exacerbation, arte-
hospital discharge and in the following 3 months. If the patient
remains hypoxemic, long-term supplemental oxygen therapy may
Home Management of Exacerbations
Nurse-administered home care (also known as “hospital-at-home”
care) represents an effective and practical alternative to hospitaliza-
tion in selected patients with exacerbations of COPD without aci-
doticrespiratory failure (160,161) (Evidence A). However, theexact
criteria for this approach as opposed to hospital treatment remain
uncertain and will vary by health care setting. Treatment recommen-
dations are the same as for hospitalized patients.
Prevention of COPD Exacerbations
COPD exacerbations can often be prevented. Smoking cessa-
therapy including inhaler technique, and treatment with long-
acting inhaled bronchodilators, with or without inhaled cortico-
steroids, and phosphodiesterase-4 inhibitors are all therapies
that reduce the number of exacerbations and hospitalizations
(75, 79, 81, 82, 166, 167). Early outpatient pulmonary rehabil-
itation after hospitalization for an exacerbation is safe and
results in clinically significant improvements in exercise capacity
and health status at 3 months (168). Patients should be encour-
aged to maintain physical activity, and anxiety, depression, and
social problems should be discussed. Principal caregivers should
be identified if the patient has a significant persisting disability.
6. COPD AND COMORBIDITIES
d COPD often coexists with other diseases (comorbid-
ities) that may have a significant impact on prognosis.
d In general, the presence of comorbidities should not
alter COPD treatment, and comorbidities should be
treated as if the patient did not have COPD.
d Cardiovascular diseases are major comorbidities in
COPD and probably both the most frequent and most
important diseases coexisting with COPD.
d Osteoporosis and depression are also major comorbid-
ities in COPD, are often underdiagnosed, and are as-
sociated with poor health status and prognosis.
d Lung cancer is frequently seen in patients with COPD
and has been found to be the most frequent cause of
death in patients with mild COPD.
COPD often coexists with other diseases (comorbidities) that
may have a significant impact on prognosis (42, 169–171). Com-
orbidities can occur at any COPD grade (50). Differential diag-
nosis may be difficult because comorbidities may mimic COPD
TABLE 6. POTENTIAL INDICATIONS FOR HOSPITAL ASSESSMENT
d Marked increase in intensity of symptoms, such as sudden development of
d Severe underlying COPD
d Onset of new physical signs (e.g., cyanosis, peripheral edema)
d Failure of an exacerbation to respond to initial medical management
d Presence of serious comorbidities (e.g., heart failure or newly occurring
d Frequent exacerbations
d Older age
d Insufficient home support
Definition of abbreviation: COPD ¼ chronic obstructive pulmonary disease.
*Local resources need to be considered.
TABLE 7. MANAGEMENT OF SEVERE BUT NOT LIFE-THREATENING
d Assess severity of symptoms, blood gases, chest radiograph
d Administer controlled oxygen therapy and obtain serial arterial
blood gas measurement
d Increase doses and/or frequency of short-acting bronchodilators
d Combine short-acting b2-agonists and anticholinergics
d Use spacers or air-driven nebulizers
d Add oral or intravenous corticosteroids
d Consider antibiotics (oral or occasionally intravenous) when signs of
d Consider noninvasive mechanical ventilation
d At all times:
d Monitor fluid balance and nutrition
d Consider subcutaneous heparin or low molecular weight heparin
d Identify and treat associated conditions (e.g., heart failure,
d Closely monitor condition of the patient
*Local resources need to be considered.
358AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 1872013
symptoms, for example, heart failure and lung cancer (breath-
lessness) or depression (fatigue and reduced physical activity).
Below is a brief guide to management of COPD and some
comorbidities in stable disease. The recommendations reported
in this document may be insufficient for the management of all
patients and cannot substitute for the use of guidelines for the
management of each comorbidity. In general, the presence of
comorbidities should not alter COPD treatment and comorbid-
ities should be treated as if the patient did not have COPD.
ease coexisting with COPD (171, 172) and include four separate
entities: ischemic heart disease, heart failure, atrial fibrillation,
Ischemic heart disease. The prevalence of ischemic heart dis-
ease (IHD) is increased in COPD, to some extent because of an
unfavorable IHD risk profile in patients with COPD (173, 174).
Yet, it is often underdiagnosed in patients with COPD (175).
TREATMENT OF IHD IN PATIENTS WITH COPD. IHD should
be treated according to usual IHD guidelines, as there is no ev-
idence that IHD should be treated differently in the presence of
COPD than recommended in the usual IHD guidelines. This
includes treatment with selective b1-blockers, which are consid-
ered safe in patients with COPD (176), although this is based on
relatively few short-term studies. The benefits of selective b1-
blockers when indicated in IHD are, however, considerably
larger than the potential risks associated with treatment, even
in patients with severe COPD.
TREATMENT OF COPD IN PATIENTS WITH IHD. COPD should
be treated as usual, as there is no evidence that COPD should be
treated differently in the presence of IHD (75, 79, 177). Al-
though no large, long-term studies on COPD medications in
patients with unstable angina have been published, it seems
reasonable to avoid high doses of b-agonists.
Heart failure. Roughly 30% of patients with stable COPD will
have some degree of heart failure (HF) (178), and worsening of
HF is a significant differential diagnosis to an exacerbation of
COPD. Conversely, approximately 30% of patients in a HF
clinic have COPD (179), and comorbid COPD is often the cause
of admission for acute HF (180)—with significant implications
for prognosis as FEV1is a strong predictor of mortality in HF
(181). HF, COPD, and asthma may be confused because of the
common cardinal symptom of breathlessness.
TREATMENT OF HF IN PATIENTS WITH COPD. HF should be
treated according to usual HF guidelines as there is no evidence
that HF should be treated differently in the presence of COPD.
Treatment with selective b1-blockers has a significant impact on
survival in HF, and the presence of COPD is the most signifi-
cant reason for patients not receiving sufficient therapy (182).
However, as in IHD, treatment with selective b1-blockers is
considered safe for heart failure patients who also have COPD
(176). The benefits of selective b1-blocker treatment in HF
clearly outweigh any potential risk associated with treatment
even in patients with severe COPD.
TREATMENT OF COPD IN PATIENTS WITH HF. COPD should
be treated as usual, as there is no direct evidence that COPD
should be treated differently in the presence of HF. As for
IHD, this statement is based on findings from large long-term
studies in patients with HF and comorbid COPD (75, 79, 177).
An observational study found an increased risk of death and
hospital admission among patients with HF treated with in-
haled b-agonists (183), possibly indicating a need for close
follow-up of patients with severe HF who are on this treatment
Atrial fibrillation. Atrial fibrillation (AF) is the most frequent
cardiac arrhythmia, and patients with COPD have an increased
incidence of AF (184). COPD with AF presents a challenge to
clinicians because of the breathlessness and disability resulting
from their coexistence.
TREATMENT OF AF IN PATIENTS WITH COPD. AF should be
treated according to usual AF guidelines, as there is no evidence
that patients with COPD should be treated differently. If
b-blockers are used, b1-selective drugs are preferred (see con-
siderations under IHD and HF above).
TREATMENT OF COPD IN PATIENTS WITH AF. COPD should
be treated as usual; however, there are no good data on the
use of COPD medication in patients with AF, and these patients
sion that care should be taken when using high doses of b2-
agonists as this can make appropriate heart rate control difficult.
TABLE 8. INDICATIONS FOR ICU ADMISSION*
d Severe dyspnea that responds inadequately to initial emergency therapy
d Changes in mental status (confusion, lethargy, coma)
d Persistent or worsening hypoxemia (PaO2, 5.3 kPa, 40 mm Hg) and/or severe/
worsening respiratory acidosis (pH , 7.25) despite supplemental oxygen and
d Need for invasive mechanical ventilation
d Hemodynamic instability—need for vasopressors
*Local resources need to be considered.
TABLE 9. INDICATIONS FOR NONINVASIVE
At least one of the following:
d Respiratory acidosis (arterial pH < 7.35 and/or PaCO2> 6.0 kPa,
45 mm Hg)
d Severe dyspnea with clinical signs suggestive of respiratory muscle
fatigue, increased work of breathing, or both, such as use of respiratory
accessory muscles, paradoxical motion of the abdomen, or retraction of the
TABLE 10. INDICATIONS FOR INVASIVE
d Unable to tolerate NIV or NIV failure
d Respiratory or cardiac arrest
d Respiratory pauses with loss of consciousness or gasping for air
d Diminished consciousness, psychomotor agitation inadequately controlled by
d Massive aspiration
d Persistent inability to remove respiratory secretions
d Heart rate , 50 min21with loss of alertness
d Severe hemodynamic instability without response to fluids and
d Severe ventricular arrhythmias
d Life-threatening hypoxemia in patients unable to tolerate NIV
Definition of abbreviation: NIV ¼ noninvasive mechanical ventilation.
TABLE 11. CHECKLIST AT TIME OF DISCHARGE FROM HOSPITAL
d Reinforce smoking cessation measures
d Assure effective home maintenance of pharmacotherapy
d Reassess inhaler technique
d Educate about maintenance regimen
d Give instruction regarding completion of steroid therapy and antibiotics, if
d Assess need for long-term oxygen therapy
d Assure follow-up visit in 4–6 wk
d Provide a management plan for comorbidities and their follow-up
GOLD Executive Summary359
Hypertension. Hypertension is likely tobethe mostfrequently
occurring comorbidity in COPD and has implications for prog-
TREATMENT OF HYPERTENSION IN PATIENTS WITH COPD. Hy-
pertension should be treated according to usual hypertension
guidelines, as there is no evidence that hypertension should
ment with selective b-blockers is less prominent in recent hy-
pertension guidelines; if these are used in patients with COPD,
a selective b1-blocker should be chosen.
TREATMENT OF COPD IN PATIENTS WITH HYPERTENSION.
COPD should betreatedasusual,asthereisnodirectevidencethat
Osteoporosis is a major comorbidity in COPD (171, 172), is
often underdiagnosed (185), and is associated with poor health
status and prognosis. Osteoporosis is more often associated with
decreased body mass index (186) and low fat-free mass (187).
Treatment of osteoporosis in patients with COPD. Osteoporo-
sis should be treated according to usual osteoporosis guidelines,
as there is no evidence that osteoporosis should be treated dif-
ferently in the presence of COPD.
Treatment of COPD in patients with osteoporosis. COPD
should be treated as usual, as there is no evidence that stable
COPD should be treated differently in the presence of osteopo-
bone mass in the Lung Health Study II (188), whereas this was
not the case for inhaled budesonide in the EUROSCOP trial
(189) or for inhaled fluticasone propionate in the TORCH trial
(190). An association between inhaled corticosteroids and frac-
tures has been found in pharmacoepidemiological studies; how-
ever, these studies have not fully taken severity of COPD or
exacerbations and their treatment into account.
Systemic corticosteroids significantly increase the risk of os-
teoporosis, and recurrent courses of systemic corticosteroids for
COPD exacerbations should be avoided if possible.
Anxiety and Depression
Anxiety and depression are major comorbidities in COPD (191–
194), and both are associated with a poor prognosis (193, 195).
Both are often associated with younger age, female gender,
smoking, lower FEV1, cough, higher St. George’s Respiratory
Questionnaire score, and a history of cardiovascular diseases
Treatment of anxiety and depression in patients with COPD.
Both disorders should be treated according to usual guidelines,
as there is no evidence that anxiety and depression should be
treated differently in the presence of COPD.
Treatment of COPD in patients with anxiety and depression.
COPD should be treated as usual, as there is no evidence that
stable COPD should be treated differently in the presence of anx-
iety and depression. The potential impact of pulmonary rehabil-
itation should be stressed, as studies have found that physical
exercise has a beneficial effect on depression in general (196).
Lung cancer is frequently seen in patients with COPD and has
been found to be the most frequent cause of death in patients
with mild to moderate COPD (197).
Treatment of lung cancer in patients with COPD. Lung cancer
should be treated according to usual lung cancer guidelines, as
there is no evidence that lung cancer should be treated differ-
ently in the presence of COPD. However, often the reduced lung
function of patients with COPD will be a factor limiting surgical
intervention for lung cancer.
TreatmentofCOPDinpatientswithlungcancer. COPD should
be treated as usual, as there is no evidence that stable COPD
should be treated differently in the presence of lung cancer.
Serious infections,especially respiratory infections, are frequently
seen in patients with COPD (198).
TreatmentofinfectionsinpatientswithCOPD. Macrolide anti-
biotics increase the serum concentration of theophylline. Apart
from this, there is no evidence that infections should be treated
differently in the presence of COPD. However, repeat courses of
antibiotics for exacerbations may increase the risk for the pres-
ence of antibiotic resistant bacterial strains, and more extensive
cultures may be warranted.
Treatment of COPD in patients with infection. COPD should
be treated as usual, as there is no evidence that stable COPD
should be treated differently in the presence of infections. In
ticosteroids, this medication may be stopped to observe whether
this medication could be the cause of repeated infections.
Metabolic Syndrome and Diabetes
Studies have shown that the metabolic syndrome and manifest
diabetes are more frequent in COPD, and the latter is likely
to impact on prognosis (169).
Treatment of diabetes in patients with COPD. Diabetes should
be treated according to usual guidelines for diabetes, as there is
no evidence that diabetes should be treated differently in the
presence of COPD. However, for patients with severe COPD,
it is not advised to aim for a body mass index less than 21 kg/m2.
Treatment of COPD in patients with diabetes. COPD should
be treated as usual, as there is no evidence that stable COPD
should be treated differently in the presence of diabetes.
Author disclosures are available with the text of this article at www.atsjournals.org.
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