Rabe Et Al 2012 Global Strategy For The Diagnosis Management and Prevention of Chronic Obstructive Pulmonary Disease

Global Strategy for the Diagnosis, Management, and
Prevention of Chronic Obstructive Pulmonary Disease

GOLD Executive Summary
Klaus F. Rabe1, Suzanne Hurd2, Antonio Anzueto3, Peter J. Barnes4, Sonia A. Buist5, Peter Calverley6,
Yoshinosuke Fukuchi7, Christine Jenkins8, Roberto Rodriguez-Roisin9, Chris van Weel10, and Jan Zielinski11
1
Leiden University Medical Center, Pulmonology, Leiden, The Netherlands; 2Global Initiative for Chronic Obstructive Lung Disease,
Gaithersburg, Maryland; 3University of Texas Health Science Center, San Antonio, Texas; 4National Heart and Lung Institute, London,
United Kingdom; 5Oregon Health and Science University, Portland, Oregon; 6University Hospital Aintree, Liverpool, United Kingdom;
7
Asian Pacific Society of Respirology, Tokyo, Japan; 8Woolcock Institute of Medical Research, North Sydney, Australia;
9
Hospital Clinic, Barcelona, Spain; 10University of Nijmegen, Nijmegen, The Netherlands; and 11Institute of TB and Lung Diseases,
Warsaw, Poland
Chronic obstructive pulmonary disease (COPD) remains a major CONTENTS

public health problem. It is the fourth leading cause of chronic
morbidity and mortality in the United States, and is projected to rank Introduction
fifth in 2020 in burden of disease worldwide, according to a study Methodology and Summary of New Recommendations
published by the World Bank/World Health Organization. Yet, Levels of Evidence
COPD remains relatively unknown or ignored by the public as well 1. Definition, Classification of Severity, and Mechanisms of
as public health and government officials. In 1998, in an effort to COPD
bring more attention to COPD, its management, and its prevention, Definition
a committed group of scientists encouraged the U.S. National Heart, Spirometric Classification of Severity and Stages of COPD
Lung, and Blood Institute and the World Health Organization to Pathology, Pathogenesis, and Pathophysiology
form the Global Initiative for Chronic Obstructive Lung Disease 2. Burden of COPD
(GOLD). Among the important objectives of GOLD are to increase
Epidemiology
awareness of COPD and to help the millions of people who suffer
Prevalence
from this disease and die prematurely of it or its complications. The
Morbidity
first step in the GOLD program was to prepare a consensus report,
Global Strategy for the Diagnosis, Management, and Prevention of
Mortality
COPD, published in 2001. The present, newly revised document Economic and Social Burden of COPD
follows the same format as the original consensus report, but has Risk Factors
been updated to reflect the many publications on COPD that have Genes
appeared. GOLD national leaders, a network of international Inhalational Exposures
experts, have initiated investigations of the causes and prevalence Sex
of COPD in their countries, and developed innovative approaches Infection
for the dissemination and implementation of COPD management Socioeconomic Status
guidelines. We appreciate the enormous amount of work the GOLD 3. The Four Components of COPD Management
national leaders have done on behalf of their patients with COPD. Introduction
Despite the achievements in the 5 years since the GOLD report was Component 1: Assess and Monitor Disease
originally published, considerable additional work is ahead of us if Initial Diagnosis
we are to control this major public health problem. The GOLD Ongoing Monitoring and Assessment
initiative will continue to bring COPD to the attention of govern- Component 2: Reduce Risk Factors
ments, public health officials, health care workers, and the general Smoking Prevention and Cessation
public, but a concerted effort by all involved in health care will be
Occupational Exposures
necessary.
Indoor and Outdoor Air Pollution
Keywords: COPD; guidelines; human; chronic disease Component 3: Manage Stable COPD
Introduction
Education
Pharmacologic Treatments
Nonpharmacologic Treatments
(Received in original form March 20, 2007; accepted in final form May 15, 2007) Special Considerations
Correspondence and requests for reprints should be addressed to Prof. Klaus F. Component 4: Manage Exacerbations
Rabe, M.D., Ph.D., Leiden University Medical Center, Pulmonology, P.O. Box Introduction
9600, NL-2300 RC, Leiden, The Netherlands. E-mail: [email protected]. Diagnosis and Assessment of Severity
This article has an online supplement, which is accessible from this issue’s table of Home Management
contents at www.atsjournals.org Hospital Management
This document is available in a different format on the Global Initiative for Chronic Hospital Discharge and Follow-up
Obstructive Lung Disease (GOLD) website at www.goldcopd.org/download.asp?
4. Translating Guideline Recommendations to the Context of
intId=380
(Primary) Care
Am J Respir Crit Care Med Vol 176. pp 532–555, 2007
Originally Published in Press as DOI: 10.1164/rccm.200703-456SO on May 16, 2007 Diagnosis
Internet address: www.atsjournals.org Respiratory Symptoms
GOLD Executive Summary 533
Spirometry mendations to recognize the need to present a positive

Comorbidities outlook for patients, to encourage the health care com-
Reducing Exposure to Risk Factors munity to take a more active role in developing programs
Implementation of COPD Guidelines for COPD prevention, and to stimulate effective manage-
ment programs to treat those with the disease.
3. The spirometric classification of severity of COPD now
INTRODUCTION includes four stages: stage I, mild; stage II, moderate;
Chronic obstructive pulmonary disease (COPD) is a major stage III, severe; stage IV, very severe. A fifth category,
cause of chronic morbidity and mortality throughout the world. ‘‘stage 0, at risk,’’ that appeared in the 2001 report is no
Many people suffer from this disease for years and die pre- longer included as a stage of COPD, as there is in-
maturely of it or its complications. The goals of the Global complete evidence that the individuals who meet the
Initiative for Chronic Obstructive Lung Disease (GOLD) are to definition of ‘‘at risk’’ (chronic cough and sputum pro-
improve prevention and management of COPD through a con- duction, normal spirometry) necessarily progress on to
certed worldwide effort of people involved in all facets of health stage I. Nevertheless, the importance of the public health
care and health care policy, and to encourage an expanded level message that chronic cough and sputum are not normal is
of research interest in this highly prevalent disease. unchanged.
One strategy to help achieve the objectives of GOLD is to 4. The spirometric classification of severity continues to
provide health care workers, health care authorities, and the recommend use of the fixed ratio post-bronchodilator
general public with state-of-the-art information about COPD FEV1/FVC , 0.7 to define airflow limitation. Using the
and specific recommendations on the most appropriate man- fixed ratio (FEV1/FVC) is particularly problematic in
agement and prevention strategies. The GOLD report, Global patients with milder disease who are elderly because the
Strategy for the Diagnosis, Management, and Prevention of normal process of aging affects lung volumes. Post-
COPD, is based on the best-validated current concepts of bronchodilator reference values in this population are
COPD pathogenesis and the available evidence on the most urgently needed to avoid potential overdiagnosis.
appropriate management and prevention strategies. A major
5. Section 2, BURDEN OF COPD, provides references to
part of the GOLD report is devoted to the clinical management
published data from prevalence surveys to estimate that
of COPD and presents a management plan with four compo-
about 15 to 25% of adults aged 40 years and older may
nents: (1) assess and monitor disease, (2) reduce risk factors, (3)
have airflow limitation classified as stage I mild COPD or
manage stable COPD, and (4) manage exacerbations. A new
higher and that the prevalence of COPD (stage I, mild
section at the end of the document will assist readers in
COPD and higher) is appreciably higher in smokers and
translating guideline recommendations to the context of (pri-
ex-smokers than in nonsmokers, in those over 40 years
mary) care.
compared with those younger than 40, and higher in men
GOLD is a partner organization in a program launched in
than in women. The section also provides new data on
March 2006 by the World Health Organization’s Global Alli-
COPD morbidity and mortality.
ance Against Chronic Respiratory Diseases (GARD). Through
the work of the GOLD committees, and in cooperation with 6. Cigarette smoke is the most commonly encountered risk
GARD initiatives, progress toward better care for all patients factor for COPD and elimination of this risk factor is an
with COPD should be substantial in the next decade. important step toward prevention and control of COPD.
However, other risk factors for COPD should be taken
Methodology and Summary of New Recommendations into account where possible, including occupational
dusts and chemicals, and indoor air pollution from
After the release of the 2001 GOLD report, a science commit- biomass cooking and heating in poorly ventilated dwell-
tee was formed and charged with keeping the GOLD docu- ings—the latter especially among women in developing
ments up-to-date by reviewing published research, evaluating countries.
the impact of this research on the management recommenda-
tions in the GOLD documents, and posting yearly updates of 7. The section on pathology, pathogenesis, and pathophys-
these documents on the GOLD website (www.goldcopd.org). iology, continues with the theme that inhaled cigarette
The methodology is described in each update (see, e.g., the 2005 smoke and other noxious particles cause lung inflamma-
update in Reference 3 and the APPENDIX in the online supple- tion, a normal response which appears to be amplified in
ment). patients who develop COPD. The section has been
In January 2005, the GOLD science committee initiated considerably updated and revised.
preparation of this revised 2006 document on the basis of the 8. Management of COPD continues to be presented in four
most current scientific literature. Multiple meetings were held, components: (1) assess and monitor disease, (2) reduce
including several with GOLD national leaders to discuss con- risk factors, (3) manage stable COPD, and (4) manage
cepts and new recommendations. Before its publications, sev- exacerbations. All components have been updated on the
eral reviewers were invited to submit comments. basis of recently published literature. Throughout it is
A summary of the issues presented in this report include the emphasized that the overall approach to managing stable
following: COPD should be individualized to address symptoms and
1. Recognition that COPD is characterized by chronic improve quality of life.
airflow limitation and a range of pathologic changes in 9. In COMPONENT 4, MANAGE EXACERBATIONS, a COPD
the lung, some significant extrapulmonary effects, and exacerbation is defined as ‘‘an event in the natural course
important comorbidities that may contribute to the se- of the disease characterized by a change in the patient’s
verity of the disease in individual patients. baseline dyspnea, cough, and/or sputum that is beyond
2. In the definition of COPD, the phrase ‘‘preventable and normal day-to-day variations, is acute in onset, and may
treatable’’ has been incorporated following the American warrant a change in regular medication in a patient with
Thoracic Society/European Respiratory Society recom- underlying COPD.’’
534 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 176 2007
10. It is widely recognized that a wide spectrum of health the patient’s quality of life. A careful differential diagnosis and
care providers is required to ensure that COPD is comprehensive assessment of severity of comorbid conditions
diagnosed accurately, and that individuals who have should be performed in every patient with chronic airflow
COPD are treated effectively. The identification of limitation.
effective health care teams will depend on the local
health care system, and much work remains to identify Spirometric Classification of Severity and Stages of COPD
how best to build these health care teams. A section on For educational reasons, a simple spirometric classification of
COPD implementation programs and issues for clinical disease severity into four stages is recommended (Table 2).
practice has been included but it remains a field that Spirometry is essential for diagnosis and provides a useful
requires considerable attention. description of the severity of pathologic changes in COPD.
Specific spirometric cut points (e.g., post-bronchodilator FEV1/
FVC ratio , 0.70 or FEV1 , 80, 50, or 30% predicted) are used
Levels of Evidence for purposes of simplicity; these cut points have not been
Levels of evidence are assigned to management recommen- clinically validated. A study in a random population sample
dations where appropriate in subsections of section 3 that found that the post-bronchodilator FEV1/FVC exceeded 0.70 in
discuss COPD management, with the system used in previous all age groups, supporting the use of this fixed ratio (6). How-
GOLD reports (Table 1). Evidence levels are enclosed ever, because the process of aging does affect lung volumes, the
in parentheses after the relevant statement—for example, use of this fixed ratio may result in overdiagnosis of COPD in
(Evidence A). the elderly, especially in those with mild disease.
The characteristic symptoms of COPD are chronic and
progressive dyspnea, cough, and sputum production. Chronic
cough and sputum production may precede the development of
1. DEFINITION, CLASSIFICATION OF SEVERITY, AND airflow limitation by many years. This pattern offers a unique
MECHANISMS OF COPD opportunity to identify smokers and others at risk for COPD,
Definition and to intervene when the disease is not yet a major health
problem. Conversely, significant airflow limitation may develop
Chronic obstructive pulmonary disease (COPD) is a preventable and without chronic cough and sputum production.
treatable disease with some significant extrapulmonary effects that
may contribute to the severity in individual patients. Its pulmonary Stage I: mild COPD: Characterized by mild airflow limitation
component is characterized by airflow limitation that is not fully (FEV1/FVC , 0.70, FEV1 > 80% predicted). Symptoms of
reversible. The airflow limitation is usually progressive and associ- chronic cough and sputum production may be present, but
ated with an abnormal inflammatory response of the lung to noxious not always. At this stage, the individual is usually unaware
particles or gases. that his or her lung function is abnormal.
The chronic airflow limitation characteristic of COPD is Stage II: moderate COPD: Characterized by worsening airflow
caused by a mixture of small airway disease (obstructive limitation (FEV1/FVC , 0.70, 50% < FEV1 , 80% pre-
bronchiolitis) and parenchymal destruction (emphysema), the dicted), with shortness of breath typically developing on
relative contributions of which vary from person to person. exertion and cough and sputum production sometimes also
Airflow limitation is best measured by spirometry, because this present. This is the stage at which patients typically seek
is the most widely available, reproducible test of lung function. medical attention because of chronic respiratory symptoms
Because COPD often develops in longtime smokers in or an exacerbation of their disease.
middle age, patients often have a variety of other diseases Stage III: severe COPD: Characterized by further worsening of
related to either smoking or aging (4). COPD itself also has airflow limitation (FEV1/FVC , 0.70, 30% < FEV1 , 50%
significant extrapulmonary (systemic) effects that lead to predicted), greater shortness of breath, reduced exercise
comorbid conditions (5). Thus, COPD should be managed with capacity, fatigue, and repeated exacerbations that almost
careful attention also paid to comorbidities and their effect on always have an impact on patients’ quality of life.
TABLE 1. DESCRIPTION OF LEVELS OF EVIDENCE

Evidence
Category Sources of Evidence Definition
A RCTs. Rich body of data. Evidence is from endpoints of well-designed RCTs that provide a consistent pattern of findings
in the population for which the recommendation is made. Category A requires substantial numbers
of studies involving substantial numbers of participants.
B RCTs. Limited body of data. Evidence is from endpoints of intervention studies that include only a limited number of patients,
post hoc or subgroup analysis of RCTs, or meta-analysis of RCTs. In general, category B pertains
when few randomized trials exist, they are small in size, they were undertaken in a population
that differs from the target population of the recommendation, or the results are somewhat
inconsistent.
C Nonrandomized trials. Evidence is from outcomes of uncontrolled or nonrandomized trials or from observational studies.
Observational studies.
D Panel consensus judgment. This category is used only in cases where the provision of some guidance was deemed valuable but
the clinical literature addressing the subject was insufficient to justify placement in one of the
other categories. The panel consensus is based on clinical experience or knowledge that does not
meet the above-listed criteria.
Definition of abbreviation: RCT 5 randomized controlled trial.

TABLE 2. SPIROMETRIC CLASSIFICATION OF CHRONIC There is now a good understanding of how the underlying
OBSTRUCTIVE PULMONARY DISEASE SEVERITY BASED ON disease process in COPD leads to the characteristic physiologic
POST-BRONCHODILATOR FEV1 abnormalities and symptoms. For example, decreased FEV1
Stage I: mild FEV1/FVC , 0.70 primarily results from inflammation and narrowing of periph-
FEV1 > 80% predicted eral airways and a dynamic airway collapse in more severe
Stage II: moderate FEV1/FVC , 0.70 emphysema, whereas decreased gas transfer arises from the
50% < FEV1 , 80% predicted parenchymal destruction of emphysema. The extent of inflam-
Stage III: severe FEV1/FVC , 0.70
mation, fibrosis, and luminal exudates in small airways is
30% < FEV1 , 50% predicted
Stage IV: very severe FEV1/FVC , 0.70 correlated with the reduction in FEV1 and FEV1/FVC ratio,
FEV1 , 30% predicted or FEV1 , 50% and probably with the accelerated decline in FEV1 character-
predicted plus chronic respiratory failure* istic of COPD (4). Gas exchange abnormalities result in hy-
poxemia and hypercapnia, and have several mechanisms in
* Respiratory failure: arterial partial pressure of oxygen (PaO2) , 8.0 kPa
COPD. In general, gas transfer worsens as the disease pro-
(60 mm Hg) with or without arterial partial pressure of CO2 (PaCO2) . 6.7 kPa
(50 mm Hg) while breathing air at sea level. gresses. Mild to moderate pulmonary hypertension may develop
late in the course of COPD and is due to hypoxic vasoconstric-
tion of small pulmonary arteries. It is increasingly recognized
that COPD involves several systemic features, particularly in
patients with severe disease, and that these have a major impact
Stage IV: very severe COPD: Characterized by severe airflow on survival and comorbid diseases (12, 13).
limitation (FEV1/FVC , 0.70, FEV1 , 30% predicted or
FEV1 , 50% predicted plus the presence of chronic re- 2. BURDEN OF COPD
spiratory failure). Respiratory failure is defined as an arterial
partial pressure of O2 (PaO2) less than 8.0 kPa (60 mm Hg), COPD prevalence, morbidity, and mortality vary across coun-
with or without an arterial partial pressure of CO2 (PaCO2) tries and across different groups within countries but, in general,
greater than 6.7 kPa (50 mm Hg) while breathing air at sea are directly related to the prevalence of tobacco smoking,
level. Respiratory failure may also lead to effects on the heart although, in many countries, air pollution resulting from the
such as cor pulmonale (right heart failure). Clinical signs of burning of wood and other biomass fuels has also been
cor pulmonale include elevation of the jugular venous identified as a COPD risk factor. The prevalence and burden
pressure and pitting ankle edema. Patients may have stage of COPD are projected to increase in the coming decades due
IV COPD even if their FEV1 is greater than 30% predicted, to continued exposure to COPD risk factors and the changing
whenever these complications are present. At this stage, age structure of the world’s population.
quality of life is very appreciably impaired and exacerbations Epidemiology
may be life threatening.
In the past, imprecise and variable definitions of COPD have
Although asthma can usually be distinguished from COPD, made it difficult to quantify prevalence, morbidity, and mortal-
in some individuals with chronic respiratory symptoms and fixed ity. Furthermore, the underrecognition and underdiagnosis of
airflow limitation it remains difficult to differentiate the two COPD lead to significant underreporting. The extent of the
diseases. In many developing countries, both pulmonary tuber- underreporting varies across countries and depends on the level
culosis and COPD are common (7). In countries where tuber- of awareness and understanding of COPD among health
culosis is very common, respiratory abnormalities may be too professionals, the organization of health care services to cope
readily attributed to this disease (8). Conversely, where the rate with chronic diseases, and the availability of medications for the
of tuberculosis is greatly diminished, the possible diagnosis of treatment of COPD (14).
this disease is sometimes overlooked. Therefore, in all subjects Prevalence. Many sources of variation can affect estimates of
with symptoms of COPD, a possible diagnosis of tuberculosis COPD prevalence, including sampling methods, response rates,
should be considered, especially in areas where this disease is quality control of spirometry, and whether spirometry is per-
known to be prevalent (9). formed pre- or post-bronchodilator. Despite these complexities,
data are emerging that enable some conclusions to be drawn
Pathology, Pathogenesis, and Pathophysiology regarding COPD prevalence. A prevalence study in Latin
Pathologic changes characteristic of COPD are found in the America (19), a systematic review and meta-analysis of studies
proximal airways, peripheral airways, lung parenchyma, and performed in 28 countries between 1990 and 2004 (15), and
pulmonary vasculature (10). The pathologic changes include an additional study from Japan (16) provide evidence that the
chronic inflammation, with increased numbers of specific in- prevalence of COPD (stage I, mild COPD and higher) is
flammatory cell types in different parts of the lung, and struc- appreciably higher in smokers and ex-smokers compared with
tural changes resulting from repeated injury and repair. In nonsmokers, in those older than 40 years compared with those
general, the inflammatory and structural changes in the airways younger than 40 years, and in men compared with women.
increase with disease severity and persist on smoking cessation. Morbidity. Morbidity measures traditionally include physi-
The inflammation in the respiratory tract of patients with cian visits, emergency department visits, and hospitalizations.
COPD appears to be an amplification of the normal inflamma- Although COPD databases for these outcome parameters are
tory response of the respiratory tract to chronic irritants such as less readily available and usually less reliable than mortality
cigarette smoke. The mechanisms for this amplification are not databases, the limited data available indicate that morbidity due
yet understood but may be genetically determined. Some pa- to COPD increases with age and is greater in men than in
tients develop COPD without smoking, but the nature of the women (17, 18). COPD in its early stages (stages I and II) is
inflammatory response in these patients is unknown (11). Lung usually not recognized, diagnosed, or treated, and therefore
inflammation is further amplified by oxidative stress and an may not be included as a diagnosis in a patient’s medical record.
excess of proteinases in the lung. Together, these mechanisms Morbidity from COPD may be affected by other comorbid
lead to the characteristic pathologic changes in COPD. chronic conditions (20) (e.g., musculoskeletal disease, diabetes
mellitus) that are not directly related to COPD but nevertheless interaction. The genetic risk factor that is best documented is
may have an impact on the patient’s health status, or may in- a severe hereditary deficiency of a1-antitrypsin (28), a major
terfere with COPD management. In patients with more circulating inhibitor of serine proteases. This rare recessive trait
advanced disease (stages III and IV), morbidity from COPD is most commonly seen in individuals of northern European
may be misattributed to another comorbid condition. origin (29).
Mortality. COPD is one of the most important causes of Genetic association studies have implicated a variety of genes
death in most countries. The Global Burden of Disease Study in COPD pathogenesis. However, the results of these genetic
(2, 21, 22) has projected that COPD, which ranked sixth as the association studies have been largely inconsistent, and functional
cause of death in 1990, will become the third leading cause of genetic variants influencing the development of COPD (other
death worldwide by 2020. This increased mortality is driven by than a1-antitrypsin deficiency) have not been definitively identi-
the expanding epidemic of smoking and the changing demo- fied (30).
graphics in most countries, with more of the population living Inhalational exposures. TOBACCO SMOKE. Cigarette smokers
longer. have a higher prevalence of respiratory symptoms and lung
function abnormalities, a greater annual rate of decline in
FEV1, and a greater COPD mortality rate than nonsmokers.
Economic and Social Burden of COPD
Pipe and cigar smokers have greater COPD morbidity and
COPD is a costly disease. In developed countries, exacerbations mortality rates than nonsmokers, although their rates are lower
of COPD account for the greatest burden on the health care than those for cigarette smokers (31). Other types of tobacco
system. In the European Union, the total direct costs of smoking popular in various countries are also risk factors for
respiratory disease are estimated to be about 6% of the total COPD (32, 33). Not all smokers develop clinically significant
health care budget, with COPD accounting for 56% (V38.6 COPD, which suggests that genetic factors must modify each
billion) of this cost of respiratory disease (23). In the United individual’s risk (34). Passive exposure to cigarette smoke may
States in 2002, the direct costs of COPD were $18 billion and also contribute to respiratory symptoms (35) and COPD (36) by
the indirect costs totaled $14.1 billion (1). Costs per patient will increasing the lungs’ total burden of inhaled particles and gases
vary across countries because these costs depend on how health (37, 38). Smoking during pregnancy may also pose a risk for the
care is provided and paid (24). Not surprisingly, there is fetus, by affecting lung growth and development in utero and
a striking direct relationship between the severity of COPD possibly the priming of the immune system (39, 40).
and the cost of care (25), and the distribution of costs changes as OCCUPATIONAL DUSTS AND CHEMICALS. Occupational expo-
the disease progresses. sures include organic and inorganic dusts and chemical agents
and fumes. A statement published by the American Thoracic
Society concluded that occupational exposures account for 10 to
Risk Factors 20% of either symptoms or functional impairment consistent
Identification of cigarette smoking as the most commonly with COPD (41).
encountered risk factor for COPD has led to the incorporation INDOOR AND OUTDOOR AIR POLLUTION. The evidence that
of smoking cessation programs as a key element of COPD indoor pollution from biomass cooking and heating in poorly
prevention, as well as an important intervention for patients ventilated dwellings is an important risk factor for COPD
who already have the disease. However, although smoking is (especially among women in developing countries) continues
the best-studied COPD risk factor, it is not the only one and to grow (42–48), with case-control studies (47, 48) and other
there is consistent evidence from epidemiologic studies that designed studies now available. High levels of urban air
nonsmokers may develop chronic airflow obstruction (26, 27) pollution are harmful to individuals with existing heart or lung
(Figure 1). disease, but the role of outdoor air pollution in causing COPD is
Genes. As the understanding of the importance of risk unclear.
factors for COPD has grown, so has the recognition that Sex. Studies from developed countries (1, 49) show that
essentially all risk for COPD results from a gene–environment the prevalence of the disease is now almost equal in men and
Figure 1. Chronic obstructive pulmonary disease risk is

related to the total burden of inhaled particles.
women, probably reflecting the changing patterns of tobacco Component 1: Assess and Monitor Disease
smoking. Some studies have suggested that women are more
susceptible to the effects of tobacco smoke than men (50– KEY POINTS
52).
Infection. A history of severe childhood respiratory infec- d A clinical diagnosis of COPD should be considered in
tion has been associated with reduced lung function and any patient who has dyspnea, chronic cough or sputum
increased respiratory symptoms in adulthood (53–55). How- production, and/or a history of exposure to risk factors
ever, susceptibility to viral infections may be related to for the disease. The diagnosis should be confirmed by
another factor, such as low birth weight, that itself is related spirometry.
to COPD. d For the diagnosis and assessment of COPD, spirometry
Socioeconomic status. There is evidence that the risk of is the gold standard because it is the most reproducible,
developing COPD is inversely related to socioeconomic status standardized, and objective way of measuring airflow
(56). It is not clear, however, whether this pattern reflects limitation. A post-bronchodilator FEV1/FVC , 0.70
exposures to cigarette smoke, indoor and outdoor air pollutants, confirms the presence of airflow limitation that is not
crowding, poor nutrition, or other factors that are related to low fully reversible.
socioeconomic status (57, 58).
d Health care workers involved in the diagnosis and
management of patients with COPD should have access
3. THE FOUR COMPONENTS OF COPD MANAGEMENT to spirometry.
d Assessment of COPD severity is based on the patient’s
Introduction
level of symptoms, the severity of the spirometric abnor-
An effective COPD management plan includes four compo- mality, and the presence of complications.
nents: (1) assess and monitor disease, (2) reduce risk factors, (3) d Measurement of arterial blood gas tensions should be
manage stable COPD, and (4) manage exacerbations. Although considered in all patients with FEV1 , 50% predicted or
disease prevention is the ultimate goal, once COPD has been clinical signs suggestive of respiratory failure or right
diagnosed, effective management should be aimed at the heart failure.
following goals:
d COPD is usually a progressive disease and lung function
d Relieve symptoms can be expected to worsen over time, even with the best
d Prevent disease progression available care. Symptoms and objective measures of
airflow limitation should be monitored to determine
d Improve exercise tolerance when to modify therapy and to identify any complica-
d Improve health status tions that may develop.
d Prevent and treat complications d Comorbidities are common in COPD and should be
d Prevent and treat exacerbations actively identified. Comorbidities often complicate the
management of COPD, and vice versa.
d Reduce mortality
These goals should be reached with minimal side effects from
treatment, a particular challenge in patients with COPD
because they commonly have comorbidities. The extent to
which these goals can be realized varies with each individual, Initial diagnosis. A clinical diagnosis of COPD should be
and some treatments will produce benefits in more than one considered in any patient who has dyspnea, chronic cough or
area. In selecting a treatment plan, the benefits and risks to sputum production, and/or a history of exposure to risk factors
the individual, and the costs, direct and indirect, to the for the disease (Table 3). The diagnosis should be confirmed by
individual, his or her family, and the community must be spirometry.
considered. ASSESSMENT OF SYMPTOMS. Dyspnea, the hallmark symptom
Patients should be identified as early in the course of the of COPD, is the reason most patients seek medical attention
disease as possible, and certainly before the end stage of the and is a major cause of disability and anxiety associated with the
illness when disability is substantial. Access to spirometry is key disease. As lung function deteriorates, breathlessness becomes
to the diagnosis of COPD and should be available to health care more intrusive. Chronic cough, often the first symptom of
workers who care for patients with COPD. However, the COPD to develop (59) and often predating the onset of dys-
benefits of community-based spirometric screening, of either pnea, may be intermittent, but later is present every day, often
the general population or smokers, are still unclear. throughout the day. In some cases, significant airflow limitation
Educating patients, physicians, and the public to recognize may develop without the presence of a cough. Patients with
that cough, sputum production, and especially breathlessness COPD commonly raise small quantities of tenacious sputum
are not trivial symptoms is an essential aspect of the public after coughing bouts. Wheezing and chest tightness are non-
health care of this disease. specific symptoms that may vary between days, and over the
Reduction of therapy once symptom control has been achieved course of a single day. An absence of wheezing or chest tight-
is not normally possible in COPD. Further deterioration of lung ness does not exclude a diagnosis of COPD. Weight loss, an-
function usually requires the progressive introduction of more orexia, and psychiatric morbidity, especially symptoms of de-
treatments, both pharmacologic and nonpharmacologic, to at- pression and/or anxiety, are common problems in advanced
tempt to limit the impact of these changes. Exacerbations of signs COPD (60, 61).
and symptoms, a hallmark of COPD, impair patients’ quality of MEDICAL HISTORY. A detailed medical history of a new pa-
life and decrease their health status. Appropriate treatment and tient known or believed to have COPD should assess the
measures to prevent further exacerbations should be imple- following:
mented as quickly as possible. d Exposure to risk factors
TABLE 3. KEY INDICATORS FOR CONSIDERING A DIAGNOSIS patients with milder COPD who are elderly because the normal
OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE process of aging affects lung volumes.
Consider COPD, and perform spirometry, if any of these indicators are ASSESSMENT OF COPD SEVERITY. Assessment of COPD
present in an individual. These indicators are not diagnostic themselves, severity is based on the patient’s level of symptoms, the severity
but the presence of multiple key indicators increases the probability of the spirometric abnormality (Table 2), and the presence of
of a diagnosis of COPD. Spirometry is needed to establish a diagnosis of COPD. complications such as respiratory failure, right heart failure,
Dyspnea that is Progressive (worsens over time) weight loss, and arterial hypoxemia.
Usually worse with exercise ADDITIONAL INVESTIGATIONS. For patients diagnosed with
Persistent (present every day) stage II, moderate, COPD and beyond, the following additional
Described by the patient as an ‘‘increased investigations may be considered.
effort to breathe,’’ ‘‘heaviness,’’ ‘‘air hunger,’’ Bronchodilator reversibility testing. Despite earlier hopes,
or ‘‘gasping
neither bronchodilator nor oral glucocorticosteroid reversibility
Chronic cough May be intermittent and may be unproductive
Chronic sputum production Any pattern of chronic sputum production testing predicts disease progression, whether judged by decline
may indicate COPD in FEV1, deterioration of health status, or frequency of exac-
History of exposure Tobacco smoke erbations (67, 68) in patients with a clinical diagnosis of COPD
to risk factors, especially, Occupational dusts and chemicals and abnormal spirometry (68). In some cases (e.g., a patient
Smoke from home cooking and heating fuels with an atypical history such as asthma in childhood and regular
Definition of abbreviation: COPD 5 chronic obstructive pulmonary disease. night waking with cough or wheeze), a clinician may wish to
perform a bronchodilator and/or glucocorticosteroid reversibil-
ity test.
Chest X-ray. An abnormal chest X-ray is seldom diagnostic
in COPD unless obvious bullous disease is present, but it is
d Past medical history, including asthma, allergy, sinusitis, or valuable in excluding alternative diagnoses and establishing
nasal polyps; respiratory infections in childhood; other the presence of significant comorbidities, such as cardiac
respiratory diseases failure. Computed tomography (CT) of the chest is not
d Family history of COPD or other chronic respiratory routinely recommended. However, when there is doubt about
disease the diagnosis of COPD, high-resolution CT scanning might
d Pattern of symptom development help in the differential diagnosis. In addition, if a surgical
procedure such as lung volume reduction is contemplated,
d History of exacerbations or previous hospitalizations for a chest CT scan is necessary because the distribution of
respiratory disorder emphysema is one of the most important determinants of
d Presence of comorbidities, such as heart disease, malignan- surgical suitability (69).
cies, osteoporosis, and muscloskeletal disorders, which may Arterial blood gas measurement. In advanced COPD, mea-
also contribute to restriction of activity (62) surement of arterial blood gases while the patient is breathing
d Appropriateness of current medical treatments air is important. This test should be performed in stable patients
with FEV1 , 50% predicted or with clinical signs suggestive of
d Impact of disease on patient’s life, including limitation of
respiratory failure or right heart failure.
activity, missed work and economic impact, effect on family
a1-Antitrypsin deficiency screening. In patients of Caucasian
routines, feelings of depression or anxiety
descent who develop COPD at a young age (, 45 yr) or who
d Social and family support available to the patient have a strong family history of the disease, it may be valuable to
d Possibilities for reducing risk factors, especially smoking identify coexisting a1-antitrypsin deficiency. This could lead to
cessation family screening or appropriate counseling.
DIFFERENTIAL DIAGNOSIS. In some patients with chronic
PHYSICAL EXAMINATION. Although an important part of pa- asthma, a clear distinction from COPD is not possible using
tient care, a physical examination is rarely diagnostic in COPD. current imaging and physiologic testing techniques, and it is
Physical signs of airflow limitation are usually not present assumed that asthma and COPD coexist in these patients. In
until significant impairment of lung function has occurred (63, these cases, current management is similar to that of asthma.
64), and their detection has a relatively low sensitivity and Other potential diagnoses are usually easier to distinguish from
specificity. COPD (Table 4).
MEASUREMENT OF AIRFLOW LIMITATION (SPIROMETRY). Spirom- Ongoing monitoring and assessment. MONITOR DISEASE PRO-
etry should be undertaken in all patients who may have COPD. GRESSION AND DEVELOPMENT OF COMPLICATIONS. COPD is usually
Spirometry should measure the volume of air forcibly exhaled a progressive disease. Lung function can be expected to worsen
from the point of maximal inspiration (FVC) and the volume of over time, even with the best available care. Symptoms and
air exhaled during the first second of this maneuver (FEV1), and objective measures of airflow limitation should be monitored to
the ratio of these two measurements (FEV1/FVC) should be determine when to modify therapy and to identify any compli-
calculated. Spirometry measurements are evaluated by compar- cations that may develop.
ison with reference values (65) based on age, height, sex, and Follow-up visits should include a physical examination and
race (use appropriate reference values; e.g., see Reference 65). discussion of symptoms, particularly any new or worsening
Patients with COPD typically show a decrease in both FEV1 symptoms. Spirometry should be performed if there is a sub-
and FVC. The presence of airflow limitation is defined by stantial increase in symptoms or a complication. The develop-
a post-bronchodilator FEV1/FVC , 0.70. This approach is ment of respiratory failure is indicated by a PaO2 , 8.0 kPa (60
pragmatic in view of the fact that universally applicable mm Hg) with or without PaCO2 . 6.7 kPa (50 mm Hg) in arterial
reference values for FEV1 and FVC are not available. Where blood gas measurements made while breathing air at sea level.
possible, values should be compared with age-related normal Measurement of pulmonary arterial pressure is not recommen-
values to avoid overdiagnosis of COPD in the elderly (66). ded in clinical practice as it does not add practical information
Using the fixed ratio (FEV1/FVC) is particularly problematic in beyond that obtained from a knowledge of PaO2.
MONITOR PHARMACOTHERAPY AND OTHER MEDICAL TREATMENT. Component 2: Reduce Risk Factors
To adjust therapy appropriately as the disease progresses, each
follow-up visit should include a discussion of the current KEY POINTS
therapeutic regimen. Dosages of various medications, adher-
ence to the regimen, inhaler technique, effectiveness of the d Reduction of total personal exposure to tobacco smoke,
current regime at controlling symptoms, and side effects of occupational dusts and chemicals, and indoor and out-
treatment should be monitored. door air pollutants are important goals to prevent the
MONITOR EXACERBATION HISTORY. Frequency, severity, and onset and progression of COPD.
likely causes of exacerbations should be evaluated. Increased d Smoking cessation is the single most effective—and cost-
sputum volume, acutely worsening dyspnea, and the presence of effective—intervention in most people to reduce the risk of
purulent sputum should be noted. Severity can be estimated by developing COPD and stop its progression (Evidence A).
the increased need for bronchodilator medication or glucocor-
ticosteroids and by the need for antibiotic treatment. Hospital- d Comprehensive tobacco control policies and programs
izations should be documented, including the facility, duration with clear, consistent, and repeated nonsmoking messages
of stay, and any use of critical care or intubation. should be delivered through every feasible channel.
MONITOR COMORBIDITIES. Comorbidities are common in d Efforts to reduce smoking through public health initia-
COPD and may become harder to manage when COPD is tives should also focus on passive smoking to minimize
present, either because COPD adds to the total level of dis- risks for nonsmokers.
ability or because COPD therapy adversely affects the comor- d Many occupationally induced respiratory disorders can
bid disorder. Until more integrated guidance about disease be reduced or controlled through a variety of strategies
management for specific comorbid problems becomes available, aimed at reducing the burden of inhaled particles and
the focus should be on identification and management of these gases.
individual problems.
d Reducing the risk from indoor and outdoor air pollution
is feasible and requires a combination of public policy
and protective steps taken by individual patients.
TABLE 4. DIFFERENTIAL DIAGNOSIS OF CHRONIC OBSTRUCTIVE Smoking prevention and cessation. Comprehensive tobacco
PULMONARY DISEASE control policies and programs with clear, consistent, and re-
Diagnosis Suggestive Features peated nonsmoking messages should be delivered through every
feasible channel, including health care providers, community
COPD Onset in midlife activities, and schools, and radio, television, and print media.
Symptoms slowly progressive
Long history of tobacco smoking
Legislation to establish smoke-free schools, public facilities, and
Dyspnea during exercise work environments should be developed and implemented by
Largely irreversible airflow limitation government officials and public health workers, and encouraged
Asthma Onset early in life (often childhood) by the public.
Symptoms vary from day to day SMOKING CESSATION INTERVENTION PROCESS. Smoking cessa-
Symptoms at night/early morning tion is the single most effective—and cost-effective—way to re-
Allergy, rhinitis, and/or eczema also present
Family history of asthma
duce exposure to COPD risk factors. All smokers—including
Largely reversible airflow limitation those who may be at risk for COPD as well as those who already
Congestive heart failure Nonspecific basilar crackles on auscultation have the disease—should be offered the most intensive smoking
Chest X-ray shows dilated heart, pulmonary edema cessation intervention feasible. Even a brief (3 min) period of
Pulmonary function tests indicate volume counseling to urge a smoker to quit results in smoking cessation
restriction, not airflow limitation rates of 5 to 10% (70). At the very least, this should be done for
Bronchiectasis Large volumes of purulent sputum
Commonly associated with bacterial infection
every smoker at every health care provider visit (70, 71).
Coarse crackles/clubbing on auscultation Guidelines for smoking cessation entitled ‘‘Treating Tobacco
Chest X-ray/CT shows bronchial dilation, Use and Dependence: A Clinical Practice Guideline’’ were
bronchial wall thickening published by the U.S. Public Health Service (72) and recom-
Tuberculosis Onset all ages mend a five-step program for intervention (Table 5), which
Chest X-ray shows lung infiltrate provides a strategic framework helpful to health care providers
Microbiological confirmation
High local prevalence of tuberculosis
interested in helping their patients stop smoking (72–75).
Obliterative bronchiolitis Onset in younger age, nonsmokers PHARMACOTHERAPY. Numerous effective pharmacotherapies
May have history of rheumatoid arthritis for smoking cessation now exist (72, 73, 76) (Evidence A), and
or fume exposure pharmacotherapy is recommended when counseling is not
CT on expiration shows hypodense areas sufficient to help patients quit smoking. Numerous studies
Diffuse panbronchiolitis Most patients are male and nonsmokers indicate that nicotine replacement therapy in any form (nicotine
Almost all have chronic sinusitis
Chest X-ray and HRCT show diffuse small
gum, inhaler, nasal spray, transdermal patch, sublingual tablet,
centrilobular nodular opacities and hyperinflation or lozenge) reliably increases long-term smoking abstinence
rates (72, 77).
Definition of abbreviations: COPD 5 chronic obstructive pulmonary disease; The antidepressants bupropion (78) and nortriptyline have
CT 5 computed tomography; HRCT 5 high-resolution computed tomography. also been shown to increase long-term quit rates (76, 77, 79), but
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
should always be used as one element in a supportive in-
COPD (especially in the developing world where other risk factors may be more tervention program rather than on their own. The effectiveness
important than cigarette smoking); asthma may develop in adult and even of the antihypertensive drug clonidine is limited by side effects
elderly patients. (77). Varenicline, a nicotinic acetylcholine receptor partial
agonist that aids smoking cessation by relieving nicotine with- emissions and improving ventilation measures, rather than
drawal symptoms and reducing the rewarding properties of simply using respiratory protection to reduce the risks of
nicotine, has been demonstrated to be safe and efficacious (80– ambient air pollution. Air cleaners have not been shown to
82). Special consideration should be given before using phar- have health benefits, whether directed at pollutants generated
macotherapy in the following selected populations: people with by indoor sources or at those brought in with outdoor air.
medical contraindications, light smokers (,10 cigarettes/d), and
pregnant and adolescent smokers. Component 3: Manage Stable COPD
Occupational exposures. Although it is not known how many
individuals are at risk of developing respiratory disease from KEY POINTS
occupational exposures in either developing or developed
countries, many occupationally induced respiratory disorders d The overall approach to managing stable COPD should
can be reduced or controlled through a variety of strategies be individualized to address symptoms and improve
aimed at reducing the burden of inhaled particles and gases quality of life.
(83–85). d For patients with COPD, health education plays an
The main emphasis should be on primary prevention, which important role in smoking cessation (Evidence A) and
is best achieved by the elimination or reduction of exposures to can also play a role in improving skills, ability to cope
various substances in the workplace. Secondary prevention, with illness, and health status.
achieved through surveillance and early case detection, is also d None of the existing medications for COPD have been
of great importance. shown to modify the long-term decline in lung function
Indoor and outdoor air pollution. Individuals experience di- that is the hallmark of this disease (Evidence A).
verse indoor and outdoor environments throughout the day, Therefore, pharmacotherapy for COPD is used to de-
each of which has its own unique set of air contaminants and crease symptoms and/or complications.
particulates that cause adverse effects on lung function (86).
Although outdoor and indoor air pollution are generally d Bronchodilator medications are central to the symptom-
considered separately, the concept of total personal exposure atic management of COPD (Evidence A). They are
may be more relevant for COPD. Reducing the risk from given on an as-needed basis or on a regular basis to
indoor and outdoor air pollution is feasible and requires prevent or reduce symptoms and exacerbations.
a combination of public policy and protective steps taken by d The principal bronchodilator treatments are b2-agonists,
individual patients. At the national level, achieving a set level of anticholinergics, and methylxanthines used singly or in
air quality standards should be a high priority; this goal will combination (Evidence A).
normally require legislative action. Reduction of exposure to d Regular treatment with long-acting bronchodilators is
smoke from biomass fuel, particularly among women and more effective and convenient than treatment with
children, is a crucial goal to reduce the prevalence of COPD short-acting bronchodilators (Evidence A).
worldwide. Although efficient nonpolluting cooking stoves have
d The addition of regular treatment with inhaled glucocor-
been developed, their adoption has been slow due to social
ticosteroids to bronchodilator treatment is appropriate for
customs and cost.
symptomatic patients with COPD with an FEV1 , 50%
The health care provider should consider COPD risk factors,
predicted (stage III, severe COPD, and stage IV, very
including smoking history, family history, exposure to indoor/
severe COPD) and repeated exacerbations (Evidence A).
outdoor pollution, and socioeconomic status, for each individual
patient. Those who are at high risk should avoid vigorous d Chronic treatment with systemic glucocorticosteroids
exercise outdoors during pollution episodes. Persons with should be avoided because of an unfavorable benefit-
advanced COPD should monitor public announcements of air to-risk ratio (Evidence A).
quality and be aware that staying indoors when air quality is d In patients with COPD, influenza vaccines can reduce
poor may help reduce their symptoms. If various solid fuels are serious illness (Evidence A). Pneumococcal polysaccha-
used for cooking and heating, adequate ventilation should be ride vaccine is recommended for patients with COPD
encouraged. Under most circumstances, vigorous attempts who are 65 years and older and for patients with COPD
should be made to reduce exposure through reducing workplace who are younger than age 65 with an FEV1 , 40%
predicted (Evidence B).
d All patients with COPD benefit from exercise training
TABLE 5. BRIEF STRATEGIES TO HELP THE PATIENT WHO IS programs, improving with respect to both exercise toler-
WILLING TO QUIT
ance and symptoms of dyspnea and fatigue (Evidence A).
1. ASK: Systematically identify all tobacco users at every visit. d The long-term administration of oxygen (. 15 h/d) to
Implement an officewide system that ensures that, for EVERY patient at
patients with chronic respiratory failure has been shown
EVERY clinic visit, tobacco use status is queried and documented.
2. ADVISE: Strongly urge all tobacco users to quit. to increase survival (Evidence A).
In a clear, strong, and personalized manner, urge every tobacco user to quit.
3. ASSESS: Determine willingness to make a quit attempt.
Ask every tobacco user if he or she is willing to make a quit attempt at this
time (e.g., within the next 30 d).
Introduction. The overall approach to managing stable COPD
4. ASSIST: Aid the patient in quitting. should be characterized by an increase in treatment, depending
Help the patient with a quit plan; provide practical counseling; provide on the severity of the disease and the clinical status of the patient.
intratreatment social support; help the patient obtain extratreatment Management of COPD is based on an individualized assessment
social support; recommend use of approved pharmacotherapy except of disease severity and response to various therapies. The clas-
in special circumstances; provide supplementary materials. sification of severity of stable COPD incorporates an individual-
5. ARRANGE: Schedule follow-up contact.
Schedule follow-up contact, either in person or via telephone.
ized assessment of disease severity and therapeutic response into
the management strategy. The severity of airflow limitation
Data from References 72–75. provides a general guide to the use of some treatments, but the
selection of therapy is predominantly determined by the patient’s (Table 6) for COPD have been shown to modify the long-term
symptoms and clinical presentation. Treatment also depends on decline in lung function that is the hallmark of this disease (51,
the patient’s educational level and willingness to apply the 95–97) (Evidence A). However, this should not preclude efforts
recommended management, on cultural and local practice con- to use medications to control symptoms.
ditions, and on the availability of medications. BRONCHODILATORS. Bronchodilator medications are central
Education. Although patient education is generally regarded to the symptomatic management of COPD (98–101) (Evidence
as an essential component of care for any chronic disease, assess- A) (Table 7). They are given either on an as-needed basis for
ment of the value of education in COPD may be difficult because relief of persistent or worsening symptoms or on a regular basis
of the relatively long time required to achieve improvements in to prevent or reduce symptoms. The side effects of bronchodi-
objective measurements of lung function. Patient education alone lator therapy are pharmacologically predictable and dose de-
does not improve exercise performance or lung function (87–90) pendent. Adverse effects are less likely, and resolve more rap-
(Evidence B), but it can play a role in improving skills, ability to idly after treatment withdrawal, with inhaled than with oral
cope with illness, and health status (91). Patient education re- treatment. When treatment is given by the inhaled route, atten-
garding smoking cessation has the greatest capacity to influence tion to effective drug delivery and training in inhaler technique
the natural history of COPD (Evidence A). Education also im- are essential.
proves patient response to exacerbations (92, 93) (Evidence B). Bronchodilator drugs commonly used in treating COPD in-
Prospective end-of-life discussions can lead to understanding of clude b2-agonists, anticholinergics, and methylxanthines. The
advance directives and effective therapeutic decisions at the end choice depends on the availability of the medications and the
of life (94) (Evidence B). patient’s response. All categories of bronchodilators have been
Ideally, educational messages should be incorporated into all shown to increase exercise capacity in COPD, without necessarily
aspects of care for COPD and may take place in many settings: producing significant changes in FEV1 (102–105) (Evidence A).
consultations with physicians or other health care workers, Regular treatment with long-acting bronchodilators is more
home-care or outreach programs, and comprehensive pulmo- effective and convenient than treatment with short-acting bron-
nary rehabilitation programs. Education should be tailored to chodilators (106–109) (Evidence A). Regular use of a long-
the needs and environment of the individual patient, interactive, acting b2-agonist (107) or a short- or long-acting anticholinergic
directed at improving quality of life, simple to follow, practical, improves health status (106–108). Treatment with a long-acting
and appropriate to the intellectual and social skills of the inhaled anticholinergic drug reduces the rate of COPD exacer-
patient and the caregivers. The topics that seem most appro- bations (110) and improves the effectiveness of pulmonary re-
priate for an education program include the following: smoking habilitation (111). Theophylline is effective in COPD, but, due
cessation; basic information about COPD and pathophysiology to its potential toxicity, inhaled bronchodilators are preferred
of the disease, general approach to therapy and specific aspects when available. All studies that have shown efficacy of theoph-
of medical treatment, self-management skills, strategies to help ylline in COPD were done with slow-release preparations.
minimize dyspnea, advice about when to seek help, self- Combining bronchodilators with different mechanisms and
management and decision making during exacerbations, and durations of action may increase the degree of bronchodilation
advance directives and end-of-life issues. for equivalent or lesser side effects. A combination of a short-
Pharmacologic treatments. Pharmacologic therapy is used to acting b2-agonist and an anticholinergic produces greater and
prevent and control symptoms (Figure 2), reduce the frequency more sustained improvements in FEV1 than either drug alone
and severity of exacerbations, improve health status, and and does not produce evidence of tachyphylaxis over 90 days of
improve exercise tolerance. None of the existing medications treatment (112–114) (Evidence A).
Figure 2. Therapy at each stage of

chronic obstructive pulmonary disease
(COPD). Post-bronchodilator FEV1 is rec-
ommended for the diagnosis and assess-
ment of severity of COPD.
TABLE 6. COMMONLY USED FORMULATIONS OF MEDICATIONS USED IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Solution for Vials for Duration of
Medication Inhaler (mg) Nebulizer (mg/ml) Oral Injection (mg) Action (h)
b2-Agonists
Short-acting
Fenoterol 100–200 (MDI) 1 0.5% (syrup) 4–6
Salbutamol (albuterol) 100, 200 (MDI and DPI) 5 5 mg (pill) 0.24% (syrup) 0.1, 0.5 4–6
Terbutaline 400, 500 (DPI) 0.2, 0.25 4–6
Long-acting
Formoterol 4.5–12 (MDI and DPI) 121
Salmeterol 25–50 (MDI and DPI) 121
Anticholinergics
Short-acting
Ipatropium bromide 20, 40 (MDI) 0.25-0.5 6–8
Oxitropium bromide 100 (MDI) 1.5 7–9
Long-acting
Tiotropium 18 (DPI) 241
Combination short-acting
b2-agonists
plus anticholinergic in
one inhaler
Fenoterol/ipratropium 200/80 (MDI) 1.25/0.5 6–8
Salbutamol/ipratropium 75/15 (MDI) 0.75/4.5 6–8
Methylxanthines
Aminophylline 200–600 mg (pill) 240 Variable, up to 24
Theophylline (SR) 100–600 mg (pill) Variable, up to 24
Inhaled glucocorticosteroids
Beclomethasone 50–400 (MDI and DPI) 0.2-0.4
Budesonide 100, 200, 400 (DPI) 0.20, 0.25, 0.5
Fluticasone 50–500 (MDI and DPI)
Triamcinolone 100 (MDI) 40 40
Combination long-acting
b2-agonists plus
glucocorticosteroids
in one inhaler
Formoterol/budesonide 4.5/160, 9/320 (DPI)
Salmeterol/fluticasone 50/100, 250, 500 (DPI) 25/50,
125, 250 (MDI)
Systemic glucocorticosteroids
Prednisone 5–60 mg (pill)
Methylprednisolone 4, 8, 16 mg (pill)
Definition of abbreviation: DPI 5 dry powder inhaler; MDI 5 metered-dose inhaler; SR 5 slow release.
The combination of a b2-agonist, an anticholinergic, and/or treatment with inhaled glucocorticosteroids is appropriate for
theophylline may produce additional improvements in lung symptomatic patients with COPD with an FEV1 , 50% pre-
function (112–118) and health status (112, 119). Increasing the dicted (stages III and IV) and repeated exacerbations (e.g.,
number of drugs usually increases costs, and an equivalent three in the last 3 yr) (123–126) (Evidence A). This treatment
benefit may occur by increasing the dose of one bronchodilator has been shown to reduce the frequency of exacerbations and
when side effects are not a limiting factor. Detailed assessments thus improve health status (127) (Evidence A), and withdrawal
of this approach have not been performed. from treatment with inhaled glucocorticosteroids can lead to
Dose–response relationships using the FEV1 as the outcome exacerbations in some patients (128). Reanalysis of pooled
are relatively flat with all classes of bronchodilators (98–101). data from several longer studies of inhaled glucocorticoste-
Toxicity is also dose related. Increasing the dose of either roids in COPD suggests that this treatment reduces all-cause
a b2-agonist or an anticholinergic by an order of magnitude, mortality (129), but this conclusion requires confirmation in pro-
especially when given by a wet nebulizer, appears to provide spective studies before leading to a change in current treatment
subjective benefit in acute episodes (120) (Evidence B) but is
not necessarily helpful in stable disease (121) (Evidence C). TABLE 7. BRONCHODILATORS IN STABLE CHRONIC
When treatment is given by the inhaled route, attention to OBSTRUCTIVE PULMONARY DISEASE
effective drug delivery and training in inhaler technique are
essential. The choice of inhaler device will depend on availabil- d Bronchodilator medications are central to symptom management in COPD.
d Inhaled therapy is preferred.
ity, cost, the prescribing physician, and the skills and ability of d The choice among b2-agonist, anticholinergic, theophylline, or
the patient. Patients with COPD may have more problems in ef- combination therapy depends on availability and individual response in
fective coordination and find it harder to use a simple metered- terms of symptom relief and side effects.
dose inhaler than do healthy volunteers or younger patients d Bronchodilators are prescribed on an as-needed or on a regular basis to
with asthma. It is essential to ensure that inhaler technique is prevent or reduce symptoms.
correct and to recheck this at each visit. d Long-acting inhaled bronchodilators are more effective and convenient.
d Combining bronchodilators may improve efficacy and decrease the risk of
GLUCOCORTICOSTEROIDS. Regular treatment with inhaled side effects compared to increasing the dose of a single bronchodilator.
glucocorticosteroids does not modify the long-term decline of
FEV1 in patients with COPD (95–97, 122). However, regular Definition of abbreviation: COPD 5 chronic obstructive pulmonary disease.
recommendations. An inhaled glucocorticosteroid combined with ventilation–perfusion balance (164, 165). Therefore, based on the
a long-acting b2-agonist is more effective than the individual available evidence, nitric oxide is not indicated in stable COPD.
components (123, 125, 126, 130, 131) (Evidence A). The dose– Narcotics (morphine). Oral and parenteral opioids are ef-
response relationships and long-term safety of inhaled gluco- fective for treating dyspnea in patients with advanced COPD
corticosteroids in COPD are not known. disease. There are insufficient data to conclude whether nebu-
Long-term treatment with oral glucocorticosteroids is not lized opioids are effective (166). However, some clinical studies
recommended in COPD (Evidence A). A side effect of long- suggest that morphine used to control dyspnea may have serious
term treatment with systemic glucocorticosteroids is steroid adverse effects and its benefits may be limited to a few sensitive
myopathy (132–134), which contributes to muscle weakness, subjects (167–171).
decreased functionality, and respiratory failure in subjects with Others. Nedocromil, leukotriene modifiers, and alternative
advanced COPD. healing methods (e.g., herbal medicine, acupunture, homeopa-
OTHER PHARMACOLOGIC TREATMENTS. Vaccines. Influenza thy) have not been adequately tested in patients with COPD
vaccines can reduce serious illness (135) and death in patients and thus cannot be recommended at this time.
with COPD by approximately 50% (136, 137) (Evidence A). Nonpharmacologic treatments. REHABILITATION. The princi-
Vaccines containing killed or live, inactivated viruses are re- pal goals of pulmonary rehabilitation are to reduce symptoms,
commended (138) because they are more effective in elderly improve quality of life, and increase physical and emotional
patients with COPD (139). The strains are adjusted each year participation in everyday activities. To accomplish these goals,
for appropriate effectiveness and should be given once each pulmonary rehabilitation covers a range of nonpulmonary prob-
year (140). Pneumococcal polysaccharide vaccine is recommen- lems that may not be adequately addressed by medical therapy
ded for patients with COPD who are 65 years and older (141, for COPD. Such problems, which especially affect patients with
142). In addition, this vaccine has been shown to reduce the stages II through IV COPD, include exercise deconditioning,
incidence of community-acquired pneumonia in patients with relative social isolation, altered mood states (especially de-
COPD who are younger than 65 years with an FEV1 , 40% pression), muscle wasting, and weight loss.
predicted (143) (Evidence B). Although more information is needed on criteria for patient
a1-Antitrypsin augmentation therapy. Young patients with selection for pulmonary rehabilitation programs, patients with
severe hereditary a1-antitrypsin deficiency and established COPD at all stages of disease appear to benefit from exercise
emphysema may be candidates for a1-antitrypsin augmentation training programs, improving with respect to both exercise
therapy. However, this therapy is very expensive, not available tolerance and symptoms of dyspnea and fatigue (172) (Evidence
in most countries, and not recommended for patients with COPD A). Data suggest that these benefits can be sustained even after
that is unrelated to a1-antitrypsin deficiency (Evidence C). a single pulmonary rehabilitation program (173–175). Benefit
Antibiotics. Prophylactic, continuous use of antibiotics has does wane after a rehabilitation program ends, but if exercise
been shown to have no effect on the frequency of exacerbations training is maintained at home, the patient’s health status remains
in COPD (144–146), and a study that examined the efficacy of above pre-rehabilitation levels (Evidence B). To date, there is no
chemoprophylaxis undertaken in the winter months over a pe- consensus on whether repeated rehabilitation courses enable
riod of 5 years concluded that there was no benefit (147). There patients to sustain the benefits gained through the initial course.
is no current evidence that the use of antibiotics, other than for Benefits have been reported from rehabilitation programs con-
treating infectious exacerbations of COPD and other bacterial ducted in inpatient, outpatient, and home settings (176–178).
infections, is helpful (148, 149) (Evidence A). Ideally, pulmonary rehabilitation should involve several
Mucolytic (mucokinetic, mucoregulator) agents (ambroxol, types of health professionals. The components of pulmonary re-
erdosteine, carbocysteine, iodinated glycerol). The regular use habilitation vary widely from program to program, but a com-
of mucolytics in COPD has been evaluated in a number of long- prehensive pulmonary rehabilitation program includes exercise
term studies with controversial results (150–152). Although training, nutrition counseling, and education. Baseline and out-
a few patients with viscous sputum may benefit from mucolytics come assessments of each participant in a pulmonary rehabil-
(153, 154), the overall benefits seem to be very small, and the itation program should be made to quantify individual gains and
widespread use of these agents cannot be recommended at target areas for improvement. Assessments should include the
present (Evidence D). following:
Antioxidant agents. Antioxidants, in particular N-acetylcys-
teine, have been reported in small studies to reduce the d Detailed history and physical examination
frequency of exacerbations, leading to speculation that these d Measurement of spirometry before and after use of a bron-
medications could have a role in the treatment of patients with chodilator drug
recurrent exacerbations (155–158) (Evidence B). However,
a large randomized controlled trial found no effect of N- d Assessment of exercise capacity
acetylcysteine on the frequency of exacerbations, except in d Measurement of health status and impact of breathlessness
patients not treated with inhaled glucocorticosteroids (159). d Assessment of inspiratory and expiratory muscle strength
Immunoregulators (immunostimulators, immunomodulators). and lower limb strength (e.g., quadriceps) in patients who
Studies using an immunoregulator in COPD show a decrease in suffer from muscle wasting
the severity and frequency of exacerbations (160, 161). How-
ever, additional studies to examine the long-term effects of this The first two assessments are important for establishing
therapy are required before its regular use can be recommended entry suitability and baseline status but are not used in outcome
(162). assessment. The last three assessments are baseline and out-
Antitussives. Cough, although sometimes a troublesome come measures.
symptom in COPD, has a significant protective role (163). OXYGEN THERAPY The long-term administration of oxygen
Thus, the regular use of antitussives is not recommended in (. 15 h/d) to patients with chronic respiratory failure has been
stable COPD (Evidence D). shown to increase survival (179, 180). It can also have a bene-
Vasodilators. In patients with COPD, inhaled nitric oxide can ficial impact on hemodynamics, hematologic characteristics,
worsen gas exchange because of altered hypoxic regulation of exercise capacity, lung mechanics, and mental state (181).
Long-term oxygen therapy is generally introduced in Component 4: Manage Exacerbations

patients with stage IV COPD, who have
d PaO2 at or below 7.3 kPa (55 mm Hg) or SaO2 at or below
88%, with or without hypercapnia (Evidence B), or KEY POINTS
d PaO2 between 7.3 kPa (55 mm Hg) and 8.0 kPa (60 mm Hg), d An exacerbation of COPD is defined as an event in the
or SaO2 of 88%, if there is evidence of pulmonary hyperten- natural course of the disease characterized by a change in
sion, peripheral edema suggesting congestive cardiac failure, the patient’s baseline dyspnea, cough, and/or sputum that
or polycythemia (hematocrit . 55%) (Evidence D). is beyond normal day-to-day variations, is acute in onset,
and may warrant a change in regular medication in
The primary goal of oxygen therapy is to increase the a patient with underlying COPD.
baseline PaO2 to at least 8.0 kPa (60 mm Hg) at sea level and
d The most common causes of an exacerbation are in-
rest, and/or produce an SaO2 of at least 90%, which will preserve
fection of the tracheobronchial tree and air pollution,
vital organ function by ensuring adequate delivery of oxygen. A
but the cause of about one-third of severe exacerbations
decision about the use of long-term oxygen should be based on
cannot be identified (Evidence B).
the waking PaO2 values. The prescription should always include
the source of supplemental oxygen (gas or liquid), method of d Inhaled bronchodilators (particularly inhaled b2-agonists
delivery, duration of use, and flow rate at rest, during exercise, with or without anticholinergics) and oral glucocorticos-
and during sleep. teroids are effective treatments for exacerbations of
VENTILATORY SUPPORT. Although long-term noninvasive COPD (Evidence A).
positive-pressure ventilation (NIPPV) cannot be recommended d Patients experiencing COPD exacerbations with clinical
for the routine treatment of patients with chronic respiratory signs of airway infection (e.g., increased sputum purulence)
failure due to COPD, the combination of NIPPV with long-term may benefit from antibiotic treatment (Evidence B).
oxygen therapy may be of some use in a selected subset of d Noninvasive mechanical ventilation in exacerbations
patients, particularly in those with pronounced daytime hyper- improves respiratory acidosis, increases pH, decreases
capnia (182). the need for endotracheal intubation, and reduces PaCO2,
SURGICAL TREATMENTS. Bullectomy. In carefully selected respiratory rate, severity of breathlessness, the length of
patients, this procedure is effective in reducing dyspnea and hospital stay, and mortality (Evidence A).
improving lung function (183) (Evidence C). A thoracic CT
scan, arterial blood gas measurement, and comprehensive re- d Medications and education to help prevent future exac-
spiratory function tests are essential before making a decision erbations should be considered as part of follow-up,
regarding suitability for resection of a bulla. because exacerbations affect the quality of life and
Lung volume reduction surgery. A large multicenter study prognosis of patients with COPD.
of 1,200 patients comparing lung volume reduction surgery
with medical treatment has shown that after 4.3 years, patients
with upper lobe emphysema and low exercise capacity who
received the surgery had a greater survival rate than similar Introduction. COPD is often associated with exacerbations
patients who received medical therapy (54 vs. 39.7%) (184). In of symptoms (197–201). An exacerbation of COPD is defined as
addition, the surgery patients experienced greater improvements ‘‘an event in the natural course of the disease characterized by
in their maximal work capacity and their health-related quality of a change in the patient’s baseline dyspnea, cough, and/or
life. The advantage of surgery over medical therapy was less sputum that is beyond normal day-to-day variations, is acute
significant among patients who had other emphysema distribution in onset, and may warrant a change in regular medication in
or high exercise capacity before treatment. Although the results of a patient with underlying COPD’’ (202, 203). Exacerbations are
this study showed some very positive results of surgery in a select categorized in terms of either clinical presentation (number of
group of patients (69, 184), lung volume reduction surgery is an symptoms [199]) and/or heath care resources utilization (202).
expensive palliative surgical procedure and can be recommended The impact of exacerbations is significant and a patient’s
only in carefully selected patients. symptoms and lung function may both take several weeks to
Lung transplantation. In appropriately selected patients with recover to the baseline values (204).
very advanced COPD, lung transplantation has been shown to The most common causes of an exacerbation are infection of
improve quality of life and functional capacity (185–188) the tracheobronchial tree and air pollution (205), but the cause
(Evidence C). Criteria for referral for lung transplantation of approximately one-third of severe exacerbations cannot be
include FEV1 , 35% predicted, PaO2 , 7.3–8.0 kPa (55–60 identified. The role of bacterial infections is controversial, but
mm Hg), PaCO2 . 6.7 kPa (50 mm Hg), and secondary recent investigations have shown that at least 50% of patients
pulmonary hypertension (189, 190). have bacteria in high concentrations in their lower airways
Special considerations. SURGERY IN COPD. Postoperative during exacerbations (206–208). Development of specific im-
pulmonary complications are as important and common as mune responses to the infecting bacterial strains, and the
postoperative cardiac complications and, consequently, are association of neutrophilic inflammation with bacterial exacer-
a key component of the increased risk posed by surgery in bations, also support the bacterial causation of a proportion of
patients with COPD. The principal potential factors contribut- exacerbations (209–212).
ing to the risk include smoking, poor general health status, age, Diagnosis and assessment of severity. MEDICAL HISTORY. In-
obesity, and COPD severity. A comprehensive definition of creased breathlessness, the main symptom of an exacerbation, is
postoperative pulmonary complications should include only often accompanied by wheezing and chest tightness, increased
major pulmonary respiratory complications, namely lung infec- cough and sputum, change of the color and/or tenacity of
tions, atelectasis, and/or increased airflow obstruction, all sputum, and fever. Exacerbations may also be accompanied
potentially resulting in acute respiratory failure and aggravation by a number of nonspecific complaints, such as tachycardia and
of underlying COPD (191–196). tachypnea, malaise, insomnia, sleepiness, fatigue, depression,
and confusion. A decrease in exercise tolerance, fever, and/or DIFFERENTIAL DIAGNOSES. Patients with apparent exacerba-
new radiologic anomalies suggestive of pulmonary disease may tions of COPD who do not respond to treatment (204, 214)
herald a COPD exacerbation. An increase in sputum volume should be reevaluated for other medical conditions that can
and purulence points to a bacterial cause, as does prior history aggravate symptoms or mimic COPD exacerbations (153),
of chronic sputum production (199, 212). including pneumonia, congestive heart failure, pneumothorax,
ASSESSMENT OF SEVERITY. Assessment of the severity of an pleural effusion, pulmonary embolism, and cardiac arrhythmia.
exacerbation is based on the patient’s medical history before the Noncompliance with the prescribed medication regimen can
exacerbation, preexisting comorbidities, symptoms, physical also cause increased symptoms that may be confused with a true
examination, arterial blood gas measurements, and other labo- exacerbation. Elevated serum levels of brain-type natriuretic
ratory tests. Physicians should obtain the results of previous peptide, in conjunction with other clinical information, can
evaluations, where possible, to compare with the current clinical identify patients with acute dyspnea secondary to congestive
data. Specific information is required on the frequency and heart failure and enable them to be distinguished from patients
severity of attacks of breathlessness and cough, sputum volume with COPD exacerbations (215, 216).
and color, and limitation of daily activities. When available, Home management. There is increasing interest in home care
prior arterial blood gas measurements are extremely useful for for patients with end-stage COPD, although the exact criteria
comparison with those made during the acute episode, as an for this approach as opposed to hospital treatment remain
acute change in these tests is more important than their absolute uncertain and will vary by health care setting (217–220).
values. Thus, where possible, physicians should instruct their BRONCHODILATOR THERAPY. Home management of COPD
patients to bring the summary of their last evaluation when they exacerbations involves increasing the dose and/or frequency of
come to the hospital with an exacerbation. In patients with stage existing short-acting bronchodilator therapy, preferably with
IV COPD, the most important sign of a severe exacerbation is a b2-agonist (Evidence A). If not already used, an anticholin-
a change in the mental status of the patient and this signals ergic can be added until the symptoms improve (Evidence D).
a need for immediate evaluation in the hospital. GLUCOCORTICOSTEROIDS. Systemic glucocorticosteroids are
Spirometry and PEF. Even simple spirometric tests can be beneficial in the management of exacerbations of COPD. They
difficult for a sick patient to perform properly. These measure- shorten recovery time, improve lung function (FEV1) and
ments are not accurate during an acute exacerbation; therefore, hypoxemia (PaO2) (221–224) (Evidence A), and may reduce
their routine use is not recommended. the risk of early relapse, treatment failure, and length of
Pulse oximetry and arterial blood gas measurement. Pulse hospital stay (225). They should be considered in addition to
oximetry can be used to evaluate a patient’s oxygen saturation bronchodilators if the patient’s baseline FEV1 is less than 50%
and need for supplemental oxygen therapy. For patients that predicted. A dose of 30 to 40 mg prednisolone per day for 7 to
require hospitalization, measurement of arterial blood gases is 10 days is recommended (221, 222, 226).
important to assess the severity of an exacerbation. A PaO2 , ANTIBIOTICS. The use of antibiotics in the management of
8.0 kPa (60 mm Hg) and/or SaO2 , 90% with or without PaCO2 COPD exacerbations is discussed below in HOSPITAL MANAGE-
. 6.7 kPa (50 mm Hg) when breathing room air indicate MENT.
respiratory failure. In addition, moderate to severe acidosis Hospital management. The risk of dying of an exacerbation
(pH , 7.36) plus hypercapnia (PaCO2 . 6–8 kPa, 45–60 mm Hg) of COPD is closely related to the development of respiratory
in a patient with respiratory failure is an indication for acidosis, the presence of significant comorbidities, and the need
mechanical ventilation (196, 213). for ventilatory support (227). Patients lacking these features are
Chest X-ray and ECG. Chest radiographs (posterior/ante- not at high risk of dying, but those with severe underlying
rior plus lateral) are useful in identifying alternative diagnoses COPD often require hospitalization in any case. Attempts at
that can mimic the symptoms of an exacerbation. An ECG aids managing such patients entirely in the community have met
in the diagnosis of right heart hypertrophy, arrhythmias, and with only limited success (228), but returning them to their
ischemic episodes. Pulmonary embolism can be very difficult to homes with increased social support and a supervised medical
distinguish from an exacerbation, especially in advanced care package after initial emergency room assessment has been
COPD, because right ventricular hypertrophy and large pulmo- much more successful (229). Savings on inpatient expenditures
nary arteries lead to confusing ECG and radiographic results. A (230) offset the additional costs of maintaining a community-
low systolic blood pressure and an inability to increase the PaO2 based COPD nursing team. However, detailed cost–benefit
above 8.0 kPa (60 mm Hg) despite high-flow oxygen also analyses of these approaches are awaited.
suggest pulmonary embolism. If there are strong indications A range of criteria to consider for hospital assessment/
that pulmonary embolism has occurred, it is best to treat for this admission for exacerbations of COPD are shown in Table 8.
together with the exacerbation. Some patients need immediate admission to an intensive care
Other laboratory tests. The complete blood count may iden- unit (ICU) (Table 9). Admission of patients with severe COPD
tify polycythemia (hematocrit . 55%) or suggest bleeding. exacerbations to intermediate or special respiratory care units
White blood cell counts are usually not very informative. The may be appropriate if personnel, skills, and equipment exist to
presence of purulent sputum during an exacerbation of symp- identify and manage acute respiratory failure successfully.
toms is sufficient indication for starting empirical antibiotic The first actions when a patient reaches the emergency
treatment (33). Streptococcus pneumoniae, Hemophilus influen- department are to provide supplemental oxygen therapy and
zae, and Moraxella catarrhalis are the most common bacterial to determine whether the exacerbation is life threatening. If so,
pathogens involved in COPD exacerbations. If an infectious the patient should be admitted to the ICU immediately. Other-
exacerbation does not respond to the initial antibiotic treatment, wise, the patient may be managed in the emergency department
a sputum culture and an antibiogram should be performed. or hospital (Table 10).
Biochemical test abnormalities can be associated with an CONTROLLED OXYGEN THERAPY. Oxygen therapy is the cor-
exacerbation and include electrolyte disturbance(s) (e.g., hypo- nerstone of hospital treatment of COPD exacerbations. Sup-
natremia, hypokalemia), poor glucose control, or metabolic plemental oxygen should be titrated to improve the patient’s
acid–base disorder. These abnormalities can also be due to hypoxemia. Adequate levels of oxygenation (PaO2 . 8.0 kPa, 60
associated comorbid conditions. mm Hg, or SaO2 . 90%) are easy to achieve in uncomplicated
TABLE 8. INDICATIONS FOR HOSPITAL ASSESSMENT OR TABLE 10. MANAGEMENT OF SEVERE BUT NOT
ADMISSION FOR EXACERBATIONS OF CHRONIC LIFE-THREATENING EXACERBATIONS OF CHRONIC
OBSTRUCTIVE PULMONARY DISEASE* OBSTRUCTIVE PULMONARY DISEASE IN THE EMERGENCY
DEPARTMENT OR THE HOSPITAL*
d Marked increase in intensity of symptoms, such as sudden development
of resting dyspnea, change in vital signs d Assess severity of symptoms, blood gases, chest X-ray
d Severe underlying COPD d Administer controlled oxygen therapy and repeat arterial blood gas
d Onset of new physical signs (e.g., cyanosis, peripheral edema) measurement after 30–60 min
d Failure of exacerbation to respond to initial medical management d Bronchodilators:
d Significant comorbidities – Increase doses and/or frequency
d Frequent exacerbations – Combine b2-agonists and anticholinergics
d Newly occurring arrhythmias – Use spacers or air-driven nebulizers
d Diagnostic uncertainty – Consider adding intravenous methylxanthines, if needed
d Older age d Add oral or intravenous glucocorticosteroids
d Insufficient home support d Consider antibiotics (oral or occasionally intravenous) when there are
signs of bacterial infection
Definition of abbreviation: COPD 5 chronic obstructive pulmonary disease. d Consider noninvasive mechanical ventilation
* Local resources need to be considered. d At all times:
– Monitor fluid balance and nutrition
– Consider subcutaneous heparin
exacerbations, but CO2 retention can occur insidiously with – Identify and treat associated conditions (e.g., heart failure, arrhythmias)
little change in symptoms. Once oxygen is started, arterial blood – Closely monitor condition of the patient
gases should be checked 30 to 60 minutes later to ensure Data from Reference 226.
satisfactory oxygenation without CO2 retention or acidosis. * Local resources need to be considered.
Venturi masks (high-flow devices) offer more accurate delivery
of controlled oxygen than do nasal prongs but are less likely to
be tolerated by the patient (196).
BRONCHODILATOR THERAPY. Short-acting inhaled b2-agonists
are usually the preferred bronchodilators for treatment of ANTIBIOTICS. On the basis of the current available evidence
exacerbations of COPD (153, 196, 231) (Evidence A). If (196, 62), antibiotics should be given to the following individuals:
a prompt response to these drugs does not occur, the addition
of an anticholinergic is recommended, even though evidence d Patients with exacerbations of COPD with the following
concerning the effectiveness of this combination is controver- three cardinal symptoms: increased dyspnea, increased spu-
sial. Despite its widespread clinical use, the role of methylxan- tum volume, and increased sputum purulence (Evidence B)
thines in the treatment of exacerbations of COPD remains d Patients with exacerbations of COPD with two of the
controversial. Intravenous methylxanthines (theophylline or cardinal symptoms, if increased purulence of sputum is
aminohylline) are currently considered second-line therapy, one of the two symptoms (Evidence C)
used when there is inadequate or insufficient response to d Patients with a severe exacerbation of COPD that requires
short-acting bronchodilators (232–236) (Evidence B). Possible mechanical ventilation (invasive or noninvasive) (Evidence B)
beneficial effects in terms of lung function and clinical end-
points are modest and inconsistent, whereas adverse effects are The infectious agents in COPD exacerbations can be viral or
significantly increased (237, 238). There are no clinical studies bacterial (140, 239). The predominant bacteria recovered from
that have evaluated the use of inhaled long-acting bronchodi- the lower airways of patients with COPD exacerbations are H.
lators (either b2-agonists or anticholinergics) with or without influenzae, S. pneumoniae, and M. catarrhalis (140, 206, 207, 240).
inhaled glucocorticosteroids during an acute exacerbation. So-called atypical pathogens, such as Mycoplasma pneumoniae
GLUCOCORTICOSTEROIDS. Oral or intravenous glucocorticos- and Chlamydia pneumoniae (240, 241), have been identified in
teroids are recommended as an addition to other therapies in patients with COPD exacerbations, but because of diagnostic
the hospital management of exacerbations of COPD (222, 223) limitations the true prevalence of these organisms is not known.
(Evidence A). The exact dose that should be recommended is RESPIRATORY STIMULANTS. Respiratory stimulants are not
not known, but high doses are associated with a significant risk recommended for acute respiratory failure (231). Doxapram,
of side effects. Thirty to 40 mg of oral prednisolone daily for a nonspecific but relatively safe respiratory stimulant available
7 to 10 days is effective and safe (Evidence C). Prolonged treat- in some countries as an intravenous formulation, should be used
ment does not result in greater efficacy and increases the risk of only when noninvasive intermittent ventilation is not available
side effects. or not recommended (242).
VENTILATORY SUPPORT. The primary objectives of mechani-
cal ventilatory support in patients with COPD exacerbations are
to decrease mortality and morbidity and to relieve symptoms.
TABLE 9. INDICATIONS FOR INTENSIVE CARE UNIT Ventilatory support includes both noninvasive intermittent
ADMISSION OF PATIENTS WITH EXACERBATIONS ventilation using either negative- or positive-pressure devices,
OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE* and invasive (conventional) mechanical ventilation by orotra-
d Severe dyspnea that responds inadequately to initial emergency therapy
cheal tube or tracheostomy.
d Changes in mental status (confusion, lethargy, coma) Noninvasive mechanical ventilation. Noninvasive intermit-
d Persistent or worsening hypoxemia (PaO2 , 5.3 kPa, 40 mm Hg), and/or tent ventilation (NIV) has been studied in several randomized
severe/worsening hypercapnia (PaCO2 . 8.0 kPa, 60 mm Hg), and/or controlled trials in acute respiratory failure, consistently pro-
severe/worsening respiratory acidosis (pH , 7.25) despite supplemental viding positive results, with success rates of 80 to 85% (182,
oxygen and noninvasive ventilation 243–245). These studies provide evidence that NIV improves
d Need for invasive mechanical ventilation
d Hemodynamic instability—need for vasopressors
respiratory acidosis (increases pH, and decreases PaCO2), and
decreases respiratory rate, severity of breathlessness, and length
* Local resources need to be considered. of hospital stay (Evidence A). More importantly, mortality —or
its surrogate, intubation rate—is reduced by this intervention TABLE 12. INDICATIONS FOR INVASIVE
(245–248). However, NIV is not appropriate for all patients, as MECHANICAL VENTILATION
summarized in Table 11 (182). d Unable to tolerate NIV or NIV failure (or exclusion criteria, see Table 11)
Invasive mechanical ventilation. The indications for initiat- d Severe dyspnea with use of accessory muscles and paradoxical
ing invasive mechanical ventilation during exacerbations of abdominal motion
d Respiratory frequency . 35 breaths/min
COPD are shown in Table 12 and include failure of an initial
d Life-threatening hypoxemia
trial of NIV (252). As experience is being gained with the
d Severe acidosis (pH , 7.25) and/or hypercapnia (Pa
CO2 . 8.0 kPa, 60 mm Hg)
generalized clinical use of NIV in COPD, several of the d Respiratory arrest
indications for invasive mechanical ventilation are being suc- d Worsening in mental status despite optimal therapy
cessfully treated with NIV. d Cardiovascular complications (hypotension, shock)
The use of invasive ventilation in patients with end-stage d Other complications (metabolic abnormalities, sepsis, pneumonia,
COPD is influenced by the likely reversibility of the precipitat- pulmonary embolism, barotrauma, massive pleural effusion)
ing event, the patient’s wishes, and the availability of intensive
Definition of abbreviation: NIV 5 noninvasive intermittent ventilation.
care facilities. Major hazards include the risk of ventilator-
acquired pneumonia (especially when multiresistant organisms
are prevalent), barotrauma, and failure to wean to spontaneous
criteria listed in Table 13. Table 14 provides items to include in
ventilation. Contrary to some opinions, acute mortality among a follow-up assessment 4 to 6 weeks after discharge from the
patients with COPD with respiratory failure is lower than
hospital. Thereafter, follow-up is the same as for patients with
mortality among patients ventilated for non-COPD causes stable COPD, including supervising smoking cessation, moni-
(253). When possible, a clear statement of the patient’s own
toring the effectiveness of each drug treatment, and monitoring
treatment wishes—an advance directive or ‘‘living will’’—makes changes in spirometric parameters (229). Home visits by
these difficult decisions much easier to resolve.
a community nurse may permit earlier discharge of patients
Weaning or discontinuation from mechanical ventilation can hospitalized with an exacerbation of COPD, without increasing
be particularly difficult and hazardous in patients with COPD
readmission rates (153, 259–261).
and the best method (pressure support or a T-piece trial) In patients who are hypoxemic during a COPD exacerba-
remains a matter of debate (254–256). In patients with COPD
tion, arterial blood gases and/or pulse oximetry should be
who fail weaning trials, noninvasive ventilation facilitates evaluated before hospital discharge and in the following 3
extubation. It can also prevent reintubation in patients with
months. If the patient remains hypoxemic, long-term supple-
extubation failure and may reduce mortality. mental oxygen therapy may be required.
OTHER MEASURES. Further treatments that can be used in the
Opportunities for prevention of future exacerbations should
hospital include the following: fluid administration (accurate be reviewed before discharge, with particular attention to
monitoring of fluid balance is essential); nutrition (supplemen-
smoking cessation, current vaccination (influenza, pneumococ-
tary when needed); deep venous thrombosis prophylaxis (me- cal vaccines), knowledge of current therapy including inhaler
chanical devices, heparins, etc.) in immobilized, polycythemic,
technique (32, 262, 263), and how to recognize symptoms of
or dehydrated patients with or without a history of thrombo- exacerbations. Pharmacotherapy known to reduce the number
embolic disease; and sputum clearance (by stimulating coughing
of exacerbations and hospitalizations and delay the time of first/
and low-volume forced expirations as in home management). next hospitalization, such as long-acting inhaled bronchodilators,
Manual or mechanical chest percussion and postural drainage
inhaled glucocorticosteroids, and combination inhalers, should
may be beneficial in patients with excessive sputum production
be specifically considered. Social problems should be discussed
or with lobar atelectasis.
and principal caregivers identified if the patient has a significant
Hospital discharge and follow-up. Insufficient clinical data
persisting disability.
exist to establish the optimal duration of hospitalization in
individual patients who develop an exacerbation of COPD (197,
257, 258). Consensus and limited data support the discharge 4. TRANSLATING GUIDELINE RECOMMENDATIONS TO
THE CONTEXT OF (PRIMARY) CARE
KEY POINTS
TABLE 11. INDICATIONS AND RELATIVE CONTRAINDICATIONS d There is considerable evidence that management of
FOR NONINVASIVE INTERMITTENT VENTILATION COPD is generally not in accordance with current guide-
Selection criteria lines. Better dissemination of guidelines and their effec-
d Moderate to severe dyspnea with use of accessory muscles and tive implementation in a variety of health care settings are
paradoxical abdominal motion urgently required.
d Moderate to severe acidosis (pH < 7.35) and/or hypercapnia
(PaCO2 . 6.0 kPa, 45 mm Hg) (251) d In many countries, primary care practitioners treat the
d Respiratory frequency . 25 breaths/min vast majority of patients with COPD and may be actively
Exclusion criteria (any may be present) involved in public health campaigns and in bringing
d Respiratory arrest
messages about reducing exposure to risk factors to both
d Cardiovascular instability (hypotension, arrhythmias, myocardial infarction)
patients and the public.
d Change in mental status; uncooperative patient
d High aspiration risk d Spirometric confirmation is a key component of the di-

d Viscous or copious secretions agnosis of COPD and primary care practitioners should
d Recent facial or gastroesophageal surgery
have access to high-quality spirometry.
d Craniofacial trauma
d Fixed nasopharyngeal abnormalities d Older patients frequently have multiple chronic health
d Burns conditions. Comorbidities can magnify the impact of
d Extreme obesity COPD on a patient’s health status, and can complicate
the management of COPD.
Data from References 196, 243, 249, and 250.
TABLE 13. DISCHARGE CRITERIA FOR PATIENTS WITH as ischemic heart disease and lung cancer; conditions that arise
EXACERBATIONS OF CHRONIC OBSTRUCTIVE as a complication of a specific preexisting disease, such as
PULMONARY DISEASE pulmonary hypertension and consequent heart failure; coexist-
d Inhaled b2-agonist therapy is required no more frequently than every 4 h ing chronic conditions with unrelated pathogenesis related to
d Patient, if previously ambulatory, is able to walk across room aging, such as bowel or prostate cancer, depression, diabetes
d Patient is able to eat and sleep without frequent awakening by dyspnea mellitus, Parkinson’s disease, dementia, and arthritis; or acute
d Patient has been clinically stable for 12–24 h illnesses that may have a more severe impact in patients with
d Arterial blood gases have been stable for 12–24 h
a given chronic disease. For example, upper respiratory tract
d Patient (or home caregiver) fully understands correct use of medications
d Follow-up and home care arrangements have been completed infections are the most frequent health problem in all age
(e.g., visiting nurse, oxygen delivery, meal provisions) groups, but they may have a more severe impact or require
d Patient, family, and physician are confident patient can manage successfully different treatment in patients with COPD.
at home
Reducing Exposure to Risk Factors
Reduction of total personal exposure to tobacco smoke, occu-
pational dusts and chemicals, and indoor and outdoor air
The recommendations provided in sections 1 through 3 pollutants, including smoke from cooking over biomass-fueled
define—from a disease perspective—best practices in the di- fires, is an important goal to prevent the onset and progression
agnosis, monitoring, and treatment of COPD. However, (pri- of COPD. In many health care systems, primary care practi-
mary) medical care is based on an engagement with patients, tioners may be actively involved in public health campaigns and
and this engagement determines the success or failure of can play an important part in bringing messages about reducing
pursuing best practice. For this reason, medical practice exposure to risk factors to patients and the public. Primary care
requires a translation of disease-specific recommendations to practitioners can also play a very important role in reinforcing
the circumstances of individual patients—with regard to the the dangers of passive smoking and the importance of imple-
local communities in which they live, and the health systems menting smoke-free work environments.
from which they receive medical care. Smoking cessation is the most effective intervention to
Diagnosis reduce the risk of developing COPD, and simple smoking
cessation advice from health care professionals has been shown
In pursuing early diagnosis, a policy of identifying patients at to make patients more likely to stop smoking. Primary care
high risk of COPD, followed by watchful surveillance of these practitioners often have many contacts with a patient over time,
patients, is advised. which provides the opportunity to discuss smoking cessation,
Respiratory symptoms. Of the chronic symptoms character- enhance motivation for quitting, and identify the need for
istic of COPD (dyspnea, cough, sputum production), dyspnea is supportive pharmacologic treatment. It is very important to
the symptom that interferes most with a patient’s daily life and align the advice given by individual practitioners with public
health status. When taking the medical history of the patient, it health campaigns to send a coherent message to the public.
is therefore important to explore the impact of dyspnea and
other symptoms on daily activities, work, and social activities, Implementation of COPD Guidelines
and provide treatment accordingly.
Spirometry. High-quality spirometry in primary care is pos- GOLD national leaders play an essential role in the dissemi-
sible (264, 265), provided that good skills training and an nation of information about prevention, early diagnosis, and
ongoing quality assurance program are provided. An alternative management of COPD in health systems around the world. A
is to ensure that high-quality spirometry is available in the major GOLD program activity that has helped to bring together
community—for example, within the primary care practice health care teams at the local level is World COPD Day, held
itself, in a primary care laboratory, or in a hospital setting, annually on the third Wednesday in November.* GOLD na-
depending on the structure of the local health care system (266). tional leaders, often in concert with local physicians, nurses, and
Ongoing collaboration between primary care and respiratory health care planners, have hosted many types of activities to
care also helps assure quality control. raise awareness of COPD. WONCA (the World Organization of
Family Doctors) is also an active collaborator in organizing World
Comorbidities COPD Day activities. Increased participation of a wide variety of
health care professionals in World COPD Day activities in many
Older patients frequently have multiple chronic health condi- countries would help to increase awareness of COPD.
tions and the severity of comorbid conditions and their impact GOLD is a partner organization in the World Health
on a patient’s health status will vary between patients and in the Organization’s GARD with the goal to raise awareness of the
same patient over time. Comorbidities for patients with COPD burden of chronic respiratory diseases in all countries of the
may include the following: other smoking-related diseases, such world, and to disseminate and implement recommendations
from international guidelines.
Although awareness and dissemination of guidelines are
TABLE 14. ITEMS TO ASSESS AT FOLLOW-UP VISIT 4–6 WEEKS important goals, the actual implementation of a comprehensive
AFTER DISCHARGE FROM HOSPITAL FOR EXACERBATIONS OF care system in which to coordinate the management of COPD will
CHRONIC OBSTRUCTIVE PULMONARY DISEASE be important to pursue. Evidence is increasing that a chronic
d Ability to cope in usual environment
disease management program for patients with COPD that
d Measurement of FEV1 incorporates a variety of interventions, includes pulmonary re-
d Reassessment of inhaler technique habilitation, and is implemented by primary care reduces hospital
d Understanding of recommended treatment regimen admissions and bed days. Key elements are patient participation
d Need for long-term oxygen therapy and/or home nebulizer (for patients and information sharing among health care providers (267).
with stage IV, very severe COPD)
*For further information on World COPD Day: http://www.goldcopd.org/WCDindex.
Definition of abbreviation: COPD 5 chronic obstructive pulmonary disease. asp.
Conflict of Interest Statement: K.F.R. has consulted, participated in advisory board 9. Bateman ED, Feldman C, O’Brien J, Plit M, Joubert JR. Guideline for
meetings, and received lecture fees from AstraZeneca, Boehringer Ingelheim (BI), the management of chronic obstructive pulmonary disease (COPD):
Chiesi Pharmaceuticals, Pfizer, Novartis, AltanaPharma, Merck, Sharp, and Dohme 2004 revision. S Afr Med J 2004;94:559–575.
(MSD), and GlaxoSmithKline (GSK). The Department of Pulmonology, and
10. Hogg JC. Pathophysiology of airflow limitation in chronic obstructive
thereby K.F.R. as head of the department, has received grants from AltanaPharma
($222,612), Novartis ($90,640), AstraZeneca ($113,155), Pfizer ($406,000), MSD pulmonary disease. Lancet 2004;364:709–721.
($118,000), Exhale Therapeutics ($90,000), BI ($90,000), Roche ($120,000), and 11. Birring SS, Brightling CE, Bradding P, Entwisle JJ, Vara DD, Grigg J,
GSK ($299,495) in the years 2001 until 2006. S.H. does not have a financial et al. Clinical, radiologic, and induced sputum features of chronic
relationship with a commercial entity that has an interest in the subject of this obstructive pulmonary disease in nonsmokers: a descriptive study.
manuscript. A.A. served as consultant in 2006 for Bayer Pharma ($2,000), Sanofi Am J Respir Crit Care Med 2002;166:1078–1083.
Aventis ($2,500), GSK ($2,000), BI ($2,000), and Sepracor ($3,000). He received 12. Wouters EF, Creutzberg EC, Schols AM. Systemic effects in COPD.
lecture fees from BI/Pfizer for $3,000, Bayer Pharma for $2,500, and for symposia
Chest 2002;121:127S–130S.
from BI for $1,500 and symposia from Kinetic Concepts, Inc. for $2,000. He also
received industry-sponsored grants from Bayer Pharma in 2004–2005 for $30,000, 13. Agusti AG, Noguera A, Sauleda J, Sala E, Pons J, Busquets X.
C.R. Bard, Inc. for $60,000, BI for $50,000, NHLBI for $200,000, and GSK for Systemic effects of chronic obstructive pulmonary disease. Eur
$200,000. P.J.B. has received research funding, lecture fees, and has served on Respir J 2003;21:347–360.
scientific advisory boards for GSK, AstraZeneca, BI, Novartis, AltanaPharma, and 14. Tirimanna PR, van Schayck CP, den Otter JJ, van Weel C, van
Pfizer. S.A.B. has served on advisory boards for GSK, Altana, Schering Plough, Herwaarden CL, van den Boom G, van Grunsven PM, van den
Merck, Novartis, Pfizer, and Sepracor. She has participated in COPD workshops Bosch WJ. Prevalence of asthma and COPD in general practice in
funded by AstraZeneca and GSK; and is Scientific Director for the Burden of
1992: has it changed since 1977? Br J Gen Pract 1996;46:277–281.
Obstructive Lung Disease (BOLD) initiative, which receives unrestricted educa-
tional grants to the Kaiser Permanente Center for Health Research from GSK, Pfizer, 15. Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino
BI, AstraZeneca, AltanaPharma, Novartis, Merck, Chiesi, Schering Plough, and DM. Global burden of COPD: systematic review and meta-analysis.
Sepracor. P.C. has spoken at scientific meetings for which he received honoraria Eur Respir J 2006;28:523–532.
(GSK, 2004—2006, $10,000; AstraZeneca, 2006, $3,000) and has served on 16. Fukuchi Y, Nishimura M, Ichinose M, Adachi M, Nagai A, Kuriyama
advisory boards (GSK, 2004–2006, $15,000; AstraZeneca, 2004, $2,500; Pfizer, T, Takahashi K, Nishimura K, Ishioka S, Aizawa H, et al. COPD in
2005–2006, $5,000). He has received industry-sponsored grants from GSK Japan: the Nippon COPD Epidemiology study. Respirology 2004;9:
($110,000) and AltanaPharma ($40,000). Y.F. does not have a financial relation- 458–465.
ship with a commercial entity that has an interest in the subject of this manuscript.
C.J. has received fees for chairing or sitting on advisory boards of GSK,
17. National Heart, Lung, and Blood Institute. Morbidity and mortality:
AstraZeneca, and Pfizer/BI, for a total value of $22,000 in the last 3 years. C.J. chartbook on cardiovascular, lung, and blood Diseases. Bethesda,
has also received fees for providing educational material and for giving lectures at MD: U.S. Department. of Health and Human Services, Public Health
industry-sponsored symposia to the value of $8,500 in the last 3 years. C.J. is Service, National Institutes of Health; 1998.
a senior researcher in the Woolcock Institute of Medical Research, which 18. Soriano JR, Maier WC, Egger P, Visick G, Thakrar B, Sykes J, Pride
participates in clinical trials sponsored by GSK, AstraZeneca, AltanaPharma (now NB. Recent trends in physician diagnosed COPD in women and men
NycoMed), and BI. The Institute is a member of a national collaborative research in the UK. Thorax 2000;55:789–794.
group, which is cofunded by government and industry. The major industry
19. Menezes AM, Perez-Padilla R, Jardim JR, Muino A, Lopez MV,
partners are GSK and Pharmaxis. R.R.-R. has participated as a lecturer and speaker
in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Valdivia G, Montes de Oca M, Talamo C, Hallal PC, Victora CG.
BI, GSK, Laboratorios Dr Esteve SA, and Pfizer; consulted with several pharmaceu- Chronic obstructive pulmonary disease in five Latin American cities
tical companies with interests in the topics discussed in the present article (Almirall, (the PLATINO study): a prevalence study. Lancet 2005;366:1875–
AltanaPharma, AstraZeneca, BI, GSK, Laboratorios Dr. Esteve SA, Novartis, Pfizer, 1881.
Viechi, and Zambon); serves on advisory boards for Almirall, BI, GSK, Novartis, 20. Schellevis FG, Van de Lisdonk EH, Van der Velden J, Hoogbergen
Pfizer, Proctor and Gamble, and Viechi; has been sponsored for several clinical SH, Van Eijk JT, Van Weel C. Consultation rates and incidence of
trials; and has received laboratory research support from AstraZeneca, BI, GSK,
intercurrent morbidity among patients with chronic disease in general
Laboratorios Dr Esteve SA, Pfizer, and Proctor and Gamble Ltd. C.v.W. has received
speakers fees from Novartis, BI, AltanaPharma, and Pfizer, which have all been practice. Br J Gen Pract 1994;44:259–262.
made available to the World Organization of Family Doctors (WONES). His 21. Murray CJL, Lopez AD, editors. The global burden of disease:
department has received unrestricted research grants from GSK, BI, AstraZeneca, a comprehensive assessment of mortality and disability from diseases,
Novartis, Novo Nordisk, and Bayer. J.Z. does not have a financial relationship with injuries and risk factors in 1990 and projected to 2020. Cambridge,
a commercial entity that has an interest in the subject of this manuscript. MA: Harvard University Press; 1996.
22. Murray CJ, Lopez AD. Alternative projections of mortality and
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Rabe Et Al 2012 Global Strategy For The Diagnosis Management and Prevention of Chronic Obstructive Pulmonary Disease

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Global Strategy for the Diagnosis, Management, and

Prevention of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) remains a major CONTENTS

Spirometry mendations to recognize the need to present a positive

TABLE 1. DESCRIPTION OF LEVELS OF EVIDENCE

Definition of abbreviation: RCT 5 randomized controlled trial.

Figure 1. Chronic obstructive pulmonary disease risk is

Figure 2. Therapy at each stage of

Long-term oxygen therapy is generally introduced in Component 4: Manage Exacerbations

cessfully treated with NIV. d Cardiovascular complications (hypotension, shock)

d High aspiration risk d Spirometric confirmation is a key component of the di-

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