Nabil Al Lawati, MD, MRCP, J.

Mark FitzGerald, MD, MB, FRCPC, FRCPCI

Acute exacerbation of
chronic obstructive
pulmonary disease
Bronchodilators, oral corticosteroids, and antibiotics may all be
needed to manage an acute exacerbation of COPD.

ABSTRACT: Acute exacerbations of

chronic obstructive pulmonary disease are associated with significant
morbidity and mortality. Clinicians
should begin by considering epidemiological aspects of acute exacerbations, including precipitating
factors and risk factors. Affected
individuals should be assessed
using accepted criteria and then
offered appropriate pharmacological
and nonpharmacological therapy.
In addition, prevention strategies
should always be discussed with
patients prone to acute exacer bations.

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hronic obstructive pulmonary disease (COPD) is

a major cause of chronic
morbidity and mortality
throughout the world. Today it is the
fourth leading cause of death in the
world1 and in Canada.2 The prevalence
of COPD in Canada has been on the
rise in both sexes, with a more significant rise in prevalence in men.2
Acute exacerbations of chronic
ob structive pulmonary disease
(AECOPD) account for over 1.5 million physician visits annually in Canada and are the most frequent cause of
medical visits, hospital admissions,
and death among patients with
COPD.3,4 In Canada COPD was the
seventh most common cause of hospitalization for men (2.3%) and the
eighth for women (2.0%), excluding
childbirth, in 20002001. The economic impact of the disease in Canada
exceeds $1.67 billion2 and is likely
underestimated. 5 In addition, frequent
exacerbations are an important determinant of quality of life6 and contribute to accelerated rates of decline
in lung function.7
Mortality among those who are
admitted to hospital with exacerbations varies depending on the severity
of the underlying COPD. Patients with

mild to moderate disease have a 4%

short-term mortality if admitted to
hospital,8 but mortality rates can be
as high as 24% if patients with acute
respiratory failure are admitted to an
intensive care unit.9-12 Patients requiring ICU admission have a 1-year
mortality rate as high as 46%.9,10,12 The
Figure shows the number of COPD
deaths in Canada that occurred between 1987 and 1999.
The figure also shows the number
of deaths expected from 2000 to 2016.

Precipitating factors
Acute exacerbations of COPD are
most commonly precipitated by bacterial or viral infection and environmental factors such as air pollution or
cold temperatures.13 It is estimated that
50% to 60% of exacerbations are due
to respiratory infections, 10% are due
to environmental pollution, and 30%
are of unknown cause.14
The likelihood of a patient having
more than one exacerbation per year
Dr Al Lawati is a fellow in the Division of
Respiratory Medicine at the University of
British Columbia. Dr FitzGerald is a professor in the Department of Medicine at UBC
and a respirologist with the Lung Centre at
Vancouver General Hospital.

Acute exacerbation of chronic obstructive pulmonary disease

increases with advanced age and

chronic mucus hypersecretion. Comorbid conditions such as ischemic
heart disease, chronic heart failure, or
diabetes mellitus increase the risk of
an exacerbation severe enough to
require hospitalization.4 A high FEV1
(forced expiratory volume in 1 second) is protective.15 COPD exacerbations may also be more common
among patients with gastroesophageal
reflux that occurs weekly.16

MenProjected
WomenProjected

12000
10000
8000
6000
4000

Assessment
The Global Initiative for Chronic
Obstructive Lung Disease (GOLD)17
defines an acute exacerbation of
COPD as an event in the natural
course of the disease characterized by
a change in the patients baseline dyspnea, cough, and/or sputum that is
beyond normal day-to-day variations,
is acute in onset, and may warrant a
change in regular medication in a
patient with underlying COPD.17
Another widely accepted definition of
AECOPD was provided by Anthonisen and colleagues,18 who proposed
the following three clinical criteria to
define acute exacerbations: increased
sputum volume, increased sputum
purulence, and increased dyspnea.
Based on these criteria, an exacerbation can be classified as one of three
types ( Table 1 ).
The type of exacerbation along
with other clinical features will deter-

MenActual
WomenActual

14000

2000
0
1987

1990

1993

1996

1999

2002

2005

2008

2011

2014

Figure. Actual and projected deaths resulting from chronic obstructive pulmonary disease
in Canada, 1987 to 2016.
Source: Adapted from Canadian Thoracic Society recommendations.2

mine if hospitalization is required.

Not all those who suffer an exacerbation require hospital admission.
( Table 2 )19

Management
Controlled oxygen therapy. This is
almost always the first treatment
given to patients with AECOPD,
mainly to prevent life-threatening
hypoxemia and optimize oxygen
delivery to peripheral tissues and alleviate symptoms, namely dyspnea.
Supplemental oxygen should be titrated, preferably via Venturi masks, to

Table 1. Anthonisen classification of AECOPD

Type I (most severe)

Type II

Type III

All three symptoms (i.e.,

increased sputum volume,
increased sputum purulence
and increased dyspnea).

Any two symptoms

present

One symptom present plus at least one

of the following:
An upper respiratory tract infection in
the past 5 days
Increased wheezing
Increased cough
Fever without an obvious source
A 20% increase in respiratory rate
Heart rate above baseline

increase PaO2 adequately in order to

maintain optimal values above 60 mm
Hg and ensure adequate SaO2 levels
(greater than 90%) without carbon
dioxide retention and acidosis.19
Bronchodilators. Short-acting
inhaled 2 agonists and anticholi nergic agents play an important role
in treating COPD exacerbations by
reducing symptoms and improving
Table 2. Criteria suggesting need for hospitalization.
High-risk comorbidities, including pneumonia, cardiac arrhythmia, congestive
heart failure, diabetes mellitus, renal
failure, or liver failure
Inadequate response of symptoms to
outpatient management
Marked increase in dyspnea
Inability to eat or sleep because of
symptoms
Worsening hypoxemia
Worsening hypercapnia
Changes in mental status
Inability to care for self (i.e., lack of
home support)
Uncertain diagnosis

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Acute exacerbation of chronic obstructive pulmonary disease

Table 3. Antibiotic treatment recommendations for purulent AECOPD.2

Treatment group

Symptoms and risk factors

Simple
(COPD without risk factors)

Complicated
(COPD with risk factors)

Most likely pathogens

First-choice antibiotics

Alternative antibiotics

Increased cough
Haemophilus influenzae
Increased sputum volume Moraxella catarrhalis
Increased sputum puru Streptococcus pneumolence
niae
Increased dyspnea

Amoxicillin
Sulfamethoxazone
Doxycycline
Trimethoprim/
sulphamethoxazole
Second- or third-generation cephalosporins
Extended spectrum
macrolides

Beta-lactam/
beta-lactamase inhibitor
Fluoroquinolone

Same as above, plus at

least one of the following:
FEV1* less than 50% predicted
More than four exacerbations per year
Ischemic heart disease
Use of home oxygen
Chronic oral steroid use
Antibiotic use in the past
3 months

Antibiotics from above

combined with oral
steroids may suffice. If not,
consider one of the following:
Beta-lactam/beta-lactamase inhibitor
Fluoroquinolone

May require parenteral

therapy

Same as above, plus the

following:
Klebsiella spp
Gram-negative spp
Increased probability of
beta-lactam resistance

Consider referral to a specialist or hospital

*FEV1: Forced expiratory volume in 1 second

airflow obstruction. There is no evidence of a difference between classes

of short-acting 2 agonists (SABAs)
in terms of bronchodilatation. Combining SABAs with anticholinergics
remains controversial.20 However, it is
recommended that anticholinergics be
added to a patients therapy if a prompt
response to SABAs does not occur.17
Bronchodilator therapy can be delivered with a handheld metered-dose
inhaler or a nebulizer, as there ap pears to be no difference in changes
achieved in FEV1 whether one or the
other is used.21
Systemic corticosteroids. There
is very good evidence that systemic
corticosteroids shorten recovery time
from an acute exacerbation of COPD
and improve lung function in terms of
FEV1 and hypoxemia (PaO2). This
group of drugs also reduces the risk of
early relapse, treatment failure, and
length of hospital stay.2,22,23 Studies
have not found corticosteroids to
cause a significant reduction in rates of
hospitalization when compared with

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placebo22 or to significantly reduce

risk of readmission.23 However, it is
unclear if the studies in question had
the power to determine this. Systemic
corticosteroid therapy should be considered in addition to bronchodilator
therapy if the patients baseline FEV1
is less than 50% of predicted. A dose
of 30 to 40 mg of prednisone per day
for 7 to 10 days is recommended.17
Antibiotics. Whereas prophylactic, continuous use of antibiotics has
been shown to have no effect on the
frequency of exacerbations in COPD,
antibiotic use in the management of
an acute exacerbation has been shown
to reduce short-term mortality and
treatment failure rates, mainly in those
with moderate to severe COPD exacerbation.24,25 The Canadian guidelines
for management of AECOPD recommend antibiotics for patients with
types I and II exacerbations as determined by the Anthonisen criteria, but
not for those with type III.26 Those
requiring antibiotics can be divided
into two groups based on the presence

of risk factors that either increase

the likelihood of treatment failure
or have an association with more virulent or resistant bacterial pathogens
( Table 3 ).2
Noninvasive positive pressure
ventilation. Noninvasive positive
pressure ventilation (NIPPV) should
be considered in patients presenting
with moderate to severe exacerbation of COPD ( Table 4 ). It should
be administered in a setting that
allows close cardiopulmonary monitoring. Patients with milder exacerbations do not benefit from NIPPV, and
there is no evidence that supports the
use of NIPPV for stable COPD
patients with chronic hypercapnia.2
NIPPV used as an adjunct to standard
medical care improves alveolar ventilation, decreases the need for
endotracheal intubation, reduces
treatment failure, and reduces mortality. It also shortens the length of hospital stay by more than 3 days and
decreases complications associated
with treatment. Last but not least,

Acute exacerbation of chronic obstructive pulmonary disease

Table 4. Indications and relative contraindications for noninvasive ventilation.

Indications for NIPPV

Relative contraindications for NIPPV

Moderate to severe dyspnea with use of

accessory muscles and paradoxical
abdominal motion

Respiratory arrest

Moderate to severe acidosis (pH 7.35)

and/or hypercapnia (PaCO2 > 6.0 kPa,
45 mm Hg)
Respiratory frequency > 25 breaths per
minute

Cardiovascular instability (hypotension,

arrhythmias, myocardial infarction)
Impaired mental status
High aspiration risk
Viscous or copious secretions
Recent facial or gastroesophageal surgery
Craniofacial trauma

Prevention
Preventive strategies are of paramount
importance in managing COPD
patients with acute exacerbations,
given the costs and the consequences
of these events. Smoking cessation,
appropriate use of maintenance medication, pulmonary rehabilitation, and
immunizations all have important
roles to play (see Part 1 of this theme
issue).

Conclusions
Acute exacerbations of COPD are a
significant cause of morbidity and
mortality. They should be treated with
bronchodilators as well as oral corti-

Inability of patient to tolerate NIPPV or

NIPPV failure
Severe dyspnea with use of accessory
muscles and paradoxical abdominal
motion
Respiratory frequency > 35 breaths
per minute
Life-threatening hypoxemia

Fixed nasopharyngeal abnormalities

Severe acidosis (pH > 7.25) and/or

hypercapnia (PaCO2 > 8.0 kPa, 60 mm Hg)

Burns

Respiratory arrest

Extreme obesity

Somnolence, impaired mental status

Source: Adapted from Global Strategy for the Diagnosis, Management, and Prevention of Chronic
Obstructive Pulmonary Disease17

NIPPV is cost-effective compared

with usual therapeutic care alone.27
Invasive mechanical ventilation.
This modality is reserved for those
with life-threatening episodes of
AECOPD ( Table 5 ). The survival is
relatively good, with mortality ranging between 11% and 49%.9,28,29 A
number of factors need to be considered before using invasive ventilation,
such as the likely reversibility of the
precipitating event, the patients wishes, and the availability of intensive
care facilities.

Table 5. Indications for invasive

mechanical ventilation.

costeroids. If the patient has acute

bronchitis, antibiotic therapy should
be considered. The clinician should
also take the opportunity to discuss
prevention strategies, to reassess
maintenance treatment, and to consider long-term prognosis and potential end-of-life management issues.
Competing interests
Dr FitzGerald has received honoraria for
consulting and providing continuing medical education as well as being an investigator on research projects which have been
funded by research grants provided to the
University of British Columbia from pharmaceutical companies who manufacture
therapies for use in chronic obstructive lung
disease.
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