5. 5
Definition of Acute COPD Exacerbation
An exacerbation of chronic obstructive pulmonary disease
(COPD) is an acute increase in symptoms beyond normal
day-to-day variation.
This generally includes an acute increase in one or more of
the following cardinal symptoms:
1. Cough increases in frequency and severity
2. Sputum production increases in volume and/or
changes character (more purulent)
3. Dyspnea increases
16. Children’s Healthcare of Atlanta
EXACERBATION FREQUENCY IS A
SUSCEPTIBILITY PHENOTYPE
Susceptible
Patient
Non-Susceptible
Patient
Sufficient Trigger
EXACERBATION
Those reporting two or more exacerbations of COPD per year are often defined
as “frequent exacerbators,” a phenotype that appears stable over time.
17. 17
7
18
33
22
33
47
0
10
20
30
40
50
GOLD II
(N=945)
GOLD III
(N=900)
GOLD IV
(N=293)
%ofpatients
Hospitalised for exacerbation in yr 1 Frequent exacerbations (2 or more)
The ‘frequent exacerbator phenotype’:
Frequency/severity by GOLD Category ECLIPSE 1 year data
Frequent exacerbators (those reporting 2 or more exacerbations per year)
is more common in the very severe GOLD Category
18. Children’s Healthcare of Atlanta
Exacerbation Frequency Worsens with COPD Severity,
but Can Occur at Any GOLD Level
• Exacerbations become more frequent and more severe as the severity
increases
Annual estimated frequencies of exacerbations
0
18
Two-thirds of exacerbations are not reported by patients
• In the ECLIPSE study (2,138 patients) the single best predictor of exacerbations
was a history of exacerbationshistory of exacerbations
29. 29
Bacteria as a Cause of Exacerbation
• Common bacteria:
– Haemophilus influenzae
– Streptococcus pneumoniae
– Moraxella catarrhalis
– Pseudomonas aeruginosa
• Indicators of bacterial infection
– Bronchoscopic sampling in pooled analysis of studies
– Purulent sputum
31. 31
Bronchoscopic studies have shown that at least 50% of
patients have bacteria in their lower airways during
exacerbations of COPD
A significant proportion of these patients also have
bacteria colonizing their lower airways in the stable
phase of the disease.
35. 35
Most Common Infectious Causes of
COPD Exacerbations
Mild to moderate exacerbations
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Chlamydia pneumoniae
Mycoplasma pneumoniae
Viruses
Severe exacerbations
Pseudomonas species
Other gram-negative enteric
bacilli
36. 36
• While the severity of exacerbation is increasing,
infecting microorganism profile shifts from
S.pneumoniae to Gram (-) enteric bacilli &
P.aeruginosa
39. 39
Diagnosis of COPD exacerbations relies exclusively on
the clinical presentation of the patient complaining of
an acute change of symptoms that is beyond normal
day-to-day variation.
40. 40
AECOPD is a clinical diagnosis of exclusion, made
where no alternative specific cause for deterioration has
been identified by clinical examination and/or corroborative
testing,such as:
Pneumonia
Pneumothorax
Pleural effusion
Pulmonary embolism
Congestive heart failure
Arrhythmia
42. 42
Determining Severity of Exacerbation
GOLD’s recommendations are quite subjective
““ Assessment of the severity of an exacerbation is based
on the patients medical history before the exacerbation,
preexisting comorbidities, symptoms, physical
examination, arterial blood gas measurements, and other
laboratory tests.
45. 45
• Sputum culture & sensitivity
– In infectious exacerbation not responding to initial antibiotic
therapy.
– Purulent sputum during an exacerbation: indication to begin
empirical antibiotic treatment.
• Biochemical tests:
– Abnormalities related to associated comorbidities e.g.
electrolytes, blood glucose
• Spirometry not useful in setting of COPD exacerbation
56. 56
Treatment
Goal:
1. Minimize the impact of the current
exacerbation.
2. Prevent the development of subsequent
exacerbations.
Setting:
Depend: severity of an exacerbation & /
severity of underlying disease, an
exacerbation can be managed in an
outpatient or inpatient setting.
57. 57
More than 80% of exacerbations can be managed
on an outpatient basis with pharmacologic
therapies including:
Bronchodilators
Corticosteroids
Antibiotics.
58. 58
At Home Treatment Plan
• ABC plan
-Antibiotic
-Bronchodilators
-Corticosteroid
60. 60
It is important to determine how to treat and
where to treat the patient
-Home, hospital, intensive care unit
-Bronchodilator dosages
-Corticosteroid durations
-Antibiotic choice
-Non-invasive, invasive mechanical ventilation
-Additional treatments (diuretics, cardiac support destek)
71. Children’s Healthcare of Atlanta
Consider appropriate exacerbation prevention strategies
Consideration and management of comorbidities
Adapted from Hurst and Wedzicha. BMC Medicine 2009; 7:40.
Increase in dose/frequency
of inhaled bronchodilators
Systemic corticosteroids
Antibiotics (if change in sputum)
Management of COPD Exacerbations
Patient use of custom action plan
Prevent and treat
respiratory failure
Oxygen
(low concentrations
to prevent
hypercapnia)
Follow-up visit 48-72 hours
Consider BIPAP
74. 74
What Is the Appropriate Use of Antibiotics
In Acute Exacerbations of COPD?
75. 75
While there is well-established evidence for the use of
steroids and bronchodilators in AECOPD, the debate
continues over the appropriate use of antibiotics in
the treatment of acute exacerbations.
76. 76
• The most frequent aetiology of COPD exacerbations is
infection of the lower airways and/or air pollution, even
though the cause of one third of exacerbations is still
ignored.
• Patients with COPD have bacteria in high concentrations
in their lower airways during both exacerbations and
stable conditions (airway colonisation).
77. 77
• There are multiple potential factors leading to
AECOPD, including viruses, bacteria, and
common pollutants; as such, antibiotic treatment
may not be indicated for all patients presenting
with exacerbations.
• Further, the risks of antibiotic treatment—
including adverse drug events, selection for
drug-resistant bacteria, and associated costs—
are not insignificant.
78. 78
• There is evidence supporting the use of
antibiotics in exacerbations when patients have
clinical signs of a bacterial infection, e.g.,
increase in sputum purulence.
• 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.
79. 79
Key Points
• Antibiotics are not recommended as empiric
therapy for all patients with AECOPD, however
when used in patient populations more likely to
have a bacterial etiology.
• Bacterial infections do play a role in
approximately 50% of patients with AECOPD
and, for this population, use of antibiotics may
confer important benefits
80. 80
Indications for Antibiotics
• Studies have suggested that sputum purulence
correlates well with the presence of acute bacterial
infection and therefore may be a reliable clinical
indicator of patients who are likely to benefit from
antibiotic therapy
81. 81
• laboratory data (sputum culture, CRP,
procalcitonin) alone should not be used to guide
initiation of antibiotics.
• Evedinice supports antibiotics for only
moderately or severely ill patients with COPD
exacerbations with increased cough and sputum
purulence.
82. 82
• While sputum purulence is associated with bacterial
infection, sputum culture is less reliable, as
pathogenic bacteria are commonly isolated from
patients with both AECOPD and stable COPD.
• In fact, the prevalence of bacterial colonization in
moderate to severe COPD might be as high as 50%.
• Therefore, a positive bacterial sputum culture, in the
absence of purulence or other signs of infection, is not
recommended as the sole basis for which to prescribe
antibiotics
83. 83
• Severity of illness is an important factor in the
decision to treat AECOPD with antibiotics.
• Patients with advanced, underlying airway
obstruction, as measured by FEV1, are more likely
to have a bacterial cause of AECOPD.
• Additionally, baseline clinical characteristics
including advanced age and comorbid conditions,
particularly cardiovascular disease and diabetes,
increase the risk of severe exacerbations
84. 84
• Specifically, treated patients had lower rates of
in-hospital mortality and readmission for
AECOPD and a lower likelihood of requiring
subsequent mechanical ventilation during the
index hospitalization.
• Data also suggest that antibiotic treatment
during exacerbations might favorably impact
subsequent exacerbations
85. 85
• Using clinical indicators , The Anthonisen
criteria -(dyspnea, sputum purulence, sputum
volume) and severity of illness (advanced
airflow limitation, presence of comorbidities,
need for mechanical ventilation) can help
identify patients who may benefit most from
antibiotics
Indications for Antibiotics
86. 86
Indications for Antibiotics
• Anthonisen and colleagues set forth three clinical
criteria -often referred to as the “cardinal
symptoms” of AECOPD, these include increased
dyspnea, sputum volume, and sputum purulence.
• Patients with Type I exacerbations, characterized
by all three cardinal symptoms, were most likely
to benefit from antibiotic therapy, followed by
patients with Type II exacerbations, in whom only
two of the symptoms were present.
90. 90
• Patients meeting criteria for treatment must
first be stratified according to the severity of
COPD and risk factors for poor outcomes
before a decision regarding a specific antibiotic
is reached.
91. 91
• When antibiotic treatment is indicated, choice of
drug is dependent on distinguishing a simple
case from a complicated case of AECOPD.
• A five-day course of oral antibiotics is
recommended for the treatment of AECOPD.
92. 92
Antibiotic Duration
• The duration of antibiotic therapy in AECOPD
has been studied extensively, with randomized
controlled trials consistently demonstrating no
additional benefit to courses extending beyond
five days.
• Advantages to shorter antibiotic courses include
improved compliance and decreased rates of
resistance.
101. 101
Mild to moderate exacerbations*
• First-line antibiotics
Doxycycline (Vibramycin), 100 mg twice daily
Trimethoprim-sulfamethoxazole (Septrin DS), one
tablet twice daily
• Amoxicillin-clavulanate potassium(Augmentin),
one 500 mg/125 mg tablet three times daily
or one 875 mg/125 mg tablet twice daily
• Macrolides
Clarithromycin (Klacid), 500 mg twice daily
Azithromycin (Zithromax), 500 mg initially,
then 250 mg daily
• Fluoroquinolones
Levofloxacin (Tavanic), 500 mg daily
Gatifloxacin (Tequin), 400 mg daily
Moxifloxacin (Avalox), 400 mg daily
Antibiotics Commonly Used in Patients
with COPD Exacerbations
102. 102
Antibiotics Commonly Used in Patients
with COPD Exacerbations
Moderate to severe exacerbations (Ý)
• Cephalosporins
Ceftriaxone (Rocephin), 1 to 2 g IV daily
Cefotaxime (Claforan), 1 g IV every 8 to 12 hours
Ceftazidime (Fortum), 1 to 2 g IV every 8 to 12 hours
• Antipseudomonal penicillins
Piperacillin-tazobactam (Tazocin), 3.375 g IV every
6 hours
Ticarcillin-clavulanate potassium (Timentin),
3.1 g IV every 4 to 6 hours
• Fluoroquinolones
Levofloxacin(Tavanic), 500 mg IV daily
Gatifloxacin(Tequin), 400 mg IV daily
• Aminoglycoside
Tobramycin (Tobracin), 1 mg per kg IV every 8 to
12 hours, or 5 mg per kg IV daily
103. 103
• The presence of purulent sputum during an
exacerbation can be sufficient indication for starting
empirical antibiotic treatment.
• The recommended length of antibiotic therapy is
usually 5-10 days (Evidence D).
• The choice of the antibiotic should be based on the
local bacterial resistance pattern.
104. 104
• The optimal choice of antibiotics must
consider cost -effectiveness, local patterns of
antibiotic resistance, tissue penetration, patient
adherence, and risk of such adverse drug events
as diarrhea.
105. 105
• The route of administration (oral or intravenous)
depends on the ability of the patient to eat and
the pharmacokinetics of the antibiotic, although
preferably antibiotics are given orally.
• Improvements in dyspnea and sputum
purulence suggest clinical success.
106. 106
• Local sensitivity data should be considered
when choosing an antibiotic.
• In areas where there are high levels of
resistance to the macrolides and doxycycline,
these agents should be avoided.
• Alternatives such as amoxycillin/clavulanate,
cefuroxime, or quinolones may be used
107. 107
• In patients with frequent exacerbations, severe
airflow limitation, and/or exacerbations requiring
mechanical ventilation, cultures from sputum or
other materials from the lung should be
performed, as gram-negative bacteria (e.g.,
Pse udo m o nas spe cie s ) or resistant pathogens
that are not sensitive to the above-mentioned
antibiotics may be present.
108. 108
• One meta-analysis found that second-line
antibiotics, when compared with first-line agents,
provided greater clinical improvement to patients
with AECOPD
• The clinical effectiveness of second-line
agents remained significantly greater than that of
first-line agents.
• Fluoroquinolones are preferred in complicated
cases of AECOPD in which there is a greater risk
109. 109
• If an exacerbation responds poorly to empirical
antibiotic treatment, the patient should be re‐
evaluated for complications with
microbiological reassessment if necessary.
Key message:
Exacerbation frequency worsens with COPD severity; however, the prevalence of exacerbations is underestimated because not all patients report them to their physicians.
Key message:
Management of exacerbationsis based on the implementation/optimization of bronchodilators and corticosteroids, the use of oxygen therapy, treatment of the cause of the exacerbation, and resolution of possible comorbidities
