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Case Study 42: Managing COPD Exacerbations: Results
Case Study 42: Managing COPD Exacerbations: Results
June 2006
Inside
Case study 42: Managing COPD exacerbations
Scenario and questions
page 3
Summary of results
page 5
Results in detail
page 6
Commentaries
Dr Julia Walters
page 14
page 16
Appendix
page 18
References
page 19
The information contained in this material is derived from a critical analysis of a wide range of authoritative evidence.
Any treatment decision based on this information should be made in the context of the clinical circumstances of each patient.
Case study 42
Managing COPD exacerbations
Scenario
Cedric, a 50-year-old man, was diagnosed with COPD 5 years ago. He presents with worsening
dyspnoea, cough and increasing purulent sputum production over the past 3 days. On examination,
BP is 130/84 mmHg, pulse 102, respiratory rate 18 and temperature 37.8 C. Auscultation of the
chest reveals widespread expiratory wheeze and inspiratory coarse crackles in the left lung base.
He is dyspnoeic but able to speak in whole sentences. No cyanosis is present.
Last spirometry results (8 months ago, after his last COPD exacerbation) were: post-bronchodilator
FEV1 55% predicted and FEV1/FVC ratio 65%. Cedric previously smoked 25 cigarettes per day
(for 30 years) but cut down to 10 cigarettes per day after his first COPD exacerbation 2 years ago.
He has attempted to quit smoking on several occasions without any success.
Cedrics regular medications for COPD are tiotropium (Spiriva) 18 micrograms once daily and
salbutamol (Airomir, Asmol, Ventolin) metered-dose inhaler 200 micrograms every 46 hours when
required. He is also taking indapamide (Dapa-Tabs, Natrilix) 2.5 mg and atorvastatin (Lipitor) 10 mg
(both in the morning) for hypertension and hypercholesterolaemia, respectively. He has no other
medical conditions, and has no known allergies.
Cease
Continue without change
Change to:
o Dose o
o Route o
o Frequency o
__________________________________________________________________________
salbutamol
Cease
Continue without change
Change to:
o Dose o
o Route o
o Frequency o
________________________________________________________________________
any other medications for this exacerbation: (please specify)
ooooooDrugoooooo
o Dose o
o Route o
o Frequency o
o Duration o
i. _________________________________________________________________________________
ii. _________________________________________________________________________________
iii. _________________________________________________________________________________
iv. _________________________________________________________________________________
Please give reasons why you did OR did not prescribe an antibiotic:
___________________________________________________________________________________
___________________________________________________________________________________
2. What would you prescribe for stable COPD management after this exacerbation?
ooooooDrugoooooo
o Dose o
o Route o
o Frequency o
o Duration o
i. __________________________________________________________________________________
ii. __________________________________________________________________________________
iii. _________________________________________________________________________________
iv. _________________________________________________________________________________
3. What else (if anything) would you include in the management plan?
During this exacerbation: ______________________________________________________________
In stable disease: _____________________________________________________________________
4. What strategies would you implement to help him quit smoking?
i. __________________________________________________________________________________
ii. __________________________________________________________________________________
iii. _________________________________________________________________________________
Summary of results
At the time of publication, 1219 responses had been received from doctors and other health
professionals. Responses from 200* general practitioners have been compiled for feedback.
Case synopsis
A patient with COPD presents with worsening dyspnoea, cough and increasing purulent sputum
production over the past 3 days. His current medications for COPD are tiotropium and salbutamol.
(See page 3 for more details.)
Drug therapy
Acute exacerbation
98.5% of participants would continue tiotropium.
98.5% would continue salbutamol but 71.5% would change the method of delivery from metereddose inhaler (MDI) to MDI with spacer or nebuliser, and/or increase the dosage.
80% would prescribe an oral steroid, most commonly prednisolone or prednisone 50 mg daily for 12
weeks.
98% would prescribe one or more antibiotics, mostly amoxycillin (69.9%) or doxycyline (14.8%), and
usually for 12 weeks.
Stable disease (n = 121)
98.3% and 70.2% would continue prescribing tiotropium and salbutamol, respectively.
46.3% would add a long-acting beta2 agonist, either as a single product (15.7%) or in combination
with an inhaled corticosteroid (30.6%). When prescribed as a single-ingredient product, about half
would review the medication after 48 weeks, but when prescribed as a combination product, most
would continue it indefinitely.
50.4% added an inhaled corticosteroid, either as a single product (19.8%) or in combination with a
long-acting beta2 agonist (30.6%). When prescribed as a single-ingredient product, most would review
the medication after 48 weeks, but when prescribed as a combination product, most would continue
it indefinitely.
Results in detail
Drug therapy for COPD exacerbation
Bronchodilator
98.5% of participants would continue tiotropium.
2% would also prescribe ipratropium in one case, instead of tiotropium.
98.5% would continue salbutamol but 71.5% would change the method of delivery (originally MDI)
and/or increase the dosage (originally 200 micrograms every 46 hours when required):
34% recommended using the MDI via a spacer, 9% with a nebuliser, and 3.5% with either
28.5% increased the dose (up to 400 micrograms without a spacer, 1200 micrograms with a
spacer, or 5 mg through a nebuliser) and 69.5% increased the frequency (up to every 12 hours)
2% would also prescribe salmeterol (in addition to salbutamol).
Oral steroid
80% would prescribe an oral steroid (prednisolone or prednisone in all cases except one).
The most commonly prescribed dose was 50 mg daily (range 1075 mg) mainly for 12 weeks
(range 3 days unspecified); 16.5% advocated a dosage reduction schedule.
Inhaled corticosteroid
4.5% would prescribe an inhaled corticosteroid (1.5% in conjunction with an oral steroid).
6.5% would prescribe combined inhaled corticosteroid plus a long-acting beta2 agonist
(3.5% in conjunction with an oral steroid).
Antibiotic
98% would prescribe one or more antibiotics, mainly for about 12 weeks (Table 1).
Most respondents based their decision to prescribe an antibiotic on the presence of one or more of the
following signs and symptoms: fever (62.5%), increased sputum purulence (59.5%), local lung signs
(39%), increased dyspnoea (20%), increased sputum volume (13%), increased cough (7%),
tachycardia (6.5%), increased respiratory rate (1.0%), and tachypnoea (1.0%).
As recommended in the COPD-X guidelines,1 26% of respondents listed increased sputum purulence
plus increased sputum volume and/or increased dyspnoea as the reason for prescribing an antibiotic.
Other reasons for prescribing an antibiotic included a presentation consistent with acute infective
exacerbation of COPD, suspected pneumonia, and to prevent hospitalisation.
Other medications
Other medications prescribed during the exacerbation included senega and ammonia mixture APF (1%)
and theophylline (0.5%).
Table 1.
Antibiotic therapy during exacerbation
Amoxycillin
500 mg every 8 hours
1000 mg every 12 hours
Other (e.g. 250 mg every 8 hours, 500 mg every 6 hours)
Doxycycline
100 mg once daily (in some cases 200 mg on the first day)
100 mg twice daily
50 mg once daily
Amoxycillin / clavulanic acid
875/125 mg twice daily
Other (500/125 mg twice daily or not specified)
Amoxycillin and roxithromycin
Roxithromycin (150 mg twice daily or 300 mg once daily)
Cephalexin (250 mg every 6 hours or 500 mg every 8 hours)
Procaine penicillin and amoxycillin
Procaine penicillin, amoxycillin and roxithromycin
% of
respondents
(n = 196)
69.9
55.1
10.2
4.6
14.8
13.3
1.0
0.5
8.7
6.1
2.6
2.6
2.0
1.0
0.5
0.5
Practice points
During acute exacerbations of COPD, increase the use of short-acting bronchodilators.
An MDI with a spacer is as effective as a nebuliser if an adequate dose is taken, and is cheaper and
more portable.1, 2 Nebulisers should be reserved for patients who are unable to use MDIs (with or
without spacer).2 The dose via a spacer that is considered equivalent to a 5 mg salbutamol nebule
varies from 815 puffs of a 100 microgram salbutamol MDI.1,3
Consider oral prednisolone 3050 mg daily for 714 days (short courses less than 14 days do not
usually require tapering).1,2,4
Consider antibiotic therapy if increased sputum purulence is present with increased sputum volume and/or
dyspnoea.1 The goal of therapy is to reduce volume and purulence of sputum; elimination of colonising
organisms is not required.2 The presence of fever is not necessarily indicative of a bacterial infection.2
Amoxycillin (500 mg every 8 hours for 5 days) or doxycycline (100 mg twice daily for 5 days) is
recommended as first-line therapy;2 other antibiotics have not been shown to be superior and are not
recommended unless patients do not respond, or resistant organisms are suspected.1,2
Amoxycillin 1000 mg twice daily is currently not recommended by Therapeutic Guidelines for
acute exacerbations of COPD.2
In a study of 395 patients with acute exacerbation of chronic bronchitis, amoxycillin 1000 mg
twice daily offered no additional benefits (in efficacy or safety) compared with amoxycillin 500 mg
every 8 hours.5 When compared with the current guidelines for antibiotic therapy in COPD
exacerbations, the study also used a longer duration of therapy and placed less emphasis on
increased sputum purulence as one of the criteria for antibiotic therapy.
If pneumonia is suspected, investigate and treat as for community-acquired pneumonia:
assessment should include history and examination, chest X-ray, measurement of arterial blood
oxygen saturation, investigations for the causal pathogen, and Pneumonia Severity Index class.2
Table 2.
% of
respondents
(n = 121*)
28.1
22.3
12.4
11.6
Tiotropium only
7.4
5.8
5.8
3.3
Miscellaneous
3.3
* Only responses that were clear about whether or not tiotropium and salbutamol were to be continued have been included in the
analysis.
Bronchodilator (n = 121)
98.3% and 70.2% of respondents stated that they would continue tiotropium and salbutamol,
respectively.
32.2% and 14.1% would add salmeterol and eformoterol, respectively. Long-acting beta2 agonists
were prescribed either on their own (15.7%) or in a combination product (30.6%). When prescribed as
a single-ingredient product, about half would review the medication after 48 weeks, but when
prescribed as a combination product, most would continue it indefinitely.
Other bronchodilators that were prescribed were ipratropium (1.7%) and terbutaline (0.8%).
Practice points
To date, the use of long-acting beta2 agonists in conjunction with tiotropium has not been investigated
in clinical trials.2 However, these drugs work by different mechanisms, and several guidelines advocate
combined bronchodilator therapy for patients who remain symptomatic on monotherapy.1,4,6
Long-acting beta2 agonists should be stopped and reassessed if there are no changes in
symptoms, ability to perform daily activities or exercise capacity after 4 weeks.2,6
Inhaled corticosteroid should be considered in patients who have documented evidence of
responsiveness to inhaled corticosteroids, or who have moderate or severe COPD (FEV1 50%
predicted) and have 2 or more exacerbations requiring treatment with antibiotics or oral corticosteroids
in a 12-month period.1,2,6
Recommended trial periods for inhaled corticosteroids vary from 6 weeks up to 6 months
(depending on the guideline).1,2,7 However, a longer trial may be necessary to assess an impact on
exacerbation rates.
There are conflicting findings regarding the efficacy of combined inhaled corticosteroid plus longacting beta2 agonist in a single inhaler, compared with inhaled corticosteroid or long-acting beta2
agonist alone in COPD.8
The option of using either long-acting beta2 agonist or inhaled corticosteroid alone should be
considered first before considering adding both medications to the existing regimen.
While combination products may be more convenient for the patient, when indicated, an initial
trial of inhaled corticosteroid and long-acting beta2 agonist in separate inhalers may allow better
assessment of the benefits offered by each medication.
Table 3.
% of
respondents*
(n = 181)
49.7
18.8
Follow-up
14.4
In 24 hours
8.8
In 48 hours
1.7
Not specified
3.9
14.3
6.6
Consider other medications (e.g. paracetamol, oral theophylline, mucolytics, long-acting beta2
agonist)
7.7
9.9
7.7
6.1
4.4
3.3
3.3
Miscellaneous (e.g. consider oxygen therapy, action plan, regular peak flow measurements)
20.4
10
Table 4.
% of
respondents*
(n = 180)
61.1
16.7
14.4
13.3
12.8
Recommend exercise
8.9
7.2
6.7
Assess compliance
3.3
Miscellaneous (e.g. advise the patient to use a peak flow meter, conduct regular reviews,
consider referral to a respiratory physician)
16.7
Practice points
Pulmonary rehabilitation is considered one of the most effective interventions in COPD and has been
shown to improve symptoms and functioning of patients with COPD.1 It should be offered to patients
with moderate to severe COPD who are sufficiently motivated and do not have severe co-morbidities
which preclude active participation in the program.2 Comprehensive programs encompassing exercise
training, patient education and psychosocial support have been shown to have the greatest benefit.1
Annual influenza vaccination is recommended to reduce the incidence of acute exacerbations of
COPD.1,6
Pneumococcal vaccination is also recommended.1,2 The current schedule for pneumococcal vaccination
is as follows:9
non-Indigenous adults 65 years, or Aboriginal and Torres Strait Islander adults 50 years: one
dose followed by a single revaccination 5 years later
non-Indigenous adults < 65 years with risk factors (includes pulmonary disease): one dose
followed by a single revaccination at 65 years of age or 10 years after the first dose, whichever
is later
Aboriginal and Torres Strait Islander adults 1549 years of age with risk factors (includes
pulmonary disease): revaccination 5 years after the first dose, then again at 50 years of age or
10 years after the first revaccination, whichever comes later.
Demonstration and repetition are essential for achieving optimal patient inhaler technique.2 Inhaler
technique should be checked regularly to ensure that patients are using their inhalers correctly1,2 and
compliance should be assessed.
Patients should be encouraged to take appropriate responsibility in managing their own condition.1
A COPD action plan may be helpful and is recommended.1,2 It may include medications for stable
and acute management, and instructions on how to identify and respond to an acute
exacerbation. You can download a template from the Australian Lung Foundation at
www.lungnet.com.au/copd/copd_action_plan.html.
Patients at risk of COPD exacerbations should keep a course of antibiotic and corticosteroid tablets
at home for use as part of self-management.2
11
Strategies
Non-pharmacological strategies
Brief counselling and/or encouragement
Refer to Quitline or other resources by the national tobacco campaign
Support, follow-up and/or review (at consultations or by telephone)
Discuss benefits of smoking cessation and/or risks of continuing to smoke
Assess readiness to change
Provide education or written material
Behavioural therapy
Intensive counseling
Use 5As (Ask, Advise, Assess, Assist, Arrange) strategy
Discuss previous attempts (e.g. what was tried, what did not work)
Refer to a smoking-cessation specialist
Miscellaneous (e.g. hypnotherapy, exercise program, local smoking-cessation program, referral
to a psychologist, setting a quit date)
56.8
44.7
30.7
12.1
5.5
5.5
4.5
4.0
4.0
2.5
2.5
19.1
Pharmacological therapies
Discuss and advise about available drug therapy options
Nicotine replacement therapy (NRT)
Bupropion
Bupropion (and intensive counselling)
Bupropion if NRT unsuccessful
24.1
52.3
27.6
6.5
Practice points
Smoking cessation is the single most important intervention to prevent or slow the progression of
COPD.1,4,10
Brief counselling (35 minutes) by a health professional has been shown to be effective4,11 and every
smoker should be offered at least this intervention at every visit.1,4 When aware of patients previous
attempts, it may be helpful to first discuss what worked or did not work in previous attempts.
Bupropion (in conjunction with counselling and support) or nicotine replacement therapy (NRT) doubles
the rate of smoking cessation compared with placebo.11,12 There are insufficient data to recommend
bupropion in preference to NRT, and vice versa.1,13
The effectiveness of bupropion has only been studied in conjunction with intensive counselling and
support program. Examples of such programs from randomised controlled trials with bupropion include
a combination of:14,15
brief intervention by a trained health professional
weekly assessment (15 minutes individual counseling session looking at motivation, identification
of triggers, coping responses, weight management and use of medications)
follow-up assessments and relapse prevention strategies
supported telephone call (e.g. 8 telephone calls of approximately 10 minutes duration for
5 months).
12
The different forms of NRT have similar effectiveness,11,12 and choice should be based on patient
preference, need and tolerance.1
Other interventions that have been shown to work include:11
intensive (> 10 minutes) counselling by a health professional
telephone counselling services
group behavioural therapy
follow-up visits to a GP
repeated telephone support by nurses after initial intervention.
13
Dr Julia Walters
Research Fellow, Discipline of Medicine
University of Tasmania
Hobart, Tasmania
Commentary 1
Key points
Medication
Cedric has now had two exacerbations within
one year and is at higher risk of more rapid
decline in lung function. He should be given a
trial of therapy with inhaled corticosteroids. His
response can be assessed by symptoms and
FEV1, although for assessment on exacerbation
rate the length of treatment needs to be
prolonged. Inhaled corticosteroids were given by
50.4% of respondents, with most reviewing
efficacy after 48 weeks. Combination products
with long-acting beta2 agonists were used by
30.6%. Use of these products in stable COPD
has preceded full consideration of their efficacy.
A Cochrane systematic review8 concluded that,
although they led to clinically meaningful
differences in quality of life, symptoms and rate
of exacerbations compared with placebo, there
were conflicting results when the different
combination therapies were compared with
either inhaled corticosteroids alone or longacting beta2 agonists alone. More data are
necessary to draw firmer conclusions about the
effects of combination therapy in a single
inhaler, and their use is not currently
recommended by guidelines.
Smoking cessation
Advice to stop smoking was the most frequent
additional management activity undertaken
during the exacerbation (49.7% of
respondents). This is important because Cedric
still smokes even 5 years after having the
diagnosis of COPD, but it was an opportunity
missed by more than half the respondents. Even
brief advice to stop smoking is valuable and
effective23 and is emphasised in all guidelines.
Only 61.1% included smoking cessation in
measures to manage Cedrics COPD when he
was stable. This should be the highest priority
for treatment, as stopping smoking is the most
effective intervention to slow progression.
Cedric has made previous efforts so far
unsuccessful in achieving sustained
abstinence and is likely to need pharmacological
therapy in addition to the counselling and
encouragement offered by 56.8% of
respondents, as this increases his chances of
success. Both bupropion and nicotinereplacement therapy double the rates of
cessation compared with placebo; 51.3%
proposed using nicotine-replacement therapy
and 24.6% bupropion to assist Cedric.
Preventing deterioration
Ensuring that influenza and pneumococcal
vaccination were up to date was noted by
12.8% of respondents. Measures to develop a
support network and self-management plan
were addressed by some respondents:
recommending respiratory rehabilitation
(13.3%), recommending exercise (8.9%) and
preparing an action plan (6.7%). As well as
enhancing physical fitness and quality of life,
respiratory rehabilitation aims to foster selfmanagement and emotional coping skills.
Completing respiratory rehabilitation and/or
having an action plan leads to better recognition
of deterioration and more appropriate treatment
of exacerbations24,25 but many patients with
COPD who would benefit do not have the
opportunity, through lack of referral or
availability.26 Access will hopefully be improved
with the launch of a toolkit this year by the
Australian Lung Foundation and Australian
Physiotherapy Association to assist health
professionals in developing programs more
widely throughout Australia.27
15
Commentary 2
Key points
16
17
Appendix
Inhaled medications used in COPD
Strength
Generic name
Device
Brand names
Bronchodilators
Short-acting beta2 agonists
Salbutamol
Autohaler
Airomir Autohaler
100
MDI
100
Nebuliser
2.5mg/2.5mL, 5mg/2.5mL
Rotahaler
Ventolin Rotacaps
200
Nebuliser
Bricanyl Respules
5mg/2mL
Turbuhaler
Bricanyl Turbuhaler
500
Aeroliser
Foradile
12
Turbuhaler
Oxis Turbuhaler
6, 12
Accuhaler
Serevent Accuhaler
50
MDI
Serevent
25
MDI
Atrovent CFC-Free
21
Nebuliser
250/mL, 500/mL
Handihaler
Spiriva
18
MDI
Combivent
100/20
Autohaler
Qvar Autohaler
50, 100
MDI
Qvar
50, 100
Nebuliser
Pulmicort Respules
500/2mL,1000/2mL
Turbuhaler
Pulmicort Turbuhaler
Ciclesonide
MDI
Alvesco
80, 160
Fluticasone
Accuhaler
Flixotide Accuhaler
MDI
Flixotide
Terbutaline
Anticholinergic bronchodilators
Ipratropium
Tiotropium
Combination bronchodilator
Salbutamol/ipratropium
Corticosteroids
Beclomethasone
Budesonide
Turbuhaler
Symbicort Turbuhaler
Accuhaler
Seretide Accuhaler
MDI
Seretide
* Long-acting beta2 agonists are approved by the Therapeutic Goods Administration for COPD (except for Oxis Turbuhaler) but are not
subsidised on the PBS for COPD
Combination bronchodilator is only subsidised for COPD under the Repatriation PBS
Inhaled corticosteroids and combination corticosteroid / long-acting beta2 agonists are not approved by the Therapeutic Goods
Administration for COPD (except for Seretide) and are not subsidised on the PBS for COPD
MDI = metered-dose inhaler
18
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