PREVENTING
COPD
EXACERBATIONS
Christopher Worsnop
Department of Respiratory and Sleep Medicine
Austin Hospital
Melbourne, Australia
COPD DEFINITION
• Progressive airflow obstruction that is
not fully reversible.
• Most COPD is due to cigarette smoking
Saetta et al AJRCCM 2001; 163: 1304
Hogg et al NEJM 2004; 350: 2645
Lancet 2009; 374: 733-743
BURDEN OF COPD IN NEW ZEALAND
• 7,716 people with COPD hospitalised in
2011/12.
• An average of 1.5 times per person.
• 30 day readmission rate of 17.9%.
• Average length stay of 4.2 days.
• Average cost per hospitalised patient was
about $7,700.
• COPD contributed to $54 million in
hospitalisation
costs
(20.3%
of
total
respiratory hospitalisation costs).
National Health Committee report, New Zealand, December 2013.
Global Strategy for Diagnosis, Management and Prevention of COPD
Assess Risk of Exacerbations
To assess risk of exacerbations use history of
exacerbations and spirometry:
 Two or more exacerbations within the last
year or an FEV1 < 50 % of predicted value are
indicators of high risk.
 One or more hospitalizations for COPD
exacerbation should be considered high risk.
© 2014 Global Initiative for Chronic Obstructive Lung Disease
GOLD STAGE
based on FEV1
2
1
A
D
>2
B
1
0
RISK
RISK
3
C
Exacerbations per year
4
SYMPTOMS
mMRC 0-1
CAT < 10
mMRC 2-4
CAT > 10
www.goldcopd.com
ACUTE COPD EXACERBATION
• The cause is often unknown
• Respiratory infections –bacterial, viral,
- URTI, bronchitis, pneumonia
• Heart failure, arrhythmia
• Systemic infection, fever
• Anaemia
• Anxiety
• Anything that increases metabolic rate
ERJ 2007; 29: 1224
COPD exacerbations
• 30 % bacterial, 23 % viral, 25 % both, 22 %
other
ERJ 2007; 29: 1224.
• Various studies show a wide range of
organisms, but few atypical bacteria
(Legionella, Chlamydia, Mycoplasma).
• Antibiotics recommended if type I
Anthonisen, or type II with purulent sputum, or
NIV.
CLASSIFICATION OF COPD EXACERBATION
• A = AIRWAY VIRAL INFECTION
• B = BACTERIAL INFECTION (including pneumonia)
• C = CO-INFECTION D = DEPRESSION/ANXIETY
• E = EMBOLISM (pulmonary)
• F = FAILURE (cardiac or lung integrity)
• G = GENERAL ENVIRONMENT
• X = NO SPECIFIC CAUSE IDENTIFIED
Martin MacDonald et al Respirology 2011; 16: 264
Features of a COPD exacerbation
• Anthonisen criteria:
- increased dyspnoea
- increased sputum production
- sputum becoming discoloured
• Antibiotics to cover Strep and Gram
negatives have been shown to be useful if all
three criteria are present.
• CXR to look for pneumonia, and cover
atypical bacteria if there is pneumonia.
COPD exacerbations
• Past exacerbations predict future ones.
ECLIPSE NEJM 2010; 363: 1128
• Patients under report exacerbations
AJRCCM 2008; 177: 396. Chest 2008; 133: 34.
ERJ 2010; 35: 1022.
Death after a COPD exacerbation
• 40 % mortality in the 12 months after a
hospital admission for a COPD exacerbation.
AJRCCM 1996; 154: 959
• Predictors of mortality:
older age, lung cancer, BMI < 20, CV disease,
past hospital admissions,
needing supplemental O2 on discharge,
use of accessory muscles. ERJ 2013: 42; 946.
MANAGEMENT OF COPD
• STOP SMOKING
• MEDICATIONS
• VACCINATIONS
• REGULER EXERCISE (pulmonary
rehabilitation)
STOP SMOKING
Smoking cessation in Lung Health
Study
• 72 ml fall over 2 years in those who
ceased smoking
• 300 ml over 2 years in those who
kept smoking.
JAMA 1994; 272: 1497
Current medical management of
COPD in New Zealand
• LONG ACTING BETA AGONIST (LABA)
– Salmeterol (Serevent) is indicated for longlasting (12 hour) bronchodilation in adults
with reversible airways obstruction due to
COPD.
– Should not be used in asthma without ICS.
• LONG ACTING MUSCARINIC ANTAGONIST
(LAMA)
– Tiotropium (Spiriva) is indicated for the
long term once daily maintenance
treatment of bronchospasm and dyspnoea
associated with COPD, including chronic
bronchitis and emphysema.
– Special Authority Criteria
TIME TO FIRST
EXACERBATION
p = 0.028
TIME TO FIRST
HOSPITALISATION
p = 0.055
Ann Intern Med 2005; 143:
317 - 326.
Spiriva
Placebo
p
27.9 %
32.3 %
0.036
Hospitalization 7.0 %
9.5 %
0.056
No. of exacerbations
0.85
per patient per year
Exacerbation days
12.6
Antibiotic days
8.1
Oral steroid days
6.3
No. of hospitalizations 0.18
per patient per year
Hospitalization days
1.4
1.05
0.033
16.0
9.8
7.4
0.25
0.019
0.0153
0.25
0.047
1.7
0.054
Exacerbation
Ann Intern Med 2005; 143: 317 - 326.
Spiriva
p < 0.008
Atrovent
Spiriva
p < 0.048
Atrovent
Eur Respir J 2002; 19: 209.
ICS/LABA
Fluticasone / salmeterol (Seretide) is
indicated for the symptomatic treatment of
patients with moderate to severe COPD (prebronchodilator FEV1<60% predicted normal),
who have significant symptoms despite
bronchodilator therapy.
Effects of ICS/LABA combination therapy on
inflammatory markers
Percentage change from baseline for lung biopsy
endpoints: median treatment differences
Study population: 140 current and past smokers with moderate to severe COPD
Reducing exacerbations with ICS/LABA in
severe COPD
Kardos et al 2007
Seretide reduces the rate of exacerbations
requiring systemic corticosteroids over 3 years
(TORCH)
Exacerbation rate
1.15
43% (p<0.001)
0.95
0.75
0.80
0.55
0.64
0.35
0.52
0.46
0.15
-0.05
placebo
SFC vs placebo
SFC vs sal
SFC vs FP
Sal
FP
SFC
Treatment effect
43%
29%
13%
Calverley PMA et al New Eng J Med 2007; 356: 775-789
p-value
<0.001
<0.001
0.02
TORCH: different stages of COPD
Adapted from Jenkins C, et al. Respiratory Research 2009; 10: 59.
Budesonide / eformoterol (Symbicort) is
indicated in the regular treatment of adult
patients with moderate to severe COPD [FEV1
≤50% of predicted normal], with frequent
symptoms despite beta2-agonist use and a
history of exacerbations.
SYMBICORT should not be used for the
initiation of bronchodilator therapy in COPD
BUD/FORM vs. each components or placebo
20
15
Percentage (%)
10
5
NS
0
*
-5
BUD/FORM
vs Placebo
BUD/FORM
vs BUD
BUD/FORM
vs FORM
NS
*
BUD vs
Placebo
FORM vs
Placebo
-10
-15
*
NS
-20
-25
*
NS = Not
Significant
NS
Reduction in severe exacerbations
Increase in FEV1
-30
Adapted from Szafranski W, et al. Eur Respir J 2003; 21: 74-81.
Symbicort plus Spiriva versus placebo plus
Spiriva
Number of severe
exacerbations
decreased by 62%
Adapted from Welte T, et al. AJRCCM 2009; 180: 741.
Pneumonia and ICS in COPD
• Double the pneumonia risk with
fluticasone (9 % vs 5% over 2 years), but
no increase in mortality.
• No difference in de novo pneumonia.
• The difference is only seen in those with
worsening COPD prior to the pneumonia.
Calverley et al INSPIRE study CHEST 2011; 139:505.
Not seen with Symbicort Turbuhaler, but seen
with the Rapihaler. Sharafkhaneh A, et al. Respir Med
2012;106:257–68.
Newly COPD drugs in New Zealand
(but not yet reimbursed)
• BREO ELLIPTA (ICS/LABA)
– Fluticasone fuorate/Vilanterol
Symptomatic treatment of patients with COPD
with FEV1 < 70 % and past exacerbations.
• ANORO ELLIPTA (LABA/LAMA)
Umeclidinium/Vilanterol
Once daily bronchodilator to relieve symptoms
in COPD patients.
PULMONARY REHABILITATION
PULMONARY REHABILITATION
•There is good evidence that it improves
symptoms in COPD reduces hospitalizations and
length of stay.
• Patients need to be well motivated.
• Two main components - improving fitness, and
education.
• A course is run over 6 - 8 weeks with twice
weekly visits.
• The exercise needs to be maintained at home.
Cochrane database 2006; Lancet 1996; 348: 1115.
VACCINES
• Influenza vaccine - reduces mortality,
hospital admissions and exacerbations.
- it does not prevent other URTI viruses.
- local side effects only.
- it is given yearly.
NEJM 1994; 331: 778
• Pneumococcal vaccine - Little evidence
about its use in COPD, but it seems like a
good idea.
- older than 65
NEJM 2003; 348: 1747
- less than 65 with major comorbidity
- less than 65 and FEV1 < 40 % 276
- it is given twice 5 years apart in COPD.
MANAGEMENT OF COPD
• STOP SMOKING
• MEDICATIONS
• VACCINATIONS
• REGULER EXERCISE (pulmonary
rehabilitation)