1. PREVENTING COPD EXACERBATIONS
Christopher Worsnop
Department of Respiratory and Sleep Medicine
Austin Hospital
Melbourne, Australia

4. 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:

5. 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.

6. © 2014 Global Initiative for Chronic Obstructive Lung Disease
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

7. Exacerbations per year4 3 2 1 C D
> 2 1
GOLD STAGE
based on FEV1
RISK
Exacerbations per year
RISK A B
SYMPTOMS
mMRC mMRC 2-4
CAT < CAT > 10

8. 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

9. 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.

10. 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

11. 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.

12. COPD exacerbations Past exacerbations predict future ones.
ECLIPSE NEJM 2010; 363: 1128
Patients under report exacerbations
AJRCCM 2008; 177: Chest 2008; 133: 34.
ERJ 2010; 35: 1022.

13. 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.

14. MANAGEMENT OF COPD STOP SMOKING MEDICATIONS VACCINATIONS
REGULER EXERCISE (pulmonary rehabilitation)

15. STOP SMOKING

16. 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

17. Current medical management of COPD in New Zealand
LONG ACTING BETA AGONIST (LABA)
Salmeterol (Serevent) is indicated for long-lasting (12 hour) bronchodilation in adults with reversible airways obstruction due to COPD.
Should not be used in asthma without ICS.

18. 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

20. TIME TO FIRST EXACERBATION
p = 0.028
TIME TO FIRST
HOSPITALISATION
p = 0.055
Ann Intern Med 2005; 143:

21. Spiriva Placebo p Exacerbation 27.9 % 32.3 % 0.036
Hospitalization 7.0 % %
No. of exacerbations
per patient per year
Exacerbation days
Antibiotic days
Oral steroid days
No. of hospitalizations
Hospitalization days
Ann Intern Med 2005; 143:

22. p < 0.008 p < 0.048 Eur Respir J 2002; 19: 209. Spiriva Atrovent

23. ICS/LABA
Fluticasone / salmeterol (Seretide) is indicated for the symptomatic treatment of patients with moderate to severe COPD (pre-bronchodilator FEV1<60% predicted normal), who have significant symptoms despite bronchodilator therapy.

24. 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

25. Reducing exacerbations with ICS/LABA in severe COPD
Kardos et al 2007

26. Seretide reduces the rate of exacerbations requiring systemic corticosteroids over 3 years (TORCH)
-0.05
0.15
0.35
0.55
0.75
0.95
1.15
placebo
Sal FP
SFC
43% (p<0.001)
0.80
0.64
0.52
0.46
Exacerbation rate
p-value
Treatment effect
SFC vs placebo
43%
<0.001
SFC vs sal
29%
<0.001
SFC vs FP
13%
0.02
Calverley PMA et al New Eng J Med 2007; 356:

27. TORCH: different stages of COPD
Adapted from Jenkins C, et al. Respiratory Research 2009; 10: 59.

28. 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

29. BUD/FORM vs. each components or placeboNS NS * *
BUD/FORM vs Placebo
BUD/FORM vs BUD
BUD/FORM vs FORM
BUD vs Placebo
FORM vs Placebo * NS * NS
NS = Not Significant
Adapted from Szafranski W, et al. Eur Respir J 2003; 21:

30. Symbicort plus Spiriva versus placebo plus Spiriva
Number of severe exacerbations
decreased by 62%
Adapted from Welte T, et al. AJRCCM 2009; 180: 741.

31. 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.

32. 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.

33. ANORO ELLIPTA (LABA/LAMA) Umeclidinium/Vilanterol
Once daily bronchodilator to relieve symptoms in COPD patients.

34. PULMONARY REHABILITATION

35. 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 weeks with twice weekly visits.
The exercise needs to be maintained at home.
Cochrane database 2006; Lancet 1996; 348: 1115.

36. 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

37. Pneumococcal vaccine - Little evidence about its use in COPD, but it seems like a good idea.
- older than 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.

38. MANAGEMENT OF COPD STOP SMOKING MEDICATIONS VACCINATIONS
REGULER EXERCISE (pulmonary rehabilitation)