1. Acute Exacerbations of COPD
Gareth Hynes
Clinical Research Fellow
University of Oxford

2. Introduction Epidemiology Causes How to know who’s exacerbating
When to use antibiotics
When to use corticosteroids
When to admit patients
Summary

3. Background COPD Epidemiology
115,000 people are diagnosed with COPD each year – equivalent to a new diagnosis every 5 minutes
9% in those over age 70
Nearly 30,000 people die from COPD each year, making it the second greatest cause of death from lung disease and the UK’s fifth biggest killer

4. Number of People Diagnosed with COPD in the UK
BLF, 2016

5. Background Exacerbations
Median number of exacerbations seen in primary care was two per year, with one in three suffering three or more exacerbations in 1 year
Frequent exacerbators (> 2 per year):
Chronic sputum producers
Housebound
Frequent colds
Poor quality of life
Raised inflammatory markers when stable

6. Exacerbations and lung function decline
The difference in the decline in FEV1 between the infrequent and frequent exacerbators was 8 ml/year, and their median exacerbation rates were 1.9 and 4.2 per year
PEF did not recover to pre-exacerbation levels within 91 days in 7.1% of exacerbations.

7. What causes an exacerbation?

8. Aetiology
Bafadhel, 2011

9. Exacerbation time course
Soler-Cataluna, 2010

10. Diagnosing an Exacerbation
An acute worsening of the patient’s usual pattern of respiratory symptoms beyond normal day-to- day variability:
Increased dyspnoea
Worsening cough
Increased sputum volume
Sputum purulence
No biomarkers of an exacerbation as yet
Dyspnoea:
Airway narrowing
Increased metabolic state
Increased ventilation–perfusion mismatch.

11. Differential System Condition Differentiating factors Respiratory
Pneumonia
Pneumothorax
Pleural effusion
Pulmonary emboli
Focal crepitations or bronchial breathing
Hyperresonance and absent breath sounds
Dull percussion and absent breath sounds basally
Risk factors (immobility, medications), swollen calf
Cardiac
Congestive cardiac failure
Ischaemic heart disease
Arrhythmias
Paroxysmal nocturnal dyspnoea, oedema
Cardiac history
Other
Upper airway obstruction TB
Stridor
Country of origin, foreign travel, exposure history

12. Antibiotics
Anthonisen et al, 1979

13. Antibiotics
Background
Van Velzen et al, 2017

14. Antibiotics ERS/ATS Statement 2017
Antibiotic therapy decreased treatment failure from 42% to 28% (RR 0.67) - therefore NNT to prevent one treatment failure is 7
The majority (58%) of patients improved without antibiotics, suggesting not all exacerbations require antibiotics

15. Antibiotics

16. Antibiotics Point of care CRP
In the placebo arm, 77% of CRP tests resulted in concentrations < 40 mg/L.
If CRP < 40, the failure rate was 12.4%
If CRP > 40, the failure rate was 65.5% (P < 0.001)
Miratvalles, 2013

17. Antibiotics
The only factors significantly associated with an increased risk of failure without antibiotics were the increase in sputum purulence (OR, 6.1) and a CRP concentration ≥ 40 mg/L (OR, 13.4). When both factors were present, the probability of failure without antibiotics was 63.7%. 
Predictive value for clinical failure of Anthonisen criteria (dotted line) (AUC 0.708) and with the addition of a C-reactive protein level ≥ 40 mg/L (solid line) (AUC 0.842) among patients with exacerbations of mild to moderate COPD not treated with antibiotics.

18. Antiobiotics Which antibiotics to use?
Targeted towards previous sputum results
Moraxella commonly found, Haemophilus may need longer courses (2 weeks), if Pseudomonas isolated > 1 occasion seek respiratory advice
What the patient usually responds to
Otherwise:
Amoxicillin 500mg TDS, Co-Amoxiclav 625mg TDS, Doxycyxline 100mg OD, Clarithromycin 500mg BD

19. Corticosteroids
NICE 2017 In the absence of significant contraindications, oral corticosteroids should be considered in all patients with significant shortness of breath which interferes with day-to-day life Prednisolone 30mg for 7 to 14 days ATS/ERS 2017 For patients with an exacerbation of COPD with suggest a short (≤ 14 days) course of prednisolone (conditional recommendation, very low quality of evidence)

20. Corticosteroids
Bafadhel, 2012

21. Corticosteroids
Bafadhel, 2012
Bafadhel, 2012

22. Admissions Major Criteria Minor Criteria Ability to cope at home
Hypoxia, saturations < 90% or > 5% drop on mild exertion
Severe breathlessness
Altered mental state
Worsening peripheral oedema
Decreased level of activity
LTOT
Rapid onset
Poor general condition
Suspicion of presence of differential such as pneumonia, pneumothorax, pulmonary emboli, myocardial infarction

23. Summary Who to give antibiotics to?
Unwell, sputum purulence, CRP > 40
Who to give corticosteroids to?
Currently all
In future ? high eosinophilics only
Who to admit?
Inability to manage at home, severe SOB, developing peripheral oedema, hypoxic
Differential diagnoses
PTX
Pneumonia
Pulmonary emboli
Myocardial infarction and arrhythmia
Working towards biomarker-directed approach