Acute Exacerbations of COPD
Gareth Hynes
Clinical Research Fellow
University of Oxford
Introduction
• Epidemiology
• Causes
• How to know who’s exacerbating
• When to use antibiotics
• When to use corticosteroids
• When to admit patients
• Summary
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
Number of People Diagnosed with COPD in the UK
BLF, 2016
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
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.
What causes an exacerbation?
Aetiology
Bafadhel, 2011
Exacerbation time course
Soler-Cataluna, 2010
Diagnosing an Exacerbation
An acute worsening of the patient’s usual pattern of respiratory symptoms beyond normal day-today variability:
• Increased dyspnoea
Dyspnoea:
• Worsening cough
• Airway narrowing
• Increased sputum volume
• Sputum purulence
• Increased metabolic state
• Increased ventilation–
perfusion mismatch.
No biomarkers of an exacerbation as yet
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
Antibiotics
Anthonisen et al, 1979
Antibiotics
• Background
Van Velzen et al, 2017
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
Antibiotics
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
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 Creactive protein level ≥ 40 mg/L (solid
line) (AUC 0.842) among patients with
exacerbations of mild to moderate COPD
not treated with antibiotics.
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
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)
Corticosteroids
Bafadhel, 2012
Corticosteroids
Bafadhel, 2012
Bafadhel, 2012
Admissions
Major Criteria
Minor Criteria
• Ability to cope at home
• Decreased level of activity
• Hypoxia, saturations < 90% or > 5% drop on
mild exertion
• LTOT
• Severe breathlessness
• Poor general condition
• Altered mental state
• Rapid onset
• Worsening peripheral oedema
Suspicion of presence of differential such as pneumonia, pneumothorax,
pulmonary emboli, myocardial infarction
Summary
Who to give antibiotics to?
Unwell, sputum purulence, CRP > 40
Differential diagnoses
• PTX
• Who to give corticosteroids to?
• Pneumonia
Currently all
• Pulmonary emboli
In future ? high eosinophilics only
• Myocardial infarction and arrhythmia
• Who to admit?
Inability to manage at home, severe SOB,
developing peripheral oedema, hypoxic
Working towards biomarker-directed approach