Download Prevalence of Asthma

FRACP Teaching
ASTHMA and COPD
Update 2007
With respect to prevalence of asthma worldwide, all are
correct except one
A. People emigrating from countries of low prevalence to
countries of high prevalence maintain the same prevalence of
asthma exhibited in their country of origin.
B. Prevalence of asthma has increased by as much as 50% in some
countries over 20 years.
C.
Has been mainly based on questionnaires which have a high
sensitivity but low specificity for diagnosis of clinical asthma.
D. The gold standard is a standardised
association with a test of BHR.
questionnaire
in
Prevalence of Asthma
• There are five fold differences in prevalence of asthma
between countries such as China, Australia and NZ
• The prevalence of asthma has almost doubled over 20
years in Australia and NZ
• The prevalence of asthma is likely to be due to
environmental exposure to allergens
• The lack of specificity in definitions of asthma make
comparisons and longitudinal trends difficult to interpret
Non Invasive measurements of Airway
Inflammation in asthma
• These include tests of airway hyperresponsiveness, induced
sputum examination and exhaled nitric oxide.
(True/False)
• ENO is the most sensitive measure of airway inflammation.
• Sputum eosinophilia is a predictor of steroid responsiveness
• Regular use of AHR and sputum examination to adjust steroid
dose in asthma for optimum control, reduces asthma
exacerbations and improves lung function in the long term.
• Regular use of ENO to adjust steroid dose in asthma for
optimum control, reduces asthma exacerbations and improves
lung function in the long term.
Measures of AI in asthma
• Symptoms + spirometry + ANOTHER MEASURE
–
–
–
–
GUIDELINE BASED CONTROL
AIRWAY HYPERRESPONSIVENESS
EXHALED NITRIC OXIDE
INDUCED SPUTUM EXAMINATION
• Guideline based control
• Aiming to achieve optimum asthma control based on
strict adherence by patient and doctor to best practice
guidelines (national/international)
• Better asthma outcomes: significantly improved quality of
life, fewer symptoms and exacerbations, less time off
work, lower economic costs .
Bateman Eur Respir J 2002;Gibson et
al Cochrane Database Syst Rev 2000;
Boulet et al Chest 2002
5
‘Inflammometry’
• The use of information gathered from measures of
airway inflammation to guide assessment and
treatment.
• Success with induced sputum eosinophil counts.
(Gold standard)
Predicts steroid
responsive disease
Pavord 1999
Pizzichini 1999
Brightling 2000
Green 2002
A rise in counts
measured longitudinally
predicts subsequent loss
of asthma control
Jatakanon 2000
Deykin 2004
Management protocols
aimed at titrating steroid
therapy to maintain
normal counts lead to
superior asthma control
Green 2002
Jayaram 2005
Chlumsky 2006
Sputum induction and examination
•Sputum induction
B2 agonist
•2 methods
•success rate
•safety
•children
•low FEV1
Sputum examination
Sputum: causes of increase in cell type
Eosinophilic: uncontrolled asthma
non compliance with medications
occupational asthma
Steroid responsive COPD
Neutrophilic:
cigarette smoking
infections - bacterial, viral
steroid resistant asthma
Does normalising the sputum eosinophil count in
asthma lead to fewer symptoms and exacerbations,
improve lung function and reduce costs?
– Green et al Lancet 2002
•
Single centre study over 12 months.
– 74 subjects attending a specialist hospital centre with moderate
asthma managed by British Thoracic Society Guidelines alone,
vs addition of sputum examination with normalisation of induced
sputum eosinophil count ( < 3%).
•
Reduced frequency of severe exacerbations in sputum group : Mean(
SEM) 0.9(0.2) vs 3.0(0.7)p=0.013 ; hospitalisations: 1 vs 6
p=0.047.
•
Trend to reduce direct costs
•
ENO measurements reduced by 48% in sputum strategy cf clinical
strategy.
Exhaled NO as an Inflammometer
• Moderate association
with eosinophilic airway
inflammation in cross
sectional studies.
• Advantageous in a
practical setting.
• Predicts steroid
responsive disease in
steroid naïve cases.
Smith et al 2005
Vs
Berry et al 2005
Smith et al 2004
r2= 0.26
r2= 0.45
• Mixed evidence for
predicting loss of
asthma control in
longitudinal studies.
Harkins et al 2004
Jones et al 2001
Deykin et al 2004
Leuppi et al 2001
Exhaled nitric oxide
• Produced by airway epithelial cells and
inflammatory cells
– marker of AI
– diffuses into airway lumen
• Increased in asthma> bronchiectasis/infections,
• Reduced in CF, PCD
– upregulation of inducible NO synthase by
proinflammatory cytokines
– Reduced by corticosteroids, smoking, alcohol
Factors thought to influence
exhaled NO
NO
NO
(Genetic factors)
Viral infections
Atopy and AHR
Smoking
Corticosteroids
Acute lung allograft rejection?
Bronchiectasis
Female sex hormones
SLE
Liver cirrhosis
Pulmonary hypertension
Immunodeficiency
Primary Ciliary Dyskinesia
Cystic Fibrosis
Factors that effect exhaled NO independent of sputum
eosinophils will result in discordance between the 2 variables.
Exhaled nitric oxide
•
Measured by rapid linearresponse chemiluminescence
•
standardised measurement
– 50 ml/sec flow rate
– reproducible,discriminates
between subjects with and
without asthma
•
normal values: mean (SD) 12
(11) ppb
– 10th percentile: 6 ppb
– 90th percentile: 23 ppb
Bates et al J Allergy Clin Immunol 2003
14
ENO and loss of asthma control
• Assessed usefulness of ENO for predicting an
exacerbation of asthma prospectively.
PPV
ENO >15 ppb
0.88(0.64,0.99)
Eosinophils >4%
0.80 (0.52,0.96)
Jones Am J Respir Crit Care Med 2001
15
ENO to guide asthma management
•
Taylor et al NEJM 2005 352: 2163-2173
•
Single blind, placebo controlled trial
•
94 subjects with asthma on ICS ( 46 ENO group, and 48 in control group)
had ICS dose adjusted stepwise based on ENO measurements or standard
guidelines.
•
Once optimal dose determined ( phase 1) subjects followed for 12 months (
P2)
•
•
Primary Outcome: frequency of asthma exacerbations
Secondary outcome: mean daily dose of ICS
•
Cut off for ENO 15 ppb at 250 ml/sec flow rate
Intensive Asthma Study 2006
Eos=3%
300
Control group
0.67*
0.38*
F E NO (ppb)
O*
0.09*
FENO group
* Exacerbations/patient/yr
100
30
FENO=26 ppb
10
3
0.1 0.3
1
3
10
30
100
Differential sputum eosinophil count (%)
AHR: Indirect challenge tests (T/F)
• Include hypertonic saline, mannitol, adenosine monophosphate
and Eucapnic Voluntary hyperpnea with dry air.
• Are more specific for asthma than histamine or methacholine
challenge
• Are more sensitive for asthma than histamine or
methacholine challenge
• Are the tests of choice to exclude asthma in divers and
police force.
• Are more sensitive to inhaled steroid dose than direct
challenges (methacholine /histamine)
Airway hyperresponsiveness
• “Abnormal increase in airflow limitation following
exposure to a nonallergic stimulus”
• Characteristic in asthma
–
sensitive not specific
• Direct: histamine, methacholine
smooth muscle
• Indirect : exercise, nonisotonic aerosols, drugs
– release endogenous mediators
Joos et al ERS Task Force.Eur Respir J
2003
smooth muscle
19
20
All of the following are correct regarding allergy testing
in asthma except one
A. Of benefit to document specific allergens suggested by
the clinical history.
B. Is useful to reinforce the need for environmental
control.
C. Is useful in identifying occupational allergens.
D. Is useful as a screening test for ABPA.
E. A positive test invariably has clinical relevance.
Allergy Testing in Asthma
 To document specific allergens suggested by the
clinical history
 To confirm and reinforce
environmental control
the
need
for
 To identify occupational allergens
Note: A positive test may not have clinical relevance. A negative
test usually rules out clinical sensitivity to that aeroallergen.
All of the following have been known to cause
asthma symptoms except one
A.
B-Blockers including B-Blocker eye drops
B.
Aspirin
C.
Metabisulphites
D.
NSAIDs
E.
Calcium Channel Blockers
Appendix 1: Medications Known to Cause Asthma Symptoms
Note: this list is an indication only.
•
Beta-blockers
All may lead to bronchoconstriction
•
Cholinergic agents
•
Cholinesterase inhibitors
•
Beta-blockers applied as eye-drops may also cause problems
•
Aspirin and NSAIDs - usually characterised by flushing and rhinorrhoea. May produce a
life threatening asthma attack
•
Carbemazepine
•
Some parenteral drugs (such as penicillin, iron dextran complex, hydrocortisone,
ipratropium bromide, aminophylline, N-acetyl cysteine)
•
Tartrazine (yellow food dye)
•
Preservatives (such as bisulphates, metabisulphates and benzalkonium chloride)
•
Echinacea (frequently recommended for colds, fl u and respiratory infections, but
triggers asthma in some people)
•
Royal Jelly (has caused fatal exacerbations in some people).
Source: Asthma Management Handbook 2002 [3].
Question
A young woman with a history of nasal polyposis presents with
severe asthma one hour after ingestion of salicylates. Which
of these treatments is more likely to be effective in her long
term management than would usually be expected?
A. Ventolin
B. Flixotide
C. Salmeterol and Flixotide in combination
D. Montelukast
(Anti–leukotriene antagonist)
E. Salmeterol
Asthma
All of the following statements around efficacy and safety of short
(SABA) and long acting beta-agonist (LABA) medications in the
management of asthma are correct except for one.
A.
Overall there is an increase in bronchial hyper-responsiveness both
during and following use of inh B-Agonists (whether SABA or LABA).
B.
Asthma control is less good when SABAs are taken regularly 4 times a
day.
C.
There is good evidence that when SABAs are withdrawn or reduced
to prn use that asthma control improves.
D.
There is an increase in both early and late phase responses to
allergens after treatment with regular salbumatol.
E.
LABAs are more effective than QID SABAs in controlling asthma.
Which of the following statements is correct with
respect to LABAs
A. They have been found to be safe whether administered
concurrently with inhaled steroids or not.
B. They have been found to have an anti-inflammatory effect in
vitro which has been reproduced in clinical trials
C.
Tachyphylaxis of broncho-protection to exercise induced
asthma has been shown with regular LABAs.
D. When LABAs are combined with inhaled steroids in the same
inhaler they are found to be more effective than when
administered in the same dose through separate inhalers.
E.
Salmeterol has a quicker onset of action than formoterol.
With respect to LABAs all are correct except for one
A. When added to 400 - 800mcg beclamethasone LABAs are
found to be more efficacous than doubling the dose of
beclamethasone.
B. Adding LABAs to 800mcg beclamethasone is more cost
effective than doubling the dose of beclamethasone.
C.
When combined with inhaled steroids varying the dose and
frequency of administration of LABAs is more effective than
staying on a fixed and regular dose.
D. Systemic availability and efficacy is dependent on the
deposition characteristics of the inhaler in which they are
administered.
E.
LABAs are equipotent to oral theophylline wrt broncho-dilation
but are preferred because they have less side effects.
All of the following are correct wrt acute asthma
therapies except for one
A.
Intravenous aminophylline contributes nothing to usually employed
doses of inhaled B-Agonists.
B.
Ipratropium contributes a small improvement in FEV1 when combined
with salbutamol compared with salbutamol alone.
C.
IV or nebulised Magnesium offers useful broncho-dilation in the
management of acute asthma.
D.
Ipratropium use in the ED does not reduce the need for admission.
E.
Spirometry is a more robust measure of assessing severity of asthma
than is PEF measurement.
F.
B-Agonists delivered by spacing devices are equivalent in efficacy to
wet nebulisation.
With respect to monitoring asthma control, all of the
following are correct except one
A. An elevated expired nitric oxide level suggests sub-optimal
control of inflammation within the airways and need for more
inhaled steroid.
B. An increase in eosinophils (>3%) within induced sputum samples
infers sub-optimal control and need for more inhaled steroid.
C.
A 15% reduction in PEF remains the most sensitive measure of
sub-optimal control and supports its use in Action Plans.
D. FEF 25 - 75%, takes the longest of all clinical measures to
improve and is least likely to return to normal in patients
treated with high dose inhaled steroids.
E.
An increase in BHR is the strongest argument for increasing
anti-inflammatory therapy.
Question 4
With respect to COPD and asthma:
A. The two disorders can never co-exist.
B. The chronic airway inflammation in asthma is predominantly
eosinophilic and driven by CD8+ lymphocytes.
C.
The chronic airway inflammation in COPD is mainly neutrophilic
and characterised by presence of increased numbers of
macrophages and CD8+T lymphocytes.
D. Nebulised anticholinergics have a proven place in acute
management of both asthma and COPD.
E.
In patients with fixed airways obstruction due to chronic
asthma, or smoking related airways disease, once FEV1 falls
below 30% predicted, mortality rates are remarkably similar.
Asthma and COPD
Asthma
COPD
Sensitising Agent
Noxious Agent
Airway Inflammation
Airway Inflammation
CD4+ Lymphocytes
CD8+T Lymphocytes
Eosinophils
Macrophages, Neutrophils
LTD4, IL-4, IL-5
LTB4, IL-8, INF-
Completely
Reversible
Airflow
Limitation
Completely
Irreversible
COPD - Definition
With respect to airflow limitation in COPD
A.
Anti-inflammatory therapy if used appropriately will reduce rate of
development of airflow limitation in persistent smokers.
B.
Airflow limitation is caused by a mixture of small airways disease
(obstructive bronchiolitis) and parenchymal destruction.
C.
Rate of decline of lung function always returns to that of the normal
population after smoking cessation.
D.
Airflow limitation is best assessed utilising regular Peak Flow
monitoring.
E.
Severity of airflow limitation is best assessed by HRCT Scan.
Mechanisms Underlying Airflow
Limitation in COPD
Inflammation
Small Airways Disease
Parenchymal Destruction
Airflow Limitation
With respect to smoking related COPD all are correct
except one
A. As a rule patients need to develop an FEV1 of around 25-30%
predicted before they develop symptoms of breathlessness.
B. Patients with a chronic productive cough are more likely to
have reduction in FEV1.
C.
Between 15-25% of patients who smoke will lose lung function
at a rate faster than that of the normal population.
D. Patients with COPD are at increased risk of developing lung
cancer, CVA, and IHD than patients who smoke but who do not
have COPD.
E.
Once patient stops, their rate of loss of lung function usually
returns to that of the normal population.
Tiotropium [Spiriva] is a new broncho-dilator. Which of
the following is incorrect
A. It is an anticholinergic with longer half life than
Ipratropium.
B. It has a unique selectivity for M3 receptors.
C. Peak effects are seen after 1-2 hours.
D. Only needed once per day.
E. Not as effective as regular SABAs or LABAs in
treatment of COPD.
Tiotropium (Spirivia)
• Long acting version of ipratropium
• Unique selectivity for M3 receptors
• Suitable for single daily dosing
• 12h + improvement in spirometry
• Peak effects seen after 1-2h
• Residual benefit at 24h
Tiotropium vs Salmeterol
623 patients (S 213, T209, P201) treated for 6 months
Donnohue et al. Chest 2002: 122: 47-55
Tiotropium vs Salmeterol
623 patients (S 213, T209, P201) treated for 6 months
Donnohue et al. Chest 2002: 122: 47-55
In relationship to steroids in COPD which is correct?
A. 20% of COPD patients will exhibit a short term (> 15%
improvement in FEV1) benefit from short course of prednisone
for 14-21 days.
B. After introduction in COPD, inhaled steroids exert most of
their effects on lung function only after at least 6 months
treatment.
C.
Inhaled steroids have no effect on frequency of exacerbations
of bronchitis.
D. Use of inhaled steroids over a 1 year period does not influence
measures of quality of life.
E.
Independent of the effect of steroids patients with COPD are
not at increased risk of osteoporosis.
Evaluation of ICS in COPD

Reversible
change
vs
irreversible
 Short term vs long term benefits
 Cost benefit
 Which outcome measures?
structural
EUROSCOP STUDY
SUMMARY
0 - 6 mths
Pulmicort
Placebo
+ 17mls
+ 1ml
6 mths - 3 years - 157mls
- 181mls
ISOLDE Study
Postbronchodilator FEV1 Over 3 Years
Fluticasone propionate 500 mcg b.I.d.
Placebo
Adjusted placebo
Adjusted fluticasone propionate
1.53
1.48
1.43
FEV1 (L)
§
1.38
1.33
1.28
0
Pre V1 V2
Pretrial steroid
withdrawal
V2
BL
2-week oral
steroid course
BL 3 6 9 12 15 18 21 24 27 30 33 36
Time (months)
Treatment phase
Adapted from Burge et al. BMJ. 2000;320:1297-1303.
Question: In utilising oxygen therapy in COPD all are
correct except one
A. Needs to be used for > 16 hours per day to show a survival
effect.
B. Has no effect on survival if patients continue to smoke.
C.
Is shown to be effective in patients with corpulmonale and
with PaO2 < 8 kPa.
D. Is beneficial wrt prolongation of life, reduced admissions and
improved quality of life if administered overnight to patients
with resting PaO2 of > 8 kPa but who desaturate to < 90% for
more than 2 hours overnight.
E.
Portable oxygen has been shown to improve quality of life but
not survival in COPD.
Types of Oxygen Therapy

Long Term Oxygen Therapy (LTOT)
> 15 days; +/- portable (Grade A 24 hrs, C normoxic)

Short Term Oxygen Therapy (STOT)
post discharge (unstable); 6-8/52 (Grade C)

Short Burst Oxygen Therapy (SBOT)
relief of SOB, palliative care (Grade B)

Ambulatory Oxygen Therapy
portable; (Grade B immediate, Grade A QoL)