asthma guidelines pharmacological treatment
TRANSCRIPT
Asthma Guidelines
and
Pharmacological
Treatment
Dr James Wilkinson
Asthma is a common disease in the UK
• 5.4 million people in the UK are currently receiving
treatment for asthma:
• 4.3 million adults (1 in 12).
• 1.1 million children (1 in 11)
• Asthma prevalence stable since the late 1990s
• UK still has some of the highest rates in Europe
• The NHS spends around 1 billion a year treating it
Asthma still kills
In 2014 (most recent data) 1216 people died from asthma.
• RCP Review of asthma deaths 2015:
• Issues with health professionals' use of asthma
guidelines that could have helped to avoid death in 46%
• 57% no specialist medical care in previous year
• 43% had not had a local surgery asthma review in
previous year
• Only 22.5% had personalised action plans
• 21% had attended a hospital A&E at least once in the
previous year
• 10% died within 28 days of discharge from hospital after
treatment for asthma
Asthma deaths in England & Wales 2003-2015
UK Asthma Guidelines
• First British Thoracic Society guideline in 1993
• Second guideline published in 1997
• Updated annually from 2004 to 2012
• Updates biennially from 2012
• NICE quality standards (2014) based on BTS/SIGN
• Latest BTS / SIGN Guidelines updated Sept 2016
What do they cover?
• Diagnosis of asthma in adults and children
• Treatment of stable asthma in adults, children and
adolescents
• Treatment of acute asthma in adults and children
• Inhaled treatment
• Asthma in pregnancy
• Occupational asthma
• Delivery of asthma care
Diagnosis of Asthma
Diagnosing Asthma
“Structured Clinical Assessment” to stratify whether
high, low or intermediate likelihood of asthma
• Variable symptoms - wheeze
- persistent cough
- sleep disturbance
- recurrent bronchitis
• Documented wheezing or low airflow measurements (Peak Flow or FEV1)
• History or family history of atopy
• Other causes of symptoms appear less likely
Likelihood of asthma after structured
clinical assessment
Low
• investigate for other causes of symptoms
High
• Record as “probably asthma”
• Trial of treatment, as for asthma, with relief inhaler +
low dose ICS
• Follow with stepwise management approach
Intermediate
• requires more investigation
Intermediate probability of asthma
This group may need more detailed investigation
• Serial Peak Flow Readings
(>20% of mean PEFR on readings TDS over 2 weeks)
• Reversibility Testing
(>15% rise in PEFR or 12% in FEV1 after bronchodilator)
• Exhaled Nitric Oxide
A marker of eosinophilic airways information (ie asthma)
Levels <15 negative. Levels >50 positive
Treating asthma
• No daytime symptoms
• No waking due to asthma
• No need for relief bronchodilator medication
• No asthma attacks
• No limitations on activity, including exercise
• Normal lung function (in practical terms FEV1 and/or
PEF 80% predicted or best)
• Minimal side effects from medication
Asthma treatment goals
Drug Treatments for Asthma
Bronchodilators
• β-agonists short acting
long acting
• Anticholinergics
short acting
long acting
• Theophyllines
Anti-Inflammatories
• Steroids inhaled
oral
parenteral
• Leukotriene
antagonists
• (Theophyllines)
• Cromones
• Biologics
• (Immunotherapy)
Biologics
Anti IgE – Omalizumab
• Binds to IgE preventing
it from attaching to its
receptor to activate
mast cells etc
• Given as weekly
injection
Anti-IL5 Mepolizumab
• Binds to IL-5 receptors
on eosinophils,
downregulating
inflammatory response
• Given as weekly
injection
The mainstay of treatment is inhalers
Relievers Steroids LABAs LAMAs ICS/LABA LAMA/LABA
No inhaler is perfect
That’s why there are so many different types!
Guideline comments on inhalers
• Prescribe inhalers only after patients have received training
in their use and have satisfactory technique.
• Assessment of technique by a competent healthcare
professional
• If the patient is unable to use a device satisfactorily, an
alternative should be found.
• A pMDI ± spacer is as effective as any other hand-held
inhaler, but patients may prefer some types of DPI.
• Avoid generic prescribing
• Encourage use of similar/same device for different drugs
Short acting ß2 agonist as required. Consider moving up if using 3 doses a week or more
Regular
preventer
Consider
monitored
initiation of
treatment with
low dose ICS
Initial add-on
therapy
Additional add-
on therapies
High dose
therapies
Continuous or
frequent use of
oral steroids
Infrequent,
short-lived
wheeze
--
--
--
--
--
--
--
--
--
--
--
--
--
-
Evaluation: - assess symptoms, measure lung function, check inhaler technique and adherence
- adjust dose – update management plan – move up and down as appropriate
Diagnosis &
Assessment
Adult asthma - diagnosedAsthma - suspected
Low dose ICS
Add inhaled
LABA to low
dose ICS
(normally as a
combination
inhaler)
No response to LABA
– stop LABA and
consider increased
ICS
If benefit from LABA
nut control still
inadequate – continue
LABA and increase
ICS to medium dose
If benefit from LABA
but vcontrol still
inadequate – continue
LABA and ICS and
consider trial of other
therapy – LTRA, S-R
theophylline, LAMA
Consider trials of:
Increasing ICS to
high dose
Additionof a fourth
drug, eg LRTA,
SR theophylline,
beta agonist
tablet, LAMA
Refer patient for
specialist care
Use daily steroid
tablet in the lowest
dose providing
adequate control
Maintain high dose
ICS
Consider other
treatments to
minimise use of
steroid tablets
Refer patient for
specialist care
Stepwise management of asthma
Confirmed asthma
• Mild Intermittent asthma
• Includes exercise-induced asthma
• Use short acting β2-agonist (SABA) as necessary
• Consider whether to start on low dose ICS
Regular Preventer
• Start patients at a dose of inhaled steroids
appropriate to the severity of their disease
• Titrate to the lowest dose at which effective control
of asthma is maintained
• Reduce dose by 25-50% at 3 month intervals if
symptoms well controlled
Daily dose of budesonide (mcg)
Symptoms
FEV1
Exercise FEV1
NO
FEF25%-75%
Pe
rce
nt
of
ma
xim
um
Barnes PJ, et al. Am J Respir Crit Care Med. 1998;157:S1-S53.
Why start inhaled steroids?
0 100 200 300 400 500 600 700 800
0
10
20
30
40
50
60
70
80
90
100
Symptoms and lung function improve with low doses of ICS
Adapted from Suissa S, et al. N Engl J Med. 2000;343:332.
Ra
te r
ati
o o
f a
sth
ma
-re
late
d d
ea
ths
ICS MDIs used per year (N)
2.0
1.5
1.0
0.5
0.0
0 1 2 3 4 5 6 7 8 9 10 11 12
Why start inhaled steroids?
Risk of death from asthma decreases with use of ICS
When should we start inhaled steroids?
• Exacerbation of asthma in the last two years
• Using β-agonist three times a week or more
• Symptomatic three times a week or more
• Waking one night a week or more
Inhaled Steroids
Steroid Low dose Medium dose High dose
Beclometasone MDI
(BDP)
100mcg
2 Puffs bd
200 mcg
2 Puffs bd
200 mcg
4 puffs bd
Clenil Modulite
(BDP)
100mcg
2 Puffs bd
200 mcg /
250mcg
2 Puffs bd
Qvar 50 mcg
2 Puffs bd
100mcg
2 Puffs bd
100mcg
4 Puffs bd
Pulmicort Turbohaler 100-200 mcg
1 Puff bd
200-400 mcg
1 Puff bd
400mcg
1 Puff bd
Flixotide Accuhaler 100mcg
1Puff bd
250mcg
1 Puff bd
500 mcg
1 Puff bd
Asmanex 100mcg
1 Puff bd
200 mcg
1 Puff bd
• Dose depends on drug and inhaler device
Initial add-on therapy
• A long-acting β2-agonist (LABA) should be added to
the initial dose of inhaled corticosteroid before the
dose of inhaled corticosteroid is increased
0.67
0.91
0.460.34
(-26%)
(-49%)(-63%)
Why add LABA? E
stim
ated
yea
rly
exac
erb
atio
n r
ate
(num
ber
/p
atie
nt/
year
)
0
0.2
0.4
0.6
0.8
1.0
BUD 400mcg b.d.
+ placebo
BUD 100mcg b.d.
+ formoterol
12mcg b.d.
BUD 400mcg b.d.
+ formoterol
12mcg b.d.
BUD 100mcg b.d.
+ placebo
Adapted from Pauwels et al. N Engl J Med 1997
p = 0.03p = 0.01
FACET study
Effect of addition of formoterol on severe exacerbations
Improvements in asthma control vs components
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Time (weeks)
Perc
en
tag
e o
f p
ati
en
ts
rem
ain
ing
fre
e o
f exacerb
ati
on
Placebo Seretide 100 Accuhaler 1 b.d.Salmeterol 50 μg Accuhaler 1 b.d. Fluticasone 100 μg Accuhaler 1 b.d.
*
*p<0.007 vs all other treatments
Salmeterol is not recommended as monotherapy in the UK
McCarthy et al. Thorax 2001
How should we add in LABAs?
• In efficacy studies….. there is no difference in
efficacy in giving inhaled corticosteroid and a long-
acting β2 agonist in combination or in separate
inhalers.
• In clinical practice…… combination inhalers aid
adherence and also have the advantage of
guaranteeing that the long-acting β2 agonist is not
taken without the inhaled corticosteroid.
Combination LABA/ICS Inhalers
• Symbicort Turbohaler twice daily DPI
- Budesonide + formoterol
• Seretide Accuhaler twice daily DPI
- Fluticasone propionate + salmeterol
• Fostair twice daily MDI
- Beclometasone + formoterol
• Flutiform twice daily MDI
- fluticasone + formoterol
• Relvar Ellipta once daily DPI
- Fluticasone furoate + vilanterol
Additional add on therapies
• If symptoms are no better on additional LABA, stop it.
Consider increasing to medium dose ICS
• If symptoms are improved but inadequately controlled
on medium strength steroid + LABA, consider increase
to medium dose ICS and/or add in one of :
• LAMA
• LTRA (montelukast, zafirlukast)
• Theophylline (uniphyllin, phyllocontin)
• Cromone (cromoglycate, nedocromil)
High dose therapies
Consider trials of:
• Increasing to high dose ICS
• Adding in fourth drug from:
• LAMA
• LTRA (montelukast, zafirlukast)
• Theophylline (uniphyllin, phyllocontin)
• Cromone (cromoglycate, nedocromil)
• Refer to specialist clinic
Continuous or frequent use of oral steroid
• Long term oral steroid required in addition to other
agents
• Continue with high dose ICS
• Refer to specialist clinic
• Consider other treatments to minimise use of
steroid tablets
• Anti IgE
• Anti IL-5
Pregnancy, labour and breastfeeding
• Maintaining good control is paramount
• SABA, LABA, ICS, Theophyllines can all be used
• LTRAs should not be withheld if needed for asthma control
• Short courses off oral steroid should be used if needed
• Women receiving oral prednisolone >7.5 mg for >2 weeks
prior to delivery should receive parenteral hydrocortisone
100 mg 6-8 hourly during labour.
• Acute severe asthma is an emergency and should be
treated in hospital.
• Asthma attacks during labour are rare.
Asthma with COPD or COPD with asthma
• Asthma and COPD are both common in adults
• Asthma / COPD overlap is not unusual. Treat primarily
as asthma.
• Severity stratification of COPD should be based on best
spirometry, when asthma component is fully controlled.
• More likely to benefit from early use of LAMA than pure
asthma.
• Avoid LABA, LAMA or LABA/LAMA combinations
without also using ICS if there is co-existing asthma.
Acute asthma exacerbations
Moderate
• increasing symptoms
• PEF 50–75% of best
or predicted
• no features of acute
severe asthma
Severe
Any one of:
• PEF 33-50% best or
predicted
• respiratory rate >25/min
• heart rate ≥110/min
• inability to complete
sentences in one breath
Life-threatening asthma
In a patient with severe asthma any one of:
• PEFR <33% best or predicted
• SpO2 <92% or PaO2 <8 kPa
• normal PaCO2 (4.6–6.0 kPa)
• silent chest
• cyanosis
• poor respiratory effort
• arrhythmia
• exhaustion
• altered conscious level
• hypotension
Treatment of acute severe asthma
• Nebulised salbutamol + ipratropium
• Oxygen to maintain SaO2 >93%
• Fluids (i-v) may be necessary
• Oral prednisolone 30-40mg daily
• If poor response consider i-v Magnesium
sulphate infusion
Asthma Management Plans
• All patients should have personal asthma
management plans
• The single most effective “non therapeutic”
intervention in asthma management
• A comprehensive personalised plan can
be downloaded for free from the Asthma
UK website: www.asthma.org.uk
A simple asthma management plan…
Best PEFR……………
if PEFR is:
< 80% of best - double dose of steroid inhaler
< 60% of best - start emergency course of
steroids and inform GP/nurse
< 40% of best - attend A&E urgently (ambulance)
Why do patients “fail” on any given level of
treatment?
• Asthma severity increasing
(environmental factors)
• Medical carers underestimate severity
• Poor concordance / compliance
We aren’t very good at gauging severity
0
10
20
30
40
50
60
70
SOB Waking Cough can't
talk
GPs
Nurses
Patients
% o
f p
ati
en
ts e
xp
eri
en
cin
g
Patients’ asthma symptoms are often worse
than they admit
(n=15,649)
0
2,000
4,000
6,000
8,000
1 2 4
10,000
Num
ber
of patie
nts
at each s
tep
BTS guidelines steps
% Patients not well controlled
53
54.6%
67.6%
55.4%
Neville et al. Eur Respir J 1999
Many UK Patients Are Non-adherent
• 25% of patients have asthma adherence rates < 30% 1
• Non-adherence problems typically involve the under-use of preventer medications2
• Non-adherence is thought to contribute to 18-48% of asthma deaths3
• Lack of adherence may be related to
- Limited patient knowledge of condition or medication
- Lack of motivation to take medication
- Issues with medication
1. Dasgupta R, et al. Pharmacoeconomics. 2003;21:357-69.
2. Farber HJ, et al. J Asthma. 2003;40:17-25.
3. National Asthma Campaign. Asthma J. 2001;6(suppl 3).
Adherence
better with bronchodilators than with steroids
Steroid ß-agonist
Reported adherence 95.4 78.2
Actual adherence 58.4 62.1
Right dose, right time 31.8 47.6
Days without treatment 24.4 20.4
Adherence
• Difficulty in using inhalers
• Inconvenient dosing regime
• Too many different medications
• Too many different devices
• Failure to understand treatment
• Fear of side effects ( esp. steroids)
• Refusal to accept chronic disease
Increasing Compliance
• Education (theory and practice!)
• Choose the right inhaler
• The right inhaler for the patient is the one they can use properly
• Minimise number of different inhalers
• Simplify dosing regimes
• Minimise side effects
• Ownership – Asthma management plans
Keys to asthma treatment success
• Right Inhaler
• Right Drug(s)
• Right amount
• Patient understanding
• Patient ownership
What can we do to help patients?
“Evidence for pharmacist-led interventions is lacking and
further high quality randomised trials testing pharmacist-led
interventions to improve asthma outcomes are needed.”
However, there are areas in which there is potential for
helpful pharmacy intervention!
What can we do to help patients?
• Medication reviews
• Inhaler technique – feedback to local surgery
• Rationalising medication
• Flagging up overuse of medication
• Exploring whether patients have management
plans
• Opportunistic lifestyle advice
Lifestyle advice
Opportunistic lifestyle advice:
• Avoiding precipitants
• Smoking cessation
• Influenza vaccination
• Weight loss
• Breastfeeding (for mother’s and baby’s
benefit)
• Ineffectiveness of ionisers, air filters, and
other measures to control house dust mite
Reducing House Dust Mite Allergen
Many studies have looked at methods of reducing HDM
• Removing soft furnishings,
• Frequent vacuuming
• Hot wash cycles (>60 degrees)
• Freezing cuddly toys
• Mite proof mattress covers
• Fungicides (kill food supply)
• Pesticides (kill mites)
• Ionisers
• Filters
No consistent significant effect on symptoms or IgE
Many studies have looked at methods of reducing HDM
• Removing soft furnishings,
• Frequent vacuuming
• Hot wash cycles (>60 degrees)
• Freezing cuddly toys
• Mite proof mattress covers
• Fungicides (kill food supply)
• Pesticides (kill mites)
• Ionisers
• Filters
No consistent significant effect on symptoms or IgE
Children & Cats
• 1/3 prefer cat to brother or sister
• 1/3 think mother prefers cat to father
• 1/6 prefer cat to granny
THE
END
Smoking
• Smoking in pregnancy impairs lung development
• Environmental Tobacco Smoke in pre-school children increases
risk of developing asthma by 30%
• Starting smoking as a teenager doubles risk of developing
asthma
Immunotherapy
• Very strong evidence of benefit
• 67 papers 1954-1998 -
• All show medication requirements
bronchial responsiveness
symptom scores
no effect on spirometry
• 1 comparative study with budesonide -
steroid more effective than immunotherapy
• NOT AVAIABLE IN UK