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

Reducing Cat

allergen load

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