Asthma British 2009

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Scottish Intercollegiate Guidelines Network

Part of NHS Quality Improvement Scotland

SIGN

British Guidelineon the Management of Asthma

A national clinical guideline

May 2008

revised June 2009

101


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NHS Quality Improvement Scotland (NHS QIS) is committed to equality and diversity. Thisguideline has been assessed for its likely impact on the six equality groups dened by age, disability,gender, race, religion/belief, and sexual orientation.

For the full equality and diversity impact assessment report please see the published guidelinessection of the SIGN website at www.sign.ac.uk/guidelines/published/numlist.html. The full reportin paper form and/or alternative format is available on request from the NHS QIS Equality andDiversity Ofcer.

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The College of

Emergency Medicine

British Thoracic Societ

Scottish Intercollegiate Guidelines Network

B G Maagm Ama

A national clinical guideline

May 2008

Revised June 2009


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British Guideline on the MAnAGeMent of AsthMA

isBn 978 1 905813 28 5

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SIGN and the BTS consent to the photocoping of this guideline for the purpose ofimplementation in the NHS in England, Wales, Northern Ireland and Scotland.

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Contents

C

1 ic 1

1.1 Statement of intent 1

2 dag 2

2.1 Diagnosis in children 2

2.2 Other investigations 8

2.3 Summar 9

2.4 Diagnosis in adults 11

2.5 Further investigations that ma beuseful in patients with an intermediateprobabilit of asthma 16

2.6 Monitoring asthma 18

3 n-pamacgca maagm 24

3.1 Primar prophlaxis 243.2 Secondar non-pharmacological

prophlaxis 27

3.3 Other environmental factors 28

3.4 Dietar manipulation 29

3.5 Complementar and alternative medicine 31

3.6 Other complementar or alternativeapproaches 32

4 Pamacgca maagm 33

4.1 Step 1: mild intermittent asthma 34

4.2 Step 2: introduction of regular

preventer therap 34

4.3 Step 3: initial add-on therap 38

4.4 Step 4: poor control on moderatedose of inhaled steroid + add-on therap:addition of fourth drug 40

4.5 Step 5: continuous or frequentuse of oral steroids 41

4.6 Stepping down 46

4.7 Specicmanagementissues 46

5 ia vc 48

5.1 Technique and training 48

5.2 2

agonist deliver 48

5.3 Inhaled steroids for stable asthma 49

5.4 Cfc propellant pmdi vs hfapropellant pmdi 49

5.5 Prescribing devices 50

5.6 Use and care of spacers 50

6 Maagm ac ama 51

6.1 Lessons from studies of asthmadeaths and near-fatal asthma 51

6.2 Acute asthma in adults 53

6.3 Treatment of acute asthma in adults 56

6.4 Further investigation and monitoring 60

6.5 Asthma management protocolsand proformas 60

6.6 Hospital discharge and follow up 60

6.7 Acute asthma in children agedover 2 ears 61

6.8 Initial treatment of acute asthma inchildren aged over 2 ears 63

6.9 Second line treatment of acute asthma inchildren aged over 2 ears 66

6.10 Assessment of acute asthma in childrenaged less than 2 ears 67

6.11 Treatment of acute asthma in childrenaged less than 2 ears 68

7 spca a 69

7.1 Difcultasthma 69

7.2 Factorscontributingtodifcultasthma 69

7.3 Asthma in pregnanc 71

7.4 Management of acute asthma inpregnanc 72

7.5 Drug therap in pregnanc 73

7.6 Management during labour 75

7.7 Drug therap in breastfeeding mothers 76

7.8 Occupational asthma 77

7.9 Management of occupational asthma 79

8 ogaa a vy ca,

a a 80

8.1 Routine primar care 80

8.2 Acute exacerbations 82

8.3 Audit 83

9 Pa ca a maagm 85

9.1 Self-management education andpersonalised asthma action plans 85

9.2 Compliance and concordance 86

9.3 Implementation in practice 88

9.4 Practical advice 88

10 dvpm g 90

10.1 Introduction 90

10.2 Executive and steering groups 90

10.3 Evidence review groups 91

10.4 Dissemination group 94

10.5 Sstematic literature review 94

10.6 Consultation and peer review 95

Abbva 96A 97rc 109

Revised

2009

Revised

2009

Revised

2009


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KeY to eVidenCe stAteMents And GrAdes of reCoMMendAtions

leVels of eVidenCe

1++ High qualit meta-analses, sstematic reviews of RCTs, or RCTs with a ver low risk of bias

1+ Well conducted meta-analses, sstematic reviews, or RCTs with a low risk of bias

1 - Meta-analses, sstematic reviews, or RCTs with a high risk of bias

2++ High qualit sstematic reviews of case control or cohort studies

High qualit case control or cohort studies with a ver low risk of confounding or bias and ahigh probabilit that the relationship is causal

2+ Well conducted case control or cohort studies with a low risk of confounding or bias and amoderate probabilit that the relationship is causal

2 Casecontrolorcohortstudieswithahighriskofconfoundingorbiasandasignicantriskthatthe relationship is not causal

3 Non-analtic studies, eg case reports, case series

4 Expert opinion

GRADES OF RECOMMENDATION

Note: The grade of recommendation relates to the strength of the evidence on which therecommendation is based. It does not reect the clinical importance of the recommendation.

A At least one meta-analsis, sstematic review, or RCT rated as 1++,and directl applicable to the target population; or

A bod of evidence consisting principall of studies rated as 1+,directl applicable to the target population, and demonstrating overall consistenc of results

B A bod of evidence including studies rated as 2++,

directl applicable to the target population, and demonstrating overall consistenc of results; or

Extrapolated evidence from studies rated as 1++ or 1+

C A bod of evidence including studies rated as 2+,directl applicable to the target population and demonstrating overall consistenc of results; or

Extrapolated evidence from studies rated as 2++

D Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+

GOOD PRACTICE POINTS

Recommended best practice based on the clinical experience of the guideline developmentgroup.

Audit point


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1

1 ic

In 1999 the British Thoracic Societ (BTS) and the Scottish Intercollegiate Guidelines Network(SIGN) agreed to jointl produce a comprehensive new asthma guideline, both having previouslpublished guidance on asthma. The original BTS guideline dated back to 1990 and the SIGN

guidelines to 1996. Both organisations recognised the need to develop the new guidelineusing explicitl evidence based methodolog. The joint process was further strengthened bcollaboration with Asthma UK, the Roal College of Phsicians of London, the Roal College ofPaediatrics and Child Health, the General Practice Airwas Group, and the British Associationof Accident and Emergenc Medicine (now the College of Emergenc Medicine). The outcomeof these efforts was the British Guideline on the Management of Asthma published in 2003.1

The 2003 guideline was developed using SIGN methodolog,2 adapted for UK-wide use.Electronic literature searches extended to 1995, although some sections required searchesback as far as 1966. The pharmacological management section utilised the North of EnglandAsthma guideline to address some of the ke questions on adult management. 3 The North ofEngland guideline literature search covered a period from 1984 to December 1997, and SIGNaugmented this with a search from 1997 onwards.

Since 2003 sections within the guideline have been updated annuall and posted on both theBTS (www.brit-thoracic.org.uk) and SIGN (www.sign.ac.uk) websites. In 2004 the sections onpharmacological management, acute asthma and patient self management and compliancewere revised. In 2005 sections on pharmacological management, inhaler devices, outcomesand audit and asthma in pregnanc were updated, and occupational asthma was rewritten withhelp from the British Occupational Health Research Foundation.

In 2006 the pharmacological management section was again updated. While the web-basedalterations appeared successful, it was felt an appropriate time to consider producing a newpaper-based version in which to consolidate the various earl updates. In addition, since 2006,the guideline has had input from colleagues from Australia and New Zealand.

The 2008 guideline considered literature published up to March 2007. It contains a completel

rewritten section on diagnosis for both adults and children; a section on special situations whichincludesoccupationalasthma,asthmainpregnancyandthenewtopicofdifcultasthma;updated sections on pharmacological and non-pharmacological management; and amalgamatedsections on patient education and compliance, and on organisation of care and audit. The2009revisions include updates to pharmacological management, the management of acute asthmaand asthma in pregnanc. Update searches were conducted on inhaler devices but there wasinsufcientnewevidencetochangetheexistingrecommendations.Theannexeshavealsobeenamendedtoreectcurrentevidence. The timescale of the literature search for each section isgiven in Annex 1. It is hoped that this asthma guideline continues to serve as a basis for highqualit management of both acute and chronic asthma and a stimulus for research into areasof management for which there is little evidence. Sections of the guideline will continue to beupdated on the BTS and SIGN websites on an annual basis.

1.1 stAteMent of intent

This guideline is not intended to be construed or to serve as a standard of care. Standardsof care are determined on the basis of all clinical data available for an individual case andaresubjecttochangeasscienticknowledgeandtechnologyadvanceandpatternsofcareevolve. Adherence to guideline recommendations will not ensure a successful outcome inever case, nor should the be construed as including all proper methods of care or excludingother acceptable methods of care aimed at the same results. The ultimate judgement must bemade b the appropriate healthcare professional(s) responsible for clinical decisions regardinga particular clinical procedure or treatment plan. This judgement should onl be arrived atfollowing discussion of the options with the patient, covering the diagnostic and treatmentchoicesavailable.Itisadvised,however,thatsignicantdeparturesfromthenationalguideline

or an local guidelines derived from it should be full documented in the patients case notesat the time the relevant decision is taken.

1 introduCtion


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2++

2++

3

Table 1: Clinical features that increase the probability of asthma

Morethanoneofthefollowingsymptoms:wheeze,cough,difcultybreathing,chesttightness, particularl if these smptoms:

are frequent and recurrent 10-13

are worse at night and in the earl morning 11,12,14

occur in response to, or are worse after, exercise or other triggers, such as exposureto pets, cold or damp air, or with emotions or laughter

occur apart from colds 10

Personal histor of atopic disorder 10,13,15

Famil histor of atopic disorder and/or asthma 10,16

Widespreadwheezeheardonauscultation

Histor of improvement in smptoms or lung function in response to adequate therap

Table 2: Clinical features that lower the probability of asthma

Smptoms with colds onl, with no interval smptoms10

Isolatedcoughintheabsenceofwheezeordifcultybreathing 17

Histor of moist cough 18

Prominentdizziness,light-headedness,peripheraltingling

Repeatedl normal phsical examination of chest when smptomatic

Normalpeakexpiratoryow(PEF)orspirometrywhensymptomatic

No response to a trial of asthma therap 19

Clinical features pointing to alternative diagnosis (see Table 3)

Severalfactorsareassociatedwithahigh(orlow)riskofdevelopingpersistingwheezingorasthma through childhood.15,20 The presence of these factors increases the probabilit that a

child with respirator smptoms will have asthma.

These factors include:

Ag a pa

The naturalhistoryofwheeze isdependentonageatrst presentation. Ingeneral, theearliertheonsetofwheeze,thebettertheprognosis.Cohortstudiesshowabreakpointataround two ears; most children who present before this age become asmptomatic b mid-childhood.6,8,9,21Co-existentatopyisariskfactorforpersistenceofwheezeindependentofageof presentation.

s

Male sex is a risk factor for asthma in pre-pubertal children. Female sex is a risk factor for the

persistence of asthma in the transition from childhood to adulthood.22,23 Bos with asthma aremorelikelytogrowoutoftheirasthmaduringadolescencethangirls.10,21,22,24-37

svy a qcy pv wzg p

Frequentorsevereepisodesofwheezinginchildhoodareassociatedwithrecurrentwheezethat persists into adolescence.5,8,13,16,21,26,38,39

2 diAGnosis


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2++

2++

3


4

Cc apc a

Ahistoryofotheratopicconditionssuchaseczemaandrhinitisincreasestheprobabilityofasthma.Positivetestsforatopyinawheezingchildalsoincreasethelikelihoodofasthma.AraisedspecicIgEtowheat,eggwhite,orinhalantallergenssuchashousedustmiteandcatdander, predicts later childhood asthma.40,41

Other markers of allergic disease at presentation, such as positive skin prick tests and a raised

blood eosinophil count, are related to the severit of current asthma and persistence throughchildhood.

famy y apy

Afamilyhistoryofatopyisthemostclearlydenedriskfactorforatopyandasthmainchildren.The strongest association is with maternal atop, which is an important risk factor for the childhoodonsetofasthmaandforrecurrentwheezingthatpersiststhroughoutchildhood.6,34,37,42,43

Abma g c

Persistent reductions in baseline airwa function and increased airwa responsiveness duringchildhood are associated with having asthma in adult life.23

Table 3: Clinical clues to alternative diagnoses in wheezy children (features not commonly

found in children with asthma)

Paa a amy y Pb ag

Smptoms present from birth or perinatallung problem

Cysticbrosis;chroniclungdiseaseof prematurit; ciliar dskinesia;developmental anomal

Famil histor of unusual chest disease Cysticbrosis;neuromusculardisorder

Severe upper respirator tract disease Defect of host defence; ciliar dskinesia

sympm a g

Persistent moist cough18 Cysticbrosis;bronchiectasis;protracted

bronchitis; recurrent aspiration; hostdefence disorder; ciliar dskinesia

Excessive vomiting Gastro-oesophagealreux(aspiration)

Dsphagia Swallowingproblems(aspiration)

Breathlessness with light-headedness andperipheral tingling

Hperventilation/panic attacks

Inspirator stridor Tracheal or larngeal disorder

Abnormal voice or cr Larngeal problem

Focal signs in chest Developmental anomal; post-infectivesndrome; bronchiectasis; tuberculosis

Finger clubbing Cysticbrosis;bronchiectasis

Failure to thriveCysticbrosis;hostdefencedisorder;gastro-oesophagealreux

ivga

Focal or persistent radiological changes Developmentalanomaly;cysticbrosis;post-infective disorder; recurrentaspiration; inhaled foreign bod;bronchiectasis; tuberculosis


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2+

5

Case detection studies have used smptom questionnaires to screen for asthma in school-agechildren. A small number of questions - about current smptoms, their relation to exercise andtheiroccurrenceatnighthasbeensufcienttodetectasthmarelativelyefciently.11,12,14,44 Theaddition of spirometr11,44 or bronchial hper-responsiveness testing45 to these questionnairesadds little to making a diagnosis of asthma in children.

B fc a am c pc avg ama :

pc ky a y a amaca ca aav ag.

Record the basis on which a diagnosis of asthma is suspected.

2.1.2 ASSESSING THE PROBABLITy OF A DIAGNOSIS OF ASTHMA

Based on the initial clinical assessment it should be possible to determine the probabilit of adiagnosis of asthma.

With a thorough histor and examination, an individual child can usuall be classed into oneof three groups (see Figure 1):

g pbaby diagnosisofasthmalikely

w pbaby diagnosisotherthanasthmalikely

ma pbaby diagnosisuncertain.

2.1.3 HIGH PROBABILITy OF ASTHMA

In children with a high probabilit of asthma based on the initial assessment, move straight toa diagnostic trial of treatment. The initial choice of treatment will be based on an assessmentof the degree of asthma severit (see section 4).

The clinical response to treatment should be reassessed within 2-3 months. In this group,reserve more detailed investigations for those whose response to treatment is poor or thosewith severe disease.19

In children with a high probabilit of asthma:

start a trial of treatment

review and assess response

reserve further testing for those with a poor response.

2.1.4 LOW PROBABILITy OF ASTHMA

Where smptoms, signs or initial investigations suggest that a diagnosis of asthma is unlikel, (seeTable 2), or the point to an alternative diagnosis (see Table 3), consider further investigations.This ma require referral for specialist assessment (see Table 4).

Reconsideradiagnosisofasthmainthosewhodonotrespondtospecictreatments.

In children with a low probabilit of asthma, consider more detailed investigation andspecialist referral.

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2+

2+

2+

3

2+


6

2.1.5 INTERMEDIATE PROBABILITy OF ASTHMA

Insomechildren,andparticularlythosebelowtheageoffourtove,thereisinsufcientevidenceattherstconsultationtomakearmdiagnosisofasthma,butnofeaturestosuggestan alternative diagnosis. There are several possible approaches to reaching a diagnosis inthisgroup.Whichapproachistakenwillbeinuencedbythefrequencyandseverityofthesmptoms.

These approaches include:

Wac wag w vw

Inchildrenwithmild,intermittentwheezeandotherrespiratorysymptomswhichoccuronlywithviralupperrespiratoryinfections(colds),itisoftenreasonabletogivenospecictreatmentand to plan a review of the child after an interval agreed with the parents/carers.

ta am w vw

The choice of treatment (for example, inhaled bronchodilators or corticosteroids) dependson the severit and frequenc of smptoms. Although a trial of therap with inhaled or oralcorticosteroids is widel used to help make a diagnosis of asthma, there is little objectiveevidencetosupportthisapproachinchildrenwithrecurrentwheeze.

Itcanbedifculttoassesstheresponsetotreatmentasanimprovementinsymptomsorlungfunction ma be due to spontaneous remission. If it is unclear whether a child has improved,careful observation during a trial of withdrawing the treatment ma clarif whether a responseto asthma therap has occurred.

spmy a vby g

Inchildren,as in adults, tests ofairowobstruction, airway responsivenessandairwayinammationmayprovidesupportforadiagnosisofasthma.12,44 However, normal results ontesting, especiall if performed when the child is asmptomatic, do not exclude a diagnosis ofasthma.46 Abnormal results ma be seen in children with other respirator diseases. Measuringlung functionin youngchildren isdifcult and requires techniqueswhicharenotwidelyavailable.

Aboveveyearsofage,conventionallungfunctiontestingispossibleinmostchildreninmostsettings.Thisincludesmeasuresofairwayobstruction(spirometryandpeakow),reversibilitywith bronchodilators, and airwa hper-responsiveness.

The relationship between asthma smptoms and lung function tests including bronchodilatorreversibilityiscomplex.Asthmaseverityclassiedbysymptomsanduseofmedicinescorrelatespoorl with single measurements of forced expirator volume in one second (FEV

1) and other

spirometric indices: FEV1is often normal in children with persistent asthma.46,47 Serial measures

ofpeakowvariabilityandFEV1

show poor concordance with disease activit and do notreliabl rule the diagnosis of asthma in or out.47 Measures of gas trapping (residual volume andthe ratio of residual volume to total lung capacit, RV/TLC) ma be superior to measurementsofexpiratoryowatdetectingairwaysobstructionespeciallyinasymptomaticchildren.46,48

AsignicantincreaseinFEV1

(>12% from baseline)49 or PEF after bronchodilator indicatesreversibleairowobstructionandsupportsthediagnosisofasthma.It isalsopredictiveofagood response to inhaled corticosteroids.50 However, an absent response to bronchodilatorsdoes not exclude asthma.51

Between 2-5 ears of age, man children can perform several newer lung function tests that donot rel on their cooperation or the abilit to perform a forced expirator manoeuvre. In general,these tests have not been evaluated as diagnostic tests for asthma. There is often substantialoverlap between the values in children with and without asthma.52Ofthetestsavailable,specicairwas resistance (sRaw), impulse oscillometr (IOS), and measurements of residual volume(RV) appear the most promising.53 While some of these tests have been useful in research, theirrole in clinical practice is uncertain.48,53,54 Most have onl been used in specialist centres and arenot widel available elsewhere. It is often not practical to measure variable airwa obstruction

inchildrenbelowtheageofve.


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2.1.6 CHILDREN WITH AN INTERMEDIATE PROBABILITy OF ASTHMA AND EVIDENCE OFAIRWAy OBSTRUCTION

Asthma is the b far the commonest cause of airwas obstruction on spirometr in children.Obstruction due to other disorders, or due to multiple causes, is much less common in childrenthan in adults. Spirometr and other lung function tests, including tests of PEF variabilit,47 lungvolumes and airwa responsiveness,45 are poor at discriminating between children with asthmaand those with obstruction due to other conditions.

In children with an intermediate probabilit of asthma who can perform spirometr andhave evidence of airwas obstruction, assess the change in FEV

1or PEF in response to an inhaled

bronchodilator(reversibility)and/ortheresponsetoatrialoftreatmentforaspeciedperiod:

if there issignicant reversibility,or if a treatmenttrial isbenecial, adiagnosis ofasthmaisprobable.Continuetotreatasasthma,butaimtondtheminimum

effective dose of therap. At a later point, consider a trial of reduction or withdrawalof treatment.

ifthereisnosignicantreversibility,andatreatmenttrialisnotbenecial,considertests for alternative conditions (see Table 3).

2.1.7 CHILDREN WITH AN INTERMEDIATE PROBABILITy OF ASTHMA WITHOUT EVIDENCE OFAIRWAy OBSTRUCTION

In this group, further investigations, including assessment of atopic status and bronchodilatorresponsiveness and if possible tests of airwa responsiveness, should be considered (see section2.2.1). This is particularl so if there has been a poor response to a trial of treatment or if smptomsare severe. In these circumstances, referral for specialist assessment is indicated.

C i c w a ma pbaby ama w ca pm pmy aav vc away bc:

c g apc a, bca vby a, pb, bcayp-pv g mac, c ma.

c pca a.

2.1.8 CHILDREN WITH AN INTERMEDIATE PROBABILITy OF ASTHMA WHO CANNOT PERFORMSPIROMETRy

Mostchildrenunderveyearsandsomeolderchildrencannotperformspirometry.Inthesechildren,offeratrialoftreatmentforaspecicperiod.Ifthereisclearevidenceofclinicalimprovement, the treatment should be continued and the should be regarded as havingasthma (it ma be appropriate to consider a trial of withdrawal of treatment at a later stage). Ifthetreatmenttrialisnotbenecial,thenconsidertestsforalternativeconditionsandreferralfor specialist assessment.

In children with an intermediate probabilit of asthma who cannot perform spirometr,

offeratrialoftreatmentforaspeciedperiod:

iftreatmentisbenecial,treatasasthmaandarrangeareview

iftreatmentisnotbenecial,stopasthmatreatmentandconsidertestsforalternative conditions and specialist referral.

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3

2++

2+

2++


8

2.2 other inVestiGAtions

2.2.1 TESTS OF AIRWAy HyPER-RESPONSIVENESS

The role of tests of airwa responsiveness (airwa hper-reactivit) in the diagnosis of childhoodasthma is unclear.45,55 For example, a methacholine challenge test has a much lower sensitivitthan smptoms in diagnosing asthma in children and onl marginall increases the diagnosticaccurac after the smptom histor is taken into account.45 However, a negative methacholinetest in children, which has a high negative predictive value, makes a diagnosis of asthmaimprobable.55 Similarl, a negative response to an exercise challenge test is helpful in excludingasthma in children with exercise related breathlessness.56

2.2.2 TEST OF EOSINOPHILIC AIRWAy INFLAMMATION

Eosinophilicinammationinchildrencanbeassessednon-invasivelyusinginducedsputumdifferential eosinophil count or exhaled nitric oxide concentrations (FENO).

Sputum induction is feasible in school age children.57,58 Higher sputum eosinophil counts areassociated with more marked airwas obstruction and reversibilit, greater asthma severit andatop.59 In children with newl diagnosed mild asthma, sputum eosinophilia is present anddeclines with inhaled steroid treatment.58 Sputum induction is possible in approximatel 75%

of children tested, but it is technicall demanding and time consuming and at present remainsa research tool.

It is feasible to measure FENO in unsedated children from the age of 3-4 ears.60 A raised FENO isneitherasensitivenoraspecicmarkerofasthmawithoverlapwithchildrenwhodonothaveasthma.61 FENO is closel linked with atopic status, age and height.62,63 In some studies, FENOcorrelated better with atopic dermatitis and allergic rhinitis than with asthma. It is not closellinked with underling lung function. FENO could not differentiate between groups once atopwas taken into account.64 Home measurements of FENO have a highl variable relationship withother measures of disease activit and var widel from da to da.65

Atpresent,thereisinsufcientevidencetosupportaroleformarkersofeosinophilicinammationin the diagnosis of asthma in children. The ma have a role in assessing severit of disease

or response to treatment.

2.2.3 TESTS OF ATOPy

Positive skin tests,66bloodeosinophilia4%10,oraraisedspecicIgEtocat,dogormite,67,68increasetheprobabilityofasthmainachildwithwheeze,particularlyinchildrenoverveears of age.66It isimportanttorecognisethatnon-atopicwheezingisasfrequentasatopicwheezinginschool-agechildren.69

2.2.4 CHEST X-RAy

A stud in primar care in children age 0-6 ears concluded that a chest X-ra (CXR), in theabsence of a clinical indication, need not be part of the initial diagnostic work up.70

Reserve chest X-ras for children with severe disease or clinical clues suggesting otherconditions.


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9

2.3 suMMArY

fc a am c pc avg ama :

presence of ke features in the histor and clinical examination

careful consideration of alternative diagnoses.

rc ba wc ag ama pc.

Using a structured questionnaire ma produce a more standardised approach to the recordingof presenting clinical features and the basis for a diagnosis of asthma.

1. i c w a g pbaby ama:

move straight to a trial of treatment

reserve further testing for those with a poor response.

2. i c w a w pbaby ama:

consider more detailed investigation and specialist referral.

3. i c w a ma pbaby ama w ca pm pmya av vc away bc, a vby a/ a a am

foraspeciedperiod:

ifthereisreversibility,oriftreatmentisbenecial,treatasasthma

ifthereisinsignicantreversibility,and/ortreatmenttrialisnotbenecial,consider tests for alternative conditions.

4. i c w a ma pbaby ama w ca pm pmy, aav vc away bc, c g apc a, bcavby a, pb, bca yp-pv g mac c.

5. i c w a ma pbaby ama, w ca pm pmy, considertestingforatopicstatusandofferingatrialoftreatmentforaspeciedperiod:

iftreatmentisbenecial,treatasasthma

iftreatmentisnotbenecial,stopasthmatreatment,andconsidertestsforalternativeconditions and specialist referral.

Table 4: Indications for specialist referral in children

Diagnosis unclear or in doubt

Smptoms present from birth or perinatal lung problem

Excessive vomiting or posseting

Severe upper respirator tract infection

Persistent wet or productive cough

Famil histor of unusual chest disease

Failure to thrive

Nasal polps

Unexpectedclinicalndingsegfocalsigns,abnormalvoiceorcry,dysphagia, inspirator stridor

Failure to respond to conventional treatment (particularl inhaled corticosteroids above400 mcg/da or frequent use of steroid tablets)

Parental anxiet or need for reassurance

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10

Clinical assessment

Considerreferral

Continue

treatment andfind minimumeffective dose

Assess compliance and

inhaler technique.Consider further

investigation and/or referral

Continuetreatment

Further investigation.Consider referral

+VE -VE

HIGH PROBABILITY:diagnosis of asthma

likely

INTERMEDIATEPROBABILITY:

diagnosis uncertainor poor response to

asthma treatment

LOW PROBABILITY:other diagnosis likely

Consider tests oflung function*

and atopy

Response? Response?

Investigate/treat othercondition

Trial of asthmatreatment

Yes No No Yes

* Lung function tests include spirometry before and after bronchodilator (test of airway reversibility) andpossible exercise or methacholine challenge (tests of airway responsiveness).Most children over the age of 5 years can perform lung function tests.

Figure 1: Presentation with suspected asthma in children


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2.4 diAGnosis in Adults

The diagnosis of asthma is based on the recognition of a characteristic pattern of smptoms andsigns and the absence of an alternative explanation for them (see Table 5). The ke is to take acareful clinical histor. In man cases this will allow a reasonabl certain diagnosis of asthma,or an alternative diagnosis, to be made. If asthma does appear likel, the histor should alsoexplore possible causes, particularl occupational.

In view of the potential requirement for treatment over man ears, it is important even inrelativel clear cut cases, to tr to obtain objective support for the diagnosis. Whether or notthis should happen before starting treatment depends on the certaint of the initial diagnosis andthe severit of presenting smptoms. Repeated assessment and measurement ma be necessarbeforeconrmatoryevidenceisacquired.

Conrmationhingesondemonstrationofairowobstructionvaryingovershortperiodsoftime.Spirometr, which is now becoming more widel available, is preferable to measurement ofpeakexpiratoryowbecauseitallowscleareridenticationof airowobstruction,and theresults are less dependent on effort. It should be the preferred test where available (althoughsome training is required to obtain reliable recordings and to interpret the results). Of note, anormal spirogram (or PEF) obtained when the patient is not smptomatic does not exclude thediagnosis of asthma.

Results from spirometr are also useful where the initial histor and examination leave genuineuncertaint about the diagnosis. In such cases, the differential diagnosis and approach toinvestigationisdifferentinpatientswithandwithoutairowobstruction(see Figure 2 andTable 6). In patients with a normal or near-normal spirogram when smptomatic, potentialdifferential diagnoses are mainl non-pulmonar; 71,72 these conditions do not respond to inhaledcorticosteroids and bronchodilators. In contrast, in patients with an obstructive spirogram thequestion is less whether the will need inhaled treatment but rather exactl what form andhow intensive this should be.

Othertestsofairowobstruction,airwayresponsivenessandairwayinammationcanalsoprovide support for the diagnosis of asthma, but to what extent the results of the tests alter theprobabilit of a diagnosis of asthma has not been clearl established, nor is it clear when these

tests are best performed.

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Table 5: Clinical features in adults that inuence the probability that episodic respiratorysymptoms are due to asthma

fa a ca pbaby ama

Morethanoneofthefollowingsymptoms:wheeze,breathlessness,chesttightnessandcough, particularl if:

smptoms worse at night and in the earl morning

smptoms in response to exercise, allergen exposure and cold air

smptoms after taking aspirin or beta blockers

Histor of atopic disorder

Famil histor of asthma and/or atopic disorder

Widespreadwheezeheardonauscultationofthechest

Otherwise unexplained low FEV1

or PEF (historical or serial readings)

Otherwise unexplained peripheral blood eosinophilia

fa a w pbaby ama

Prominentdizziness,light-headedness,peripheraltingling

Chronicproductivecoughintheabsenceofwheezeorbreathlessness

Repeatedl normal phsical examination of chest when smptomatic

Voice disturbance

Smptoms with colds onl

Signicantsmokinghistory(ie>20pack-years)

Cardiac disease

Normal PEF or spirometr when smptomatic*

* A normal spirogram/spirometr when not smptomatic does not exclude the diagnosis of asthma. Repeated

measurements of lung function are often more informative than a single assessment.

Baseinitialdiagnosisonacarefulassessmentofsymptomsandameasureofairowobstruction:

in patients with a high probabilit of asthma move straight to a trial of treatment.Reserve further testing for those whose response to a trial of treatment is poor.

in patients with a low probabilit of asthma, whose smptoms are thought to be dueto an alternative diagnosis, investigate and manage accordingl. Reconsider thediagnosis of asthma in those who do not respond.

the preferred approach in patients with an intermediate probabilit of having asthmais to carr out further investigations, including an explicit trial of treatments for

aspeciedperiod, before conrminga diagnosis andestablishingmaintenance

treatment.

d Spirometryisthepreferredinitialtesttoassessthepresenceandseverityofairowbc.


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2.4.1 FURTHER INVESTIGATION OF PATIENTS WITH AN INTERMEDIATE PROBABILITy OFASTHMA

Pa w away bc

Testsofpeakexpiratoryowvariability,lungvolumes,gastransfer,airwayhyper-responsivenessandairwayinammationareoflimitedvalueindiscriminatingpatientswithestablishedairowobstructionduetoasthmafromthosewhoseairowobstructionisduetootherconditions.73-

76Patientsmayhavemorethanonecauseofairowobstruction,whichcomplicatestheinterpretation of an test. In particular, asthma and chronic obstructive pulmonar disease(COPD) commonl coexist.

Offer patients with airwas obstruction and intermediate probabilit of asthma a reversibilitytestand/oratrialoftreatmentforaspeciedperiod:

ifthereissignicantreversibility,orifatreatmenttrialisclearlybenecialtreatas asthma

ifthereisinsignicantreversibilityanda treatmenttrialisnotbenecial,considertests for alternative conditions.*

Pa w away bc

In patients with a normal or near-normal spirogram it is more useful to look for evidence ofairwayhyper-responsivenessand/orairway inammation 71,77-79 These tests are sensitive sonormal results provide the strongest evidence against a diagnosis of asthma.

In patients without evidence of airwas obstruction and with an intermediate probabilitof asthma, arrange further investigations* before commencing treatment.

* see section 2.5 for more detailed information on further tests

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Clinical assessment including spirometry

(or PEF if spirometry not available)

Continue

treatment

Assess compliance andinhaler technique.

Consider furtherinvestigation and/or referral

Continue

treatment

Further investigation.

Consider referral

HIGH PROBABILITY:

diagnosis of asthma

likely

LOW PROBABILITY:

other diagnosis likely

Response? Response?

Investigate/

treat othercondition

Trial of

treatment*

Yes No No Yes

Figure 2: Presentation with suspected asthma in adults

Presentation with suspected asthma

FEV1

/ FVC0.7

INTERMEDIATE

PROBABILITY:

diagnosis uncertain

* See section 2.5.1 See Table 6


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Table 6: Differential diagnosis of asthma in adults, according to the presence or absence ofairow obstruction (FEV

1/FVC 1 x 10 9/l)

Poor response to asthma treatment

Severe asthma exacerbation

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2.5 further inVestiGAtions thAt MAY Be useful in PAtients With An

interMediAte ProBABilitY of AsthMA

Three studies have looked at tests to discriminate patients with asthma from those with conditionsthat are commonl confused with asthma.71,77,79 These studies provide a basis for evaluating thediagnosticvalueofdifferenttests.Table7summarisesthesensitivityandspecicityofdifferentndingsoninvestigation.Asnotallstudiesincludedpatientswithuntreatedasthma,thesevalues

ma underestimate the value of the investigations in clinical practice, where man patients willbe investigated before treatment is started. The diagnostic value of testing ma also be greaterwhen more than one test is done or if there are previous lung function results available in thepatients notes. The choice of test will depend on a number of factors including severit ofsmptoms and local availabilit of tests.

Analternativeandpromisingapproachtotheclassicationofairwaysdiseaseistousetestswhichbest identif patients who are going to respond to corticosteroid therap.78,80 A raised sputumeosinophil count and an increased exhaled nitric oxide concentration (FENO) are more closelrelated to corticosteroid response than other tests in a variet of clinical settings.78,81-83 Thereisalsoevidencethatmarkersofeosinophilicairwayinammationareofvalueinmonitoringthe response to corticosteroid treatment.84-86 More experience with these techniques and moreinformation on the long term response to corticosteroid in patients who do not have a raised

sputum eosinophil count or FENO is needed before this approach can be recommended.Table 7: Estimates of sensitivity and specicity of test results in adults with suspected asthmaand normal or near-normal spirometric values.71,77,79

t nma ag Vay

vy specicity

Methacholine PC20 >8 mg/ml High Medium

Indirect challenges* varies Medium# High

FENO


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A >400 ml improvement in FEV1to either

2agonists or corticosteroid treatment trials strongl

suggests underling asthma. Smaller improvements in FEV1

are less discriminator71 and adecision on continuation of treatment should be based on objective assessment of smptomsusing validated tools (see Table 8). Trials of treatment withdrawal ma be helpful where thereis doubt.

C A feV1

( Pef) a/ ympm:

b a a 400 mcg a abam pa w agc cay andairowobstructionpresentatthetimeofassessment

pa, a cmp p a abam, a a cc(200 mcg twice daily beclometasone equivalent for6-8 weeks) a p (30 mg once daily for 14 days).

2.5.2 PEAK EXPIRATORy FLOW MONITORING

PEF should be recorded as the best of three forced expirator blows from total lung capacitwith a maximum pause of two seconds before blowing.88 The patient can be standing or sitting.Further blows should be done if the largest two PEF are not within 40 l/min.88

PEFisbestusedtoprovideanestimateofvariabilityofairowfrommultiplemeasurements

made over at least two weeks. Increased variabilit ma be evident from twice dail readings.More frequent readings will result in a better estimate 89 but the improved precision is likel tobe achieved at the expense of reduced patient compliance.90

PEF variabilit is best calculated as the difference between the highest and lowest PEF expressedas a percentage of either the mean or highest PEF.91-93

The upper limit of the normal range for the amplitude % highest is around 20% using four ormore PEF readings per da 91,93,94 but ma be lower using twice dail readings.95 Epidemiologicalstudies have shown sensitivities of between 19 and 33% for identifing phsician-diagnosedasthma. 92,96

PEF variabilit can be increased in patients with conditions commonl confused with asthma71,73sothespecicityofabnormalPEFvariabilityislikelytobelessinclinicalpracticethanit

is in population studies.PEF records from frequent readings taken at work and awa from work are useful whenconsidering a diagnosis of occupational asthma (see section 7.8). A computer generated analsisof occupational records which provides an index of the work effect is available.97

Peakowrecordsshouldbeinterpretedwithcautionandwithregardtotheclinicalcontext. The are more useful in the monitoring of patients with established asthma thanin making the initial diagnosis.

2.5.3 ASSESSMENT OF AIRWAy RESPONSIVENESS

Tests of airwa responsiveness have been useful in research but are not et widel available ineverda clinical practice. The most widel used method of measuring airwa responsiveness

relies on measuring response in terms of change in FEV1 a set time after inhalation of increasingconcentrations of histamine or methacholine. The agent can be delivered b breath-activateddosimeter, via a nebuliser using tidal breathing, or via a hand held atomiser.98 The response isusuallyquantiedastheconcentration(ordose)requiredtocausea20%fallinFEV

1(PC20 or

PD20) calculated b linear interpolation of the log concentration or dose-response curve.

Communit studies in adults have consistentl shown that airwa responsiveness has aunimodal distribution with between 90 and 95% of the normal population having a histamineor methacholine PC20 of >8 mg/ml (equivalent to a PD20 of >4 micromoles).92,99,100 This valuehas a sensitivit of between 60-100% in detecting phsician-diagnosed asthma.92,96,99,100

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In patients with normal or near-normal spirometric values, assessment of airwa responsivenessis signicantlybetterthan othertests indiscriminatingpatientswithasthma frompatientswith conditions commonl confused with asthma (see Table 6).71,77 In contrast, tests of airwaresponsivenessareoflittlevalueinpatientswithestablishedairowobstructionasthespecicityis low.73,76

Other potentiall helpful constrictor challenges include indirect challenges such as inhaledmannitol and exercise.101 A positive response to these indirect stimuli (ie a >15% fall in FEV

1

)isaspecicindicatorofasthmabutthetestsarelesssensitivethantestsusingmethacholineand histamine, particularl in patients tested while on treatment.101,102

2.5.4 TESTS OF EOSINOPHILIC AIRWAy INFLAMMATION

Eosinophilicairwayinammationcanbeassessednon-invasivelyusingtheinducedsputumdifferential eosinophil count or the exhaled nitric oxide concentration (FENO).103,104 A raisedsputum eosinophil count (>2%) or FENO (>25 ppb at 50 ml/sec) is seen in 70-80% of patientswith untreated asthma.74,103Neitherndingisspecictoasthma:30-40%ofpatientswithchroniccough 82,105,106 and a similar proportion of patients with COPD81 have abnormal results. There isgrowingevidencethatmeasuresofeosinophilicairwayinammationaremorecloselylinkedto a positive response to corticosteroids than other measures even in patients with diagnosesother than asthma. 81,83,105

Experience with induced sputum and FENO is limited to a few centres and more research needsto be done before an recommendations can be made.

C In patients inwhom thereisdiagnostic uncertainty andnoevidence ofairowbc a am, away pv wv pb.

2.6 MonitorinG AsthMA

In the majorit of patients with asthma smptom-based monitoring is adequate. Patients achievingcontrol of smptoms with treatment have a low risk for exacerbations.107

Table 8 summarises the methodolog, measurement characteristics and interpretation of some

of the validated tools used to assess smptoms and other aspects of asthma. Some measuresprovide information about future risk (ie sputum eosinophil count, airwa responsiveness andFENO) rather than immediate clinical control. Risk reduction, eg minimising future adverseoutcomes such as exacerbations and accelerated decline in lung function, is also a goal ofasthma management.

Amanagementstrategythatcontrolseosinophilicairwayinammation 84-86 or airwa hper-responsiveness108 results in better control of exacerbations than one which controls immediateclinicalmanifestations.Thebenetsofthismoreintensiveapproacharegreaterinpatientswithsevere asthma, when exacerbations can occur frequentl and unpredictabl. More research isneeded to assess the relative roles of the different measures and to address the feasibilit andcost of incorporating them into monitoring protocols before the can be recommended morewidel.


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2.6.1 MONITORING IN PRIMARy CARE

Asthma is best monitored in primar care b routine clinical review on at least an annual basis(see section 8.1.2).

The factors that should be monitored and recorded include:

smptomatic asthma control: best assessed using directive questions such as the RCP 3questions,109 or the Asthma Control Questionnaire or Asthma Control Test (see Table 8),

sincebroadnon-specicquestionsmayunderestimatesymptoms

lung function, assessed b spirometr or b PEF. Reduced lung function compared topreviousl recorded values ma indicate current bronchoconstriction or a long term declinein lung function and should prompt detailed assessment

exacerbations, oral corticosteroid use and time off work or school since last assessment

inhaler technique (see section 5)

compliance (see section 9.2)whichcanbeassessed byreviewingprescriptionrellfrequenc

bronchodilatorreliancewhichcanbeassessedbyreviewingprescriptionrellfrequency

possession of and use of self management plan/personal action plan (see section 9.1).

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Table 8: Summary of tools that can be used to assess asthma.

Mam MgyMamcaacc

Cmm

Spirometr110, 111 Widel available.

Enables cleardemonstration ofairowobstruction.

FEV1

largelindependent ofeffort and highlrepeatable.

Less applicable inacute severe asthma.Onl assesses oneaspect of the diseasestate.

Normal rangeswidel available and

robust.

Short term (20minute) 95% rangefor repeat measureof FEV

160 l/min increasein PEF suggestedas best criteria fordeningreversibility.

Normal range of PEFvariabilitydenedasamplitude % highest


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Mam MgyMamcaacc

Cmm

Roal College ofPhsicians (RCP)3 Questions109

yes/no or gradedresponse to thefollowing threequestions:

In the last week (ormonth)

1. Have ou haddifcultysleepingbecause of ourasthma smptoms(including cough)?

2. Have ou hadour usual asthmasmptoms during theday(cough,wheeze,

chest tightness orbreathlessness)?

3. Has our asthmainterfered with ourusual activities (eghousework, work/school etc)?

No to all questionsconsistent withcontrolled asthma.

Not well validated.

Simplicit isattractive for use inda to da clinical

practice.

Asthma ControlQuestionnaire113-115

Response to 7questions, 5 relatingto smptoms, 1rescue treatment useand 1 FEV

1

.

Response usuallassessed over thepreceding week.

Shortened,vequestion smptomonl questionnaire isjust as valid.

Well controlled0.75,inadequatelycontrolled1.5.95% range for repeatmeasure +/- 0.36.

Minimal importantdifference 0.5.

Well validatedcomposite scoringsstem with a strongbias to smptoms.

Could be used toassess responseto longer termtreatment trials.

Shortenedve-pointquestionnaire isprobabl best forthose with normal ornear normal FEV

1.

Asthma ControlTest (ACT)116, 117

Response to 5questions, 3 related

to smptoms, 1medication use and1 overall control. 5point response score

Well controlled>19.

Within subjectintraclass correlationcoefcient0.77.

95% range forrepeat measure andminimall clinicallimportant differencenotdened.

Could be used toassess response

to longer termtreatment trials,particularl in thosewith normal or near-normal spirometricvalues.

95% range forrepeat measure andminimall clinicallimportant differenceneedtobedened.

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Mam MgyMamcaacc

Cmm

Mini AsthmaQualit of LifeQuestionnaire(AQLQ)114, 118

Response to 15questions in 4domains (smptoms,activit limitations,

emotional functionand environmentalstimuli).

Response usuallassessed over thepreceding week.Closel relatedto larger 32-itemasthma qualit of lifequestionnaire.

95% range for repeatmeasure +/- 0.36.

Minimal importantdifference 0.5.

Well validatedqualit of lifequestionnaire.

Could be used to

assess responseto longer termtreatment trials.

Airwaresponsiveness98,108

Onl available inselected secondarcare facilities.

Responsive tochange (particularlindirect challengessuch as inhaledmannitol).

Less of a ceilingeffect.

Not applicable insevere asthma or in

acute severe asthma

Normalmethacholine PC20

> 8 mg/ml.

95% range for repeatmeasure +/- 1.5-2doubling doses.

Has not been widelused to monitordisease and assesstreatment responses.

Some evidencethat using airwaresponsiveness as anadditional measurefor monitoringasthma results in areduction in asthmaexacerbations andimproved airwa

patholog.


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Mam MgyMamcaacc

Cmm

Exhaled nitricoxide (FENO)78, 85,103, 119, 120

Not widelavailable.

Monitors stillexpensive,

although expectthe technolog tobecome cheaper andmore widespread.

Measurementscan be obtained inalmost all adultsand children over 5ears.

Immediate resultsare available.

Reasonabl closerelationshipbetween FENO andeosinophilic airwainammation,whichis independentof gender, age,atop and inhaledcorticosteroid use.

Relationship is lostin smokers.

Not closel relatedto other measures ofasthma morbidit.

Normal range 50 ppb highlpredictive ofeosinophilic airwainammation.

50 ppb) verpredictive of apositive response to

corticosteroids.Use of FENO toguide corticosteroidtreatment has beenshown to result inanon-signicant25% reductionin exacerbationswith 40% lesscorticosteroid.

Low FENO (


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3.1.2 FOOD ALLERGEN AVOIDANCE

Sensitisation to foods, particularl eggs, frequentl precedes the development of aeroallergand subsequent asthma.135 Food allergen avoidance in pregnanc and postnatall has not beenshown to prevent the later development of asthma.136 Allergen avoidance during pregnancma adversel affect maternal, and perhaps fetal, nutrition.137 High-dose food allergen exposureduring pregnanc ma reduce subsequent sensitisation rates b inducing tolerance.138

B Intheabsenceofanyevidenceofbenetandgiventhepotentialforadverseeffects,maa ag avac g pgacy a aca cmma a agy pvg c ama.

3.1.3 BREAST FEEDING

A sstematic review of observational studies on the allerg preventive effects of breast feedingindicates that it is effective for all infants irrespective of allergic heredit. The preventive effectis more pronounced in high-risk infants provided the are breast fed for at least four months.139However,notallstudieshavedemonstratedbenetandinalargebirthcohorttherewasnoprotective effect against atop and asthma and mabe even an increase in risk.140

Observational studies have the potential to be confounded b, for example, higher rates of breast

feeding in atopic families, and taking this into account, the weight of evidence is in favour ofbreast feeding as a preventive strateg.

C Breastfeedingshouldbeencouragedforitsmanybenets,andasitmayalsohaveapa pcv c a ay ama.

3.1.4 MODIFIED INFANT MILK FORMULAE

Trialsofmodiedmilkformulaehavenotincludedsufcientlylongfollowuptoestablishwhetherthereisanyimpactonasthma.ACochranereviewidentiedinconsistenciesinndingsand methodological concerns amongst studies, which mean that hdrolsed formulae cannotcurrentl be recommended as part of an asthma prevention strateg.141 A review of the use ofsoyformulaefoundnosignicanteffectonasthmaoranyotherallergicdisease.142

Intheabsenceofanyevidenceofbenetfromtheuseofmodiedinfantmilkformulaeitis pb cmm a a agy pvg c ama.

3.1.5 WEANING

Thereareconictingdataontheassociationbetweenearlyintroductionofallergenicfoodsintotheinfantdietandthesubsequentdevelopmentofallergyandatopiceczema.Noevidencewasidentiedinrelationtoasthma.143 In one stud late introduction of egg was associated with anon-signicantincreaseinpre-schoolwheezing.144

i abc vc cm a ama cmma modiedweaningcanbemade.

3 non-PhArMAColoGiCAl MAnAGeMent


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3.1.6 NUTRITIONAL SUPPLEMENTATION - FISH OILS

Fish oils have a high level of omega-3 polunsaturated fatt acids (n-3PUFAs). Western dietshave a low intake of n-3 PUFAs with a corresponding increase in intake of n-6 PUFAs. Thischange has been associated with increasing rates of allergic disease and asthma. 143 Tworandomisedcontrolledstudieshaveinvestigatedearlylifeshoildietarysupplementationinrelation to asthma outcomes in children at high risk of atopic disease (at least one parent orsibling had atop with or without asthma). In a stud, powered onl to detect differences incordblood,maternaldietaryshoilsupplementationduringpregnancywasassociatedwithreduced ctokine release from allergen stimulated cord blood mononuclear cells. However,effectsonclinicaloutcomesatoneyear,inrelationtoatopiceczema,wheezeandcough,weremarginal.145Inasecondstudy,shoilsupplementationcommencinginearlyinfancywithorwithoutadditionalhousedustmiteavoidance,wasassociatedwithasignicantreductioninwheezeat18monthsofage.Byveyearsofageshoilsupplementationwasnotassociatedwith effects on asthma or other atopic diseases.146

Intheabsenceofanyevidenceofbenetfromtheuseofshoilsupplementationinpregnancy pb cmm a a agy pvg c ama.

3.1.7 OTHER NUTRIENTS

A number of observational studies have suggested an increased risk of subsequent asthmafollowing reduced (maternal) intakes of selenium (based on umbilical cord levels),147or vitaminE based on maternal pregnanc intake.148 No intervention studies in relation to selenium orvitaminEhaveyetbeenconductedandoverallthereisinsufcientevidencetomakeanyrecommendations on maternal dietar supplementation as an asthma prevention strateg.143Observational studies suggest that intervention trials are warranted.

3.1.8 MICROBIAL EXPOSURE

Thehygienehypothesissuggestedthatearlyexposuretomicrobialproductswouldswitchoff allergic responses thereb preventing allergic diseases such as asthma. The hpothesis issupported b some epidemiological studies comparing large populations who have or havenot had such exposure.149,150

Theconceptissometimesdescribedasthemicrobialexposurehypothesis.Adoubleblindplacebo controlled trial of the probiotic lactobacillus GG given to mothers resulted in a reducedincidenceofatopiceczemaintheirchildrenbuthadnoeffectonIgEantibodyorallergicskintestresponses.Thesmallsamplesizeandshortfollowupinthisstudylimititsinterpretation.151Othertrialsofarangeofprobioticsandprebioticsarenowinprogress.Thereremainsinsufcientunderstandingoftheecologyofgutoraininfancyinrelationtooutcomes.Bido-bacteriamaybe more important than lactobacilli in reducing susceptibilit to allergic disease.152

Thereisinsufcientevidencetoindicatethattheuseofdietaryprobioticsinpregnancyc cc c ama.

This is a ke area for further work with longer follow up to establish outcomes in relation toasthma.

3.1.9 AVOIDANCE OF TOBACCO SMOKE AND OTHER AIR POLLUTANTS

No evidence has been found to support a link between exposure to environmental tobaccosmoke (ETS) or other air pollutants and the induction of allerg.

Thereisanincreasedriskofinfantwheezingassociatedwithmaternalsmokingduringpregnancywhich adversel affects infant lung function.153-156 Evidence suggests that earl life ETS exposure isassociated with later persistent asthma157,158 with a strong interaction with genetic polmorphismswhich affect antioxidant activit.159

B Pa a pa--b b av may av c wc mkg a c cg ca wzg acy a ca k pama.


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The limited data on antenatal or earl life exposure to other pollutants suggest similar effectstothoseforETS,namelyincreasedinfantwheezing,enhancedbyadditionalETSexposureand antioxidant gene variations.160-162 There is one small stud suggesting that vitamin Csupplementation will modif the combined effects of genetic polmorphisms and pollution onlung function in children with asthma.163 Further research is required before recommendationsfor practice can be made.

3.1.10 IMMUNOTHERAPy

Three observational studies with contemporaneous untreated controls in over 8,000 patientshave shown that allergen immunotherap in individuals with a single allerg reduces thenumbers subsequentl developing new allergic sensitisation over a three to four ear followup.164-166 One trial compared pollen allergen immunotherap in children with allergic rhinitiswith contemporaneous untreated controls and showed a lower rate of onset of asthma duringthree ears of treatment.167 This effect was sustained for two ears after stopping the therap.168More studies are required to establish whether immunotherap might have a role in primarprophlaxis.

3.1.11 IMMUNISATION

Inkeepingwiththemicrobialexposurehypothesissomestudieshavesuggestedanassociationbetween tuberculin responsiveness and subsequent reduced prevalence of allerg, impling aprotective effect of BCG. At present, it is not possible to disentangle whether poor tuberculinresponsiveness represents an underling defect which increases the risk of allerg and asthmaor whether the immunisation itself has a protective effect.169

Investigation of the effects of an other childhood immunisation suggests that at worst thereisnoinuenceonsubsequentallergicdiseaseandmaybesomeprotectiveeffectagainstthedevelopment of asthma.170

C A c mma pc may a vc aav c cc ama.

3.2 seCondArY non-PhArMAColoGiCAl ProPhYlAxis

3.2.1 HOUSE DUST MITE AVOIDANCE

Increased allergen exposure in sensitised individuals is associated with an increase in asthmasmptoms, bronchial hper-responsiveness and deterioration in lung function.127,171,172 However,evidence that reducing allergen exposure can reduce morbidit and/or mortalit in asthma istenuous.Inuncontrolledstudies,childrenandadultshavederivedbenetfromremovaltoalowallergenenvironmentsuchasoccursathighaltitude,althoughthebenetsseenarenotnecessaril attributable to allergen avoidance alone.173

Cochrane reviews on house dust mite control measures in a normal domestic environmenthave concluded that chemical and phsical methods aimed at reducing exposure to housedust mite allergens cannot be recommended.174 Subsequent studies involving large numbersof patients tend to support this conclusion.175,176 Heterogeneit between studies with regardto the intervention and monitoring of outcomes makes interpretation of the sstematic reviewdifcult.

Studiesofmattressbarrier systemshavesuggestedthat benets in relation to treatmentrequirements for asthma and lung function can occur.177,178 Larger and more carefull conductedcontrolled studies emploing combinations of house dust mite reduction strategies are required.At present house dust mite control measures do not appear to be a cost-effective method ofachievingbenet,althoughitisrecognisedthatmanyfamiliesareverycommittedtoattemptsto reduce exposure to triggers.



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Measures to decrease house dust mites have been shown to reduce numbers of house dustmites, but have not been shown to have an effect on asthma severit.

Families with evidence of house dust mite allerg and who wish to tr mite avoidancemight consider the following:

complete barrier bed-covering sstems

removal of carpets

removal of soft tos from bedhigh temperature washing of bed linen

acaricides to soft furnishings

goodventilationwithorwithoutdehumidication.

3.2.2 OTHER ALLERGENS

Animal allergens, particularl from cat and dog, are potent provokers of asthma smptoms.Thereportedeffectsofremovalofpetsfromhomesareparadoxical,witheithernobenetfor asthma179,180 or a potential for continued high exposure to induce a degree of tolerance.181Inhomeswherethereisnocatbutstilldetectablecatallergen,theremaybeabenetfromintroducingadditionalavoidancemeasures suchasairltersand highefciencyvacuum

cleaners for cat allergic patients.182,183

Although fungal exposure has been strongl associated with hospitalisation and increasedmortalityinasthma,nocontrolledtrialshaveaddressedtheefcacyofreductionoffungalexposure in relation to control of asthma. Cockroach allerg is not a common problem in the UKandstudiesofattemptstoavoidthisallergenelsewherehaveproducedconictingresults.184

Studies of individual aeroallergen avoidance strategies show that single interventions havelimitedornobenet.Amultifacetedapproachismorelikelytobeeffectiveifitaddressesallthe indoor asthma triggers. Such approaches ma even be cost effective.185 A strateg with apotential impact on mites, mould allergens and indoor pollutants is the use of a mechanicalventilation sstem to reduce humidit and increase indoor air exchange. The onl trial thathasassessedthisinacontrolledfashionfailedtodemonstrateanysignicanteffects,butthenumbers involved were small.120 A sstematic review of this topic concluded that more research

is required.186

3.3 other enVironMentAl fACtors

3.3.1 SMOKING

Direct or passive exposure to cigarette smoke adversel affects qualit of life, lung function,need for rescue medications for acute episodes of asthma and long term control with inhaledsteroids.187-190

There are ver few trials which have assessed smoking cessation in relation to asthma control.Two studies have demonstrated decreases in childhood asthma severit when parents wereable to stop smoking.191,192 One stud in adults with asthma suggested that smoking cessation

improvedasthma-specicqualityoflife,symptomsanddrugrequirements. 193 Intervention toreduce smoking has had disappointing outcomes.194,195 It is likel that more intensive interventionwill be required to achieve meaningful outcomes.196

Uptake of smoking in teenagers increases the risks of persisting asthma. One stud showeda doubling of risk for the development of asthma over six ears in 14 ear old children whostarted to smoke197(see section 4.2.4 for effect of smoking on treatment).

C Pa w ama b av ab ag mkg mva c w ama a apppa pp p mkg.


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3.3.2 AIR POLLUTION

Challenge studies demonstrate that various pollutants can enhance the response of patients withasthma to allergen inhalation.198,199 Time-series studies suggest that air pollution ma provokeacute asthma attacks or aggravate existing chronic asthma although the effects are ver muchless than those with infection or allergen exposure.200,201 While it might seem likel that movingfrom a highl polluted environment might help, in the UK, asthma is more prevalent in 12-14ear olds in non-metropolitan rather than metropolitan areas.202 Much less attention has beenfocused on indoor pollutants in relation to asthma and more work is required.203,204

3.3.3 IMMUNOTHERAPy

sbca mmapy

Trialsof allergenspecic immunotherapyby subcutaneousinjectionof increasingdosesofallergenextractshaveconsistentlydemonstratedbenecialeffectscomparedwithplacebointhemanagement of allergic asthma. Allergens included house dust mite, grass pollen, tree pollen, catand dog allergen and moulds. Cochrane reviews have concluded that immunotherap reducesasthma smptoms, the use of asthma medications and improves bronchial hper-reactivit. Themost recent review included 36 trials with house dust mite, 20 with pollen, 10 with animalallergens, two with cladosporium mould, one with latex and six with multiple allergens.205

Evidence comparing the roles of immunotherap and pharmacotherap in the management ofasthma is lacking. One stud directl compared allergen immunotherap with inhaled steroidsand found that smptoms and lung function improved more rapidl in the group on inhaledsteroids.206 Further comparative studies are required.

Immunotherap for allergic rhinitis has been shown to have a carr over effect after theraphas stopped.207

B Immunotherapycanbeconsideredinpatientswithasthmawhereaclinicallysignicantag ca b av. t pa v agc ac apym b y c w pa.

sbga mmapy

There has been increasing interest in the use of sublingual immunotherap, which is associatedwith far fewer adverse reactions than subcutaneous immunotherap. A sstematic reviewsuggestedthereweresomebenetsforasthmacontrolbutthemagnitudeoftheeffectwassmall.208 Further randomised controlled trials are required.

B sbga mmapy ca cy b cmm am ama pacc.

3.4 dietArY MAniPulAtion

3.4.1 ELECTROLyTES

Increasing dietar sodium has been implicated in the geographical variations in asthma mortalit209and high sodium intake is associated with increased bronchial hper-responsiveness.210,211 Asystematicreviewofinterventionstudiesreducingsaltintakeidentiedonlyminimaleffectsand concluded that dietar salt reduction could not be recommended in the management ofasthma.212 Low magnesium intakes have been associated with a higher prevalence of asthmawith increasing intake resulting in reduced bronchial hper-responsiveness and higher lungfunction.213Magnesiumplaysabenecialroleinthetreatmentofasthmathroughbronchialsmooth muscle relaxation, leading to the use of intravenous or inhaled preparations ofmagnesium sulphate for acute exacerbations of asthma.214 Studies of oral supplementation arelimited and more trials are required.215-217



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3.4.2 FISH OILS/LIPIDS

In vitro studies suggest that supplementing the diet with omega n-3 fatt acids, which are mostcommonlyfoundinshoils,mightreducetheinammationassociatedwithasthma. 218,219 Resultsfrom observational studies are inconsistent and a Cochrane review of nine randomised controlledtrialsconcludedthattherewasinsufcientevidencetorecommendshoilsupplementationfor the treatment of asthma.220

3.4.3 ANTIOXIDANTS

Observational studies have reported that low vitamin C, vitamin E and selenium intakes areassociated with a higher prevalence of asthma.143 Intervention studies suggest that neithersupplementationwithvitaminC,vitaminEorseleniumisassociatedwithclinicalbenetsinpeople with asthma.221-223 Observational studies in both adults and children have also consistentlshown that a high intake of fresh fruit and vegetable is associated with less asthma and betterpulmonar function.224-230 No intervention studies evaluating the intake of fruit or vegetablesand their effects on asthma have been reported.

3.4.4 WEIGHT REDUCTION IN OBESE PATIENTS WITH ASTHMA

Several studies have reported an association between increasing bod mass index and smptoms

of asthma.231-234 One randomised parallel group stud has shown improved asthma controlfollowing weight reduction in obese patients with asthma.235

C Wg c cmm b pa w ama pm gaa a mpv ama c.

3.4.5 PROBIOTICS

Studieshavesuggestedthatanimbalanceingutoraisassociatedwithahigherriskofdevelopment of allerg.236 Trials have investigated the use of probiotics in the treatment ofestablished allergic disease with variable results.237,238 Onl one stud focused on asthma,ndingadecreaseineosinophiliabutnoeffectonclinicalparameters.239

Intheabsenceofevidenceofbenet,itisnotpossibletorecommendtheuseofprobiotics maagm ama.

3.4.6 IMMUNISATIONS

Anumberoflargestudieshaveconcludedthathighvaccinationcoveragehasnosignicantimpact on an allergic outcome or asthma. There is a suggestion that the higher the vaccinecoverage the greater the possibilit that there is a degree of protection against the developmentofallergyintherstyearsoflife.240-243

There is some discussion about whether BCG immunisation ma confer protection againstallerg and asthma. Research has focused on primar prophlaxis, though there are some studiesinvestigating the use of BCG, with or without allergen, as a means to switch off allergic immuneresponses.Therearesomeobservationssuggestingthatbenetmightoccur,244 but results of

trials have been disappointing.245,246 This is an area that requires further investigation.

Therehas beenconcern thatinuenzavaccinationmightaggravate respiratorysymptoms,thoughanysucheffectwouldbeoutweighedbythebenetsofthevaccination. 247 Studies inchildren have suggested that immunisation with the vaccine does not exacerbate asthma248 buthasasmallbenecialeffectonqualityoflifeinchildrenwithasthma. 249 The immune responseto the immunisation ma be adversel affected b high-dose inhaled corticosteroid therap andthis requires further investigation.250 A Cochrane review of pneumococcal vaccine found verlimitedevidencetosupportitsusespecicallyinindividualswithasthma.251

B imma b am p ay ca a ama. rp vacc may b aa by g- a .


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3.5 CoMPleMentArY And AlternAtiVe MediCine

Successive reviews have concluded that the evidence to support an recommendations oncomplementar or alternative medicine is lacking.252 It is recognised that a lack of evidencedoes not necessaril mean that treatment is ineffective and high qualit research, conducted inthe same rigorous and objective fashion as that for conventional therap, is required.

3.5.1 ACUPUNCTURE

A Cochrane review of 21 trials highlighted man methodological problems with the studiesreviewed. Onl seven of the trials in 174 patients emploed randomisation to active (recognisedintraditionalChinesemedicinetobeofbenetinasthma)orshamacupuncturepoints(withno recognised activit) for the treatment of persistent or chronic asthma. Blinding was a majorproblem in the assessment of the results and there were considerable inconsistencies inmethodology.Thereviewconcludedthattherewasnoevidenceforaclinicallyvaluablebenetforacupunctureandnosignicantbenetsinrelationtolungfunction.253 A later sstematicreview and meta-analsis of 11 randomised controlled trials found no evidence of an effectin reducing asthma severit but a suggestion that where broncho-constriction was induced toestablishefcacyofacupuncturetherewasabenecialeffect.Concernwasexpressedaboutpotential preferential publication in favour of positive outcome studies.254 Two other trials of

acupuncture in relation to induced asthma were also negative.

255,256

3.5.2 AIR IONISERS

Ionisershavebeenwidelypromotedasbeingofbenetforpatientswithasthma.ACochranereviewofvestudiesusingnegativeiongeneratorsandonewithapositiveiongeneratorfoundnoevidenceofbenetinreducingsymptomsinpatientswithasthma. 257 One stud demonstratedanincreaseinnight-timecoughtoalevelwhichapproachedstatisticalsignicance.258

A A a cmm am ama.

3.5.3 BREATHING EXERCISES INCLUDING yOGA AND THE BUTEyKO BREATHINGTECHNIQUE

The principle of oga and Buteko breathing technique is to control hperventilation b loweringrespirator frequenc. A Cochrane review of breathing exercises found no change in routinemeasures of lung function.259 One stud showed a small reduction in airwa responsiveness tohistamine utilising pranaama, a form of oga breathing exercise.260

TheButeykobreathingtechniquespecicallyfocusesoncontrolofhyperventilationandanyensuinghypocapnia.Fourclinicaltrialssuggestbenetsintermsofreducedsymptomsandbronchodilator usage but no effect on lung function.261-264

B Byk bag cq may b c p pa c ympm ama.

3.5.4 HERBAL AND TRADITIONAL CHINESE MEDICINE

ACochranereviewidentied17trials,nineofwhichreportedsomeimprovementinlungfunction but it was not clear that the results would be generalisable.265 A more recent double blindplacebo controlled trial of a Chinese herb decoction (Ding Chuan Tang) showed improvementin airwa hper-responsiveness in children with stable asthma.266Itisdifculttodisentanglethe effects of multiple ingredients; Ding Chuan Tang for example contains nine components.Inasecondstudy,100childrenwithasthmafoundthatave-herbmixturegavesomebenetsin relation to lung function and smptoms compared with placebo.267

The conclusions of these trials of Chinese herbal therap are not generalisable due to variationsin the herbal mixtures and stud designs. There are likel to be pharmacologicall activeingredients in the mixtures and further investigations are warranted. There is a need for largeappropriatel powered placebo controlled studies.



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3.5.5 HOMEOPATHy

ACochranereviewidentiedonlythreemethodologicallysoundrandomisedcontrolledtrials,two of which reported some positive effects. A criticism of the studies was that the did notemplo individualised homeopath, which is the essence of this approach to treatment. 268

A more recent trial of individualised homeopath in childhood asthma, which was placebocontrolledandappropriatelypowered,failedtoshowanyevidenceofbenetoverconventionaltreatment in primar care.269

3.5.6 HyPNOSIS AND RELAXATION THERAPIES

Asystematicreviewofrelaxationtherapies,includinghypnotherapy,identiedvecontrolledtrials,twoofwhichshowedsomebenets.Overallthemethodologyofthestudieswaspoorandthereviewconcludedthattherewasalackofevidenceofefcacybutthatmusclerelaxationcouldconceivablybenetlungfunctioninpatientswithasthma.270

3.6 other CoMPleMentArY or AlternAtiVe APProAChes

3.6.1 MANUAL THERAPy INCLUDING MASSAGE AND SPINAL MANIPULATION

ACochranereviewidentiedfourrelevantRCTs.271 The two trials of chiropractic suggest thatthere is no place for this modalit of treatment in the management of asthma. No conclusionscan be drawn on massage therap.

3.6.2 PHySICAL EXERCISE TRAINING

A Cochrane review 259 has shown no effect of phsical training on PEF, FEV1, FVC or VEmax.

However, oxgen consumption, maximum heart rate, and work capacit all increasedsignicantly.Moststudiesdiscussedthepotentialproblemsofexerciseinducedasthma,butnone made an observations on this phenomenon. As phsical training improves indices ofcardiopulmonaryefciency,itshouldbeseenaspartofageneralapproachtoimprovinglifestyleand rehabilitation in asthma, with appropriate precautions advised about exercise inducedasthma (see section 4.7.2).

3.6.3 FAMILy THERAPy

ACochranereview identied two trials, in55 children, showing that familytherapymaybe a useful adjunct to medication in children with asthma.272Smallstudysizelimitstherecommendations.

Indifcultchildhoodasthma,theremaybearoleforfamilytherapyasanadjuncttopharmacotherap.


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4 Pamacgca maagm

Theaimofasthmamanagementiscontrolofthedisease.Controlofasthmaisdenedas:

no datime smptoms

no night-time awakening due to asthma

no need for rescue medication

no exacerbations

no limitations on activit including exercise

normal lung function (in practical terms FEV1

and/or PEF>80% predicted or best) withminimal side effects.

In clinical practice patients ma have different goals and ma wish to balance the aims ofasthma management against the potential side effects or inconvenience of taking medicationnecessar to achieve perfect control.

Lung function measurements cannot be reliabl used to guide asthma management inchildren under five ears of age.

Astepwiseapproachaimstoabolishsymptomsassoonaspossibleandtooptimisepeakowb starting treatment at the level most likel to achieve this. Patients should start treatment at thestep most appropriate to the initial severit of their asthma. The aim is to achieve earl controland to maintain b stepping up treatment as necessar and stepping down when control is good(see gures 4, 5 and 6 for summaries of stepwise management in adults and children).

Before initiating a new drug therap practitioners should check compliance with existingtherapies (see section 9.2), inhaler technique (see section 5) and eliminate trigger factors(see section 3).

Until Ma 2009 all doses of inhaled steroids in this section have been referenced againstbeclometasone (BDP) given via CFC-MDIs (metered dose inhaler). As BDP CFC is phased out,the reference inhaled steroid will be the BDP-HFA equivalent, which can be used at the samedosage. Adjustments to doses will have to be made for other devices and other corticosteroidmolecules (see section 4.2).

In this and the following section, each recommendation has been graded and the supportingevidence assessed for adults (>12 ears old), children 5-12 ears, and children under 5 ears.The evidence is less clear in children under two and the threshold for seeking an expert opinionshould be lowest in these children.

1 2 3 1 A2 C ag 5-12 ya3 C 5 ya

rcmma appy ag gp.

4 PhArMAColoGiCAl MAnAGeMent

Revised

2009


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5-12ears

>12ears

12ears

10-12 puffs per da is a marker of poorl

controlled asthma that puts patients at risk of fatal or near-fatal asthma.

Patients with a high usage of inhaled short-acting 2

agonists should have their asthmamanagement reviewed.

4.2 steP 2: introduCtion of reGulAr PreVenter therAPY

For steps 2, 3, and 4, treatments have been judged on their abilit to improve smptoms,improve lung function, and prevent exacerbations, with an acceptable safet profile.Improvement of qualit of life, while important, is the subject of too few studies to be used to

make recommendations at present.

4.2.1 COMPARISON OF INHALED STEROIDS

Man studies comparing different inhaled steroids are of inadequate design and have beenomitted from further assessment. In view of the clear differences between normal volunteersand asthma patients in the absorption of inhaled steroids, data from normal volunteers havenot been taken into account. Onl studies in which more than one dose of at least one of theinhaledsteroidsorbothsafetyandefcacyhadbeenstudiedtogetherinthesametrialwereevaluated. Non-blinded studies also had to be considered because of the problems of obtainingcompetitors deliver devices. A series of Cochrane reviews comparing different inhaled steroidsusing a different methodolog have come to the same conclusion.

BDP and budesonide are approximatel equivalent in clinical practice, although there ma bevariations with different deliver devices. There is limited evidence from two open studies ofless than ideal design that budesonide via the turbohaler is more clinicall effective.295 However,at present a 1:1 ratio should be assumed when changing between BDP and budesonide.

Fluticasone provides equal clinical activit to BDP and budesonide at half the dosage. Theevidence that it causes fewer side effects at doses with equal clinical effect is limited.

Mometasone appears to provide equal clinical activit to BDP and budesonide at half thedosage.296 The relative safet of mometasone is not full established.


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Table 8b: Equivalent doses of inhaled steroids relative to BDP and current licensed ageindications

These dosage equivalents are approximate and will depend on other factors such as inhalertechnique.

uK cc cv

s eqva >12

ya

5 12

ya


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4.2.3 SAFETy OF INHALED STEROIDS

Thesafetyofinhaledsteroidsisofcrucialimportanceandabalancebetweenbenetsandrisks for each individual needs to be assessed. Account should be taken of other topical steroidtherap when assessing sstemic risk. It has been suggested that steroid warning cards should beissuedtopatientsonhigherdoseinhaledsteroids,butthebenetsandpossibledisadvantages,particularlywithregardtocompliance,ofsuchapolicyremaintobedened.

Adults

There is little evidence that doses below 800 mcg BDP per da cause an short term detrimentaleffects apart from the local side effects of dsphonia and oral candidiasis. However, the possibilitof long term effects on bone has been raised. One sstematic review reported no effect onbone densit at doses up to 1,000 mcg BDP per da.291Thesignicanceofsmallbiochemicalchanges in adrenocortical function is unknown.

Titrate the dose of inhaled steroid to the lowest dose at which effective control of asthmais maintained.

Children

Administration of inhaled steroids at or above 400 mcg BDP a da or equivalent ma be associated

with sstemic side effects.292 These ma include growth failure and adrenal suppression. Isolatedgrowth failure is not a reliable indicator of adrenal suppression and monitoring growth cannotbe used as a screening test of adrenal function.290,293

Clinicaladrenalinsufciencyhasbeenidentiedinasmallnumberofchildrenwhohavebecome acutel unwell at the time of intercurrent illness. Most of these children had beentreated with high doses of inhaled corticosteroids. The dose or duration of inhaled steroidtreatmentrequiredtoplaceachildatriskofclinicaladrenalinsufciencyisunknownbutislikelytooccurat800mcgBDPperdayorequivalent.Thelow-doseACTHtestisconsideredto provide a phsiological stimulation of adrenal responsiveness but it is not known how usefulsuchasensitivetestisatpredictingclinicallyrelevantadrenalinsufciency. 59,294 In addition,it is unknown how frequentl tests of adrenal function would need to be repeated if a childremained on high-dose inhaled corticosteroid. At higher doses, add-on agents, for example,

long-acting 2 agonists, should be activel considered.

While the use of inhaled corticosteroids ma be associated with adverse effects (including thepotential to reduced bone mineral densit) with careful inhaled steroid dose adjustment thisrisk is likel to be outweighed b their abilit to reduce the need for multiple bursts of oralcorticosteroids.771

Monitor height of children on high doses of inhaled steroids on a regular basis.

The lowest dose of inhaled steroids compatible with maintaining disease control shouldbe used.

Forchildrentreatedwith800mcgBDPperdayorequivalent:

Specific written advice about steroid replacement (eg Steroid Alert Card) in the event ofa severe intercurrent illness or surger should be part of the management plan.

The child should be under the care of a specialist paediatrician for the duration of thetreatment.

Considerthepossibilityofadrenalinsufciencyinanychildmaintainedoninhaledsteroidspresenting with shock or a decreased level of consciousness; serum biochemistr and bloodglucose levels should be checked urgentl. Consider whether intramuscular (IM) hdrocortisoneis required.

4 PhArMAColoGiCAl MAnAGeMent


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12ears

5- 306,307

Thereisnoclearevidenceofbenetwithsodiumcromoglicateinchildrenaged-


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Figure 4: Summary of stepwise management in adults

Inhaledshort-acting

2

agonistasrequired

STEP1

Mildintermittentasthma

Addinhaledsteroid200-800

mcg/day*

400mcgisanappropriate

startingdoseformanypatients

Startatdoseofinhaled

steroidappropriateto

severityofdisease.

STEP2

Regularpreventertherapy

1.A

ddinhaledlong-acting

1.A


2agonist(LABA)

2.A

ssesscontrolofasthma:

goodresponseto

LABA-continueLABA

benefitfromLABAbut

controlstillinadequate

-continueLABAand

increaseinhaledsteroid

doseto800mcg/day*(if

notalreadyonthisdose)

noresponsetoLABA

-stopLABAandincrease

inhaledsteroidto800

mcg/day.*Ifcontrol

stillinadequate,institute

trialofothertherapies,

leukotrienereceptor

antagonistorSR

theophylline

1.A


STEP3

Initialadd-ontherapy

Considertrialsof:

increasinginhaledsteroid

upto20

00mcg/day*

addition

ofafourthdrug

e.g.leukotrienereceptor

antagon

ist,SRtheophylline,

2agonisttablet

S

TEP4

Persiste

ntpoorcontrol

Usedailysteroidtablet

inlowestdosep

roviding

adequatecontro

l

Maintainhighdoseinhaled

steroidat2000mcg/day*

Considerothert

reatmentsto

minimisetheuseofsteroid

tablets

Referpatientforspecialistcare

STEP

5

Continuouso

rf

Documents

Asthma British 2009