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J Townshend, S Hails and M MckeanManagement of asthma in children

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CLINICAL REVIEW

Management of asthma in childrenJ Townshend, S Hails, M Mckean

This review on childhood asthma focuses on acuteand chronic management in relation to the asthmaphenotypes reviewed in our previous article.1 Itincludes when to refer to hospital services and updateson new and emerging treatments.

Managing asthma requires not only an understand-ing of specific treatments but also a commitment to

supporting the child and family as they learn to dealwith this long term illness. Key areas of managementinclude acute asthma management plans, day to daypreventer treatments, monitoring for side effects,and an emphasis on trying to achieve a normal levelof functioning. For young children and those withatypical features, repeated review also provides anopportunity to revisit the diagnosis.

What is the acute management of asthma and episodic

viral wheeze?

An exacerbation of asthma can occur at any time and inchildhoodis mostcommonly precipitated by viral upper

respiratory tract infections. The British ThoracicSociety/Scottish Intercollegiate Guidelines Networkguideline recommends that all patients with asthmashould have a written, individualised asthma manage-ment plan that includes clear and easy to follow instruc-tions on acute management and guidance on dailytreatment and when to call emergency services (fig 1).2

The management of episodic viral wheeze is contro-versial. Many doctors still favour an acute wheezemanagement plan similar to that used in acute asthma,with the use of regular bronchodilators and corticoster-oids. Little evidence exists in the literature to supportthis approach, however. A Cochrane review of short

acting2 agonists found eight studies involving 229patients and found no benefit in episodic viralwheeze and persistent wheeze in children under theage of 2 years.4 The benefit of anticholinergics in the

management of episodic viral wheeze is similarlyunclear. A Cochrane review of six studies involving321 infants under the age of 2 years showed no impacton symptoms or clinical course of the acute illness.5

The studies were heterogeneous, however, leaving thepossibility of a subgroup that may benefit. Currently, theindiscriminateuse of anticholinergics andshortacting2

agonists in the management of acute episodic viralwheeze is not recommended. Although these agentsare still used for young children with wheeze, the doctorshould ensure that a clear clinical benefit is achievedbefore they are regularly prescribed.

A short course of systemic corticosteroids at theonset of symptoms of episodic viral wheeze has beenshown to reduce the need for additional drugs ininfants admitted to hospital,67 and the use of highdose (1.6-2.25 mg/day) inhaled corticosteroids mayalso have some benefit if given at the onset of symp-toms of upper respiratory tract infection in childrenknown to have episodic viral wheeze.8

What is the long term management of atopic asthma?

The British Thoracic Society/Scottish IntercollegiateGuidelines Network guideline has clearly defined thelong term management of atopic asthma,2 with varia-tions according to the age of the child (figures 2 and 3).Treatment follows a stepwise approach until control isachieved, and patients arethen maintained on the low-est level of treatment that still achieves control. Thelatest update to the guidelines in 2005 recommendedchanges in four key areas. (1) Inhaled corticosteroidsshould be introduced in milder cases than previouslyrecommended. (2) Education should be offered to

families, and each child should receive an individualasthma management plan. (3) Clinicians in primarycare should have specific training in asthma manage-ment, as this improves diagnosis, prescribing, educa-tion, monitoring, and continuity of care. (4) Patientswith asthma who are admitted to hospital should bereviewed by clinicians with particular expertise inasthma management, preferably within 30 days.

We will not repeat in this review all the advice givenin the guideline. However, a few areas are worthspecific comment.

Inhaled corticosteroidsfriend or foe?

The introduction of inhaled corticosteroids has trans-formed the management of chronic asthma.9

Searches and selection criteria

This review draws on the chapter on asthma and otherwheezing disorders in children in Clinical Evidence,search date October 2006. We searched Medline inJanuary 2007 with the terms asthma, viral inducedwheeze, childhood, prevalence, symptoms, diagnosis,management, corticosteroids, and adrenalsuppression. We alsoused theBritish Thoracic Society/Scottish Intercollegiate Guidelines Network guideline

on the management of asthma

See last weeks review of

diagnosis of asthma in children(pp 198-202)

Paediatric Respiratory Unit,Royal Victoria Infirmary,Newcastle upon Tyne, NE1 4LP

Correspondence to: M Mckeanm.c.mckean@ncl.ac.uk

BMJ 2007;335:253-7

doi:10.1136/bmj.39255.692222.AE

BMJ | 4 AUGUST 2007 | VOLUME 335 253

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Considerable benefit for all major clinical outcomemeasures is seen with low and moderate doses(beclametasone to 400 g/day or fluticasone to200 g/day). Beyond this, however, the dose responsecurve is relatively flat,10 and increases bring onlylimited improvement.

Although side effects areunlikelyat doses of 400g/day of beclometasone equivalent,11 they have becomeapparent at the higherdoses. A Cochranereview of the

effect of inhaled corticosteroids on height hassuggested that height velocity in the short term isreduced with doses of over 400g/day beclometasone(0.8 cm/year),1213 but longer term studies have shownthat children do in fact attain a normaladult height.14 Amore worrying concern in recent years has beenreports of adrenal suppression in children takinghigher dose inhaled corticosteroid,1516 several reportswith clinical evidence of acute adrenal crisis withhypoglycaemia,1117 and one reported death in 2001.18

These reports have prompted some asthma specialists

to recommend that all children on off licence dosesof inhaled corticosteroid (licensed doses for childrenare up to 800 g/day beclometasone or budesonide,which is equivalent to 400 g/day fluticasone) shouldhave a low dose short adrenocorticotrophic hormonestimulationtest.15 Caution is neededin interpretingthe

results of this test, however, as the repeatability inchildren with asthma has recently been questioned.19

Practically, if a child seems to need higher doses ofinhaled corticosteroid than those recommended by themanufacturer, questions that need to be considered are: Is the diagnosis correct? Is the asthma genuinely severe? Are avoidable triggers present? Is concordance and delivery adequate? Are other treatments available that could be added

to reduce the dose of inhaled corticosteroidneeded?

This will ensure that all treatment options are

maximised and alternatives considered before thedose of inhaled corticosteroid is increased to one thatmay result in serious adverse effects.

Long acting agonists in asthma

Onemethod of achieving better asthma control withoutincreasing the dose of inhaled corticosteroids is theaddition of long acting2 agonists. These offer a longerdurationof bronchodilation in children whenusedinter-mittently asa singledose,20andin adolescents andadultstheadditionof a long acting2 agonist to regular inhaledcorticosteroids provides better control of symptomsthan does doubling the dose of inhaled

corticosteroids.21

The British Thoracic Society/ScottishIntercollegiate Guidelines Network guideline advocatesa trial of the addition of short acting 2 agonists inpatients not controlled sufficiently on inhaled cortico-steroid alone. However, in the paediatric population, noevidence exists of a bronchodilator effect or protectionagainst exacerbations with the addition of short acting2agonists to inhaled corticosteroids.22Moreover,severalstudies have shown an increasedriskof exacerbationandhospital admission in children on this combination.22

Evidence also exists of reduced protection against

Asthma exacerbation

2-10 puffs salbutamol 100 g up tofour hourly via large volume spacer*

Little or noimprovement Responding to highdoses four hourly Respondingwell

Call ambulanceGive one puffsalbutamol every30 secondsthrough largevolume spacer

Start oralcorticosteroids

Start oralcorticosteroids

for 3-5 days

Continue treatmentLook for signsof deterioration

Fig 1 | Informationto be incorporated intoan individual asthma

management plan.

*Use of large volume spacer to deliver bronchodilator has

been shown to be as effective as delivery through nebuliser,3

but adequate doses of bronchodilator must be administered

Features thatwarrant referral to a specialist clinic

Feature Comment

Poor response to 800 g/day beclometasone (or equivalent) Patient has reached step 4 of BTS/SIGN guideline and should be on otherasthma treatments; concordance and drug delivery need carefulassessment

Poor response to 400 g/day beclometasone (or equivalent) and needsadd-on treatments that general practitioner is unfamiliar with

Young child (

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exercise induced asthma with regular short acting2agonists. Recent studies in adults have shown anincrease in the relative risk of death from asthma withthe use of salmeterol.

These findings have raised concern about the use ofshortacting2 agonistsas regular preventive treatmentin the paediatric population. A subgroup of paediatricasthma patients who benefit from the addition of shortacting2 agonists to inhaled corticosteroids may wellexist, but until appropriate studies are done the safetyof these drugs remains unclear.23 A short term trial inpatients poorly controlled on short acting2 agonistsand inhaled corticosteroids alone should therefore befollowed by regular review and careful assessment of

the response to treatment, so that treatments can bestopped if no clear benefit is shown.

Can inhaled corticosteroids help to prevent asthma

developing?

The development of asthma often starts with recurrentdiscrete wheezy episodes.24 Early intervention in theform of either episodic or regular inhaled cortico-steroids has been suggested to prevent these infantsdeveloping asthma in later life. However, severalstudies have shown no disease modifying effect in thisgroup of patients.24-26 The current recommendations

are that inhaled corticosteroids should be reservedfor children with persistent symptoms.

How can drug delivery be optimised, both at home and

school?

To achieve optimum inhaled drug delivery for children

with asthma, the correct device must be prescribedalongside education on how to use it, as poor inhalertechnique can mean that more than 80% of the drug isswallowed, thus reducing effectiveness.27 The NationalInstitute for Health and Clinical Excellence haspublished guidance on recommended inhaler devicesfor children aged under 5 and 5-15 years.2829

Receipt of asthma inhalers by children at school canoften be of concern to parents. School staff are notrequired to administer asthma drugs to pupils except inan emergency situation, but many staff are happy tohelp. School staff should have education on managingpupils with asthma readily available, along with instruc-tion on the correct ways to administer inhaled drugs.This can be done through the school health adviser.All schools should have their own policy on asthma.Asthma UK (www.asthma.org.uk) has published com-prehensive guidelines for the management of pupilswith asthma and recommendations for policy develop-ment to which head teachers should be directed.

Do effective treatments for long term management of

episodic viral wheeze exist?

No regular drugs are currently recommended for theprevention of episodic viral wheeze. Unlike atopicasthma, regular low dose inhaled corticosteroids offerno benefit in the prevention of episodic viral wheeze.8

Recently, leukotriene receptor antagonists have shownsomepromiseinthepreventionofepisodicviralwheeze.Onemulticentredouble blind study showed that regulartreatment with montelukast reduced the rate of exacer-bations by 32% and corticosteroid use by 30%,30 butlarger independent trials are needed to support this.

When is referral to tertiary services warranted?

The point of referral to a specialised clinic depends onmany variables, including the expertise of the primarycare team, the support they have from nursing staff,their locality,and ease of accessto a specialised service.Most general paediatricians will have good knowledge

and expertise in assessing and managing childhoodasthmaand canprovide a usefulsecond opinion. How-ever, not all have access to specialist asthma nurses orinvestigationsthatmighthelptosecurethediagnosisor

Refer to respiratory paediatrician

In children 2-5 years consider trial of leukotriene receptor antagonistIn children

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explore differential diagnoses. The British ThoracicSociety/Scottish Intercollegiate Guidelines Networkguideline recommends referral to a paediatrician withspecialised expertise in childhoodasthma whena childreaches step 4 (patients needing an increase in inhaledbeclometasone up to 800 g/day or equivalent).2

However, if the general practitioner is unfamiliarwith treatments that are added on to inhaledcorticosteroids an earlier referral is sensible; indeedmost asthma specialist services will wish to receivereferrals if 400g/day of beclometasone or equivalentis not achieving control. The table shows features thatmight warrant referral.

What are the therapeutic options in severe asthma?

Occasionally, children do not respond well to conven-tional treatments and continue to have symptoms oreven have severe, acute, or life threatening episodes ofasthma. These children aremanaged with long term oralprednisolone and need frequent visits to the specialised

asthma clinic, where symptoms and side effects can bemonitored. Themostcommoncausefora poor responseto oralcorticosteroids is non-compliance.31 If symptomspersist despite regular steroid treatment, monthlysubcutaneousinjections of steroid canbe givento ensurecompliance. For those who continue to have poorcontrol, additional immunosuppression, such asciclosporin or methotrexate, may be tried. Althoughlittle evidence exists for benefit in children, this optionis used in those who have severe side effects from oralcorticosteroids or continue to have severe asthmadespite exhausting all alternatives.

Alternative treatments include continuous subcuta-neous terbutaline, which has been used with success inthe past and can be well tolerated.32 More recently, theanti-IgE monoclonal antibody omalizumab has beenused in children with asthma as an alternative tomethotrexate. It binds to the IgE epitope that binds theIgE receptor, thus preventing IgE mediated mast celldegranulation. Several trials have shown clinical benefitfrom omalizumab in the form of significantly fewerexacerbations per patient and a significantly lowerpercentage of patients having exacerbations.33 The twoweekly or four weekly subcutaneous injections seem tobe well tolerated, and some specific benefit seems to beachieved, with measurablereductions in the dose of oralprednisolone needed.

Some specialists advocate detailed invasive investiga-tions in these difficult to treat patients, includingmeasurement of airway eosinophils and neutrophils inbroncho-alveolar lavages. They hypothesise thatdifferent mechanisms are responsible in individualcases and that targeting treatment to recognised sub-groupsfor example, ciclosporin for persistent eosino-philic inflammation or azithromycin for persistentneutrophilic inflammation31is a more effectivestrategy.Much still remains to be learnt, however, aboutspecific treatments in this difficult group of patients.

Contributors: All authors contributed to the collection of data and to the text

of the paper. MM is the guarantor.Competing interests: None declared.

Provenance and peer review: Commissioned; externally peer reviewed.

1 TownshendJ, Hails S, MckeanM. Diagnosisof asthmain childrenand management. BMJ2007;335:198-202.

2 British ThoracicSociety,ScottishIntercollegiate Guidelines Network.British guideline on the management of asthma: a national clinicalguideline. Revised edition November2005 (www.brit-thoracic.org.uk/Guidelinessince%201997_asthma_html).

3 Dewar AL,Stewart A, Cogswell JJ, Connett GJ. A randomisedcontrolled trial toassessthe relativebenefits of large volume spacersand nebulisers to treat acuteasthma in hospital.ArchDis Child1999;80:421-3.

4 Chavasse R,SeddonP, BaraA, McKeanM. Short actingbeta2-agonists forrecurrent wheezein children under twoyears of age.CochraneDatabase SystRev2002;(2):CD002873.

5 Everard ML, BaraA, KurianM, Elliott TM, DucharmeF, Mayowe V.

Anticholinergic drugs forwheeze in children under theage of twoyears.CochraneDatabaseSyst Rev2005;(3):CD001279.

SUMMARY POINTS

Inhaled corticosteroids, although safe if given at therecommended dose, can have important adverse effects ifgiven above it, including adrenal suppression

Longacting2 antagonistscan be usedas add-on treatmentto avoid further increases in the dose of inhaled

corticosteroid but can be associated with increased risk ofexacerbations and hospital admission

Long acting2 antagonists should therefore be continuedonly if a demonstrable response to treatment occurs

Inhaled corticosteroids do not prevent the development ofasthma

Low dose inhaled corticosteroid should not be used aspreventive treatment for episodic viral wheeze

Referral to a specialist centre should be considered when achild reaches step4 of the British ThoracicSociety/ScottishIntercollegiate Guidelines Network guideline or earlier,depending on the expertise of the general practitioner andthe resources available

ADDITIONAL EDUCATIONAL RESOURCES

British Thoracic Society, Scottish IntercollegiateGuidelines Network. British guideline on themanagement of asthma: a national clinical guideline.Revised edition November 2005 (www.brit-thoracic.org.uk/Guidelinessince%201997_asthma_html)

Lung and Asthma Information Agency (www.laia.ac.uk/)Provides epidemiological data on asthma

Information resources for patients

Asthma UK (www.asthma.org.uk)

Comprehensiveinformation resource on asthma for parents andchildren, including chat rooms and information oneducational holidays

Patient UK. Asthma (www.patient.co.uk/showdoc/23068680/)Provides information on what asthma isand on the different treatment options available

Scottish Intercollegiate Guidelines Network (www.sign.ac.uk/)Provides a link to the updated guidelines onthe management of asthma and the evidence behindthe guidelines

British Thoracic Society (www.brit-thoracic.org.uk/)Provides a link to the updated guidelines on themanagement of asthma and the evidence behind the

guidelines

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6 OommenA, Lambert PC, Grigg J. Efficacyof a short courseof parent-initiated oral prednisolone for viral wheeze in children aged1-5 years: randomised controlled trial. Lancet2003;362:1433-8.

7 CsonkaP, KailaM, LaippalaP, Iso-MustajarviM, VesikariT, AshornP.Oral prednisolone in theacutemanagementof childrenaged 6 to35 months with viral respiratory infection-induced lower airwaysdisease: a randomised placebo controlled trial.J Pediatr2003;143:725-30.

8 McKeanM, Duchame F. Inhaled steroidsfor episodicviralwheeze of

childhood.CochraneDatabaseSystRev2000;(1):CD001107.9 Russell G. Very high dose inhaled steroids: panacea or poison?Arch

DisChild2006;91:802-4.10 Masoli M, Weatherall M, Holt S, Beasley R. Systematic reviewof the

dose-response relation of inhaled fluticasone propionate.ArchDisChild2004;89:902-7.

11 Todd GRG, AceriniCL, Ross-RussellR, ZahraS, WarnerJT, McCance D.Survey of adrenal crisis associated with inhaled corticosteroids inthe United Kingdom.ArchDisChild2002;87:457-61.

12 McKenzie SA,Bush A. Difficultasthma in children.ArchDisChild2003;88:168-9.

13 SkonerDP, Szefler SJ, Welch M, Walton-Bowen K, Cruz-Rivera M,Smith JA. Longitudinal growth in infants and young children treatedwith budesonide inhalation suspension for persistent asthma.JAllergyClin Immunol2000;105:259-68.

14 Agertoft L, PedersenS. Effectof long-termtreatmentwith inhaledbudesonide on adult height in children with asthma.N EnglJ Med2000;343:1064-9.

15 Russell G. Steroidsand adrenal suppression: plus a change.ArchDisChild2004;89:893-5.

16 Russell G. Inhaled corticosteroids andadrenalinsufficiency.ArchDisChild2002;87:455-6.

17 Drake A J, Howells R J, ShieldJPH, PrendivilleA, Ward PS,Crowne EC.Symptomatic adrenalinsufficiency presentingwith hypoglycaemia inchildren with asthma receiving high dose inhaled fluticasonepropionate. BMJ2002;324:1081-2.

18 Todd G. High-dose inhaled fluticasone, adrenal crisis anda fatalaccident inquiry.ArchDisChild2007;92:372-3.

19 Shyam R, Ullmann D, Spencer D. Limited repeatability of thelowdose synacthen testin children with asthma maintained on inhaledcorticosteroids. ArchDis Child2007;92(suppl):A1.

20 BisgaardH. Long acting2agonists in the managementof childhoodasthma: a critical review of the literature.PediatrPulmonol2000;29:221-34.

21 BisgaardH. Effectof long acting2 agonistson exacerbationrates ofasthma in children.Pediatr Pulmonol2003;36:391-8.

22 BisgaardH, Szefler S.Longacting2agonistsand paediatric asthma.Lancet2006;367:286-8.

23 Martinez F. Safety of long-acting beta-agonistsan urgentneed toclear theair.N EnglJ Med2005;353:2637-9.

24 BisgaardH, Hermansen MN,Loland L, HalkjaerLB, Buchvald F.Intermittent inhaled corticosteroids in infants with episodicwheezing.N EnglJ Med2006;354:1998-2005.

25 MurrayC, Woodcock A, Langley S, CustovicA. Secondary preventionof asthmaby theuse of inhaled fluticasone propionate in wheezyinfants (IFWIN): double-blind, randomized, controlled study. Lancet2006;368:754-62.

26 GuilbertT, Morgan W,Zeiger R,Mauger D,BoehmerS, Szefler S,et al.Long-term inhaled steroids in pre-school children at high risk forasthma. N EnglJ Med2006;354:1985-997.

27 OCallaghan C, Barry PW. Asthma drugdeliverydevices for children.BMJ2000;320:664.

28 National Institute for Clinical Excellence. Guidanceon theuse ofinhaler systems (devices)in childrenunder theage of 5 yearswithchronic asthma. London: NICE, 2000.

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30 Panickar JR,GriggJ. Controversies in themanagementof pre-schoolviral wheeze.PaediatrRespir Rev2006;7:293-8.

31 Payne D, Bush A. Phenotype-specific treatmentof difficultasthma inchildren.Pediatr Respir Rev2004;5:116-23.

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33 Skunk RC,Bloomberg GR.Omalizumab forasthma.N Engl J Med2006;354:2689-95.

Accepted: 19 June 2007

My memorable patient story

When it comes to medical interviews, there are a fewclassic questions, includingTell me about a memorablepatient. I used to hate this question. As a senior houseofficer, I took memorable to mean the complex, clevermedical diagnosis or the difficult case that required cleverhandling. Most people I knew, myself included, wouldmake up impressive sounding cases tailored to fit theinterview. Occasionally,I would usea real patient, as longas there wassomething about their case that demonstratedmy skills or my ability to improve myself. As I wasgenerally successful at interviews, I assumed this was agood approach.

One evening on call, I was idly chatting with theconsultant. He mentioned thatTell me about amemorable patient was his favourite question.He felt that the type of patient the candidate deemed

memorable was far more important than the details of thecase, and that this choice of patient told him more aboutthe candidate than any other question. I paid lit tleattention at the time, but, two years later, I still rememberthis remark.

As Ive progressed through my training, my attitudesand opinions have changed. Memorable no longermeanschallenging or complex. Of course, Ive not been askedthequestionsince,butIwishsomeonewould.Ifyouaskedme today,I would nottell youaboutthe cleverdiagnoses Ihave made or the newborns I have successfullyresuscitated; I would tell you about just one childmyfavourite patient. Id tell you about this boy who washappy, well adjusted, and polite despite debilitatingchronic disease. Id tell you how he never minded anyexamination or test and how he had the wonderful gift of

making everyone around him feel happy and relaxed,myself included.

With so many of my colleagues anxiouslypreparing forinterviews for specialist training posts, I am constantlybeing asked for advice. While I try to help them formulateanswers, I remember my conversationwith the consultantand my memorable patient. I tell my colleagues thatinterviews are not just about you the doctor; theyre alsoabout you the person. Tell the interviewers about thesilliest, funniest, nastiest, or nicest children or parents youhave ever met: this reflection on your personality is just asvalid as, and probably more interesting than, a medicaldiagnosis. And incidentally, although I remember thechilds name, face, and personality perfectly, I cantremember his diagnosis.

Deborah Bird specialist registrar in paediatrics,Darent Valley Hospital, Dartford

deborahbird@doctors.org.uk

We welcome articles up to 600 words on topics suchas A memorable patient, A paper that changed my practice,My most unfortunate mistake, or any other piececonveying instruction, pathos or humour. Pleasesubmit the article on http://submit.bmj.comPermission is needed from the patient or a relative ifan identifiable patient is referred to. We also welcomecontributions for Endpieces, consisting of quotationsof up to 80 words (but most are considerably shorter)from any source, ancient or modern, which haveappealed to the reader.

C L I N I CA L R E V I E W

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