Treatment of Asthma Exacerbation Sin Children

7/22/2019 Treatment of Asthma Exacerbation Sin Children

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Treatment of asthma exacerbations in

children

Sejal Saglani

Clinical Senior Lecturer Respiratory PaediatricsImperial College London


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Outline

Risk factors for exacerbations

Predictors of exacerbations in children

Predictors of severe exacerbations

Treatment

Pre-school wheeze

Steroids LTRA

Magnesium sulphate


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Impact of exacerbations

Severe exacerbation accelerated lung

function decline 30ml/ year greater

decline in FEV1

Significant morbidity

Hospitalisation

Fatal

McDonald V & Gibson PG CEA 2010;42:670-7


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Risk factors for asthma deaths in

children: 2001-2006 (UK)

Observational case series

Hospital and primary care post mortem reports

Asthma severity, admissions, adherence, precipitating

factors

20 deaths: 9/20- mild-moderate

10/20 deaths between June and August

Importance of seasonal allergyAnagnostou K Prim Care Respir J 2012


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Risk factors for exacerbation in children

Poor control

Exacerbation in previous year

Younger age

Allergen exposure Season

Tobacco smoke exposure

Pollution Non-white race

Forno E & Celedon JC Curr Opin Pulm Med 2012


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The Epidemiology and Natural History of

Asthma: Outcomes and Treatment Regimens

study (TENOR)

3 year, multi-centre, observational cohort

Total n=4756

n=497; 13-17 years, n=770; 6-12 years

Severe or difficult-to-treat asthma

Strongest predictors of exacerbation:

recent exacerbation history (12 monthspreviously)

uncontrolled asthma

Chipps BE JACI 2012 EPub


7/43Haselkorn T et al JACI 2009;124:921-7

Synergistic predictors of exacerbations


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Clinical score to predict exacerbations

Forno E Chest 2010;138:1156-65

Good PPV for no hospitalisation (94-99%),

but only 70% ability to predict exacerbation


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Exhaled breath IL-5 and asthma control

score predict exacerbations

Robroeks C et al CEA 2012;42:792-8

Good PPV low risk of exacerbation predicted

Poor NPV


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No role for FeNO in predicting /

preventing exacerbations

90 children aged 6-17 years randomised toFeNO driven control or conventional

FeNO + reported symptoms used to changemedication in FeNO group

12 month duration

No difference in exacerbation rate between the 2groups

Pike K et al Clin Respir J 2012


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No role for sputum eosinophils in

predicting / preventing exacerbations

Fleming L et al Thorax 2012;67:193-8


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Sputum phenotype variability in children

Not related to FeNO, change in ICS, asthma control,

disease severity

Fleming L et al Thorax 2012;67:675-81


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Vitamin D & exacerbations CAMP study

VitD level and risk of hospitalisation / emergency

visit over 4 years

35% of all children had vitD insuffuciency

(


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Vitamin D and exacerbation severity560 Puerto Rican children aged 6-14 years

Vitamin D insufficiency associated with severe exacerbations

regardless of race, atopy, disease severity or control

Brehm JM et al AJRCCM 2012;186:140-6


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Does vitD supplementation reduce

exacerbations?

Majak PJACI 2011;127:1294-6


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ERS Task Force definitions of preschool wheeze

phenotypesBrand et al ERJ 2008;32:1096-110

Temporal pattern of

wheeze

Definition

Episodic (viral) wheeze Wheeze at discrete times

Often with evidence of viral coldNO symptoms in between

episodes

Multiple-trigger wheeze Wheeze with discrete

exacerbationsAND symptoms between

episodes

NB: Phenotype can be applied at the time of consultation


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Viral wheeze & oral steroids initiated at

home: no benefit

Oommen Lancet 2003;362:1433-8


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Viral wheeze & oral steroids in

hospitalised children: no benefit

687 children aged 10 months-6 years

Oral prednisolone or placebo for 5 days

Primary outcome: Duration of hospitalisation

Secondary outcomes:

Symptom severity & duration Use of beta-agonists

No difference between groups

Panickar J NEJM 2009;360:329-38


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Intermittent inhaled steroids vs

montelukast for viral wheeze

Age 12-59 months

> 2 wheezing episodes with RTI in last yr

At least 1 episode in last 6/12 At least 1 episode needing oral steroids

No controller medication

No evidence of persistent symptoms

No more than 6 courses pred in past year

Bacharier et al JACI 2008;122:1127-35


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Randomisation

Budesonide neb 1mg bd Montelukast 4mg od

Placebo

At onset of RTI for 7 days Primary outcome

episode free days over 12 months

Secondary outcomes

Symptom severity in 14 days from initiation of therapy

Total courses of oral steroids

Number of wheezing episodes



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Results



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Imperial College LondonPage 22


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Imperial College London Page 23

Viral wheeze & parent-administered high dose

ICS

129 children aged 1-6 years previous intermittentwheeze

750mcg bd fluticasone / placebo

Start at onset of URTI for up to 10 days

Primary outcome: Rescue oral steroids

Secondary outcomes: Symptoms

Use of beta-agonsits

Hospitalisations

Change in growth & bone mineral density

Ducharme F et al NEJM 2009;360:339-53


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Imperial College London Page 24

Intermittent high dose ICS in viral wheeze

Median study duration 40 weeks:

8% of fluticasone group needed rescue steroids

18% of placebo group needed rescue steroids

Fluticasone group:

Smaller gain in height and weight

No group difference in cortisol or bone

mineral density

Ducharme F et al NEJM 2009;360:339-53


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Daily or intermittent budesonide for

preschool recurrent wheezing?

278 children

Age 12 53 months

Positive Asthma Predictive Index

Recurrent wheezing episodes

>1 exacerbation in past year

Zeiger RS et al NEJM 2011;365:1990-2001


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No difference between intermittent or continuous

budesonide regimen



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No significant group differences in

adverse effects

Total budesonide exposure lower in intermittent regimen group

(45.7mg) compared to daily regimen group (149.9mg)



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Bacterial infections and preschool wheeze

Cohort study children from asthmatic mothers

Age 4 weeks 3 years

Planned follow-ups and during acute symptoms

Assessment of viral and bacterial infection withand without acute wheeze

Bisgaard H BMJ 2010


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Bisgaard H BMJ 2010

Wheezy episodes associated with both bacterial

and viral infection - independently


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Clarithromycin in acute asthma

Koutsoubari I et al Pediatr Allergy Immunol 2012;23:385-90


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Duration of exacerbation reduced in

clarithromycin group

Koutsoubari I et al Pediatr Allergy Immunol 2012;23:385-90


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Bhogal S Ann

Emerg Med

2012;60:84-91

Early oral

corticosteroids

and outcome


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Bhogal S Ann

Emerg Med

2012;60:84-91


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Single dose dexamethasone or 3 days

prednisolone?

Advantages

Single oral dose

Compliance assured

Long half-life: 36-72hours

Disadvatages

Only mild moderate

exacerbations

More potent thanprednisolone (6x)

Cross KP Can Fam Phys 2011;57:1134-6


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No difference in initial A&E outcomes

Altamimi et al Ped Emerg Med 2006


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No difference in 5 day outcomes

Altamimi et al Ped Emerg Med 2006


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Oral montelukast for acute asthma:

Hospitalisation

Watts K Cochrane Syst Database Rev 2012


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IV montelukast: Hospitalisation


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MgSO4

Single dose IV MgSO4 effective in childrenwhen

Poor initial response to inhaled/nebulised

bronchodilators

Severe exacerbation

High risk of admission

Should be used in A&E to prevent admission

No role for inhaled / oral Mg


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Non-invasive ventilation

Advantages

Trial in status asthmaticuswhen conventionalmanagement fails

CPAP or BiPAP

May avoid need for

intubation & IPPV

Minimal sedation needed

Disadvantages

Cannot be used with

altered mental state

Need patient co-operation

Variable tolerability,

especially in younger

patients

Levine DA Curr Opin Pediatr 2008;20:261-5

S


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Summary Prevention and prediction of exacerbations is critical, especially with

increasing disease severity

- ?vitD supplementation future preventative intervention

Important risk factors / predictors

Exacerbation in previous year

Poor asthma control

Synergistic effects of risk factors

Most common infectious precipitants:

Viruses (HRV)

?equal role of bacteria in pre-school children

Pre-school wheeze

Contrasting effects of oral and inhaled steroids

Treatment of Asthma Exacerbation Sin Children

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