Asthma Management Handbook

Managing flare-ups in children aged 1–5 years

Recommendations

Manage wheezing with an inhaled short-acting beta2 agonist bronchodilator (reliever) as needed for relief of symptoms, according to age and clinical significance. Educate parents/carers how and when to give reliever.

Note: The recommended dose for non-emergency bronchodilator in children aged 1–5 years is salbutamol 2–4 puffs (100 microg per puff) as needed, 1 puff at a time, via pressurised metered-dose inhaler plus spacer and face mask for infants aged 1–2 years or pressurised metered-dose inhaler plus spacer for children aged 3–5 years (if able to cooperate). Repeat as needed.

  • Do not prescribe oral salbutamol. Inhalation is the recommended route for delivering relievers for all children and adults.
How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

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For children with acute asthma/wheezing that is associated with increased work of breathing and is severe enough to require hospital admission, consider a course of oral corticosteroids, e.g. 1 mg/kg prednisolone (maximum 50 mg) each morning for 3 days.

How this recommendation was developed

Consensus recommendation following inconclusive literature search

Based on clinical experience and expert opinion after literature review yielded insufficient evidence for an evidence-based recommendation

Key evidence considered:

  • Foster et al. 20181
  • Castro-Rodriguez et al. 20162
  • van Asperen et al. 20103
  • Panickar et al. 20094
  • Chang et al. 20085
  • Smith et al. 20036
  • Rowe et al. 20017

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For wheezing children younger than 6 years, do not instruct parents/carers to start a course of oral corticosteroids at their own discretion and do not prescribe or recommend oral corticosteroids to be started at home as part of the child’s written asthma action plan.

Instruct parents/carers to seek medical advice each time.

How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • van Asperen et al. 20103
  • Brand et al. 20148

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If oral corticosteroids are needed to manage severe acute flare-ups, reassess regular medicine regimen (including adherence and inhaler technique) and consider specialist referral.

How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • van Asperen et al. 20103

Last reviewed version 2.0

Do not prescribe long-term oral corticosteroids without specialist assessment by a paediatric respiratory physician.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

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Advise parents/carers that children taking a preventer medicine should continue taking it during wheezing episodes.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

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In children not taking regular preventer treatment, do not initiate inhaled corticosteroid treatment to manage worsening asthma symptoms or wheeze or during an acute flare-up, and do not recommend intermittent use of inhaled corticosteroids as part of a written asthma action plan.

How this recommendation was developed

Consensus recommendation following inconclusive literature search

Based on clinical experience and expert opinion after literature review yielded insufficient evidence for an evidence-based recommendation

Key evidence considered:

  • Kew et al. 20169
  • Chong et al. 201510
  • Yousef et al. 201211

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For a child taking low-dose inhaled corticosteroid regularly, do not prescribe high-dose inhaled corticosteroids to manage worsening asthma symptoms or wheeze, and do not recommend that parents/carers give children high doses of inhaled corticosteroid treatment during wheezing episodes (e.g. as part of a written asthma action plan).

Table. Definitions of ICS dose levels in children

Inhaled corticosteroid

Daily dose (microg)

Low

High

Beclometasone dipropionate

100–200

>200 (maximum 400)

Budesonide

200–400

>400 (maximum 800)

Ciclesonide

80–160

>160 (maximum 320)

Fluticasone propionate

100–200

>200 (maximum 500)

† Dose equivalents for Qvar (TGA-registered CFC-free formulation of beclometasone dipropionate)

‡ Ciclesonide is registered by the TGA for use in children aged 6 and over

Source

van Asperen PP, Mellis CM, Sly PD, Robertson C. The role of corticosteroids in the management of childhood asthma. The Thoracic Society of Australia and New Zealand, 2010. Available from: 
http://www.thoracic.org.au/clinical-documents/area?command=record&id=14

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How this recommendation was developed

Consensus recommendation following inconclusive literature search

Based on clinical experience and expert opinion after literature review yielded insufficient evidence for an evidence-based recommendation

Key evidence considered:

  • Kew et al. 20169
  • Chong et al. 201510
  • Yousef et al. 201211

Last reviewed version 2.0

For children with intermittent asthma symptoms and no interval symptoms for whom regular preventer is not indicated, a short course of montelukast at the onset of worsening asthma or wheezing can be considered (e.g. continue for 7 days or until symptoms have resolved for 48 hours). Advise parents/carers that montelukast does not work for all children.

How this recommendation was developed

Consensus recommendation following inconclusive literature search

Based on clinical experience and expert opinion after literature review yielded insufficient evidence for an evidence-based recommendation

Key evidence considered:

  • Watts et al. 201212
  • Capsomidis & Tighe. 201013
  • Schuh et al. 200914
  • Robertson et al. 200715
  • Nwokoro et al. 201416
  • Valovirta et al. 201117
  • Bacharier et al. 200818
  • Harmanci et al. 200619

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More information

Short-acting beta-2 agonist relievers for children: 1–5 years

Infants under 12 months

In infants under 12 months, bronchiolitis is the most likely cause of acute respiratory distress. Bronchodilators are not recommended in children under 12 months old, consistent with current guidelines for the management of acute bronchiolitis.20

Children aged 1–5 years

Inhaled short-acting beta2 agonists are effective bronchodilators in children aged 1–5 years.21

Short-acting beta2 agonists may be less effective for wheezing in children under 2 years old than in older children.22 However, many clinical trials in infants have included those with bronchiolitis, so there is limited evidence for the effects of short-acting beta2 agonists specifically in asthma.22 Studies conducted in emergency departments have shown that short-acting beta2 agonists are more effective than placebo in controlling acute wheeze in children under 2 years, but may not achieve clinically significant improvements.22

Inhaled short-acting beta2 agonists are generally well tolerated in children aged 1–5 years.21 Adverse effects can include muscle tremor, headache, palpitations and agitation. Muscle tremor and agitation are common with initial use of standard doses, but often settle over time. Serious adverse effects such as hypokalaemia have been reported at very high doses.21

Oral short-acting beta2 agonists are associated with adverse effects21 and should not be used for the treatment of asthma in any age group.

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Administration of inhaled medicines in children: 1-5 years

To use inhaler devices correctly, parents and children need training in inhaler technique and in the care and cleaning of inhalers and spacers.

Children need careful supervision when taking their inhaled medicines (e.g. at preschool), especially when using a reliever for acute asthma symptoms. 

Types of inhalers suitable for preschool children

Preschool children cannot use pressurised metered-dose inhalers properly unless a spacer is attached (with mask when necessary), because it is difficult for them to coordinate inspiratory effort with actuating the device.21 Note that breath-actuated pressurised metered-dose inhalers cannot be used with a spacer.

Dry-powder inhalers are usually ineffective for preschool children because they cannot generate sufficient inspiratory air flow.21

Drug delivery is very variable in young children with any type of inhaler, including pressurised metered dose inhalers and spacers.23 Filter studies have shown high day-to-day variability in delivered doses in preschool children.21 This variation might explain fluctuations in effectiveness, even if the child’s parents have been trained to use the device correctly.

Table. Types of inhaler devices for delivering asthma and COPD medicines Opens in a new window Please view and print this figure separately: http://www.asthmahandbook.org.au/table/show/75

Pressurised metered-dose inhalers plus spacers for relievers

During acute wheezing episodes, delivery of short-acting beta2 agonist to airways is more effective with a pressurised metered-dose inhaler plus spacer than with a nebuliser.21 In older children, salbutamol has also been associated with a greater increase in heart rate when delivered by nebuliser than when delivered by pressurised metered-dose inhaler plus spacer.24

When administering salbutamol to relieve asthma symptoms in a preschool child, the standard recommendation is to shake the inhaler, actuate one puff at a time into the spacer and have the child take 4–6 breaths in and out of the spacer (tidal breathing).25 Fewer breaths may suffice; in children with asthma aged 2–7 years (not tested during an acute asthma episode), the number of tidal breaths needed to inhale salbutamol adequately from a spacer has been estimated at 2 breaths for small-volume spacers, 2 breaths for a spacer made from a 500-mL modified soft drink bottle, and 3 breaths for a large (Volumatic) spacer.26

Face masks for infants

When using a spacer with face mask (e.g. for an infant too young or uncooperative to be able to use a mouthpiece), effective delivery of medicine to the airways depends on a tight seal around the face.

When masks are used for inhaled corticosteroids, there is a risk of exposure to eyes and skin if the seal over the mouth and nose is not adequate. Parents should be advised to wash the child's face after administering inhaled corticosteroids by mask.

Babies are unlikely to inhale enough medicine while crying.24 The use of a spacer and face mask for a crying infant may require patience and skill: the child can be comforted (e.g. held by a parent, in own pram, or sitting on the floor) while the mask is kept on, and the actuation carefully timed just before the next intake of breath. Most infants will tolerate the spacer and mask eventually. The child may be more likely to accept the spacer and mask if allowed to handle them first (and at other times), if the devices are personalised (e.g. with stickers), or if the mask has a scent associated with the mother (e.g. lip gloss). The use of a spacer with a coloured valve allows parents to see the valve move as the child breathes in and out.

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Preparation of new spacers before first use

Spacers are made of plastic, antistatic polymer/polycarbonate polyurethane, or cardboard.

Plastic spacers (e.g. Breath-A-Tech, Volumatic)

Electrostatic surface charge on new spacers made of plastic (e.g. Breath-A-Tech, Volumatic) reduces the proportion of medicine available for delivery to the airway. This charge can be reduced by washing the plastic spacer in dishwashing liquid and allowing it to air dry or drip-dry without rinsing or wiping.21

Alternatively, priming the spacer by actuating the device several times into the spacer also overcomes the charge, but this wastes medicine. The optimal number of actuations for priming is not known and the findings of in vitro studies vary widely. One study (using older, CFC-based formulations of asthma medicines) reported that up to 40 actuations fired into a new plastic spacer overcame the effect of the electrostatic charge.27 Others have concluded that the electrostatic charge on plastic spacers does not reduce in vivo efficacy of bronchodilator therapy in children with asthma.28 The number of actuations necessary may be known when the results of recent studies become available.

When a new plastic spacer must be used immediately (e.g. for a person with asthma symptoms), patients, parents and carers should follow the manufacturer's priming instructions. In hospitals and emergency departments, a new spacer that has not been pre-treated by washing can be primed using multiple (at least 10) puffs of salbutamol. (This is an arbitrary number of actuations in the absence of evidence that would enable a precise guideline.)

Non-plastic spacers

Disposable cardboard spacers (e.g. DispozABLE, LiteAire) and polyurethane/antistatic polymer spacers (e.g. Able A2A, AeroChamber Plus, La Petite E-Chamber, La Grande E-Chamber) do not require preparation before first use.21

Note: The term 'priming' is also used for the preparation process that is necessary for new pressurised metered-dose inhalers that have not been used for more than a week. This involves first actuating the inhaler into the air (away from the patient). Users should follow the manufacturer’s instructions for the particular brand of inhaler, which specify the number of actuations required.

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Parent/carer-initiated oral corticosteroids for wheezing and asthma flare-ups
  • Oral corticosteroids are associated with adverse effects on behaviour and bone health. Frequent courses may affect the hypothalamus–pituitary–adrenal axis.

Children aged 1–5 years

Short courses of oral corticosteroids initiated by parents/carers in response to children’s wheezing, or at the first sign of a cold, are not effective in managing symptoms in preschool children.29, 304

There is inconsistent evidence for the benefits of systemic corticosteroids in preschool children with acute viral-induced wheezing presenting to acute care services.4131 Current evidence does not strongly support their use in this age group.2

The Thoracic Society of Australia and New Zealand position statement on the use of corticosteroids in children3 recommends that oral corticosteroid treatment in preschool children, particularly those with intermittent viral-induced wheezing, should be limited to children with wheeze severe enough to need admission to hospital.

Children aged 6 years and over

A Cochrane systematic review found that there was insufficient evidence supporting the use of parent-initiated courses of oral corticosteroids in school-aged children,32 although some clinical trials have reported benefits.

In a clinical trial in children aged 6–14 years with a history of recurrent episodes of acute asthma, short courses of oral prednisolone (1 mg/kg a day), initiated by parents in response to an asthma flare-ups, reduced asthma symptoms and the number of missed school days.33 Another quasi-experimental study found that home initiation of corticosteroids reduced the rate of emergency department visits among school-aged children with moderate-to-severe persistent asthma, compared with rates pre-intervention.34

The Thoracic Society of Australia and New Zealand position statement on the use of corticosteroids in children3 recommends a short course of systemic corticosteroid therapy for children with moderate-to-severe acute asthma or when there is an incomplete response to beta-agonists, and does not recommend against parent/carer-initiated courses.

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Oral corticosteroids for children: adverse effects

Oral corticosteroids may have adverse psychiatric effects in children, including aggression and hyperactivity.35 Effects in the general population include euphoria, hypomania, depression, disturbances of mood, cognition, sleep and behaviour.36

A short course of oral corticosteroid therapy (less than 2 weeks) is associated with little risk of long-term suppression of the hypothalamus–pituitary–adrenal axis.3 However, risk can accumulate if frequent courses (four or more per year) are given.3

Recurrent courses of oral corticosteroids may also affect bone mineral density, especially in boys.3,37

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Increasing the inhaled corticosteroid dose to control flare-ups in children

In children taking regular inhaled corticosteroid-containing preventers, there is conflicting evidence for whether, and by how much, the dose should be increased when symptoms worsen or at the onset of an acute flare-up.

Overall, current evidence from highly controlled randomised controlled trials does not support increasing the dose of inhaled corticosteroid as part of a self-initiated action plan to manage flare-ups in children younger than 12 years.38

There is some evidence that high doses of inhaled steroids used pre-emptively might be effective in preventing severe acute asthma in children aged under 5 years, based on studies in children not taking regular inhaled corticosteroids.39 However, very high pre-emptive doses affect children’s growth40 and are not recommended.

Recent randomised controlled trials reported a lack of effect with a range of dose increases:

  • A five-fold increase in the inhaled corticosteroid dose at early signs of worsening asthma did not reduce the rate of severe acute asthma in children aged 5–11 years with well-controlled asthma while taking maintenance inhaled corticosteroid treatment (with high adherence).41 This strategy was associated with a small reduction in linear growth.41
  • Dose increases of four or eight times usual inhaled corticosteroid maintenance dose at the onset of an acute flare-up in children aged 2–17 years did not reduce requirement for oral corticosteroids, compared with doubling the dose.11

A Cochrane systematic review38 in children and adults reported that increasing the inhaled corticosteroid dose did not prevent severe flare-ups, regardless of how soon the increase was initiated after the onset of symptoms or the magnitude of the dose increase (doubling versus quadrupling). The results did not differ between children under 15 and adults or older adolescents.38 However, there were too few studies in children to make firm conclusions.

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Montelukast for children: efficacy
  • Montelukast use has been associated with behavioural and/or neuropsychiatric adverse effects, including suicidality.

Overview

Montelukast is a leukotriene receptor antagonist preventer. It is registered by the TGA for the treatment of asthma in children aged 2 years and older, and for the symptomatic treatment of allergic rhinitis.42

Montelukast can be used as an alternative to inhaled corticosteroids or as an add-on treatment in a child already taking regular inhaled corticosteroids.

However, it is not effective for all children. Overall, only approximately 20–30% of children will respond to montelukast treatment. The effect is thought to depend mainly on the child’s genotype.43, 16, 44 Clinically, it is not possible to predict accurately which children will benefit most from montelukast treatment.

Montelukast as first-line preventer in children aged 2–5 years

Viral-induced wheezing

Overall, regular maintenance montelukast treatment does not reduce the risk of wheezing episodes requiring oral corticosteroid treatment among preschool children who only have wheezing episodes when they have viral upper respiratory tract infections.45

However, montelukast may be effective for some children. Some randomised controlled trials have reported a reduction the risk of flare-ups in preschool children with intermittent asthma/wheeze,46, 47 while others have not.17

Persistent asthma or wheezing

A systematic review comparing montelukast with inhaled corticosteroids in preschoolers with asthma or recurrent wheezing requiring daily preventer treatment48 reported that inhaled corticosteroids appeared to achieve better symptom control and reduce flare-ups (including severe flare-ups requiring treatment with systemic corticosteroids). However, results were inconsistent and meta-analysis was not possible due to heterogeneity of outcomes measured in available clinical trials.48

Some preschool children with persistent asthma/wheeze respond to montelukast. A crossover study in preschool children with persistent asthma/wheeze reported that some children showed their best response to montelukast, while most responded better to regular inhaled corticosteroids.49 Predictors of a better response to inhaled corticosteroids than montelukast were aeroallergen hypersensitivity and blood eosinophilia (eosinophil counts ≥ 300/μL).49 However, routine blood eosinophil count is not feasible or recommended for this purpose.

Montelukast as first-line preventer children aged 6 years and over

In school-aged children with persistent asthma, inhaled corticosteroids are more effective overall than montelukast in improving lung function and controlling asthma symptoms.50, 52

However, symptoms will respond to a treatment trial of montelukast in approximately one-quarter to one-third of children,50, 53,54 and some may benefit more than from an inhaled corticosteroid.50 More severe asthma and markers of allergic inflammation may predict a better response to inhaled corticosteroids.50

Montelukast as add-on treatment

A systematic review of studies in children over 6 years and adolescents with mild-to-moderate persistent asthma found that the addition of montelukast to inhaled corticosteroids did reduce flare-ups requiring oral corticosteroids or hospital admissions for asthma, compared with the same or an increased dose.52

In a study comparing step-up treatments in children with asthma symptoms uncontrolled by low-dose inhaled corticosteroids, the addition of a long-acting beta2 agonist was effective in more children than either montelukast or increasing the dose of inhaled corticosteroid for controlling asthma symptoms and preventing flare-ups requiring systemic corticosteroids.55 However, some studies in school-aged children with persistent asthma already taking regular inhaled corticosteroids have reported that add-on montelukast reduced the risk of flare-ups55, 56 and exercise-induced asthma symptoms.56 Not all children will respond.

In a small study in children with persistent asthma already taking regular inhaled corticosteroids who were homozygous for the Arg16 genotype, montelukast was more effective as an add-on therapy than long-acting beta2 agonist in reducing symptoms, reliever use and days absent from school due to asthma, depending on the child’s beta receptor genotype.44 However, children were given inhaled corticosteroid and long-acting beta2 agonists in separate inhalers, which is which is known to be associated with increased risks.

However, genotyping it is not currently feasible in clinical practice. In practice, a treatment trial of 4–6 weeks can determine which preventer is suitable for controlling a child’s asthma symptoms,50 but longer treatment may be required to evaluate effect on flare-ups, because flare-ups may be independent of symptom control.

Exercise-induced symptoms

In school-aged children who experience exercise-induced symptoms despite taking regular inhaled corticosteroids, the addition of montelukast is effective in controlling symptoms, but not all children experience a response.5758

See: Investigation and management of exercise-induced bronchoconstriction

Short-term use in the management of flare-ups

Some, but not all studies suggest that a short course of montelukast, introduced at the first signs of an upper respiratory tract infection, may be effective in controlling flare-ups. An Australian study reported that this strategy could achieve a small reduction in symptoms, school absence and medical consultations in preschool and school-aged children with episodic wheeze.15

However, the evidence is inconsistent, with some studies showing no benefit.17,12, 13, 14, 18 The findings of one study suggested that whether or not intermittent montelukast is effective in wheezing children aged 5 years and under depends on genotype.16

Montelukast is not TGA-approved or PBS-subsidised for intermittent use.

Note: PBS status as at March 2019: Montelukast is not subsidised by the PBS for adolescents 15 years and over.

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Thunderstorm asthma

Certain types of thunderstorms in spring or early summer in regions with high grass pollen concentrations in the air can cause life-threatening allergic asthma flare-ups in individuals sensitised to rye grass, even if they have not had asthma before.59, 60, 61, 62, 63

Sensitisation to rye grass allergen is almost universal in patients who have reported flare-ups consistent with thunderstorm asthma in Australia.

People with allergic rhinitis and allergy to ryegrass pollen (i.e. most people with springtime allergic rhinitis symptoms) are at risk of thunderstorm asthma if they live in, or are travelling to, a region with seasonal high grass pollen levels – even if they have never had asthma symptoms before. This includes people with undiagnosed asthma, no previous asthma, known asthma.5960 Lack of inhaled corticosteroid preventer treatment has been identified as a risk factor.59

Epidemics of thunderstorm asthma can occur when such a storm travels across a region and triggers asthma in many susceptible individuals. Epidemic thunderstorm asthma events are uncommon, but when they occur can they make a high demand on ambulance and health services.646365

Data from thunderstorm asthma epidemics suggest that the risk of asthma flare-ups being triggered by a thunderstorm is highest in adults who are sensitised to grass pollen and have seasonal allergic rhinitis (with or without known asthma).59

The worst outcomes are seen in people with poorly controlled asthma.64 Treatment with an inhaled corticosteroid asthma preventer was significantly protective in a well-conducted Australian case-control study.60

There is insufficient evidence to determine whether intranasal corticosteroids help protect against thunderstorm asthma. Intranasal corticosteroids reduce symptoms of allergic rhinitis and limited indirect evidence suggests they may protect against asthma flare-ups in people not taking inhaled corticosteroids.66

The effectiveness of specific allergen immunotherapy in protecting against thunderstorm asthma has not been evaluated in randomised clinical trials, but data from a small Australian open-label study suggest that short-term treatment with five-grass sublingual immunotherapy may have been protective in individuals.67

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Asthma triggers in children: respiratory tract infections

Viral respiratory infections, such as the common cold, are a frequent cause of wheezing and asthma flare-ups in children, especially in preschool children.

The findings of observational cohort studies and limited randomised controlled trials show that influenza vaccination reduces the number, frequency and duration of asthma flare-ups in children, and lower the rate of emergency department visits and hospitalisation for asthma.68

Although bacterial respiratory infections may also trigger wheezing, antibiotics are not routinely indicated for asthma flare-ups or wheezing, and should only be given if they would otherwise be indicated.

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Asthma triggers in children: environmental allergens

There is insufficient evidence on which to base recommendations for the reduction of exposure to environmental allergens in the treatment of wheezing in preschool children.21

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Asthma triggers in children: tobacco smoke

There is consistent, high-quality evidence that exposure to environmental tobacco smoke can both cause and worsen wheezing in preschool children.2169

The Introduction of environmental tobacco controls has led to significant reduction in asthma hospitalisations among children.

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References

  1. Foster SJ, Cooper MN, Oosterhof S, Borland ML. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018; 6: 97-106. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29373235
  2. Castro-Rodriguez JA, Beckhaus AA, Forno E. Efficacy of oral corticosteroids in the treatment of acute wheezing episodes in asthmatic preschoolers: Systematic review with meta-analysis. Pediatric pulmonology 2016; 51: 868-76. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27074244
  3. van Asperen PP, Mellis CM, Sly PD, Robertson C. The role of corticosteroids in the management of childhood asthma. The Thoracic Society of Australia and New Zealand, 2010. Available from: https://www.thoracic.org.au/journal-publishing/command/download_file/id/25/filename/The_role_of_corticosteroids_in_the_management_of_childhood_asthma_-_2010.pdf
  4. Panickar J, Lakhanpaul M, Lambert PC, et al. Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med. 2009; 360: 329-328. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19164186
  5. Chang, A B, Clark, R, Sloots, T P, et al. A 5- versus 3-day course of oral corticosteroids for children with asthma exacerbations who are not hospitalised: a randomised controlled trial. Med J Aust. 2008; 189: 306-310.Available from: https://www.ncbi.nlm.nih.gov/pubmed/18803532/
  6. Smith M, Iqbal S, Elliot TM et al. Corticosteroids for hospitalised children with acute asthma. Cochrane Database Syst Rev. 2003; Issue 2: CD002886. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12804441
  7. Rowe BH, Spooner C, Ducharme F, et al. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001; Issue 1: CD002178. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11279756
  8. Brand PL, Caudri D, Eber E et al. Classification and pharmacological treatment of preschool wheezing: changes since 2008. Eur Respir J. 2014; 43: 1172-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24525447
  9. Kew, KM; Quinn, M; Quon, B. S; Ducharme, FM;. Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children. Cochrane Database Syst Rev. 2016; Issue 6: CD007524: . Available from: https://www.ncbi.nlm.nih.gov/pubmed/27272563
  10. Chong J, Haran C, Chauhan BF, Asher I. Intermittent inhaled corticosteroid therapy versus placebo for persistent asthma in children and adults. Cochrane Database Syst Rev. 2015; : Cd011032. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26197430
  11. Yousef, E., Hossain, J., Mannan, S., et al. Early intervention with high-dose inhaled corticosteroids for control of acute asthma exacerbations at home and improved outcomes: a randomized controlled trial. Allergy Asthma Proc. 2012; 33: 508-13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23394509
  12. Watts, K, Chavasse, R J P G. Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children. Cochrane Database Syst Rev. 2012; Issue 5: . Available from: http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD006100.pub2/full
  13. Capsomidis, A., Tighe, M.. Archimedes. Question 2. Is oral montelukast beneficial in treating acute asthma exacerbations in children?. Arch Dis Child. 2010; 95: 948-50. Available from: http://adc.bmj.com/content/95/11/948.long
  14. Schuh, S, Willan, AR, Stephens, D, et al. Can montelukast shorten prednisolone therapy in children with mild to moderate acute asthma? A randomized controlled trial. J Pediatr. 2009; 155: 795-800. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19656525
  15. Robertson CF, Price D, Henry R, et al. Short-course montelukast for intermittent asthma in children: a randomized controlled trial. Am J Respir Crit Care Med. 2007; 175: 323-329. Available from: http://ajrccm.atsjournals.org/content/175/4/323.long
  16. Nwokoro C, Pandya H, Turner S, et al. Intermittent montelukast in children aged 10 months to 5 years with wheeze (WAIT trial): a multicentre, randomised, placebo-controlled trial. Lancet Respir Med. 2014; 2: 796-803. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25212745
  17. Valovirta, E., Boza, M. L., Robertson, C. F., et al. Intermittent or daily montelukast versus placebo for episodic asthma in children. Ann Allergy Asthma Immunol. 2011; 106: 518-26. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21624752
  18. Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol. 2008; 122: 1127-1135. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18973936
  19. Harmanci, K, Bakirtas, A, Turktas, I, Degim, T. Oral montelukast treatment of preschool-aged children with acute asthma. Ann Allergy Asthma Immunol. 2006; 96: 731-735. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16729788
  20. Paediatric Research in Emergency Departments International Collaborative. Australasian bronchiolitis guideline. PREDICT; 2016. Available from: http://www.predict.org.au/publications/2016-pubs/
  21. Brand PL, Baraldi E, Bisgaard H, et al. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J. 2008; 32: 1096-1110. Available from: http://erj.ersjournals.com/content/32/4/1096.full
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