Asthma Management Handbook

Reviewing initial treatment in children 6 years and over

Recommendations

When prescribing any preventer medicine for a child, consider each treatment adjustment as a treatment trial: monitor response continually, review within 4 weeks, and adjust treatment according to response.

Figure. Stepped approach to adjusting asthma medication in children Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/figure/show/18

Table. Reviewing and adjusting preventer treatment for children aged 6 years and over Opens in a new window Please view and print this figure separately: https://www.asthmahandbook.org.au/table/show/26

Table. Definitions of ICS dose levels in children

Inhaled corticosteroid

Daily dose (mcg)

Low

High

Beclometasone dipropionate

100–200

>200 (up to 400)

Budesonide

200–400

>400 (up to 800)

Ciclesonide

80–160

>160 (up to 320)

Fluticasone propionate

100–200

>200 (up to 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

Adapted from existing guidance

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

  • van Asperen et al. 20101
  • National Asthma Council Australia, 20102

If symptoms are not controlled by an initial low dose of inhaled corticosteroids, do not increase the dose or change the regimen until you have (all of):

  • checked adherence to the inhaled corticosteroid
  • checked the child’s inhaler technique
  • reviewed the diagnosis (consider whether symptoms may be due to a comorbidity or alternative diagnosis such as rhinosinusitis, de-conditioning, obesity or upper airway dysfunction).

Table. Definitions of ICS dose levels in children

Inhaled corticosteroid

Daily dose (mcg)

Low

High

Beclometasone dipropionate

100–200

>200 (up to 400)

Budesonide

200–400

>400 (up to 800)

Ciclesonide

80–160

>160 (up to 320)

Fluticasone propionate

100–200

>200 (up to 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

Adapted from existing guidance

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

  • van Asperen et al. 20101

If asthma is not well controlled by regular low-dose inhaled corticosteroid treatment (and adherence is good, inhaler technique is correct and diagnosis has been confirmed), consider one of the following options:

  • Increase the inhaled corticosteroid dose.
  • Continue low-dose inhaled corticosteroid and add montelukast.
  • Switch to an inhaled corticosteroid/long-acting beta2 agonist combination at low dose.
  • Advise parents about potential adverse psychiatric effects of montelukast

Note: TGA-registered indications for inhaled corticosteroid/long-acting beta2 agonist combinations differ between products.

How this recommendation was developed

Adapted from existing guidance

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

  • van Asperen et al. 20101

In children taking regular inhaled corticosteroid treatment, the dose of inhaled corticosteroid should be adjusted to the lowest dose needed to maintain control.

How this recommendation was developed

Adapted from existing guidance

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

  • van Asperen et al. 20101

More information

Approaches to assessment and monitoring of asthma control in children

Assessment of asthma control in children is based mainly on recent asthma symptom control (assessed by the frequency and severity of symptoms between flare-ups and the degree to which asthma symptoms affect daily activities such as interference with physical activity or missed school days), the frequency of flare-ups, and spirometry in children who are able to perform the test reliably.

Parents commonly underestimate the severity of their child's asthma and overestimate asthma control.3

Standardised questionnaires

Questionnaire-based instruments have been validated for assessing asthma control in children:

Measures of airway inflammation

Measures of airway inflammation (e.g. sputum test, exhaled nitric oxide) are not used in clinical practice to guide treatment decisions. Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide appears to achieve only a small benefit in children, and may lead to higher doses.9 

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Eliminating common reasons for poor response to preventer treatment

Apparent lack of response to asthma treatment is commonly due to one or more of the following:10

  • poor adherence (which may be due to misunderstanding of the purpose and effects of asthma medicines or inability to follow a written asthma action plan that is unclear)
  • poor inhaler technique
  • mishandling devices (e.g. failure to clean spacer, allowing mouthpiece of dry-powder inhalers to become blocked)
  • incorrect dose or frequency
  • expired medicines
  • continued exposure to smoke or allergen triggers.

Failure to identify these causes before adjusting medicines could result in over-medication with preventers.

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Correct use of inhaler devices

The majority of patients do not use inhaler devices correctly. Australian research studies have reported that only approximately 10% of patients use correct technique.1112

High rates of incorrect inhaler use among children with asthma and adults with asthma or COPD have been reported,13, 14, 15, 16, 17 even among regular users.18 Regardless of the type of inhaler device prescribed, patients are unlikely to use inhalers correctly unless they receive clear instruction, including a physical demonstration, and have their inhaler technique checked regularly.19

Poor inhaler technique has been associated with worse outcomes in asthma and COPD. It can lead to poor asthma symptom control and overuse of relievers and preventers.13, 20, 18, 21, 22 In patients with asthma or COPD, incorrect technique is associated with a 50% increased risk of hospitalisation, increased emergency department visits and increased use of oral corticosteroids due to flare-ups.18

Correcting patients' inhaler technique has been shown to improve asthma control, asthma-related quality of life and lung function.23, 24

Common errors and problems with inhaler technique

Common errors with manually actuated pressurised metered dose inhalers include:19

  • failing to shake the inhaler before actuating
  • holding the inhaler in wrong position
  • failing to exhale fully before actuating the inhaler
  • actuating the inhaler too early or during exhalation (the medicine may be seen escaping from the top of the inhaler)
  • actuating the inhaler too late while inhaling
  • actuating more than once while inhaling
  • inhaling too rapidly (this can be especially difficult for chilren to overcome)
  • multiple actuations without shaking between doses.

Common errors for dry powder inhalers include:19

  • not keeping the device in the correct position while loading the dose (horizontal for Accuhaler and vertical for Turbuhaler)
  • failing to exhale fully before inhaling
  • failing to inhale completely
  • inhaling too slowly and weakly
  • exhaling into the device mouthpiece before or after inhaling
  • failing to close the inhaler after use
  • using past the expiry date or when empty.

Other common problems include:

  • difficulty manipulating device due to problems with dexterity (e.g. osteoarthritis, stroke, muscle weakness)
  • inability to seal the lips firmly around the mouthpiece of an inhaler or spacer
  • inability to generate adequate inspiratory flow for the inhaler type
  • failure to use a spacer when appropriate
  • use of incorrect size mask
  • inappropriate use of a mask with a spacer in older children.

How to improve patients’ inhaler technique

Patients’ inhaler technique can be improved by brief education, including a physical demonstration, from a health professional or other person trained in correct technique.19 The best way to train patients to use their inhalers correctly is one-to-one training by a healthcare professional (e.g. nurse, pharmacist, GP, specialist), that involves both verbal instruction and physical demonstration.25, 13, 26, 27 Patients do not learn to use their inhalers properly just by reading the manufacturer's leaflet.26 An effective method is to assess the individual's technique by comparing with a checklist specific to the type of inhaler, and then, after training in correct technique, to provide written instructions about errors (e.g. a sticker attached to the device).11, 24

The National Asthma Council information paper on inhaler technique includes checklists for correct technique with all common inhaler types used in asthma or COPD.

Inhaler technique must be rechecked and training must be repeated regularly to help children and adults maintain correct technique.23, 13, 14 

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Step-up options in children with asthma that is not controlled by low-dose inhaled corticosteroids

In children whose asthma is inadequately controlled by low-dose inhaled corticosteroids alone (and adherence is good, inhaler technique is correct and diagnosis has been confirmed), treatment options include:

  • increasing the inhaled corticosteroid dose
  • adding montelukast
  • switching to inhaled corticosteroid/long-acting beta2 agonist combination.

Table. Step-up options for children when good asthma control is not achieved with low-dose ICS

Option

TGA-registered indications for add-on therapy

PBS considerations

High-dose ICS

N/A

Subsidised

ICS plus montelukast

2 years and over

2–5 years: not subsidised*

6–14 years: not subsidised unless for exercise-induced bronchoconstriction despite ICS treatment

15 years and over: not subsidised

ICS/long-acting beta2 agonist combination

4 years and over for fluticasone propionate/ salmeterol xinafoate

12 years and over for budesonide/formoterol fumarate dihydrate

Subsidised

  • Advise parents about potential adverse psychiatric effects of montelukast

* Montelukast is not subsidised for use in combination with other preventers or for children who require inhaled corticosteroids.

 Montelukast is subsidised for prevention of exercise-induced asthma if asthma is otherwise well controlled while taking optimal-dose inhaled corticosteroids – it is not otherwise subsidised in combination with inhaled corticosteroids (or inhaled corticosteroid/long-acting beta2 agonist combinations). 

‡ Montelukast is not subsidised for people aged over 15 years.

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In the majority of children with persistent asthma that requires preventive treatment, control can be achieved with one of these options.1

Increasing inhaled corticosteroid dose versus adding a long-acting beta2 agonist

In children with persistent asthma taking regular inhaled corticosteroid, the addition of long-acting beta2 agonists improves lung function and reduces reliever use, compared with placebo or increasing the dose of inhaled corticosteroid, but does not appear to reduce the rate of asthma flare-ups requiring treatment with oral corticosteroids.282930

Overall, evidence from randomised clinical trials suggests that, for children and adolescents (aged 4–18 years) with persistent asthma that is inadequately controlled despite treatment with regular inhaled corticosteroids, increasing the dose of inhaled corticosteroid is equally effective as maintaining the inhaled corticosteroid dose but adding a long-acting beta2 agonist (i.e. switching to long-acting beta2 agonist/inhaled corticosteroid combination therapy) in in reducing the rate of asthma flare-ups that require treatment with systematic corticosteroids.30

Children appear to benefit less from combination inhaled corticosteroid/long-acting beta2 agonist treatment than adolescents. In adolescents with persistent asthma that is not controlled by a low dose of inhaled corticosteroids, the combination of a long-acting beta2 agonist and an inhaled corticosteroid is modestly more effective in reducing the risk of flare-ups requiring oral corticosteroids than a higher dose of inhaled corticosteroids.31

Adding montelukast versus adding a long-acting beta2 agonist 

There is insufficient evidence from randomised clinical trials to determine, overall, whether adding a long-acting beta2 agonist or adding montelukast is more effective overall in children whose asthma is not controlled by regular inhaled corticosteroids.32

Clinical response to long-acting beta2 agonists partly depends on genetics. A beta2 receptor genotype  (Arg16 polymorphism in the beta2 receptor gene) pre-disposes children with asthma to down-regulation of the beta2 receptor and increased susceptibility to flare-ups during regular treatment with regular long-acting beta2 agonists.33 However, routine genetic testing to tailor asthma therapy is not yet available in clinical practice.

Among children 6 years and over with asthma that is not controlled by low-dose inhaled corticosteroids, the optimal regimen varies between individuals.34 Responses vary between individuals: best response is achieved in some children by adding a long-acting beta2 agonist, others by adding montelukast, and others by increasing the dose of inhaled corticosteroid or adding montelukast.34

For children aged 6–14 years with persistent asthma and exercise-induced bronchoconstriction, adding montelukast is more effective in protecting against exercise-induced bronchoconstriction than switching to a combination of inhaled corticosteroid and a long-acting beta2 agonist.35 The use of montelukast also avoids beta-receptor tolerance associated with long-acting beta2 agonists, so a short-acting beta2 agonist taken after exercise produces a greater bronchodilator response than it does in children taking regular long-acting beta2 agonist.35

Overall, adding montelukast is the best option when effects on exercise-induced symptoms and safety are also considered.36

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Montelukast for children

Montelukast is registered by the TGA for use in children aged 2 years and older.37

Based on data from placebo-controlled trials, it has not been possible to define clinical indicators that predict which children will benefit most from montelukast therapy, compared with other treatment options.238

Comparative studies suggest that the main role for montelukast is as an alternative to low-dose inhaled corticosteroid in children with frequent intermittent asthma or mild persistent asthma.2

Children 0–5 years

In preschool children with multiple-trigger wheeze, montelukast protects against airway hyperresponsiveness when taken with or without inhaled corticosteroids.39 Inhaled corticosteroids are more effective than montelukast in children with multiple-trigger wheeze aged 2–8 years,40 but this comparison has not been made in preschool children as a separate group.39

In children aged 2–5 years with episodic (viral) wheeze, regular montelukast treatment reduces the risk of wheezing episodes.41 However, montelukast may not reduce symptoms in children aged 6–24 months with recurrent wheeze.42 

Note: Montelukast is not TGA-registered for use in children younger than 2 years.

A short course of montelukast, introduced at the first signs of an asthma episode or upper respiratory tract infection, can achieve a small reduction in symptoms, school absence and medical consultations in preschool and school-aged children with episodic wheeze.43 However, montelukast is not TGA-registered for intermittent use.

Children 6 years and over

In school-aged children with persistent asthma, inhaled corticosteroids are more effective than montelukast for a range of measures, including lung function.2

In school-aged children with persistent exercise-induced symptoms despite taking regular inhaled corticosteroids, montelukast is effective in controlling symptoms and is more effective than long-acting beta2 agonists.135

In children who are already taking regular inhaled corticosteroids and have a beta2 receptor genotype associated with increased susceptibility to flare-ups during regular long-acting beta2 agonist therapy,33 montelukast may be more effective than salmeterol in reducing symptoms, reliever use and days absent from school due to asthma, based on the findings of a small randomised controlled clinical trial.33

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Montelukast for children: warning parents about potential psychiatric adverse effects

Montelukast is generally very well tolerated.1 However, post-marketing surveillance reports suggested a slight increase in the rate of psychiatric disorders that was possibly associated with use of leukotriene receptor antagonists in children;44 this association may have been confounded by asthma severity and concomitant medication.1 Montelukast use has also been associated with suicidal ideation, but a recent nested case-control study concluded that children with asthma aged 5–18 years taking leukotriene receptor antagonists were not at increased risk of suicide attempts.45 Behavioural and psychiatric adverse effects were rare in clinical trials.46,47

A recent analysis of databases of adults and children taking montelukast suggests it is associated with nightmares, depression, and aggression.48 Allergic granulomatous angiitis has also been reported, but a causal relationship has not been established.48

The Thoracic Society of Australia and New Zealand advises that it is prudent to mention to parents the potential association of montelukast with behaviour-related adverse events when commencing treatment, and to cease therapy if such adverse events are suspected.1

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Cromones for children

0-5 years

Few clinical trials have assessed the use of inhaled sodium cromoglycate in preschool children and none have assessed nedocromil.39 Overall, sodium cromoglycate has not been shown to be effective in preschool children with multiple-trigger wheeze.39, 49

However, cromones are well tolerated and registered for use in infants. Therefore, a treatment trial can be considered before considering other preventers, particularly for children less than 2 years old.

6 years and over

Cromones are rarely prescribed in school-aged children.

Inhaled sodium cromoglycate might be effective in school-aged children, but interpretations of available evidence are inconsistent.1 Sodium cromoglycate is less effective than inhaled corticosteroid in achieving asthma control and improving lung function in children with persistent asthma.50

Nedocromil sodium appears to be have some benefit in children with persistent asthma, but its relative effectiveness compared with inhaled corticosteroids is not clear.51 Long-term (4–6 years) treatment with budesonide achieved better asthma control than long-term nedocromil in children with mild-to-moderate asthma aged 5–12 in a randomised placebo-controlled clinical trial.52

Practical issues

Cromones (sodium cromoglycate and nedocromil) may not be practical for some patients, because they require three–four times daily dosing until control is gained, and inhaler devices for cromones tend to block easily.1

Nedocromil can cause an unusual or unpleasant taste53 and is not tolerated by some children.

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Inhaled corticosteroids for children: overview

The effectiveness of ICS in children appears to depend on several factors including the child’s age, which triggers are causing symptoms, wheezing phenotype, tobacco smoke exposure and genotype.54 Overall, inhaled corticosteroids seem to be more effective in older children and those with more severe disease.1

Early introduction of inhaled corticosteroid for children with recurrent wheeze does not prevent airway remodelling, improve long-term lung function or prevent the onset of persistent asthma, according to current evidence from long-term randomised controlled clinical trials in preschool children and school-aged children with intermittent or mild persistent asthma.1

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Inhaled corticosteroids for children: 6 years and over

Most clinical trials of regular inhaled corticosteroid treatment in children have been conducted among children with persistent asthma.1 Beclometasone dipropionate, budesonide, ciclesonide and fluticasone propionate have all been shown to be effective in children. However, there have been relatively fewer studies of ciclesonide (a newer inhaled corticosteroid)1 but, overall, randomised clinical trials show that it is equally effective as budesonide or fluticasone propionate in improving asthma symptoms and reducing flare-ups.55

In school-aged children with mild persistent asthma, regular low-dose daily inhaled corticosteroid treatment reduces the rate of flare-ups that require treatment with oral corticosteroids, compared with no regular treatment and as-needed short-acting beta2 agonist for wheezing episodes.56

The Thoracic Society of Australia and New Zealand’s current position statement on the use of inhaled corticosteroids in children recommends regular treatment with inhaled corticosteroid for school-aged children with moderate-to-severe persistent asthma, or those with frequent intermittent asthma or mild persistent asthma if symptoms are not controlled by a 2- to 4-week treatment trial with a cromone (nedocromil or sodium cromoglycate) or montelukast.1

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Inhaled corticosteroids for children: doses

In the majority of children, asthma control can be achieved with any of the following initial doses:1

  • budesonide 400 mcg/day
  • beclometasone (Qvar) 200 mcg/day
  • ciclesonide 160 mcg/day
  • fluticasone propionate 200 mcg/day.

If these doses do not achieve control of symptoms, possible explanations include alternative diagnoses, adherence, incorrect inhaler technique, psychosocial factors and exposure to tobacco smoke or other triggers such as allergens.1

Dose–response studies of inhaled corticosteroids show that the maximal efficacy is generally achieved at a dose equivalent to approximately 200 mcg/day fluticasone propionate,1 while the risk of adrenal suppression increases exponentially at doses above 500 mcg/day.1 Therefore (based on theoretical equivalents between different agents), upper limits of daily doses for children are:

  • budesonide 800 mcg/day
  • beclometasone dipropionate [Qvar] 400 mcg/day
  • ciclesonide 320 mcg/day
  • fluticasone propionate 500 mcg/day.

Higher doses are unlikely to be more effective, and are likely to cause systemic effects.1

Most studies of inhaled corticosteroids in children have used twice-daily dosing.1  Ciclesonide is effective when given once daily.1 The dose of inhaled corticosteroid delivered to the lungs will depend on many factors, including the delivery device, the age of the child, individual variation in inhaler technique, and adherence.1

Note: Do not use beclometasone dose recommendations from outdated or overseas guidelines based on older formulations containing CFC propellant – doses are different.

Table. Definitions of ICS dose levels in children

Inhaled corticosteroid

Daily dose (mcg)

Low

High

Beclometasone dipropionate

100–200

>200 (up to 400)

Budesonide

200–400

>400 (up to 800)

Ciclesonide

80–160

>160 (up to 320)

Fluticasone propionate

100–200

>200 (up to 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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Inhaled corticosteroids for children: adverse effects

Topical

Hoarseness and pharyngeal candidiasis are not commonly reported among preschool children when using a metered-dose inhaler with spacer,39 or among school-aged children.1

Inhaled corticosteroids, particular dry-powder formulas with pH <5.5, may dissolve tooth enamel in children.1

Topical effects can be reduced by use of spacer devices (which reduce oropharyngeal deposition), and by mouth-rinsing and spitting after use.1 Immediate quick mouth-rinsing removes more residual medicine in the mouth than delayed rinsing.57

Systemic

Systemic effects of inhaled corticosteroids in children depend on the dose, but clinically significant adverse effects are uncommon.1 The use of spacers and mouth rinsing will not reduce systemic effects, but may increase efficacy so that a lower dose is required.

Short-term suppression of linear growth has been demonstrated in children, but only minimal long-term effects on growth or bone density have been reported.1 Some children may experience delay in the normal pubertal growth spurt due to asthma itself.1 Treatment beginning before puberty is associated with a small (mean approximately 1 cm) reduction in adult height.58

A research study using biochemical testing in a research setting showed that hypothalamic–pituitary–adrenal axis suppression may occur in up to two-thirds of children treated with inhaled corticosteroids, and may occur at even low doses.59 However, clinically cases are rare.

Cases of symptomatic, clinically significant adrenal insufficiency in children due to inhaled corticosteroid treatment have been reported,6061 including cases in Australia.62 Most cases have involved children given more than 500 mcg per day fluticasone propionate.60

The risk of hypothalamic–pituitary–adrenal axis suppression is higher among children receiving concomitant intranasal steroids and those with lower body mass index.59 Risk is lower in obese children.59

There are no nationally accepted protocols for routine assessment of adrenal function because it has not yet been possible to identify precisely which children should be tested, to interpret test results reliably, to identify the appropriate interval for retesting, and because a clinical benefit has not been clearly demonstrated.

Table. Definitions of ICS dose levels in children

Inhaled corticosteroid

Daily dose (mcg)

Low

High

Beclometasone dipropionate

100–200

>200 (up to 400)

Budesonide

200–400

>400 (up to 800)

Ciclesonide

80–160

>160 (up to 320)

Fluticasone propionate

100–200

>200 (up to 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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Inhaled corticosteroid/long-acting beta-2 agonist combinations for children: 6 years and over

Available combinations

Three combinations of inhaled corticosteroid and long-acting beta2 agonist in a single inhaler are currently available:

  • The combination of fluticasone propionate and salmeterol xinafoate in a single inhaler is registered for use in children aged 4 years and over.63
  • The combination of budesonide and formoterol in a single inhaler is registered for use in children aged 12 years and older.64
  • The combination of fluticasone propionate and formoterol in a single inhaler is TGA-registered for use in children aged 12 years and older.65

Role of combination therapy in children

Evidence from clinical trials does not support the use of combination therapy with a long-acting beta2 agonist plus an inhaled corticosteroid as initial preventer treatment in children who are not already taking inhaled corticosteroids.6631

Combination therapy is a step-up option for some children whose asthma is not well controlled by low-dose inhaled corticosteroids alone.

Beta2 receptor regulation

Clinical response to long-acting beta2 agonists partly depends on genetics. A beta2 receptor genotype  (Arg16 polymorphism in the beta2 receptor gene) pre-disposes children with asthma to down-regulation of the beta2 receptor and increased susceptibility to flare-ups during regular treatment with long-acting beta2 agonists.33 However, routine genetic testing to tailor asthma therapy is not yet available in clinical practice.

Systematic reviews and meta-analyses have led to concern about the possibility that the use of long-acting beta-agonists (even in combination with inhaled corticosteroids) might even increase the risk of flare-ups that require treatment with oral steroids or hospital admission, or of severe flare-ups.1, 36, 67  A meta-analysis by the US Food and Drug Administration found that the use of long-acting beta2 agonists was associated with increased risk of severe asthma-associated adverse events (both overall and among the subset of people using concomitant inhaled corticosteroid and long-acting beta2 agonist), and that this risk was greatest in children aged 4–11 years.67

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Managing cough in children

When cough is the predominant symptom in a young child, careful assessment is needed to avoid making an incorrect diagnosis of asthma, or instigating inappropriate treatment.68 Cough alone (recurrent non-specific cough) is most likely due to recurrent viral bronchitis, which is unresponsive to both bronchodilators and preventive therapy including inhaled corticosteroids. Recurrent non-specific cough usually resolves by age 6 or 7 years and leaves no residual pulmonary pathology.

If cough is a problem for a child with known asthma, it should be managed according to national Cough in Children and Adults: Diagnosis and Assessment (CICADA) guidelines.68

  • There are significant concerns about use of cough medicines in children.
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References

  1. 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
  2. National Asthma Council Australia. Leukotriene receptor antagonists in the management of childhood asthma. National Asthma Council Australia, Melbourne, 2010. Available from: http://www.nationalasthma.org.au/publication/ltras-their-role-in-childhood-asthma
  3. Carroll WD, Wildhaber J, Brand PL. Parent misperception of control in childhood/adolescent asthma: The room to breathe survey. Eur Respir J. 2011; 39: 90-96. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21700607
  4. Juniper EF, Gruffydd-Jones K, Ward S, Svensson K. Asthma Control Questionnaire in children: validation, measurement properties, interpretation. Eur Respir J. 2010; 36: 1410-6. Available from: http://erj.ersjournals.com/content/36/6/1410.long
  5. Murphy KR, Zeiger RS, Kosinski M, et al. Test for respiratory and asthma control in kids (TRACK): a caregiver-completed questionnaire for preschool-aged children. J Allergy Clin Immunol. 2009; 123: 833-9. Available from: http://www.jacionline.org/article/S0091-6749(09)00212-7/fulltext
  6. Zeiger RS, Mellon M, Chipps B, et al. Test for Respiratory and Asthma Control in Kids (TRACK): clinically meaningful changes in score. J Allergy Clin Immunol. 2011; 128: 983-8. Available from: http://www.jacionline.org/article/S0091-6749(11)01287-5/fulltext
  7. Liu AH, Zeiger R, Sorkness C, et al. Development and cross-sectional validation of the Childhood Asthma Control Test. J Allergy Clin Immunol. 2007; 119: 817-25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17353040
  8. Liu AH, Zeiger RS, Sorkness CA, et al. The Childhood Asthma Control Test: retrospective determination and clinical validation of a cut point to identify children with very poorly controlled asthma. J Allergy Clin Immunol. 2010; 126: 267-73, 273.e1. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20624640
  9. Petsky HL, Cates CJ, Li A, et al. Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults. Cochrane Database Syst Rev. 2009; Issue 4: CD006340. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006340.pub3/full
  10. Bush A, Saglani S. Management of severe asthma in children. Lancet. 2010; 376: 814-25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20816548
  11. Basheti IA, Armour CL, Bosnic-Anticevich SZ, Reddel HK. Evaluation of a novel educational strategy, including inhaler-based reminder labels, to improve asthma inhaler technique. Patient Educ Couns. 2008; 72: 26-33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18314294
  12. Bosnic-Anticevich, S. Z., Sinha, H., So, S., Reddel, H. K.. Metered-dose inhaler technique: the effect of two educational interventions delivered in community pharmacy over time. The Journal of asthma : official journal of the Association for the Care of Asthma. 2010; 47: 251-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20394511
  13. Price, D., Bosnic-Anticevich, S., Briggs, A., et al. Inhaler competence in asthma: common errors, barriers to use and recommended solutions. Respiratory medicine. 2013; 107: 37-46. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23098685
  14. Capanoglu, M., Dibek Misirlioglu, E., Toyran, M., et al. Evaluation of inhaler technique, adherence to therapy and their effect on disease control among children with asthma using metered dose or dry powder inhalers. The Journal of asthma : official journal of the Association for the Care of Asthma. 2015; 52: 838-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20394511
  15. Lavorini, F., Magnan, A., Dubus, J. C., et al. Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD. Respiratory medicine. 2008; 102: 593-604. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18083019
  16. Federman, A. D., Wolf, M. S., Sofianou, A., et al. Self-management behaviors in older adults with asthma: associations with health literacy. Journal of the American Geriatrics Society. 2014; 62: 872-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24779482
  17. Crane, M. A., Jenkins, C. R., Goeman, D. P., Douglass, J. A.. Inhaler device technique can be improved in older adults through tailored education: findings from a randomised controlled trial. NPJ primary care respiratory medicine. 2014; 24: 14034. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25188403
  18. Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011; 105: 930-8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21367593
  19. National Asthma Council Australia. Inhaler technique for people with asthma or COPD. National Asthma Council Australia, Melbourne, 2016. Available from: https://www.nationalasthma.org.au/living-with-asthma/resources/health-professionals/information-paper/hp-inhaler-technique-for-people-with-asthma-or-copd
  20. Bjermer, L.. The importance of continuity in inhaler device choice for asthma and chronic obstructive pulmonary disease. Respiration; international review of thoracic diseases. 2014; 88: 346-52. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25195762
  21. Haughney, J., Price, D., Barnes, N. C., et al. Choosing inhaler devices for people with asthma: current knowledge and outstanding research needs. Respiratory medicine. 2010; 104: 1237-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20472415
  22. Giraud, V., Roche, N.. Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability. The European respiratory journal. 2002; 19: 246-51. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11866004
  23. Basheti IA, Reddel HK, Armour CL, Bosnic-Anticevich SZ. Improved asthma outcomes with a simple inhaler technique intervention by community pharmacists. J Allergy Clin Immunol. 2007; 119: 1537-8. Available from: http://www.jacionline.org/article/S0091-6749(07)00439-3/fulltext
  24. Giraud, V., Allaert, F. A., Roche, N.. Inhaler technique and asthma: feasability and acceptability of training by pharmacists. Respiratory medicine. 2011; 105: 1815-22. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21802271
  25. Basheti, I. A., Reddel, H. K., Armour, C. L., Bosnic-Anticevich, S. Z.. Counseling about turbuhaler technique: needs assessment and effective strategies for community pharmacists. Respiratory care. 2005; 50: 617-23. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15871755
  26. Lavorini, F.. Inhaled drug delivery in the hands of the patient. Journal of aerosol medicine and pulmonary drug delivery. 2014; 27: 414-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25238005
  27. Newman, S.. Improving inhaler technique, adherence to therapy and the precision of dosing: major challenges for pulmonary drug delivery. Expert opinion on drug delivery. 2014; 11: 365-78. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24386924
  28. Ni Chroinin M, Lasserson TJ, Greenstone I, Ducharme FM. Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2009; Issue 3: CD007949. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007949/full
  29. Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst Rev. 2010; Issue 5: CD005535. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005535.pub2/full
  30. Castro-Rodriguez JA, Rodrigo GJ. A systematic review of long-acting β2-agonists versus higher doses of inhaled corticosteroids in asthma. Pediatrics. 2012; 130: e650-7. Available from: http://pediatrics.aappublications.org/content/130/3/e650.abstract
  31. Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma. Cochrane Database Syst Rev. 2010; Issue 4: CD005533. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005533.pub2/full
  32. Ducharme FM, Lasserson TJ, Cates CJ. Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma. Cochrane Database Syst Rev. 2011; Issue 5: CD003137. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003137.pub4/full
  33. Lipworth BJ, Basu K, Donald HP, et al. Tailored second-line therapy in asthmatic children with the Arg(16) genotype. Clin Sci (Lond). 2013; 124: 521-528. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23126384
  34. Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med. 2010; 362: 975-985. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1001278#t=article
  35. Fogel RB, Rosario N, Aristizabal G, et al. Effect of montelukast or salmeterol added to inhaled fluticasone on exercise-induced bronchoconstriction in children. Ann Allergy Asthma Immunol. 2010; 104: 511-517. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20568384
  36. van Asperen PP. Long-acting beta agonists for childhood asthma. Aust Prescr. 2012; 35: 111-3. Available from: http://www.australianprescriber.com/magazine/35/4/111/3
  37. Merck, Sharp and Dohme Australia Pty Ltd. Product Information: Singulair (montelukast sodium) Tablets. Therapeutic Goods Administration, Canberra, 2013. Available from: https://www.ebs.tga.gov.au/
  38. Ducharme FM. Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma. Cochrane Database Syst Rev. 2004; Issue 1: CD003133. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003133.pub2/full
  39. 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
  40. Szefler SJ, Baker JW, Uryniak T, et al. Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma. J Allergy Clin Immunol. 2007; 120: 1043-50. Available from: http://www.jacionline.org/article/S0091-6749(07)01726-5/fulltext
  41. Bisgaard H, Zielen S, Garcia-Garcia ML, et al. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma. Am J Respir Crit Care Med. 2005; 171: 315-322. Available from: http://ajrccm.atsjournals.org/content/171/4/315.long
  42. Pelkonen AS, Malmström K, Sarna S, et al. The effect of montelukast on respiratory symptoms and lung function in wheezy infants. Eur Respir J. 2013; 41: 664-670. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23060628
  43. 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
  44. Wallerstedt SM, Brunlöf G, Sundström A, Eriksson AL. Montelukast and psychiatric disorders in children. Pharmacoepidemiol Drug Saf. 2009; 18: 858-864. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19551697
  45. Schumock GT, Stayner LT, Valuck RJ, et al. Risk of suicide attempt in asthmatic children and young adults prescribed leukotriene-modifying agents: a nested case-control study. J Allergy Clin Immunol. 2012; 130: 368-75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22698520
  46. Philip G, Hustad C, Noonan G, et al. Reports of suicidality in clinical trials of montelukast. J Allergy Clin Immunol. 2009; 124: 691-6.e6. Available from: http://www.jacionline.org/article/S0091-6749(09)01247-0/fulltext
  47. Philip G, Hustad CM, Malice MP, et al. Analysis of behavior-related adverse experiences in clinical trials of montelukast. J Allergy Clin Immunol. 2009; 124: 699-706.e8. Available from: http://www.jacionline.org/article/S0091-6749(09)01248-2/fulltext
  48. Haarman, MG, van Hunsel, F, de Vries, TW. Adverse drug reactions of montelukast in children and adults. Pharmacol Res Perspect. 2017; 5: e00341. Available from: http://onlinelibrary.wiley.com/doi/10.1002/prp2.341/full
  49. van der Wouden JC, Uijen JH, Bernsen RM, et al. Inhaled sodium cromoglycate for asthma in children. Cochrane Database Syst Rev. 2008; Issue 4: CD002173. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002173.pub2/full
  50. Guevara JP, Ducharme F M, Keren R, et al. Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma. Cochrane Database Syst Rev. 2006; Issue 2: CD003558. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003558.pub2/full
  51. Sridhar AV, McKean M. Nedocromil sodium for chronic asthma in children. Cochrane Database Syst Rev. 2006; Issue 3: CD004108. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004108.pub2/full
  52. The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. The Childhood Asthma Management Program Research Group. N Engl J Med. 2000; 343: 1054-63. Available from: http://www.nejm.org/doi/full/10.1056/NEJM200010123431501#t=article
  53. Sanofi-Aventis Australia Pty Ltd. Product information: Tilade CFC-free (nedocromil sodium). Therapeutic Goods Administration, Canberra, 2008. Available from: https://www.ebs.tga.gov.au/
  54. Ducharme FM, Krajinovic M. Steroid responsiveness and wheezing phenotypes. Paediatr Respir Rev. 2011; 12: 170-176. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21722845
  55. Kramer S, Rottier BL, Scholten RJ, Boluyt N. Ciclesonide versus other inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2013; Issue 2: CD010352. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010352/full
  56. Martinez FD, Chinchilli VM, Morgan WJ, et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial. Lancet. 2011; 377: 650-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21324520
  57. Yokoyama H, Yamamura Y, Ozeki T, et al. Effects of mouth washing procedures on removal of budesonide inhaled by using Turbuhaler. Yakugaku Zasshi. 2007; 127: 1245-1249. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17666876
  58. Kelly HW, Sternberg AL, Lescher R, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012; 367: 904-12. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1203229
  59. Zöllner EW, Lombard CJ, Galal U, et al. Hypothalamic-adrenal-pituitary axis suppression in asthmatic school children. Pediatrics. 2012; 130: e1512-19. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23147980
  60. Ahmet A, Kim H, Spier S. Adrenal suppression: A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy. Allergy Asthma Clin Immunol. 2011; 7: 13. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177893/
  61. Priftis KN, Papadimitriou A, Anthracopoulos MB, et al. Endocrine-immune interactions in adrenal function of asthmatic children on inhaled corticosteroids. Neuroimmunomodulation. 2009; 16: 333-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19571594
  62. Macdessi JS, Randell TL, Donaghue KC, et al. Adrenal crises in children treated with high-dose inhaled corticosteroids for asthma. Med J Aust. 2003; 178: 214-6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12603184
  63. GlaxoSmithKline Australia Pty Ltd. Product Information: Seretide (fluticasone propionate; salmeterol xinafoate) Accuhaler and MDI. Therapeutic Goods Administration, Canberra, 2013. Available from: https://www.ebs.tga.gov.au/
  64. AstraZeneca Pty Ltd. Product Information: Symbicort (budesonide and eformoterol fumarate dihydrate) Turbuhaler. Therapeutic Goods Administration, Canberra, 2010. Available from: https://www.ebs.tga.gov.au/
  65. Mundipharma Pty Ltd. Product Information: Flutiform (fluticasone propionate and eformoterol fumarate dihydrate). Therapeutic Goods Administration, Canberra, 2013. Available from: https://www.ebs.tga.gov.au
  66. Ni Chroinin M, Greenstone I, Lasserson TJ, Ducharme FM. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children. Cochrane Database Syst Rev. 2009; Issue 4: CD005307. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005307.pub2/full
  67. McMahon AW, Levenson MS, McEvoy BW, et al. Age and risks of FDA-approved long-acting β2-adrenergic receptor agonists. Pediatrics. 2011; 128: e1147-1154. Available from: http://pediatrics.aappublications.org/content/128/5/e1147.long
  68. Gibson PG, Chang AB, Glasgow NJ, et al. CICADA: cough in children and adults: diagnosis and assessment. Australian cough guidelines summary statement. Med J Aust. 2010; 192: 265-271. Available from: http://www.lungfoundation.com.au/professional-resources/guidelines/cough-guidelines