Asthma Management Handbook

Managing difficult-to-treat and severe asthma in children aged 6 years and over


If asthma symptoms remain uncontrolled (persisting symptoms or flare-ups) despite maximal regular preventer treatment:

  • assess adherence
  • check inhaler technique
  • review the diagnosis
  • check that the dose and regimen is appropriate
  • assess comorbidities (e.g. allergic rhinitis)
  • check whether the child is exposed to environmental triggers (e.g. allergens, cigarette smoke).

Table. Reviewing and adjusting preventer treatment for children aged 6–11 years Opens in a new window Please view and print this figure separately:

Figure. Stepped approach to adjusting asthma medication in children aged 6-11 years Opens in a new window Please view and print this figure separately:

How this recommendation was developed


Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • Chung et al. 20141
  • Bush et al. 20112
  • Bush et al. 20103

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If good asthma control is still not achieved after eliminating common reasons for treatment failure, offer referral to a paediatric respiratory physician or paediatrician.

How this recommendation was developed


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

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Regular treatment with a theophylline is not recommended routinely for children.

How this recommendation was developed


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

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Identify children with uncontrolled asthma who might benefit from monoclonal antibody therapy and offer referral for specialist assessment (after checking and correcting common causes of uncontrolled asthma such as incorrect inhaler technique and suboptimal adherence).

Omalizumab is indicated as add-on treatment for uncontrolled severe allergic asthma in children ≥6 years.
Before becoming eligible for PBS subsidy for monoclonal antibody therapy treatment, patients must have been treated by the same specialist (paediatric respiratory physician, clinical immunologist, allergist or a paediatrician or general physician experienced in the management of patients with severe asthma, in consultation with a respiratory physician), for at least 6 months. Stringent criteria for starting and continuing therapy apply.

How this recommendation was developed

Adapted from existing guidance

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

  • National Asthma Council Australia 20184

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More information

Definitions of severe and difficult-to-treat asthma

Although most people's asthma can be effectively treated with currently available medicines, a substantial subset of people have uncontrolled asthma (as indicated by persisting symptoms, low lung function and/or flare-ups) despite treatment. These patients are described as having difficult-to-treat asthma.

Some patients with difficult-to-treat asthma have severe asthma. Asthma severity is classified retrospectively according to the level of treatment needed to achieve or maintain good asthma control, rather than by the intensity or frequency of symptoms.5 International guidelines have been published for the assessment and management of patients with severe asthma.6 'Severe asthma' (also called severe refractory asthma' or 'severe treatment-resistant asthma') is defined as asthma for which good control is not achieved despite the highest level of recommended treatment, or asthma for which control can be maintained only with the highest level of recommended treatment.6 It is estimated that 5-10% of patients with asthma have severe asthma.6

Not all patients with difficult-to-treat asthma have severe asthma. 'Difficult-to-treat asthma' includes asthma that is uncontrolled due to adherence issues, inappropriate or incorrect use of medicines, environmental triggers or comorbidities. Patients whose asthma control improves rapidly with correction of such problems are not considered to have severe asthma.6

Treatment-resistant asthma or severe refractory asthma can only be diagnosed after confirming the diagnosis, confirming good adherence to high-dose inhaled corticosteroid and correct inhaler technique, excluding alternative or overlapping diagnoses, identifying and minimising exposure to preventable triggers including allergens, irritants and medicines that cause bronchoconstriction, managing comorbidities, and closely monitoring for at least 6 months.76

Omalizumab is a treatment option for some adults, adolescents and children with severe asthma.

The definition of severe asthma proposed by the World Health Organization (WHO) Consultation on Severe Asthma for global use is 'uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children)'.8 The WHO definition of severe asthma includes a category called 'severe untreated asthma', a term recommended only for use in countries that lack access to standard asthma medications such as inhaled corticosteroids.

Patients with severe symptoms due to untreated asthma may be found, after starting regular treatment, to have mild asthma (i.e. asthma that is easily controlled with low-dose inhaled corticosteroids).5

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:3

  • poor adherence (which may be due to lack of perceived need for the medication, concern about potential or actual side-effects, cost of medicines, a busy lifestyle, misunderstanding of the purpose and effects of asthma medicines, or inability to follow the medical instructions)
  • poor inhaler technique
  • mishandling devices (e.g. failure to clean spacer, allowing mouthpiece of dry-powder inhalers to become blocked)
  • incorrect dose or frequency
  • empty inhaler
  • 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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Classification of recent asthma symptom control in children

Ongoing review of asthma involves both assessing recent asthma symptom control and assessing risks for poor asthma outcomes such as flare-ups and adverse effects of medicines.

Recent asthma symptom control is assessed according to the frequency of asthma symptoms over the previous 4 weeks.

Table. Definition of levels of recent asthma symptom control in children (regardless of current treatment regimen)

Good control Partial control Poor control

All of:

  • Daytime symptoms ≤2 days per week (lasting only a few minutes and rapidly relieved by rapid-acting bronchodilator)
  • No limitation of activities
  • No symptoms§ during night or when wakes up
  • Need for SABA reliever# ≤2 days per week

Any of:

  • Daytime symptoms >2 days per week (lasting only a few minutes and rapidly relieved by rapid-acting bronchodilator)
  • Any limitation of activities*
  • Any symptoms during night or when wakes up††
  • Need for SABA reliever# >2 days per week

Either of:

  • Daytime symptoms >2 days per week (lasting from minutes to hours or recurring, and partially or fully relieved by SABA reliever)
  • ≥3 features of partial control within the same week

SABA: short-acting beta2 agonist

† e.g. wheezing or breathing problems

‡ child is fully active; runs and plays without symptoms

§ including no coughing during sleep

# not including doses taken prophylactically before exercise. (Record this separately and take into account when assessing management.)

​* e.g. wheeze or breathlessness during exercise, vigorous play or laughing

†† e.g. waking with symptoms of wheezing or breathing problems


Recent asthma control is based on symptoms over the previous 4 weeks. Each child’s risk factors for future asthma outcomes should also be assessed and taken into account in management.

Validated questionnaires can be used for assessing recent symptom control:
Test for Respiratory and Asthma Control in Kids (TRACK) for children < 5 years
Childhood Asthma Control Test (C-ACT) for children aged 4–11 years

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Table. Risk factors for life-threatening asthma flare-ups in children

Asthma-related factors

Poor asthma control

Admission to hospital in preceding 12 months

History of intubation for acute asthma

Over-use of short-acting beta2 agonist reliever

Abnormal spirometry findings

Reversible expiratory airflow limitation on spirometry despite treatment

Poor adherence to preventer

Incorrect inhaler technique for preventer

Poor adherence to asthma action plan

Exposure to clinically relevant allergens

Exposure to tobacco smoke

Other clinical factors

Allergies to foods, insects, medicines


Family-related factors

Frequent failure to attend consultations/lack of follow-up after an acute flare-up

Significant parental psychological or socioeconomic problems

Parent/carer unequipped to manage asthma emergency

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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


TGA-registered indications for add-on therapy

PBS considerations

High-dose ICS



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


  • 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.9

Few studies have been conducted in preschool-aged children. The preferred step-up option for children aged 6–12 years is controversial and guidelines differ in their recommendations.10

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

In school-aged children with persistent asthma taking regular inhaled corticosteroid, the addition of a long-acting beta2 agonist does not reduce the rate of asthma flare-ups requiring systemic steroids compared with the same or higher doses of inhaled corticosteroid.1112 However, the long-acting beta2 agonist–inhaled corticosteroid was superior for improving lung function.11  Growth is reduced in children treated with higher-dose inhaled corticosteroid, compared with those taking same dose plus a long-acting beta2 agonist.11 

Adolescents may benefit more from combination inhaled corticosteroid/long-acting beta2 agonist treatment than children under 12 years. 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.13

Adding montelukast versus adding a long-acting beta-2 agonist or increasing inhaled corticosteroid dose

Children aged 1–5 years

In one study in children aged 5 years or less with persistent asthma/wheeze requiring preventer treatment, raised blood eosinophil levels and atopy predicted better short-term response to high-dose inhaled corticosteroid than to montelukast.14 However, routine eosinophil counts are currently not recommended to guide treatment in children.

In children aged 1–5 years with asthma/wheeze that is not adequately controlled by low-dose inhaled corticosteroid alone, adding montelukast is preferable to increasing the dose of inhaled corticosteroids when the safety profiles of these options are compared.15 Long-acting beta2 agonists are not recommended for this age group.

  • Montelukast use has been associated with behavioural and/or neuropsychiatric adverse effects.

Note: Montelukast is TGA-approved for children aged 2 years and over.

Children aged 6 years and over

Among children 6 years and over with asthma that is not controlled by low-dose inhaled corticosteroids, the optimal regimen varies between individuals.16 In one study of children selected for high adherence with maintenance treatment, short-term responses varied between individuals: in some children the best response was achieved by adding a long-acting beta2 agonist, in others by adding montelukast, and in others by increasing the dose of inhaled corticosteroid.16

Note: The use of inhaled corticosteroids and long-acting beta2 agonists in separate inhalers is not recommended for either children or adults because of the potential for increased risk due to selective non-adherence to the inhaled corticosteroid.17

Overall, the addition of montelukast to an inhaled corticosteroid does not reduce the need for rescue oral corticosteroids or hospital admission, compared with the same or an increased dose of inhaled corticosteroids, in children aged 6 years and over or adolescents with mild-to-moderate asthma.18

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.19 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.19

A treatment trial of montelukast for 4–6 weeks is the best option when effects on exercise-induced symptoms and safety are also considered.15

  • Montelukast use has been associated with behavioural and/or neuropsychiatric adverse effects.

See: Investigation and management of exercise-induced bronchoconstriction


Genetic influence on effect of long-acting beta2 agonists

Clinical response to long-acting beta2 agonists partly depends on genetics. A beta2receptor 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 beta2agonists.20 However, routine genetic testing to tailor asthma therapy is not yet available in clinical practice.

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Tiotropium for children aged 6 years and over

Tiotropium (5 microg administered via mist inhaler as two puffs once daily) is approved by TGA for use in children aged 6 years and older with moderate-to-severe asthma.

Tiotropium is subsidised by then PBS for children aged 6–17 years when used in combination with maintenance ICS+LABA treatment, for patients with severe asthma treated by, or in consultation with, a specialist (respiratory physician, paediatric respiratory physician, clinical immunologist, allergist, paediatrician or general physician experienced in severe asthma management), with frequent moderate exacerbations or ≥ one documented severe exacerbation that required systemic corticosteroids in the previous 12 months despite maintenance treatment with a medium-to-high dose of inhaled corticosteroid in combination with a long-acting beta2 agonist, and correct inhaler technique has been assessed, demonstrated and documented (see PBS for details).

Children aged 6–11

A systematic review of three randomised controlled trials reported that, in children aged 6–11 years with moderate-to-severe symptomatic asthma, tiotropium improved lung function, improved symptoms, and reduced the rate of flare-ups.21 Tiotropium was generally well tolerated.21

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Specific allergen immunotherapy (desensitisation)
  • Specific allergen immunotherapy should not be started unless the patient has stable asthma, including spirometry-demonstrated forced expiratory volume in 1 second (FEV1) greater than 80% predicted for subcutaneous immunotherapy and greater than 70% predicted for sublingual immunotherapy.22, 23 For patients with unstable asthma (e.g. frequent symptoms, marked variability in airflow measured by spirometry or peak flow monitor), the risks of treatment should be considered. These patients will need specialist supervision during treatment.

Options available in Australia

Two forms of specific allergen immunotherapy are available:

  • sublingual immunotherapy
  • subcutaneous immunotherapy.

Both forms of specific allergen immunotherapy require 3–5 years of treatment. Specific allergy immunotherapy can be repeated.

Although some specific allergen therapies can be prescribed by primary care health professionals, it is recommended that they are initiated under the care of an allergy specialist (allergist or clinical immunologist), where possible.

Commercial allergen preparations for immunotherapy are available in Australia for aeroallergens including house dust mite, pollens (e.g. grass, tree and weed pollens), animal dander and moulds.

Overview of efficacy

There is strong evidence that allergen immunotherapy is effective in the treatment of seasonal and perennial allergic rhinitis.24, 25, 26 There is less evidence supporting specific allergen immunotherapy in children than in adults.25 Specific allergen immunotherapy in children with seasonal allergic rhinoconjunctivitis might prevent development of asthma.27, 28, 29

Single-allergen specific allergen immunotherapy is effective in patients sensitised to one allergen and those sensitised to multiple allergens.30, 31, 32 In selected cases more than one allergen may be administered as separate extracts. There is weak evidence for the efficacy of allergen mixes.33

A systematic review of studies directly comparing subcutaneous immunotherapy and sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma found:34

  • low-grade evidence that subcutaneous immunotherapy is more effective than sublingual immunotherapy for reducing asthma symptoms and for reducing a combined measure of rhinitis symptoms and medication use
  • moderate-grade evidence that subcutaneous immunotherapy is more effective than sublingual immunotherapy for reducing nasal and/or eye symptoms.

Sublingual immunotherapy is associated with a lower rate of severe adverse effects (anaphylaxis and death) than subcutaneous immunotherapy, based on indirect comparison.35, 36, 37

Sublingual immunotherapy

Sublingual immunotherapy (self-administered at home) is effective for the treatment of allergic rhinitis in adults and children.38, 39 The greatest benefits have been demonstrated in those with allergies to temperate grass pollens or house dust mite.39 Therapeutic Goods Administration (TGA)-approved indications for commercially available preparations vary according to age group.

The extract must be held under the tongue without swallowing for 2 minutes (liquid extracts) or 1 minute (tablets).

Sublingual immunotherapy is generally well tolerated.38 Local adverse effects are common in children receiving sublingual immunotherapy.35 Systemic adverse reactions, such as anaphylaxis, are very rare.35 The majority of adverse events occur soon after beginning treatment.39

TGA-approved indications

Asthma: Acarizax (house dust mite) is indicated for adults 18–65 years with house dust mite allergic asthma that is not well controlled by inhaled corticosteroids and is associated with mild-to-severe house dust mite allergic rhinitis.40 It is contraindicated in patients with FEV1 <70% predicted after adequate treatment, and for patients who have experienced a severe flare-up within the previous 3 months.40

Allergic rhinitis: Several commercial preparations of aeroallergens for sublingual immunotherapy in patients with allergic rhinitis are used in Australia, including:

  • Acarizax (house dust mite) – indicated for adults 18–65 years with persistent moderate to severe house dust mite allergic rhinitis despite symptomatic treatment.40
  • Actair (house dust mite) – indicated for the treatment of house dust mite allergic rhinitis with or without conjunctivitis in adults and adolescents over 12 years diagnosed with house dust mite allergy.41
  • Grazax (Timothy grass [Phleum pratense] pollen extract) – indicated for adults, adolescents and children older than 5 years with allergic rhinitis induced by Timothy grass42
  • Oralair tablets (mix of grass pollens) – indicated for adults and children over 5 years with grass pollen allergic rhinitis.43

Various single allergens and/or multiple allergen mixes are available for use as advised by the treating allergist, available as liquid extracts. Age restrictions vary between products.

Note: PBS status as at October 2016: Treatment with sublingual immunotherapy specific allergen preparations is not subsidised by the PBS.

Subcutaneous immunotherapy

Subcutaneous immunotherapy involves injections in which the dose is gradually increased at regular intervals (usually weekly), or until a therapeutic/maintenance dose is reached. This can take approximately 3–6 months.44 Treatment is then continued for a further 3–5 years.

Subcutaneous immunotherapy is generally not suitable for younger children (e.g. less than 7 years) because they may not be able to tolerate frequent injections.

Several commercial preparations of aeroallergens for subcutaneous immunotherapy are available in Australia, including various single allergens and/or multiple allergen mixes for use as advised by the treating allergist. Age restrictions vary between products.

Subcutaneous immunotherapy is effective for the treatment of allergic rhinitis and asthma, particularly when single-allergen immunotherapy regimens are used.36 There is strong evidence that it reduces asthma symptoms, asthma medication usage, rhinitis/rhinoconjunctivitis symptoms, conjunctivitis symptoms, and rhinitis/rhinoconjunctivitis disease-specific quality of life, in comparison to placebo or usual care.36 There is also moderate evidence that subcutaneous immunotherapy reduces rhinitis/rhinoconjunctivitis medication usage.36

Subcutaneous immunotherapy is associated with local adverse effects (e.g. injection-site swelling) and, less frequently, serious systemic adverse effects.35, 39 The most common systemic reactions are respiratory symtoms. There have been few reports of anaphylaxis.35

Note: PBS status as at March 2019: Treatment with subcutaneous specific allergen immunotherapy preparations is not subsidised by the PBS.

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Oral corticosteroids for children: adverse effects

Oral corticosteroids may have adverse psychiatric effects in children, including aggression and hyperactivity.45 Effects in the general population include euphoria, hypomania, depression, disturbances of mood, cognition, sleep and behaviour.46

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.9 However, risk can accumulate if frequent courses (four or more per year) are given.9

Recurrent courses of oral corticosteroids may also affect bone mineral density, especially in boys.9,47

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Correct use of inhaler devices

Checking and correcting inhaler technique is essential to effective asthma management.

Most patients with asthma or COPD do not use their inhalers properly,48, 49,5050, 51 and most have not had their technique checked or corrected by a health professional.

Incorrect inhaler technique when using maintenance treatments increases the risk of severe flare-ups and hospitalisation for people with asthma or COPD.48, 49, 52, 53, 54, 55

Poor asthma symptom control is often due to incorrect inhaler technique.56, 57

Incorrect inhaler technique when using inhaled corticosteroids increases the risk of local side effects like dysphonia and oral thrush.

The steps for using an inhaler device correctly differ between brands. Checklists of correct steps for each inhaler type and how-to videos are available from the National Asthma Council website.

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  9. 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:
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  33. Fonseca-Aten, M, Okada, P J, Bowlware, K L, et al. Effect of clarithromycin on cytokines and chemokines in children with an acute exacerbation of recurrent wheezing: a double-blind, randomized, placebo-controlled trial. Ann Allergy Asthma Immunol. 2006; 97: 457-463.
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  40. Seqirus. Product Information: Acarizax (standardised allergen extract from the house dust mites. Therapeutic Goods Administration, Canberra, 2016. Available from:
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  46. Australian Medicines Handbook. Last modified July 2018: Australian Medicines Handbook Pty Ltd. 2018
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