Asthma Management Handbook

Conducting further review after adjustment of initial treatment in children 6 years and over

Recommendations

If symptoms have been controlled for at least 3 months in a child taking regular inhaled corticosteroid treatment, reduce the dose and review within 4 weeks.

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

How this recommendation was developed

Adapted from existing guidance

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

  • van Asperen et al. 2010 1

If symptoms have been controlled for at least 3 months in a child taking regular low-dose inhaled corticosteroid/long-acting beta2 agonist combination, consider replacing with (one of):

  • low-dose inhaled corticosteroid and concomitant montelukast
  • low-dose inhaled corticosteroid
  • montelukast
  • a cromone.
  • Advise parents about potential adverse psychiatric effects of montelukast

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

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 well controlled for at least 3 months on the lowest available inhaled corticosteroid dose, consider the following options:

  • Stop preventer treatment completely, while monitoring the response, to judge whether symptoms have resolved.
  • Replace inhaled corticosteroid with a trial of montelukast or a cromone. If well controlled for a further 3 months, stop preventer treatment and monitor the response.
  • Advise parents about potential adverse psychiatric effects of montelukast
How this recommendation was developed

Consensus

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

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

In children with persistent exercise-induced respiratory symptoms despite regular treatment with inhaled corticosteroids, consider adding montelukast (children 6–14 years).

  • Advise parents about potential adverse psychiatric effects of montelukast
How this recommendation was developed

Consensus

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

  • van Asperen et al. 2010 1
  • Fogel et al. 2010 3

If asthma seems to be severe or is difficult to control, review the diagnosis, check the child’s technique when using inhaler devices, check that the dose and regimen is correct, and whether the child is exposed to environmental triggers.

How this recommendation was developed

Consensus

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

  • Bush and Saglani, 2010 4
  • Bush et al. 2011 5

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

How this recommendation was developed

Consensus

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

  • Chung et al. 20146

Regular treatment with a theophylline (aminophylline or theophylline) is not recommended routinely for children, but might be considered by a specialist respiratory physician for children with difficult-to-treat asthma.

How this recommendation was developed

Consensus

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

Omalizumab treatment may be considered for adolescents 12 years and over with moderate-to-severe allergic asthma despite inhaled corticosteroid treatment, and raised IgE levels.

Note: For adolescents with severe allergic asthma who may be eligible for PBS subsidy, whose asthma is not well-controlled despite optimal inhaled therapy, refer immediately for specialist assessment, because patients only become eligible for PBS subsidisation for omalizumab after at least 12 months’ care by a specialist experienced in the management of severe asthma. After treatment is established, ongoing treatment with omalizumab may be administered by a GP, with 6-monthly review of ongoing eligibility at the specialist clinic.

How this recommendation was developed

Adapted from existing guidance

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

  • Katelaris et al. 2009 7
  • Chung et al. 2014 6

Omalizumab treatment can be considered for children aged 6 to 11 years with severe allergic asthma (documented exacerbations despite daily high-dose inhaled corticosteroids with or without another maintenance treatment) and raised IgE levels.

Note: For children with severe allergic asthma who may be eligible for PBS subsidy, whose asthma is not well-controlled despite optimal inhaled therapy, refer immediately for specialist assessment, because patients only become eligible for PBS subsidisation for omalizumab after at least 6 months' care by the same specialist.

How this recommendation was developed

Adapted from existing guidance

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

  • Chung et al. 20146
  • Katelaris et al. 20097

More information

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:4

  • 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.89

High rates of incorrect inhaler use among children with asthma and adults with asthma or COPD have been reported,10, 11, 12, 13, 14 even among regular users.15 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.16

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.10, 17, 15, 18, 19 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.15

Correcting patients' inhaler technique has been shown to improve asthma control, asthma-related quality of life and lung function.20, 21

Common errors and problems with inhaler technique

Common errors with manually actuated pressurised metered dose inhalers include:16

  • 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:16

  • 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.16 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.22, 10, 23, 24 Patients do not learn to use their inhalers properly just by reading the manufacturer's leaflet.23 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).8, 21

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.20, 10, 11 

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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.

Asset ID: 27

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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.252627

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.27

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.28

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.29

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.30 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.31 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.31

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.3 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.3

Overall, adding montelukast is the best option when effects on exercise-induced symptoms and safety are also considered.32

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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.33 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.346

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)'.35 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).33

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Omalizumab

Omalizumab is a treatment option for some adults and children aged 6 years and over with severe allergic asthma.6 Omalizumab is given by subcutaneous injection every 2-4 weeks, with the dose based on the patient's weight and baseline total serum IgE level.

Omalizumab is approved by the Therapeutic Goods Administration for use in:36

  • adults and adolescents aged 12 years and over with moderate-to-severe allergic asthma that is not controlled while taking inhaled corticosteroid and who have raised IgE levels.
  • children aged 6 to 11 years with severe allergic asthma who have documented exacerbations despite daily high-dose inhaled corticosteroids and who have raised IgE levels.

For PBS-subsidised treatment with omalizumab, patients must meet several additional criteria (see Note).

When given in addition to inhaled corticosteroids in double-blind randomised placebo-controlled trials, omalizumab reduced rates of asthma flare-ups and hospitalisation in patients with moderate or severe allergic asthma.37 In non-blinded studies in patients with severe allergic asthma, omalizumab improved lung function and asthma control, reduced symptoms, severe flare-ups, work or school days lost due to severe flare-ups, and hospitalisations, and improved quality of life.38

Omalizumab treatment is generally well tolerated. The most common adverse events are injection site reactions and, in children aged 6-11 years, pyrexia, upper gastrointestinal pain and headache.36 Anaphylactoid reactions have been reported, including among Australian patients.39 Early reports suggested that omalizumab may be associated with an increased risk of malignancy. However, subsequent pooled results indicate that a causal relationship between omalizumab therapy and malignancy is unlikely.40, 36

Note: Omalizumab treatment in adults and adolescents is subsidised through the PBS for use in patients with severe allergic asthma who meet certain criteria, including monitoring for at least 12 months by a specialist (respiratory physician, clinical immunologist, allergist or general physician) experienced in the management of patients with severe asthma. PBS criteria for continuation of treatment include demonstration of a therapeutic response by recording asthma symptom control, at baseline and after 6 months of treatment, using the 5-item Asthma Control Questionnaire (ACQ-5).

Omalizumab treatment for children aged 6 to 11 years is subsidised through the PBS for use in patients with severe allergic asthma who meet certain criteria, including monitoring for at least 6 months by a specialist (paediatric respiratory physician, clinical immunologist, or paediatrician or general physician experienced in the management of patients with severe asthma, in consultation with a respiratory physician). PBS criteria for continuation of treatment include demonstration of a therapeutic response by recording asthma symptom control, at baseline and after 6 months of treatment, using either the ACQ-5 or Asthma Control Questionnaire interviewer administered version (ACQ-IA), or reduction in time-adjusted exacerbation rates compared with the 12 months before treatment.

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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;41 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.42 Behavioural and psychiatric adverse effects were rare in clinical trials.43,44

A recent analysis of databases of adults and children taking montelukast suggests it is associated with nightmares, depression, and aggression.45 Allergic granulomatous angiitis has also been reported, but a causal relationship has not been established.45

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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References

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  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. 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
  4. 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
  5. Bush A, Pedersen S, Hedlin G, et al. Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?. Eur Respir J. 2011; 38: 947-58. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21737557
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  14. 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
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  16. 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
  17. 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
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  19. 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
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  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
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  37. Normansell R, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. **. 2014; : . Available from: https://www.ncbi.nlm.nih.gov/pubmed/24414989
  38. Abraham I, Alhossan A, Lee CS, et al. 'Real-life' effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review. **. 2016; : 593-610. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26644231
  39. Gibson PG, Reddel HK, McDonal VM, et al. Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry. **. 2016; 46: 1054-1062. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27350385
  40. Busse W, Buhl R, Fernandez Vidaurre C, et al. Omalizumab and the risk of malignancy: results from a pooled analysis. J Allergy Clin Immunol. 2012; 129: 983-9.e6. Available from: http://www.jacionline.org/article/S0091-6749(12)00069-3/fulltext
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