Stepping down treatment in children aged 1–5 years
If symptoms have been well controlled for at least 6 months in a child taking regular inhaled corticosteroid treatment, consider reducing the dose.
Monitor symptom control within 4–6 weeks after stepping down.
Do not attempt to step down treatment at the start of the preschool year or during the child’s peak asthma season (if there is a predictable seasonal pattern).
If symptoms have been well controlled for at least 6 months in a child taking regular treatment with a fixed-dose combination of inhaled corticosteroid–long-acting beta2 agonist, consider switching to inhaled corticosteroid only.
Monitor symptom control within 4–6 weeks after stepping down.
Do not attempt to step down treatment at the start of the preschool year or during the child’s peak asthma season (if there is a predictable seasonal pattern). Take into account previous treatment response, the result of any previous attempts to step down, and changes in the child’s environment that could affect exposure to triggers.
- Combination inhaled corticosteroid plus long-acting beta2 agonist is not recommended for children younger than 6 years.
- How this recommendation was developed
Consensus recommendation following inconclusive literature search
Based on clinical experience and expert opinion after literature review yielded insufficient evidence for an evidence-based recommendation
Key evidence considered:
Last reviewed version 2.0
If symptoms are well controlled for at least 6 months on the lowest available inhaled corticosteroid dose, consider stopping treatment and monitor for symptoms and flare-ups.
- Stepping down preventer treatment in children
Stepping down can be considered when asthma has been well controlled for 6 months (depending on severity of previous symptoms). This will help identify the minimal dose or regimen needed to maintain control and may minimise the risk of treatment-related adverse effects and help identify the minimal dose or regimen needed to maintain control.
Children who have stable asthma are at increased risk of a flare-up when stepping down treatment, so close monitoring is needed. Stepping down should not be attempted at the beginning of the school year.5
Stepping down from regular inhaled corticosteroid
For children already taking the lowest available dose, options are stop preventer treatment entirely, or switch to montelukast. Few studies have compared different options for stepping down.
Stepping down from regular inhaled corticosteroid plus long-acting beta-2 agonist
Options for stepping down from regular treatment with a combination inhaled corticosteroid and long-acting beta2 agonist are to reduce the inhaled corticosteroid dose or switch to inhaled corticosteroid only (i.e. discontinue the long-acting beta2 agonist).
There is insufficient evidence from randomised trials on which to base recommendations on whether and how to discontinue long-acting beta2 agonist treatment in children once good asthma control has been achieved with the combination of inhaled corticosteroid and long-acting beta2 agonist.9
In a study of children aged 4–11 years whose asthma was well controlled while using a combination of inhaled corticosteroid and long-acting beta2-agonist, stepping down to inhaled corticosteroid monotherapy was associated with a higher rate of flare-ups than continuing on combination therapy.10
In a study of children aged 5–15 years with well-controlled asthma, halving the inhaled corticosteroid component and discontinuing the long-acting beta2 agonist had equivalent outcomes for asthma symptoms and lung function.11
In a study of children with asthma well controlled on twice-daily fluticasone propionate, switching to montelukast was associated with a higher rate of treatment failure and poorer asthma control than halving the fluticasone dose and adding salmeterol.12
Stepping down from montelukast
In children taking montelukast, treatment can be stopped abruptly.
Asthma control should be monitored and the child’s written asthma action plan updated to ensure parents/carers know how to manage symptoms.
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- Inhaled corticosteroids for children: adverse effects
Local adverse effects
Topical effects can be reduced by use of spacer devices (which reduce oropharyngeal deposition), and by mouth-rinsing and spitting after use.2 Immediate quick mouth-rinsing removes more residual medicine in the mouth than delayed rinsing.14
Systemic adverse effects
Systemic effects of inhaled corticosteroids in children depend on the dose, but clinically significant adverse effects are uncommon.2
The use of spacers and mouth rinsing will not reduce systemic effects, but the use of a spacer may increase efficacy so that a lower dose is required.
Short-term suppression of linear growth has been demonstrated in children taking inhaled corticosteroids.16,17 The effect seems to be maximal during the first year of therapy and only one study has reported an effect in subsequent years of treatment.17 A Cochrane systematic review concluded that regular use of inhaled corticosteroid at low or medium daily doses is associated with a mean reduction of 0.48 cm per year in linear growth velocity and 0.61 cm less gain in height during 1 year of treatment in children with mild to moderate persistent asthma.17
One study of patients who participated in a clinical trial of inhaled corticosteroids as children, reported a reduction in adult height of approximately 1 cm,16, 18, 19, 20 whereas several studies have reported that children taking inhaled corticosteroids attained normal adult height.21, 22, 23
Other factors affect growth in children with asthma. Uncontrolled asthma itself reduces growth and final adult height.22 One study found that inhaled corticosteroid equivalent to budesonide 400 microg/day affected growth less than low socioeconomic status.23
Inhaled corticosteroids have not been associated with effects on bone density or fractures in children. 2 However, data from a recent study in Australia suggested asthma itself is associated with increased incidence of fractures in children, independent of medication.24
Given that the total dose of corticosteroids (both inhaled corticosteroids and oral corticosteroids) influences bone health, the aim of asthma management is to maintain symptom control using the lowest inhaled corticosteroid dose required, and to avoid repeated courses of oral corticosteroids.
Biochemical testing in a research setting suggests 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.25 The risk is higher among children receiving concomitant intranasal steroids and those with lower body mass index,25 and is influenced by genetics.26
Clinical adrenal insufficiency in children taking inhaled corticosteroids is rare but has been reported, 27, 28, 29 including cases in Australia.29 Most cases have involved children given more than 500 microg per day fluticasone propionate.27
Adrenal suppression is associated with hypoglycaemia, hypotension, weakness, failure to grow, and is potentially fatal. Hypothalamic–pituitary–adrenal axis suppression may not be detected until adrenal crisis is precipitated by physical stress.30
Written information (e.g. a steroid alert card) can be prepared for children receiving long-term high-dose inhaled corticosteroids. Parents/carers can be instructed to present the card if the child ever needs to go to the emergency department (for any reason) or be admitted to hospital. A steroid alert card should state that child has asthma and the inhaled corticosteroid dose. A medical alert bracelet could also be considered.
There are no nationally accepted protocols for routine assessment of adrenal function in primary care 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.
Regular monitoring of height might help detect adrenal suppression, based on the findings of a study in which a reduction in linear growth velocity occurred before adrenal suppression.31
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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)
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- 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
- the degree to which asthma symptoms affect daily activities such as interference with physical activity or missed school days)
- the frequency of flare-ups
- spirometry in children who are able to perform the test reliably.
Questionnaire-based instruments have been validated for assessing asthma control in children:
Lung function tests
Frequent spirometry to guide asthma treatment in children has not been shown to achieve superior outcomes to symptom-based treatment.36 Current evidence does not support use of home spirometers to guide asthma treatment in children.37 However, low FEV1 predicts clinically significant flare-ups, so spirometry should be performed at asthma reviews for children who are old enough to do the test.
The quality and utility of spirometry depends on the skill, clinical expertise and experience of the person doing and interpreting spirometry.
The results of one study in children aged 6–16 years with moderate atopic asthma suggest that asthma treatment guided by airway hyperresponsiveness (measured by bronchial provocation testing) may have a benefit over symptom-guided treatment in improving lung, but this effect was lost after 3–7 years of usual care.38, 39 Repeated bronchial provocation testing is not feasible in clinical practice.
Measures of airway inflammation
Measures of airway inflammation (e.g. sputum eosinophil count, exhaled nitric oxide measurement) are not recommended in primary care to guide treatment decisions, but are increasingly used in specialist clinics.
Asthma treatment guided by sputum eosinophil count has been shown to reduce the frequency of flare-ups in adults with asthma, but there is insufficient evidence to ascertain its value for children.40
Exhaled nitric oxide measurement may be useful in guiding asthma management in some children. In children not taking inhaled corticosteroid, a high nitric oxide level probably predicts a good short-term response to inhaled corticosteroid treatment,41 but it does not distinguish between asthma and eosinophilic bronchitis and is often high in children with atopy. There is insufficient evidence to ascertain whether a low exhaled nitric oxide level predicts successful withdrawal from inhaled corticosteroids without asthma relapse,41 or safety of treating asthma without inhaled corticosteroids.
A Cochrane review42 found that exhaled nitric oxide-guided management was significantly better than other approaches to adjusting medicines for reducing the number of children with flare-ups and the number of children who needed oral corticosteroids, but did not reduce the frequency of flare-ups or the rate of flare-ups requiring hospitalisation, improve lung function or symptoms scores, or reduce inhaled corticosteroid doses. The authors concluded that it could not be recommended for all children but may be beneficial for a subset not yet defined.42
Towards personalised asthma care
Emerging understanding of asthma phenotypes and of genetic factors that predict therapeutic response to preventer options is leading to the possibility of personalised, genomics-based treatment for asthma in children.43 In the near future, individual tailored therapy is may replace the standardised step model based on population data.
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- 'Wheeze-detecting' devices
Some hand-held devices and smart phone applications are marketed for detecting and measuring wheeze by audio recording and analysis.
There is not enough evidence to recommend these devices and apps for use in monitoring asthma symptoms or asthma control in adults or children, or in distinguishing wheeze from other airway sounds in children.
- Reliance on these devices could result in over- or under-treatment.
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- 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
- van Asperen PP, Mellis CM, Sly PD, Robertson C. The role of corticosteroids in the management of childhood asthma. The Thoracic Society of Australia and New Zealand, 2010. Available from: https://www.thoracic.org.au/journal-publishing/command/download_file/id/25/filename/The_role_of_corticosteroids_in_the_management_of_childhood_asthma_-_2010.pdf
- Kew KM, Beggs S, Ahmad S. Stopping long-acting beta2-agonists (LABA) for children with asthma well controlled on LABA and inhaled corticosteroids. Cochrane Database Syst Rev. 2015; Issue 5: CD011316. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25997166
- Rank, M. A., Johnson, R., Branda, M., et al. Long-term outcomes after stepping down asthma controller medications: a claims-based, time-to-event analysis. Chest. 2015; 148: 630-639. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556120/
- Rank, M. A., Branda, M. E., McWilliams, D. B., et al. Outcomes of stepping down asthma medications in a guideline-based pediatric asthma management program. Ann Allergy Asthma Immunol. 2013; 110: 354-358.e2. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23622006
- Kwong KY, Morphew T, Huynh P et al. Loss of asthma control in inner city children with asthma after withdraw of asthma controller medication. J Asthma 2009; 46: 1001-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19995137
- Rank MA, Hagan JB, Park MA, et al. The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol. 2013; 131: 724-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23321206
- Ciolkowski, J., Mazurek, H., Stasiowska, B.. Evaluation of step-down therapy from an inhaled steroid to montelukast in childhood asthma. Allergol Immunopathol (Madr). 2014; 42: 282-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23684855
- Kew, K. M., Beggs, S., Ahmad, S.. Stopping long-acting beta2-agonists (LABA) for children with asthma well controlled on LABA and inhaled corticosteroids. Cochrane Database Syst Rev. 2015; Issue 5: CD011316. Available from: [https://www.ncbi.nlm.nih.gov/pubmed/25997166 Full text at: http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD011316.pub2/full](https://www.ncbi.nlm.nih.gov/pubmed/25997166 Full text at: http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD011316.pub2/full)
- Stempel, D. A., Szefler, S. J., Pedersen, S., et al. Safety of adding salmeterol to fluticasone propionate in children with asthma. N Engl J Med. 2016; 375: 840-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27579634
- Akashi K, Mezawa H, Tabata Y, et al. Optimal step-down approach for pediatric asthma controlled by salmeterol/fluticasone: A randomized, controlled trial (OSCAR study). Allergol Int. 2016; 65: 306-11. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27155753
- Peters SP, Anthonisen N, Castro M, et al. Randomized comparison of strategies for reducing treatment in mild persistent asthma. N Engl J Med. 2007; 356: 2027-39. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17507702
- Cazeiro C, Silva C, Mayer S et al. Inhaled corticosteroids and respiratory infections in children with asthma: a meta-analysis. Pediatrics. 2017; 139. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28235797
- 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
- Godara N, Godara R, Khullar M. Impact of inhalation therapy on oral health. Lung India. 2011; 28: 272-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22084541
- Loke YK, Blanco P, Thavarajah M, Wilson AM. Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis. PloS One. 2015; 10: e0133428. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26191797
- Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database Syst Rev. 2014: Cd009471. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25030198
- 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
- Pruteanu AI, Chauhan BF, Zhang L et al. Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth. Cochrane Database Syst Rev. 2014: Cd009878. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25030199
- De Leonibus C, Attanasi M, Roze Z et al. Influence of inhaled corticosteroids on pubertal growth and final height in asthmatic children. Pediatr Allergy Immunol. 2016; 27: 499-506. Available from:https://www.ncbi.nlm.nih.gov/pubmed/26919136
- Pauwels RA, Pedersen S, Busse WW, et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet. 2003; 361: 1071-1076. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12672309
- Pedersen S. Do inhaled corticosteroids inhibit growth in children? Am J Respir Crit Care Med. 2001; 164: 521-35. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11520710
- Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. 2000; 343: 1064-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11027740
- Degabriele EL, Holloway KL, Pasco JA et al. Associations between asthma status and radiologically confirmed fracture in children: A data-linkage study. J Paediatr Child Health. 2018; 54(8): 855-860. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29614205
- 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
- Hawcutt DB, Francis B, Carr DF et al. Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study. Lancet Respir Med. 2018; 6:442-450. Available from: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(18)30058-4/fulltext
- 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/
- Priftis, K N, Papadimitriou, A, Anthracopoulos, M B, Fretzayas, A, Chrousos, G P. Endocrine-immune interactions in adrenal function of asthmatic children on inhaled corticosteroids. Neuroimmunomodulation 2008; 16: 333-339.
- 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
- Rao Bondugulapati LN, Rees DA. Inhaled corticosteroids and HPA axis suppression: how important is it and how should it be managed? Clin Endocrinol (Oxf). 2016; 85: 165-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27038017
- Liddell BS, Oberlin JM, Hsu DP. Inhaled corticosteroid related adrenal suppression detected by poor growth and reversed with ciclesonide. J Asthma. 2017; 54: 99-104. Available from:https://www.ncbi.nlm.nih.gov/pubmed/27284755
- 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
- 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
- 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
- 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
- Abramson MJ, Schattner RL, Holton C et al. Spirometry and regular follow-up do not improve quality of life in children or adolescents with asthma: Cluster randomized controlled trials. Pediatr Pulmonol 2015; 50: 947-54. (Available from: https://www.ncbi.nlm.nih.gov/pubmed/25200397
- Deschildre A, Beghin L, Salleron J, et al. Home telemonitoring (forced expiratory volume in 1 s) in children with severe asthma does not reduce exacerbations. Eur Respir J. 2012; 39: 290-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21852334
- Nuijsink M, Hop WC, Sterk PJ et al. Long-term asthma treatment guided by airway hyperresponsiveness in children: a randomised controlled trial. Eur Respir J 2007; 30: 457-66. (Available from: https://www.ncbi.nlm.nih.gov/pubmed/17537770
- Nuijsink M, Vaessen-Verberne AA, Hop WC et al. Long-term follow-up after two years of asthma treatment guided by airway responsiveness in children. Respir Med 2013; 107: 981-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23672993
- Petsky HL, Li A, Chang AB. Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults. Cochrane Database Syst Rev 2017; 8: Cd005603. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28837221
- Lehtimaki L, Csonka P, Makinen E et al. Predictive value of exhaled nitric oxide in the management of asthma: a systematic review. Eur Respir J 2016; 48: 706-14. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27492830
- Petsky HL, Kew KM, Chang AB. Exhaled nitric oxide levels to guide treatment for children with asthma. Cochrane Database Syst. Rev 2016; Issue 11: CD011439. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27825189/
- Turner S, Francis B, Vijverberg S et al. Childhood asthma exacerbations and the Arg16 beta2-receptor polymorphism: A meta-analysis stratified by treatment. J Allergy Clin Immunol 2016; 138: 107-13.e5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26774659