Asthma management targets symptom control and risk reduction.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Control-based management relies on a continual cycle of assessing, adjusting, and reviewing response to pharmacological and non-pharmacological treatment. Risk reduction is essential because patients may continue to be at risk of moderate to severe exacerbations (even with well-controlled symptoms), may have ongoing symptoms, or may experience adverse effects associated with increasing inhaled corticosteroid doses (e.g., impacting growth). Exacerbation history is less useful because of the continued risk of severe exacerbations in patients with otherwise good symptom control. Children should be prescribed the minimum number of medications at the lowest doses that achieve good control. Good education of the patient and parent or carer is fundamental to paediatric asthma management (see Patient discussions).
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What are the effects of interventions to improve inhaler technique in children with asthma?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2622/fullShow me the answer Most children will have mild intermittent asthma and will not require daily therapy.
This topic covers the treatment of children aged 11 years or younger with non-acute asthma, primarily according to the stepwise approach in the GINA guideline.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Children aged 12 years and older are typically treated as adults, and their management should not be extrapolated to younger age groups.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[138]de Nijs SB, Venekamp LN, Bel EH. Adult-onset asthma: is it really different? Eur Respir Rev. 2013 Mar 1;22(127):44-52.
https://err.ersjournals.com/content/22/127/44.long
http://www.ncbi.nlm.nih.gov/pubmed/23457164?tool=bestpractice.com
[139]McMahon AW, Levenson MS, McEvoy BW, et al. Age and risks of FDA-approved long-acting β₂-adrenergic receptor agonists. Pediatrics. 2011 Nov;128(5):e1147-54.
http://www.ncbi.nlm.nih.gov/pubmed/22025595?tool=bestpractice.com
See Acute asthma exacerbation in children for more information about the management of acute exacerbations.
See Asthma in adults for more information about the management of children aged 12 years and older.
Stepwise therapy for long-term management
Guidelines recommend viewing asthma severity and control in a stepwise manner where medication can be stepped up or stepped down based on disease severity and control.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[103]National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma. Aug 2007 [internet publication].
http://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/full-report.htm
[124]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.
https://www.jacionline.org/article/S0091-6749(20)31404-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33280709?tool=bestpractice.com
International guidance from GINA differentiates treatment steps for children aged 0-5 and 6-11 years. However, specific guidance may vary both within and between countries.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[8]British Thoracic Society. British guideline on the management of asthma. Jul 2019 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma
[124]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.
https://www.jacionline.org/article/S0091-6749(20)31404-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33280709?tool=bestpractice.com
[140]Koldeweij C, Appelbaum N, Rodriguez Gonzalvez C, et al. Mind the gap: mapping variation between national and local clinical practice guidelines for acute paediatric asthma from the United Kingdom and the Netherlands. PLoS One. 2022;17(5):e0267445.
http://www.ncbi.nlm.nih.gov/pubmed/35580117?tool=bestpractice.com
According to GINA, step 1 covers as-needed therapy and step 2 onward covers therapy for persistent asthma, with successive steps taken based on asthma severity and control. Treatment response is typically reviewed at 2- to 3-month intervals or based on clinical need, at which point further treatment decisions are made. Only one medication should usually be changed at a time to allow its effect to be assessed.
This approach should not replace personalised clinical decision-making, which includes assessment of symptom control, risk factors, inhaler availability and correct use, treatment cost, and environmental impact.
Treatment terminology
Therapeutic options are classified as follows:[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Maintenance: medications used continuously, even when asymptomatic (i.e., frequency of administration, not drug class). Includes inhaled corticosteroid (ICS)-containing medications, leukotriene receptor antagonists (LTRA), and biologics.
Controller: any medication that targets both symptom control and future risk. The introduction of reliever inhalers that contain an anti-inflammatory means that this class is no longer synonymous with ICS-containing or maintenance treatment.
Reliever: as-needed inhalers used for rapid symptom relief or before exercise. Includes short-acting beta agonists (SABAs) and as needed ICS-formoterol and ICS-SABA combinations.
Anti-inflammatory reliever (AIR): inhalers that contain a low-dose ICS and rapid-acting bronchodilator. Includes budesonide-formoterol, and any ICS-salbutamol combination. AIR-only therapy is used in steps 1-2 for aged 12 years and older.
Maintenance and reliever therapy (MART): the use of combination ICS-formoterol inhalers every day for both maintenance and symptom relief. Includes budesonide-formoterol, but excludes ICS with other long-acting beta agonists (LABAs) or SABAs. Used in steps 3-5 for children aged 6-11 years.
GINA stepwise therapy aged 0-5 years
All children who experience wheezing episodes should be provided with a short-acting beta agonist (SABA) inhaler for symptom relief. Regular controller therapy, such as an ICS, is only started at step 2 if the child has a persistent asthma phenotype. Management then follows a stepwise approach guided by asthma severity and control. Those taking a controller medication should also take a SABA when required.
Step 1. Children with infrequent viral wheezing episodes and no or few interval symptoms
As-needed inhaled SABA is preferred for children aged ≤5 years with mild asthma.
There is insufficient evidence for the use of a daily controller.
Children with intermittent viral-induced wheeze despite a SABA may benefit from intermittent high-dose ICS, especially if there is underlying atopy. Short courses of ICS can also be given at the onset of viral illness.
If prescribed, ensure that the ICS is used appropriately and the child is monitored for adverse effects.
Step 2. Symptoms consistent with asthma, symptoms that are not well-controlled, or 3 or more exacerbations per year.
Daily low-dose ICS plus as-needed inhaled SABA is preferred.
An alternative is an LTRA (e.g., montelukast).
Intermittent high-dose ICS (as-needed or episodic) may be considered for frequent viral-induced wheezing and interval symptoms, but only after a trial of daily low-dose ICS.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[141]Zeiger RS, Mauger D, Bacharier LB, et al; CARE Network of the National Heart, Lung, and Blood Institute. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med. 2011 Nov 24;365(21):1990-2001.
https://www.nejm.org/doi/full/10.1056/NEJMoa1104647#t=article
http://www.ncbi.nlm.nih.gov/pubmed/22111718?tool=bestpractice.com
[142]Chauhan BF, Chartrand C, Ducharme FM. Intermittent versus daily inhaled corticosteroids for persistent asthma in children and adults. Cochrane Database Syst Rev. 2013 Feb 28;(2):CD009611.
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009611.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/23450606?tool=bestpractice.com
[143]Kaiser SV, Huynh T, Bacharier LB, et al. Preventing exacerbations in preschoolers with recurrent wheeze: a meta-analysis. Pediatrics. 2016 Jun;137(6):e20154496.
http://www.ncbi.nlm.nih.gov/pubmed/27230765?tool=bestpractice.com
If good asthma control is not achieved with an initial treatment option, trial each of the alternative step 2 treatments for 3 months before stepping up treatment. If these treatments fail to control symptoms, or exacerbations still occur, confirm that the symptoms are due to asthma, check inhaler technique and adherence, and exclude risk factors (e.g., allergen or tobacco smoke exposure) before stepping up treatment.
The treatment options in step 2 may also be given as a 3-month diagnostic trials for symptom patterns not consistent with asthma when children require a SABA reliever for 3 or more wheezing episodes each year. Referral is then required before step 3.
Step 3. Diagnosed asthma and poor control on low-dose ICS.
Daily medium-dose (or double low-dose) ICS, plus as-needed inhaled SABA, is preferred.
An alternative is daily low-dose ICS plus an LTRA (based on evidence from older children).
Clinicians should also consider specialist referral. ICS-LABA therapy is not recommended at step 3 in this age group.
Step 4. Asthma not well-controlled on medium-dose (or double ‘low-dose’) ICS.
The preferred treatment is to continue controller and reliever treatment from step 3 and refer for specialist assessment if symptom control remains poor, exacerbations persist, and adverse effects develop. Before referral, check the asthma diagnosis, check inhaler technique and adherence, and exclude risk factors (e.g., allergen or tobacco smoke exposure).
Although the best treatment has not yet been established, several options are available:
While the addition of LABAs may have a beneficial role in persistent asthma management, the response to LABAs in children is different from that reported in adults and should not be extrapolated.[144]Chauhan BF, Chartrand C, Ni Chroinin M, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2015 Nov 24;(11):CD007949.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007949.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/26594816?tool=bestpractice.com
[145]Edwards SJ, von Maltzahn R, Naya IP, et al. Budesonide/formoterol for maintenance and reliever therapy of asthma: A meta analysis of randomised controlled trials. Int J Clin Pract. 2010 Apr;64(5):619-27.
http://www.ncbi.nlm.nih.gov/pubmed/20456215?tool=bestpractice.com
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In children with chronic asthma, what are the benefits and harms of adding long-acting beta2-agonists compared with adding anti-leukotrienes to inhaled corticosteroids?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.350/fullShow me the answer There is a lack of evidence regarding the efficacy and safety of ICS-LABA available for the 0- to 4-year age group.[144]Chauhan BF, Chartrand C, Ni Chroinin M, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2015 Nov 24;(11):CD007949.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007949.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/26594816?tool=bestpractice.com
GINA stepwise therapy ages 6-11 years
All children aged 6-11 years should receive ICS-containing medication as maintenance treatment and as-needed SABA as reliever therapy. ICS-formoterol is suitable for MART in steps 3 and 4, but AIR-only treatment lacks evidence for recommendation in steps 1 and 2.
Although the management described in the following stepwise approach targets symptom control, it is important to ensure risk reduction at every step through a continual cycle of assessing, adjusting, and reviewing the patient’s treatment. For example, patients may continue to be at risk of moderate to severe exacerbations despite well-controlled symptoms, may have ongoing symptoms, or may experience adverse effects associated with increasing ICS doses.
Step 1. Infrequent asthma symptoms 1-2 days/week or less.
The preferred treatment is as-needed SABA with low-dose ICS taken at the same time (combined or in separate inhalers).
Daily maintenance low-dose ICS, plus as-needed SABA, is an alternative but risks poor adherence due to the infrequent symptoms. SABA-only therapy is no longer recommended.
Step 2. Asthma symptoms 2-5 days/week.
The preferred treatment is regular low-dose ICS plus as-needed SABA.
An alternative is as-needed SABA with low-dose ICS taken at the same time (combined or in separate inhalers).
Another alternative is daily LTRA, but this is less effective than ICS.
Step 3. Asthma symptoms 4-5 days/week or waking due to asthma at least once a week.
The preferred controller options are daily medium-dose ICS, daily low-dose ICS plus LABA, or switch to MART with a very low dose of ICS-formoterol.
An alternative is daily low-dose ICS and LTRA, although there appears to be little evidence to support this approach.[146]Chauhan BF, Ducharme FM. Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma. Cochrane Database Syst Rev. 2014 Jan 24;(1):CD003137.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003137.pub5/full
http://www.ncbi.nlm.nih.gov/pubmed/24459050?tool=bestpractice.com
As-needed SABA should be prescribed with all controllers except MART.
Step 4. Asthma symptoms daily or most days, waking with asthma at least once a week, and low lung function.
The preferred controller treatments are daily medium-dose ICS plus LABA or low-dose ICS-formoterol as MART. The child should be referred to a specialist if medium-dose ICS therapy is ineffective (not required for short courses of high-dose ICS).
Other options at this step include high-dose ICS-LABA, add-on tiotropium, or add-on LTRA.
As-needed SABA should be prescribed with all controllers except MART.
Children who present with an acute exacerbation may require a short course of oral corticosteroids.
Step 5. Persistent symptoms and/or exacerbations despite correct inhaler technique, good adherence with treatment at step 4, and unsuccessful trials of other controller options.
Specialist referral is necessary for further investigation and management.[147]Global Initiative for Asthma. Diagnosis and management of difficult-to-treat and severe asthma. 2022 [internet publication].
https://ginasthma.org/severeasthma
Continue with existing treatment until specialist assessment.
Options at this step include:[147]Global Initiative for Asthma. Diagnosis and management of difficult-to-treat and severe asthma. 2022 [internet publication].
https://ginasthma.org/severeasthma
Higher dose ICS-LABA
Add-on tiotropium
Add-on biological agent (e.g., omalizumab, mepolizumab, or dupilumab; availability may differ by region)
Add-on low-dose oral corticosteroid
If a child presents during an acute exacerbation, manage according to the Acute asthma exacerbation in children topic. Children in this age group will usually then commence maintenance therapy at step 3 or 4.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Exercise-induced bronchoconstriction
A common presentation in childhood, with effective treatment allowing patients to continue recommended levels of physical activity.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[8]British Thoracic Society. British guideline on the management of asthma. Jul 2019 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma
[148]Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2013 May 1;187(9):1016-27.
https://www.atsjournals.org/doi/full/10.1164/rccm.201303-0437ST
http://www.ncbi.nlm.nih.gov/pubmed/23634861?tool=bestpractice.com
[149]Klain A, Indolfi C, Dinardo G, et al. Exercise-induced bronchoconstriction in children. Front Med (Lausanne). 2021;8:814976.
http://www.ncbi.nlm.nih.gov/pubmed/35047536?tool=bestpractice.com
For most children, exercise-induced bronchoconstriction (EIB) will reflect poor asthma control and should prompt a check of inhaler technique and adherence followed by an increase in controller treatment, as necessary.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[8]British Thoracic Society. British guideline on the management of asthma. Jul 2019 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma
Shortness of breath or wheezing induced by exercise may also result from comorbid obesity, lack of fitness, or inducible laryngeal obstruction.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[150]Zhang C, Hicks M, Ospina MB, et al. The impact of identifying laryngeal obstruction syndromes on reducing treatment of pediatric asthma: a systematic review. Pediatr Pulmonol. 2022 Jun;57(6):1401-15.
http://www.ncbi.nlm.nih.gov/pubmed/35355450?tool=bestpractice.com
The primary pharmacological agent for the prevention of EIB is as-needed SABA approximately 5-20 minutes before exercise. If this approach is not effective, as-needed mast cell stabilising agents (e.g., sodium cromoglicate) and/or an inhaled anticholinergic (e.g., ipratropium) can be added. For patients whose symptoms remain inadequately controlled with as-needed medication, maintenance controller therapy should be commenced. Options include daily ICS with or without LABA (including MART) and/or an LTRA; if allergic, an antihistamine can be added.[148]Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2013 May 1;187(9):1016-27.
https://www.atsjournals.org/doi/full/10.1164/rccm.201303-0437ST
http://www.ncbi.nlm.nih.gov/pubmed/23634861?tool=bestpractice.com
Regular treatment with ICS and LTRA has been shown to significantly reduce the severity of EIB in children.[151]Stelmach I, Grzelewski T, Majak P, et al. Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma. J Allergy Clin Immunol. 2008 Feb;121(2):383-9.
http://www.ncbi.nlm.nih.gov/pubmed/17980416?tool=bestpractice.com
Non-pharmacological interventions also reduce the incidence and severity of EIB. These include sufficient warm-up exercise, dietary modification, and breathing through a face mask or scarf to pre-warm and humidify air (if exercising in cold weather).[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[148]Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2013 May 1;187(9):1016-27.
https://www.atsjournals.org/doi/full/10.1164/rccm.201303-0437ST
http://www.ncbi.nlm.nih.gov/pubmed/23634861?tool=bestpractice.com
There is insufficient evidence to recommend for or against training for the prevention of EIB.[152]Souza Silva BRV, da Silva GAS, de Albuquerque Rodrigues Filho E, et al. Can physical exercise assist in controlling and reducing the severity of exercise-induced bronchospasm in children and adolescents? A systematic review. Clin Respir J. 2023 Jan;17(1):3-12.
http://www.ncbi.nlm.nih.gov/pubmed/36463836?tool=bestpractice.com
Non-pharmacological treatment
Patients should be encouraged to improve their physical fitness, be treated for coexisting allergic rhinitis, and receive education about avoiding allergens and high levels of outdoor pollution based on their disease severity.
Inhaled short-acting beta agonists (SABAs)
An inhaled SABA is the first-line therapy used to rapidly reverse airflow limitation. SABA-only therapy is still recommended for children aged ≤5 years with mild asthma (step 1). GINA recommends that older children should no longer receive a SABA without maintenance therapy at any step.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Use of a SABA inhaler on average more than twice a week over 1 month suggests poor asthma control (or incorrect inhaler technique) and the possible need to step up treatment.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Anxiety, tachycardia, and supraventricular ectopy are associated with intermittent use.[153]Leung JS, Johnson DW, Sperou AJ, et al. A systematic review of adverse drug events associated with administration of common asthma medications in children. PLoS One. 2017;12(8):e0182738.
http://www.ncbi.nlm.nih.gov/pubmed/28793336?tool=bestpractice.com
However, when used appropriately within prescribed limits as reliever therapy, SABA therapy did not contribute to excess mortality, serious adverse events, or treatment discontinuation in children aged 12 years and older.[154]Sriprasart T, Waterer G, Garcia G, et al. Safety of SABA monotherapy in asthma management: a systematic review and meta-analysis. Adv Ther. 2023 Jan;40(1):133-58.
http://www.ncbi.nlm.nih.gov/pubmed/36348141?tool=bestpractice.com
Inhaled corticosteroids (ICS)
The beneficial effect of ICS is established and is generally considered to outweigh the potential adverse effects.[155]Calpin C, Macarthur C, Stephens D, et al. Effectiveness of prophylactic inhaled steroids in childhood asthma: a systemic review of the literature. J Allergy Clin Immunol. 2010 Mar 18;362(11):975-85.
http://www.ncbi.nlm.nih.gov/pubmed/9338536?tool=bestpractice.com
[156]Zhang L, Lasmar LB, Castro-Rodriguez JA. The impact of asthma and its treatment on growth: an evidence-based review. J Pediatr (Rio J). 2019 Mar-Apr;95(suppl 1):10-22.
http://www.ncbi.nlm.nih.gov/pubmed/30472355?tool=bestpractice.com
[
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How do anti-leukotriene agents compare with inhaled corticosteroids in the management of recurrent and/or chronic asthma in children?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.175/fullShow me the answer Adverse effects may be minimised by using the lowest dose that achieves good control, using a spacer (limiting oropharyngeal deposition), and rinsing the mouth after medication delivery.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[157]Adams NP, Bestall JC, Jones P, et al. Fluticasone at different doses for chronic asthma in adults and children. Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD003534.
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003534.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/18843646?tool=bestpractice.com
[158]Adams N, Bestall J, Jones P. Beclomethasone at different doses for long-term asthma. Cochrane Database Syst Rev. 1999 Oct;1999(4):CD002879.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002879/full
http://www.ncbi.nlm.nih.gov/pubmed/11279769?tool=bestpractice.com
Growth should be monitored in all children who take corticosteroids.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Categorisation tables are provided in international guidelines to outline the ICS dosing for options referred to as 'low dose', 'medium dose', and 'high dose'; do not assume equivalence of potency between medications in these categories, because any switch between brands may cause a clinically significant dose change.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[8]British Thoracic Society. British guideline on the management of asthma. Jul 2019 [internet publication].
https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma
[103]National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma. Aug 2007 [internet publication].
http://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/full-report.htm
Maintenance ICS is associated with modest improvements in pre-bronchodilator FEV1, with the greatest benefits observed in the first year of treatment.[159]Tan DJ, Bui DS, Dai X, et al. Does the use of inhaled corticosteroids in asthma benefit lung function in the long-term? A systematic review and meta-analysis. Eur Respir Rev. 2021 Mar 31;30(159):200185.
http://www.ncbi.nlm.nih.gov/pubmed/33472957?tool=bestpractice.com
Multiple dosing strategies have been shown to reduce exacerbation risk, allowing for treatment personalisation based on individual patient phenotypes and preferences.[160]Jackson DJ, Bacharier LB. Inhaled corticosteroids for the prevention of asthma exacerbations. Ann Allergy Asthma Immunol. 2021 Nov;127(5):524-9.
http://www.ncbi.nlm.nih.gov/pubmed/34400314?tool=bestpractice.com
Intermittent or as-needed ICS, as add-on therapy to SABAs, may be effective for deterioration during otherwise stable periods (e.g., at the onset of a respiratory illness in step 1).[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[124]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.
https://www.jacionline.org/article/S0091-6749(20)31404-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33280709?tool=bestpractice.com
[161]Rodriguez-Martinez CE, Sossa-Briceño MP, Garcia-Marcos L. Use of inhaled corticosteroids on an intermittent or as-needed basis in pediatric asthma: a systematic review of the literature. J Asthma. 2022 Nov;59(11):2189-200.
http://www.ncbi.nlm.nih.gov/pubmed/34806537?tool=bestpractice.com
The ICS dose should be increased gradually and cautiously according to patient response and adverse effects. When starting therapy with corticosteroids, initial low dose is as effective as initial high dose with subsequent down-titration.[162]Powell H, Gibson PG. High dose versus low dose inhaled corticosteroid as initial starting dose for asthma in adults and children. Cochrane Database Syst Rev. 2004 Apr;2004(2):CD004109.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004109.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/15106238?tool=bestpractice.com
Some children with asthma may require high doses of ICS, but these should be treated under specialist supervision to monitor for serious adverse effects.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[163]Guilbert TW, Mauger DT, Allen DB, et al; Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Growth of preschool children at high risk for asthma 2 years after discontinuation of fluticasone. J Allergy Clin Immunol. 2011 Nov;128(5):956-63.e1-7.
https://www.jacionline.org/article/S0091-6749%2811%2900999-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/21820163?tool=bestpractice.com
To minimise adverse effects, high-dose ICS therapy should be limited to short-term use over a maximum of 3-6 months.
Increased respiratory infection has not been associated with ICS use in children.[164]Cazeiro C, Silva C, Mayer S, et al. Inhaled corticosteroids and respiratory infections in children with asthma: a meta-analysis. Pediatrics. 2017 Mar;139(3).
http://www.ncbi.nlm.nih.gov/pubmed/28235797?tool=bestpractice.com
[165]Sielinou Kamgang KH, Rhedin SA, Almqvist C, et al. Use of inhaled corticosteroids and the risk of hospitalisation for pneumonia in children with asthma: a nationwide cohort study. Thorax. 2024 Apr 15;79(5):395-402.
http://www.ncbi.nlm.nih.gov/pubmed/38184370?tool=bestpractice.com
Follow-up of the Childhood Asthma Management Program (CAMP) study cohort has shown that children treated with low to medium doses of ICS as maintenance therapy are not at increased risk of cataract.[166]Raissy HH, Sternberg AL, Williams P, et al. Risk of cataracts in the Childhood Asthma Management Program Cohort. J Allergy Clin Immunol. 2010 Aug;126(2):389-92.
https://www.jacionline.org/article/S0091-6749%2810%2900741-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/20621348?tool=bestpractice.com
At medium doses, the main adverse effects are local (e.g., candidiasis) or involve a transient slowing of growth, that requires monitoring.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Prospective cohort studies have shown that early life exposure to ICS before age 6 years was associated with reduced height but no change in bone density during continued therapy.[167]Kunøe A, Sevelsted A, Chawes BLK, et al. Height and bone mineral content after inhaled corticosteroid use in the first 6 years of life. Thorax. 2022 Aug;77(8):745-51.
http://www.ncbi.nlm.nih.gov/pubmed/35046091?tool=bestpractice.com
The benefit attributable to use of ICS may exceed the potential risk of a relatively small suppression in linear growth in children with asthma.[156]Zhang L, Lasmar LB, Castro-Rodriguez JA. The impact of asthma and its treatment on growth: an evidence-based review. J Pediatr (Rio J). 2019 Mar-Apr;95(suppl 1):10-22.
http://www.ncbi.nlm.nih.gov/pubmed/30472355?tool=bestpractice.com
[168]Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database Syst Rev. 2014 Jul 17;2014(7):CD009471.
http://www.ncbi.nlm.nih.gov/pubmed/25030198?tool=bestpractice.com
Adrenal insufficiency is a potential complication with high cumulative doses of ICS.[169]Kwda A, Gldc P, Baui B, et al. Effect of long term inhaled corticosteroid therapy on adrenal suppression, growth and bone health in children with asthma. BMC Pediatr. 2019 Nov 5;19(1):411.
http://www.ncbi.nlm.nih.gov/pubmed/31684902?tool=bestpractice.com
[170]Lapi F, Kezouh A, Suissa S, et al. The use of inhaled corticosteroids and the risk of adrenal insufficiency. Eur Respir J. 2013 Jul;42(1):79-86.
http://www.ncbi.nlm.nih.gov/pubmed/23060630?tool=bestpractice.com
Specialist pulmonary assessment should be sought before initiating this therapy. It should be noted that the manufacturer's recommended maximum dose is lower than the doses suggested in the guidelines.
Fluticasone furoate and ciclesonide have longer half-lives and more favourable adverse effect profiles than some older ICS medications. These medications have a higher budesonide equivalent when comparing doses. One Cochrane review could neither demonstrate nor refute the benefit of ciclesonide compared with budesonide and fluticasone propionate.[171]Kramer S, Rottier BL, Scholten RJ, et al. Ciclesonide versus other inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2013 Feb 28;(2):CD010352.
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010352/full
http://www.ncbi.nlm.nih.gov/pubmed/23450613?tool=bestpractice.com
[
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How does ciclesonide compare with other inhaled corticosteroids in children and adolescents with chronic asthma?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.250/fullShow me the answer
Oral corticosteroids
Long-term oral corticosteroid use is less common in children/adolescents than adults (9.9% vs. 22.4%).[172]Bleecker ER, Menzies-Gow AN, Price DB, et al. Systematic literature review of systemic corticosteroid use for asthma management. Am J Respir Crit Care Med. 2020 Feb 1;201(3):276-93.
http://www.ncbi.nlm.nih.gov/pubmed/31525297?tool=bestpractice.com
Short courses of oral corticosteroids may be needed to achieve control of exacerbations, while long-term low-dose oral corticosteroids may be needed as part of chronic asthma management for children with severe asthma not adequately controlled on maximal therapy.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
It is important to monitor children/adolescents receiving oral corticosteroids for common and serious long-term systemic adverse effects.[172]Bleecker ER, Menzies-Gow AN, Price DB, et al. Systematic literature review of systemic corticosteroid use for asthma management. Am J Respir Crit Care Med. 2020 Feb 1;201(3):276-93.
http://www.ncbi.nlm.nih.gov/pubmed/31525297?tool=bestpractice.com
Growth should be monitored in all children who take corticosteroids.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Oral corticosteroid bursts have been shown to decrease bone mineral accretion and increase the risk of osteopenia.[173]Kelly HW, Van Natta ML, Covar RA, et al. CAMP Research Group. The effect of long-term corticosteroid use on bone mineral density in children: a prospective longitudinal assessment in the childhood Asthma Management Program (CAMP) study. Pediatrics. 2008 Jul;122(1):e53-61.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928657
http://www.ncbi.nlm.nih.gov/pubmed/18595975?tool=bestpractice.com
In one systematic review, common adverse acute events related to oral corticosteroid use ≤14 days' duration were vomiting, behaviour change, and sleep disturbance (incidence 5.4%, 4.7%, and 4.3%, respectively).[174]Aljebab F, Choonara I, Conroy S. Systematic review of the toxicity of short-course oral corticosteroids in children. Arch Dis Child. 2016 Apr;101(4):365-70.
http://www.ncbi.nlm.nih.gov/pubmed/26768830?tool=bestpractice.com
Other less common but serious adverse events were infection (incidence of 0.9%), increased blood pressure (39%), hypothalamic-pituitary axis suppression (81%), and weight gain (28%).[174]Aljebab F, Choonara I, Conroy S. Systematic review of the toxicity of short-course oral corticosteroids in children. Arch Dis Child. 2016 Apr;101(4):365-70.
http://www.ncbi.nlm.nih.gov/pubmed/26768830?tool=bestpractice.com
Another systematic review of oral corticosteroid treatment for ≥15 days reported incidence rates for weight gain (22.4%), cushingoid features (20.6%), and growth retardation (18.9%), together with increased susceptibility to infection that could result in death.[175]Aljebab F, Choonara I, Conroy S. Long-course oral corticosteroid toxicity in children. Arch Dis Child. 2016 Sep;101(9):e2.
http://www.ncbi.nlm.nih.gov/pubmed/27540239?tool=bestpractice.com
Cataracts have been reported in 15% to 35% of children receiving oral corticosteroids for more than 1 year.[166]Raissy HH, Sternberg AL, Williams P, et al. Risk of cataracts in the Childhood Asthma Management Program Cohort. J Allergy Clin Immunol. 2010 Aug;126(2):389-92.
https://www.jacionline.org/article/S0091-6749%2810%2900741-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/20621348?tool=bestpractice.com
Long-acting beta agonists (LABAs)
Response to the addition of a LABA to an ICS differs with age, such that favourable results seen in adult cohorts should not be extrapolated to children.[144]Chauhan BF, Chartrand C, Ni Chroinin M, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2015 Nov 24;(11):CD007949.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007949.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/26594816?tool=bestpractice.com
[145]Edwards SJ, von Maltzahn R, Naya IP, et al. Budesonide/formoterol for maintenance and reliever therapy of asthma: A meta analysis of randomised controlled trials. Int J Clin Pract. 2010 Apr;64(5):619-27.
http://www.ncbi.nlm.nih.gov/pubmed/20456215?tool=bestpractice.com
[
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In children with chronic asthma, what are the benefits and harms of adding long-acting beta2-agonists compared with adding anti-leukotrienes to inhaled corticosteroids?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.350/fullShow me the answer
In one randomised controlled trial of 280 children, 46% who had poorly controlled asthma and at least one grandparent who identified as black had better response to an increased dose of ICS over the addition of a LABA, conflicting with results in black adults and white people of all ages.[176]Wechsler ME, Szefler SJ, Ortega VE, et al. Step-up therapy in black children and adults with poorly controlled asthma. N Engl J Med. 2019 Sep 26;381(13):1227-39.
https://www.nejm.org/doi/full/10.1056/NEJMoa1905560
http://www.ncbi.nlm.nih.gov/pubmed/31553835?tool=bestpractice.com
Although concerns exist about the possibility of increased exacerbations with LABAs used alone, data suggest that they are safe when used with corticosteroids.[144]Chauhan BF, Chartrand C, Ni Chroinin M, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2015 Nov 24;(11):CD007949.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007949.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/26594816?tool=bestpractice.com
[177]Ducharme FM, Ni Chroinin M, Greenstone I, et al. 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 May 12;(5):CD005535.
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005535.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/20464739?tool=bestpractice.com
[178]Ni Chroinin M, Greenstone I, Lasserson TJ. 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 Oct 7;(4):CD005307.
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005307.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/19821344?tool=bestpractice.com
[179]Cates CJ, Schmidt S, Ferrer M, et al. Inhaled steroids with and without regular salmeterol for asthma: serious adverse events. Cochrane Database Syst Rev. 2018 Dec 3;(12):CD006922.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006922.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/30521673?tool=bestpractice.com
[180]Food and Drug Administration. FDA drug safety communication: FDA review finds no significant increase in risk of serious asthma outcomes with long-acting beta agonists (LABAs) used in combination with inhaled corticosteroids (ICS). Jan 2018 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-review-finds-no-significant-increase-risk-serious-asthma-outcomes
[181]Lemanske RF Jr, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J Med. 2010 Mar 18;362(11):975-85.
https://www.nejm.org/doi/full/10.1056/NEJMoa1001278#t=article
http://www.ncbi.nlm.nih.gov/pubmed/20197425?tool=bestpractice.com
[
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What adverse events are associated with formoterol when used for the regular treatment of chronic asthma?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.924/fullShow me the answer No evidence of benefit exists for children <4 years of age.[144]Chauhan BF, Chartrand C, Ni Chroinin M, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2015 Nov 24;(11):CD007949.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007949.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/26594816?tool=bestpractice.com
Due to safety concerns, recommendations should be adhered to strictly until there is more evidence in paediatric settings
Few studies have compared ICS in combination with different LABA medications in children under 12 years of age.[182]Lasserson TJ, Ferrara G, Casali L. Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD004106.
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004106.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/22161385?tool=bestpractice.com
One review of the efficacy of fluticasone with either formoterol or salmeterol found that although the salmeterol group showed clear improvements in lung function, asthma symptoms, and sleep disturbance compared with the formoterol group, the salmeterol group showed a greater improvement in PEF.[183]Guan R, Liu Y, Ren D, et al. The efficacy and safety of fluticasone propionate/formoterol compared with fluticasone propionate/salmeterol in treating pediatric asthma: a systematic review and meta-analysis. J Int Med Res. 2020 Mar;48(3):300060519889442.
http://www.ncbi.nlm.nih.gov/pubmed/31852314?tool=bestpractice.com
For children aged 4-12 years with chronic asthma, there is insufficient evidence to determine whether there are differences in the safety profiles of ICS combinations with formoterol or salmeterol.[184]O'Shea O, Stovold E, Cates CJ. Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events. Cochrane Database Syst Rev. 2021 Apr 14;4(4):CD007694.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007694.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/33852162?tool=bestpractice.com
Maintenance and reliever therapy (MART)
In children aged 4 years and older with moderate to severe persistent asthma, the 2020 US asthma guidelines recommend ICS-formoterol in a single inhaler as maintenance and reliever therapy (MART).[124]Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, et al. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-70.
https://www.jacionline.org/article/S0091-6749(20)31404-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33280709?tool=bestpractice.com
The rapid onset of bronchodilatory effect and dose-response relationship of ICS-formoterol allows patients to use this combination as either regular therapy with a SABA reliever or as part of a MART regimen.[185]Mukhopadhyay A, Waked M, Gogtay J, et al. Comparing the efficacy and safety of formoterol/budesonide pMDI versus its mono-components and other LABA/ICS in patients with asthma. Respir Med. 2020 Aug-Sep;170:106055.
http://www.ncbi.nlm.nih.gov/pubmed/32843176?tool=bestpractice.com
Guideline recommendations regarding the use of MART in children <12 years differ; GINA does not recommend MART in children with asthma aged ≤5 years and younger).[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
ICS-formoterol should not be used as the reliever in patients treated with an alternative ICS-LABA combination as maintenance therapy.[186]Reddel HK, Brusselle G, Lamarca R, et al. Safety and effectiveness of as-needed formoterol in asthma patients taking inhaled corticosteroid (ICS)-formoterol or ICS-salmeterol maintenance therapy. J Allergy Clin Immunol Pract. 2023 Jul;11(7):2104-14.e3.
https://www.jaci-inpractice.org/article/S2213-2198(23)00398-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37054881?tool=bestpractice.com
Leukotriene receptor antagonists (LTRAs)
LTRAs are available as an oral formulation, which has the potential to improve adherence.[187]Maspero JF, Duenas-Meza E, Volovitz B, et al. Oral montelukast versus inhaled beclomethasone in 6- to 11-year-old children with asthma: results of an open-label extension study evaluating long-term safety, satisfaction, and adherence with therapy. Curr Med Res Opin. 2001 Jan 1;17(2):96-104.
http://www.ncbi.nlm.nih.gov/pubmed/11759189?tool=bestpractice.com
One systematic review found that LTRA monotherapy compared with placebo reduced exacerbations and increased lung function, while another reported that adding LTRA to daily ICS in adolescents and adults with persistent asthma and suboptimal control led to improved lung function and asthma control.[188]Miligkos M, Bannuru RR, Alkofide H, et al. Leukotriene-receptor antagonists versus placebo in the treatment of asthma in adults and adolescents: a systematic review and meta-analysis. Ann Intern Med. 2015 Nov 17;163(10):756-67.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648683
http://www.ncbi.nlm.nih.gov/pubmed/26390230?tool=bestpractice.com
[189]Chauhan BF, Jeyaraman MM, Singh Mann A, et al. Addition of anti-leukotriene agents to inhaled corticosteroids for adults and adolescents with persistent asthma. Cochrane Database Syst Rev. 2017 Mar 16;3:CD010347.
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD010347.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/28301050?tool=bestpractice.com
[
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What are the benefits and harms of adding anti‐leukotriene agents to inhaled corticosteroids for adults and adolescents with persistent asthma?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2407/fullShow me the answer However, other reviews have reported the superiority of daily ICS over LTRA as monotherapy both in preschoolers with asthma or recurrent wheezing, and in adults and children with persistent asthma.[190]Castro-Rodriguez JA, Rodriguez-Martinez CE, Ducharme FM. Daily inhaled corticosteroids or montelukast for preschoolers with asthma or recurrent wheezing: a systematic review. Pediatr Pulmonol. 2018 Dec;53(12):1670-7.
http://www.ncbi.nlm.nih.gov/pubmed/30394700?tool=bestpractice.com
[191]Chauhan BF, Ducharme FM. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev. 2012 May 16;(5):CD002314.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002314.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/22592685?tool=bestpractice.com
One systematic review concluded that LTRA added to ICS does not reduce the need for rescue oral corticosteroid dosing in children and adolescents with mild to moderate asthma.[192]Chauhan BF, Ben Salah R, Ducharme FM. Addition of anti-leukotriene agents to inhaled corticosteroids in children with persistent asthma. Cochrane Database Syst Rev. 2013 Oct 2;(10):CD009585.
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009585.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/24089325?tool=bestpractice.com
Despite a lack of data to confirm the equivalence or superiority of LTRA compared with LABA as adjunctive treatment to ICS in children, data in adults suggest significantly greater improvements in asthma outcomes with the addition of a LABA to an ICS.[146]Chauhan BF, Ducharme FM. Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma. Cochrane Database Syst Rev. 2014 Jan 24;(1):CD003137.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003137.pub5/full
http://www.ncbi.nlm.nih.gov/pubmed/24459050?tool=bestpractice.com
One systematic review concluded that, in children aged 4-18 years with asthma, salmeterol with fluticasone was more effective than either montelukast alone, or montelukast with fluticasone.[193]Zhou XJ, Qin Z, Lu J, et al. Efficacy and safety of salmeterol/fluticasone compared with montelukast alone (or add-on therapy to fluticasone) in the treatment of bronchial asthma in children and adolescents: a systematic review and meta-analysis. Chin Med J (Engl). 2021 Nov 15;134(24):2954-61.
http://www.ncbi.nlm.nih.gov/pubmed/34784306?tool=bestpractice.com
For exercise-induced asthma, LTRA monotherapy or add-on therapy to ICS may be superior to LABA in some children.[151]Stelmach I, Grzelewski T, Majak P, et al. Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma. J Allergy Clin Immunol. 2008 Feb;121(2):383-9.
http://www.ncbi.nlm.nih.gov/pubmed/17980416?tool=bestpractice.com
[194]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 Jun;104(6):511-7.
http://www.ncbi.nlm.nih.gov/pubmed/20568384?tool=bestpractice.com
Adverse effects of montelukast
Gastrointestinal and neuropsychiatric disorders are common with LTRA use in children and young people.[195]Dixon EG, Rugg-Gunn CE, Sellick V, et al. Adverse drug reactions of leukotriene receptor antagonists in children with asthma: a systematic review. BMJ Paediatr Open. 2021;5(1):e001206.
http://www.ncbi.nlm.nih.gov/pubmed/34712847?tool=bestpractice.com
The US Food and Drug Administration (FDA) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have warned of potentially serious behaviour and mood-related adverse effects associated with montelukast.[196]Food and Drug Administration. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. Mar 2020 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-boxed-warning-about-serious-mental-health-side-effects-asthma-and-allergy-drug
[197]Medicines and Healthcare products Regulatory Agency. Montelukast: reminder of the risk of neuropsychiatric reactions. Apr 2024 [internet publication].
https://www.gov.uk/drug-safety-update/montelukast-reminder-of-the-risk-of-neuropsychiatric-reactions
These include new-onset nightmares, behavioural problems (e.g., agitation, hyperactivity, irritability, nervousness, aggression, and headache), and suicidal ideation. Healthcare professionals are advised to consider the benefits and risks of montelukast before prescribing, to have an open discussion with parents about potential adverse effects, and to monitor for the emergence of adverse effects during treatment.[196]Food and Drug Administration. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. Mar 2020 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-boxed-warning-about-serious-mental-health-side-effects-asthma-and-allergy-drug
[198]Ekhart C, van Hunsel F, Sellick V, et al. Neuropsychiatric reactions with the use of montelukast. BMJ. 2022 Mar 29;376:e067554.
http://www.ncbi.nlm.nih.gov/pubmed/35351683?tool=bestpractice.com
Good-quality evidence is lacking on the effects of deprescribing in children with established asthma, but asthma control should be monitored carefully during discontinuation.[199]Dixon EG, King C, Lilley A, et al. Deprescribing montelukast in children with asthma: a systematic review. BMJ Open. 2022 Jan 31;12(1):e053112.
http://www.ncbi.nlm.nih.gov/pubmed/35105629?tool=bestpractice.com
In a retrospective study of more than 100 children starting LTRA (median age 5 years) the incidence of drug cessation due to neuropsychiatric adverse drug reactions was approximately 15%, with most occurring within the first 2 weeks of starting the medication.[200]Benard B, Bastien V, Vinet B, et al. Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice. Eur Respir J. 2017 Aug 17;50(2):1700148.
https://erj.ersjournals.com/content/50/2/1700148.long
http://www.ncbi.nlm.nih.gov/pubmed/28818882?tool=bestpractice.com
Long-acting muscarinic antagonists (LAMAs)
Tiotropium is the only LAMA licensed for the management of childhood asthma. It is appropriate for use as add-on therapy in children aged ≥6 years old with severe asthma who have experienced at least one severe asthma exacerbation in the preceding year.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[201]Sunther M, Marchon K, Gupta A. Tiotropium in the management of paediatric and adolescent asthma: systematic review. Paediatr Respir Rev. 2021 Jun;38:58-62.
http://www.ncbi.nlm.nih.gov/pubmed/33243704?tool=bestpractice.com
Few published studies have evaluated the efficacy and safety of LABAs, LTRAs, and LAMAs as add-on therapies to ICS in patients aged ≤5 years or compared the results with older age groups.[202]Kaplan A, FitzGerald JM, Buhl R, et al. Comparing LAMA with LABA and LTRA as add-on therapies in primary care asthma management. NPJ Prim Care Respir Med. 2020 Nov 11;30(1):50.
http://www.ncbi.nlm.nih.gov/pubmed/33177503?tool=bestpractice.com
One small RCT in children aged 1-5 years found that tiotropium as add-on therapy to ICS, with or without additional controller medications, was not associated with a significant difference in asthma symptoms over 12 weeks.[203]Vrijlandt EJLE, El Azzi G, Vandewalker M, et al. Safety and efficacy of tiotropium in children aged 1-5 years with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018 Feb;6(2):127-37.
http://www.ncbi.nlm.nih.gov/pubmed/29361462?tool=bestpractice.com
For children aged ≥6 years with moderate to severe asthma, evidence suggests that triple therapy (ICS, LAMA, LABA) may be associated with fewer severe asthma exacerbations and improved asthma control.[204]Kim LHY, Saleh C, Whalen-Browne A, et al. Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-analysis. JAMA. 2021 Jun 22;325(24):2466-2479.
https://www.doi.org/10.1001/jama.2021.7872
http://www.ncbi.nlm.nih.gov/pubmed/34009257?tool=bestpractice.com
Biological therapy
GINA only recommends biological therapy for severe asthma and when existing treatment has been optimised, regardless of regulatory approvals.[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
Biologics have been shown to reduce the rates of severe exacerbations, and in some cases improve lung function (e.g., dupilumab), in children with uncontrolled severe asthma.[205]Agache I, Beltran J, Akdis C, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma. Allergy. 2020 May;75(5):1023-42.
http://www.ncbi.nlm.nih.gov/pubmed/32034960?tool=bestpractice.com
[206]Agache I, Rocha C, Beltran J, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma. Allergy. 2020 May;75(5):1043-57.
http://www.ncbi.nlm.nih.gov/pubmed/32064642?tool=bestpractice.com
[207]Jackson DJ, Bacharier LB, Phipatanakul W, et al. Dupilumab pharmacokinetics and effect on type 2 biomarkers in children with moderate-to-severe asthma. Ann Allergy Asthma Immunol. 2023 Jul;131(1):44-51.e4.
http://www.ncbi.nlm.nih.gov/pubmed/36958470?tool=bestpractice.com
[208]Bacharier LB, Maspero JF, Katelaris CH, et al. Dupilumab in children with uncontrolled moderate-to-severe asthma. N Engl J Med. 2021 Dec 9;385(24):2230-40.
http://www.ncbi.nlm.nih.gov/pubmed/34879449?tool=bestpractice.com
[209]Agache I, Akdis CA, Akdis M, et al. EAACI biologicals guidelines - recommendations for severe asthma. Allergy. 2021 Jan;76(1):14-44.
http://www.ncbi.nlm.nih.gov/pubmed/32484954?tool=bestpractice.com
Biologics appear to reduce the number of people having asthma attacks and improve lung function to a clinically relevant level.[210]Khaleva E, Rattu A, Brightling C, et al. Development of core outcome measures sets for paediatric and adult severe asthma (COMSA). Eur Respir J. 2023 Apr;61(4):2200606.
http://www.ncbi.nlm.nih.gov/pubmed/36229046?tool=bestpractice.com
[211]Gallagher A, Edwards M, Nair P, et al. Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma. Cochrane Database Syst Rev. 2021 Oct 19;10(10):CD012929.
http://www.ncbi.nlm.nih.gov/pubmed/34664263?tool=bestpractice.com
The availability and approval of each agent differs by region, and they should only be prescribed by specialists after checking local guidance. Most biologics are associated with a risk of hypersensitivity reactions.[209]Agache I, Akdis CA, Akdis M, et al. EAACI biologicals guidelines - recommendations for severe asthma. Allergy. 2021 Jan;76(1):14-44.
http://www.ncbi.nlm.nih.gov/pubmed/32484954?tool=bestpractice.com
Add-on omalizumab
Omalizumab is a monoclonal antibody against IgE that interferes with the binding of IgE to receptors on basophils and eosinophils.[212]Kulus M, Hébert J, Garcia E, et al. Omalizumab in children with inadequately controlled severe allergic (IgE-mediated) asthma. Curr Med Res Opin. 2010 Jun;26(6):1285-93.
http://www.ncbi.nlm.nih.gov/pubmed/20377320?tool=bestpractice.com
Can be considered in children aged 6-11 years with severe allergic asthma (i.e., evidence of allergic sensitisation and an elevated IgE serum level).[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[205]Agache I, Beltran J, Akdis C, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma. Allergy. 2020 May;75(5):1023-42.
http://www.ncbi.nlm.nih.gov/pubmed/32034960?tool=bestpractice.com
[206]Agache I, Rocha C, Beltran J, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma. Allergy. 2020 May;75(5):1043-57.
http://www.ncbi.nlm.nih.gov/pubmed/32064642?tool=bestpractice.com
[209]Agache I, Akdis CA, Akdis M, et al. EAACI biologicals guidelines - recommendations for severe asthma. Allergy. 2021 Jan;76(1):14-44.
http://www.ncbi.nlm.nih.gov/pubmed/32484954?tool=bestpractice.com
[213]Atkinson CE, Schworer SA, Matthews K, et al. Omalizumab is associated with improved asthma outcomes in children and adolescents with serum immunoglobulin E above dosing guidelines. J Allergy Clin Immunol Pract. 2022 Oct;10(10):2756-7.e1.
http://www.ncbi.nlm.nih.gov/pubmed/35803538?tool=bestpractice.com
Anaphylaxis occurs in approximately 0.2%, but it is generally considered safe and effective in this patient group.[212]Kulus M, Hébert J, Garcia E, et al. Omalizumab in children with inadequately controlled severe allergic (IgE-mediated) asthma. Curr Med Res Opin. 2010 Jun;26(6):1285-93.
http://www.ncbi.nlm.nih.gov/pubmed/20377320?tool=bestpractice.com
[214]Cheng L, Yang T, Ma X, et al. Effectiveness and safety studies of omalizumab in children and adolescents with moderate-to-severe asthma. J Pharm Pract. 2023 Apr;36(2):370-82.
http://www.ncbi.nlm.nih.gov/pubmed/34384308?tool=bestpractice.com
Add-on mepolizumab
Mepolizumab is an interleukin (IL)-5 antagonist monoclonal antibody. Can be considered in children aged 6-11 years with severe eosinophilic asthma (e.g., blood eosinophils above a locally specified level).[1]Global Initiative for Asthma. 2024 Global strategy for asthma management and prevention. May 2024 [internet publication].
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[209]Agache I, Akdis CA, Akdis M, et al. EAACI biologicals guidelines - recommendations for severe asthma. Allergy. 2021 Jan;76(1):14-44.
http://www.ncbi.nlm.nih.gov/pubmed/32484954?tool=bestpractice.com
[215]McClain V. Differing definitions. J Hum Lact. 1992 Mar;8(1):7.
http://www.ncbi.nlm.nih.gov/pubmed/1558662?tool=bestpractice.com
It is effective in reducing asthma exacerbation frequency, but not quality of life or lung function.[210]Khaleva E, Rattu A, Brightling C, et al. Development of core outcome measures sets for paediatric and adult severe asthma (COMSA). Eur Respir J. 2023 Apr;61(4):2200606.
http://www.ncbi.nlm.nih.gov/pubmed/36229046?tool=bestpractice.com
[216]Jackson DJ, Bacharier LB, Gergen PJ, et al. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet. 2022 Aug 13;400(10351):502-11.
http://www.ncbi.nlm.nih.gov/pubmed/35964610?tool=bestpractice.com
[217]Farne HA, Wilson A, Milan S, et al. Anti-IL5 therapies for asthma. Cochrane Database Syst Rev. 2022 Jul 12;7(7):CD010834.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010834.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/35838542?tool=bestpractice.com
Add-on dupilumab
Dupilumab is an IL-4/IL-13 antagonist monoclonal antibody.[207]Jackson DJ, Bacharier LB, Phipatanakul W, et al. Dupilumab pharmacokinetics and effect on type 2 biomarkers in children with moderate-to-severe asthma. Ann Allergy Asthma Immunol. 2023 Jul;131(1):44-51.e4.
http://www.ncbi.nlm.nih.gov/pubmed/36958470?tool=bestpractice.com
[208]Bacharier LB, Maspero JF, Katelaris CH, et al. Dupilumab in children with uncontrolled moderate-to-severe asthma. N Engl J Med. 2021 Dec 9;385(24):2230-40.
http://www.ncbi.nlm.nih.gov/pubmed/34879449?tool=bestpractice.com
Can be considered in children aged 6-11 years with a severe eosinophilic asthma (e.g., blood eosinophils above a locally specified level) or oral corticosteroid-dependent asthma. The most frequently reported adverse events are nasopharyngitis, pharyngitis, and upper respiratory tract infection.[218]Bacharier LB, Maspero JF, Katelaris CH, et al. Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study. Lancet Respir Med. 2024 Jan;12(1):45-54.
http://www.ncbi.nlm.nih.gov/pubmed/37956679?tool=bestpractice.com