Management of Asthma in Children 5 Years and Under - Hossny E (Updated 2020)

Management of Asthma in Children 5 Years and Under

Updated: November 2020

Elham Hossny, MD, PhD
Pediatric Allergy and Immunology Unit
Children's Hospital, Ain Shams University, Cairo 11566, Egypt

Original Author:

Paul C. Potter, MD
Allergy Diagnostic and Clinical Research Unit
University of Cape Town Lung Institute, Mowbray 7700, South Africa

 

Introduction

The diagnosis of asthma in children under five years is difficult due to changing concepts of what true asthma is in this age group.¹ Wheezing can occur in this age without asthma and confirmatory lung function tests are difficult to perform.² Many preschool wheezers become asymptomatic by school age irrespective of treatment.³ Asthma management in very young patients is based largely on clinical judgment, expert opinion, and cost of medications owing to the lack of clinical evidence in this particular patient population. The younger the child, the less available is the guidance and/or benefit from medical progress.^4,5  

Asthma guidelines have been developed to increase the awareness of asthma among health professionals, to improve asthma management, to evaluate published reports on asthma and to promote international collaboration in asthma research.⁶ The rising interest in electronic health records has improved accessibility to guidelines. The global nature of asthma has led various organizations to introduce their own management guidelines. The 3 most recognized and quoted guidelines are the National Institute for Health and Care Excellence (NICE; United Kingdom), the Global Initiative for Asthma (GINA), and the Expert Panel Report of the National Asthma Education and Prevention Program (NAEPP) from the US National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI). The development of national guidelines in many countries is a dynamic process that needs continuous updating.⁷

 

Diagnostic issues of asthma in preschool wheezers

Asthma predictive index

Preschool children consume a disproportionately high amount of health-care resources compared with older children and adults with wheeze or asthma. However, the diagnosis of persistent asthma remains imperfect, with only 40% of these infants experiencing continued wheezing symptoms in later childhood and with variation in expression of both symptoms and risk factors over time.⁸

For clinicians and researchers, the ability to accurately predict which children will develop asthma is a challenge. A simplified predictive approach was provided for young wheezers who might develop asthma namely the asthma predictive index (API)⁹ and was modified later. In the modified asthma predictive index (mAPI), recurrent wheezing (4 or more episodes with at least one physician diagnosis) with 1 major criterion (parental history of asthma, history of atopic dermatitis or allergic sensitization to ≥ 1 aeroallergen) or 2 of 3 minor criteria (allergic sensitization to milk, egg, or peanuts, wheezing unrelated to colds or Blood eosinophils ≥4%) predicts asthma in later childhood.¹⁰ The API and mAPI have a high specificity but relatively low sensitivity.¹¹

A Pediatric Asthma Risk Score (PARS) aimed to better predict asthma development in young children was recently developed and validated by Biagini Myers  et al.¹² It is a continuous risk score for asthma, constructed by integrating demographic and clinical data to determine risk factors for asthma in a multivariate model. The data include parental asthma, eczema, early wheezing, wheezing when healthy, ancestry, presence of allergies and positive skin prick testing. PARS showed an 11% increase in sensitivity over the API and mAPI and performed better in children with mild to moderate asthma. These children are the most common, the most difficult to predict, and may be the most amenable to prevention strategies. A PARS web application is provided by the Cincinnati Children’s Hospital at https://pars.research.cchmc.org.¹³

Some Diagnostic clues

Theoretically, phenotyping provides an opportunity for predicting treatment response and prognosis, but this is limited in preschoolers due to the narrow range of available asthma medications in this age group and instability of phenotypic classification over time.¹⁴ Phenotypic classification of young asthmatics according to the age of onset (early, persistent or late onset wheeze) and types of triggers (multi-trigger versus episodic viral wheeze) have failed to demonstrate clinical usefulness.¹

In a child presenting with acute symptoms of airflow obstruction (wheeze, signs of increased work of breathing), a trial of short acting beta agonists ± oral steroids should be given to assess response. If there is clear improvement and the child has had similar episodes previously, a diagnosis of asthma can be made. In a child that has a history of recurrent asthma symptoms (wheeze, work of breathing, cough) but is not acutely symptomatic the frequency and severity of the reported symptoms should be considered. If the child has a history of severe exacerbations (requiring oral steroids, emergency room visits or hospitalization) or frequent symptoms, a trial of daily inhaled corticosteroids should be undertaken to determine response. If the frequency and/or severity of symptoms improve, a diagnosis of asthma can be made. If the symptoms are infrequent and mild, the child can be assessed when symptomatic to better determine the nature of the symptoms and their acute response to treatment.^1,15,16

 

The GINA guidelines for asthma treatment in children 5 years and younger

The goals of asthma management in young children are to achieve good control of symptoms and maintain normal activities, minimize risk of flare-ups, maintain lung functions, and minimize side effects from medications. The Global Initiative for Asthma (GINA) offered a stepwise approach to treatment that is customized to the individual child taking into account the effectiveness of available medications, their safety, and their cost to the payer or family.

The 2020 GINA main report, adopted and updated the asthma treatment steps proposed by the previous reports for children 5 years and younger: ^2,17-19

Step 1: As-needed inhaled short-acting beta2-agonist (SABA)

This is the preferred approach. Another option in case of poor response particularly in those with underlying atopy is intermittent high dose inhaled corticosteroid. Oral bronchodilator therapy is contraindicated.

Step 2: Initial controller treatment, plus as-needed SABA

It should be given for at least 3 months to establish its effectiveness in achieving good asthma control. As an alternative, leukotriene receptor antagonist (LTRA) may be considered to reduce the need for OCS; however, this was not documented by several systematic reviews.^20-22 Also the adverse effects of montelukast on sleep and behavior of children should be considered especially that the FDA has required a box warning about it.^23,24

Step 3: Additional controller treatment plus as-needed SABA

For children whose symptoms are not controlled after 3 months of low dose ICS, doubling the initial dose is often the best option and reassess after 3 months. Another option is adding LTRA to low-dose ICS based on data from older children. FDA warning should be considered. The use of ICS-LABA is not recommended in this age group due to paucity of data on efficacy and/or safety.

This step up should be preceded by excluding other diagnoses, checking inhaler techniques and adherence and control of environmental factors such as tobacco smoke exposure.

Step 4: Continue controller treatment and refer for expert assessment

If the asthma diagnosis is confirmed and factors that hinder response to the previous step are excluded, further elevation of ICS dose is considered with monitoring for side effects. Other options include the addition of regular LTRA after considering the risk-benefit;²³ adding LABA with ICS based on data in children > 4 years; low dose OCS till asthma control improves with monitoring for side effects or adding intermittent high dose ICS at the onset of viral illness.

The need for additional controller treatment should be re-evaluated at each visit and maintained as short as possible taking into account potential risks and benefit. Asthma-like symptoms remit in a substantial proportion of children aged five years and younger, so stepping down treatment should be considered.

 

Risk factors for poor asthma outcomes in children ≤5 years ^18,19

Risk factors for exacerbations in the next few months

• Uncontrolled asthma symptoms
• One or more severe exacerbation (ED attendance, hospitalization or course of OCS)  in previous year
• The start of the child’s usual ‘flare-up’ season (especially if autumn/fall)
• Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens (e.g. house dust mite, cockroach, pets, mold), especially in combination with viral infection
• Major psychological or socio-economic problems for child or family
• Poor adherence with controller medication, or incorrect inhaler technique
• Outdoor pollution (NO and others)

Risk factors for fixed airflow limitation

• Severe asthma with several hospitalizations
• History of bronchiolitis

Risk factors for medication side-effects

• Systemic: Frequent courses of OCS; high-dose and/or potent ICS
• Local: moderate/high-dose or potent ICS; incorrect inhaler technique; failure to protect skin or eyes when using ICS by nebulizer or spacer with face mask
•  

Treatment of flare-ups

A flare-up or exacerbation is defined as an acute or sub-acute deterioration in symptom control that is sufficient to cause distress and necessitates a visit to a health care provider or requires treatment with systemic corticosteroids.

Table 1. Initial assessment of acute asthma exacerbations in children ≤5 years¹⁸

Symptoms	Mild	Severe*
Altered consciousness	No	Agitated, confused or drowsy
Oximetry on presentation (SaO2)**	>95%	<92%
Speech***	Sentences	Words
Pulse rate	<100 beats/min	>200 beats/min (0–3 yr); >180 beats/min (4–5 yr)
Central cyanosis	Absent	Likely to be present
Wheeze intensity	Variable	Chest may be quiet

*Any of these features indicates a severe exacerbation

**Oximetry before treatment with oxygen or bronchodilator

***Take into account the child’s normal developmental capability

An asthma action plan should enable family members and care givers to recognize asthma worsening or flare-up, initiate treatment, and identify when urgent hospital care is necessary.

Table 2. Initial management of asthma exacerbations in children ≤5 years²

Therapy	Dose and administration
Supplemental oxygen	By face mask (usually 1L/min) to maintain oxygen saturation 94-98%
Inhaled SABA	2-6 puffs of salbutamol by spacer, or 2.5 mg by nebulizer, every 20 min for first hour, then reassess severity. If symptoms persist or recur, give additional 2-3 puffs per hour. Admit to hospital if >10 puffs required in 3-4 hours.
Systemic corticosteroids	Give initial dose of oral prednisolone (1-2mg/kg up to maximum of 20mg for children <2 years; 30 mg for 2-5 years)
Additional options in the first hour of treatment
Ipratropium bromide	For moderate/severe exacerbations, give 2 puffs of ipratropium bromide 80 mcg (or 250mcg by nebulizer) every 20 minutes for one hour only
Magnesium sulphate*	Consider nebulized isotonic MgSO4 (150mg) 3 doses in first hour for children ≥2 years with severe exacerbation

* The role of magnesium sulphate (IV) is not established < 5 years due to lack of studies.

Urgent transfer to hospital is indicated in case of any of the following 3 situations. First, if at initial or subsequent assessment, Child is unable to speak or drink, cyanosed, respiratory rate > 40/min, oxygen saturation <92% when breathing room air or silent chest on auscultation. Second, if there is lack of response to initial bronchodilator therapy namely 6 puffs of inhaled SABA over 1-2 hours or persistent tachypnea despite 3 administrations of inhaled SABA. The third indication is when the social environment impedes delivery of acute treatment at home or the parent/care taker is unable to manage acute asthma at home.¹⁹

 

The 2019 BTS/SIGN British Guideline on the Management of Asthma²⁵

The main recommendations of this guideline in preschoolers include:

• If symptoms are not controlled by up to 10 puffs of salbutamol via a pMDI and spacer, parents/care takers should seek urgent medical attention.
• Children with SpO2 <94% should receive high flow oxygen via a tight-fitting face mask or nasal cannula at sufficient flow rates to achieve normal saturations of 94–98%.
• Oral prednisolone is the steroid of choice for acute asthma attacks in a dose of 10 mg for children under two years of age and 20 mg for children aged 2–5 years. The course length should be individualized as needed but three days are usually sufficient. Tapering is unnecessary unless the course of steroids exceeds 14 days.
• Oral and intravenous steroids are of similar efficacy. Intravenous hydrocortisone (4 mg/kg repeated four hourly) should be reserved for severely affected children who are unable to retain oral medication.
• Inhaled corticosteroids should continue at the usual maintenance dose during an asthma attack together with the additional lines of therapy.
• Antibiotics should not be routinely given in the management of acute asthma.
• Consider aminophylline for children with severe or life-threatening asthma unresponsive to maximal doses of bronchodilators and steroids.
• Many non-atopic children under five with recurrent episodes of viral-induced wheezing do not require treatment with regular ICS.
• There is no clear evidence of benefit with sodium cromoglicate in children aged <5
• Antihistamines and ketotifen are ineffective.
• LABA are not licensed for use in children less than four years of age.
• For children aged 0–5, there are no enough data comparing nebulizers with other inhalers
• There is currently insufficient evidence to recommend use of SLIT in adults or children with asthma due to heterogeneity in studies (including in doses, allergens, treatment duration, other asthma medication and presence of asthma symptoms), together with the lack of data on its long-term effectiveness.
•  

UK National Institute for Health and Care Excellence (NICE)

The NICE developed a pharmacological treatment pathway for children under 5 in 2017 and was updated lately in February 2020.¹⁶ It provides recommendations for treating preschool children with suspected or confirmed asthma, or with asthma symptoms that are uncontrolled on their current treatment. This guidance involves the following steps:

• Offer a SABA as reliever therapy to children under 5 with suspected asthma. This should be used for symptom relief alongside all maintenance therapy.
• Consider an 8‑week trial of a pediatric moderate dose of an ICS in children under 5 with symptoms at presentation that clearly indicate the need for maintenance therapy (for example, asthma-related symptoms 3 times a week or more, or causing waking at night) or suspected asthma that is uncontrolled with a SABA alone.
• After 8 weeks, stop ICS treatment and continue to monitor the child's symptoms.

• If symptoms did not resolve during the trial period, review whether an alternative diagnosis is likely.
• If symptoms resolved then reoccurred within 4 weeks of stopping ICS treatment, restart the ICS at a pediatric low dose as first-line maintenance therapy.
• If symptoms resolved but reoccurred beyond 4 weeks after stopping ICS treatment, repeat the 8‑week trial of a pediatric moderate dose of ICS.

• If suspected asthma is uncontrolled in children under 5 on a pediatric low dose of ICS as maintenance therapy, consider an LTRA in addition to the ICS.
• If suspected asthma is uncontrolled in children under 5 on a pediatric low dose of ICS and an LTRA as maintenance therapy, stop the LTRA and refer the child to a healthcare professional with expertise in asthma for further investigation and management.

 

The NHLBI Expert Panel Report (EPR):

This report is produced by an expert panel of the US National Heart, Lung and Blood institution (NHLBI).  The Expert Panel 4 (EPR-4) Working Group was established in 2018 to update the 2007 Guidelines for the Diagnosis and Management of Asthma Expert Panel Report 3 (EPR-3). The EPR-4 Working Group members will use findings from five systematic reviews to update the guidelines.²⁶ The EPR-3 contained a special section on management of children, 0-4 years but its recommendations were based mainly on data extrapolated from older children and adults, and also on expert opinion.²⁷ The report recommended studies to address the large gaps of knowledge in this population including the use of combination therapy with ICS + LABA and the add-on therapies.²⁸ The guidelines will be updated to generate evidence-based recommendations for such issues as fraction of exhaled nitric oxide, immunotherapy, indoor allergen reduction, bronchial thermoplasty, and intermittent inhaled corticosteroids and long acting muscarinic antagonists.²⁶

 

Japanese guidelines for childhood asthma

According to the Japanese guidelines 2020, children under 5 years of age and younger are diagnosed as “infant and preschool asthma” when they have more than 3 episodes of wheezing persisting for more than 24 h and diminished wheezing and heavy breathing, and increased percutaneous oxygen saturation (SpO2) levels after inhalation of SABA. In addition, improvement after one month of therapeutic trial with controller treatment, and worsening after cessation may support the diagnosis.²⁹

 

Adherence to therapy

For young children, studies have found adherence rates frequently below 50%.²⁹ Parents may have difficulty following asthma management recommendations, such as identification and avoidance of triggers and proper use of inhalation devices. As a result, many children experience flares that may significantly alter their quality of life and well being that could otherwise have been avoided.³⁰

Caregivers’ beliefs toward their child’s asthma therapy heavily influence children’s adherence to treatment. Common concerns caregivers have toward asthma medications include the safety and long-term side effects of, for example, use of ICS and growth suppression, and dependence on medication. These concerns can inhibit caregivers from adhering consistently to asthma treatment plans.³¹

Another caregiver-level factor that impacts adherence is health literacy level. Caregivers with low health literacy levels have scored lower on assessments of asthma knowledge, report higher usage of rescue inhalers, and are less likely to report a proper inhaler technique. As a result, their children would experience more severe asthma symptoms and are more likely to visit emergency departments.³² Some interventions may improve asthma care delivery in very young asthmatics. These include visual asthma severity charts, appointment transportation vouchers, appointment telephone assistance, telephone coaching, and peer parent coaches.³¹

 

Unmet Needs and Recommendations        

Despite current advances in asthma management and the development of evidence-based and evidence-informed guidelines, preschoolers remain inadequately served: 

• Prevention of disease progression and prediction of future risk, including persistence into adulthood, is a global concern.³³
• Diagnostic criteria, cultural perceptions of asthma, and best treatment by age group need to be identified especially in low-middle-income countries.³³
• There is considerable gap in reliable recommendations on the management of non-asthmatic preschool wheeze.³⁴
• Physicians should recognize that preschoolers are different from older children in treatment strategies. ICS therapy should always aim to reach the lowest effective dose because most adverse effects are dose-dependent. The potential adverse effects of ICS need to be weighed against their benefit especially that its safety profile is markedly better than oral glucocorticoids.³⁵
• Non-severe asthma remains a major health problem, not only for parents but also for healthcare professionals who take care of these patients. Maintenance and reliever therapy (MART) is an option for moderate disease.³⁶
• Variability in response to medications appears to be considerable and a personalized approach should be considered.^36,37
• There are no enough data on the use of biological therapies in children <5 years with severe asthma symptoms and more evidence is needed to provide higher quality recommendations.³⁸
• Significant variability exists in the content and format of written action plans which results in inconsistent educational messages and suboptimal health outcomes.³⁹
• Another weak point is education. Asthma education should not be regarded as a single event but rather as a continuous process. This mandates that asthma education follow a repetitive pattern and involve literal explanation and physical demonstration of the optimal use of inhaler devices. Education should be tailored according to the socio-cultural background of the family.^35,40
• Although there were some concerns about the morbidity expected from SARS-CoV-2 infection in asthmatics, children did not seem to be adversely affected by COVID-19.^41-43  

Finally, the quality of life of young asthmatics and their parents could be seriously impacted highlighting the importance of optimizing asthma treatment. Parents of young children with asthma are likely to be sleep-deprived, which may contribute to their own difficulties with emotion regulation and adherence to prescribed treatment regimens.^44,45

 

References

1. Yang CL, Gaffin JM, Radhakrishnan D. Question 3: Can we diagnose asthma in children under the age of 5 years? Paediatr Respir Rev 2019;29:25-30.
2. GINA Report 2020; Global Strategy of Asthma Management and Prevention. https://ginasthma.org/wp-content/uploads/2020/06/GINA-2020-report_20_06_04-1-wms.pdf.
3. Durrani S, Guilbert TW. Early treatment in preschool children: an evidence-based approach. Curr Opin Allergy Clin Immunol 2015;15(2):175-83.
4. Szefler SJ, Chmiel JF, Fitzpatrick AM, Giacoia G, Green TP, Jackson DJ, et al. Asthma across the ages: knowledge gaps in childhood asthma. J Allergy Clin Immunol 2014;133(1):3-13.
5. Papadopoulos NG, Čustović A, Cabana MD, Dell SD, Deschildre A, Hedlin G, et al. Pediatric asthma: An unmet need for more effective, focused treatments. Pediatr Allergy Immunol 2019;30(1):7-16.
6. Potter PC. Current guidelines for the management of asthma in young children. Allergy Asthma Immunol Res 2010;2(1):1-13.
7. Ballas ZK. Asthma clinical practice guidelines: Time for an update. J Allergy Clin Immunol 2018;142(3):787.
8. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995;332:133-8.
9. Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med 2000; 162:1403-6.
10. Guilbert TW. Identifying and managing the infant and toddler at risk for asthma. J Allergy Clin Immunol 2010;126(2):417-22.
11. Chang TS, Lemanske RF, Jr., Guilbert TW, Gern JE, Coen MH, Evans MD, et al. Evaluation of the modified asthma predictive index in high-risk preschool children. J Allergy Clin Immunol Pract 2013; 1:152-6.
12. Biagini Myers JM, Schauberger E, He H, Martin LJ, Kroner J, Hill GM, et al. A Pediatric Asthma Risk Score to better predict asthma development in young children. J Allergy Clin Immunol 2019;143(5):1803-10.
13. The Pediatric Asthma Risk Score (PARS). Cincinnati Children’s, 2019. Available from: https://pars.research.cchmc.org.
14. Schultz A, Devadason SG, Savenije OE, Sly PD, Le Souëf PN, Brand PL. The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze. Acta Paediatr 2010;99(1):56-60.
15. Ducharme FM, Dell SD, Radhakrishnan D, Grad RM, Watson WT, Yang CL, et al. Diagnosis and management of asthma in preschoolers: A Canadian Thoracic Society and Canadian Paediatric Society position paper. Can Respir J 2015;22(3):135-43.
16. National Institute for Health and Care Excellence (NICE). Pharmacological treatment pathway for children under 5. NICE guideline [NG80]. Published: 29 November 2017. Last updated: 12 February 2020.  https://www.nice.org.uk/guidance/ng80/chapter/Recommendations#pharmacological-treatment-pathway-for-children-under-5.
17. Global Initiative for Asthma (GINA). Pocket Guide for Asthma Management and Prevention in Children 5 Years and Younger, April 2015. Available from www.ginasthma.org.
18. GINA Report 2017; Global Strategy of Asthma Management and Prevention. https://ginasthma.org/wp-content/uploads/2019/04/wmsGINA-2017-main-report-final_V2.pdf
19. GINA Report 2019; Global Strategy of Asthma Management and Prevention. https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf.
20. Brodlie M, Gupta A, Rodriguez-Martinez CE, Castro-Rodriguez JA, Ducharme FM, McKean MC. Leukotriene receptor antagonists as maintenance and intermittent therapy for episodic viral wheeze in children. Cochrane Database Syst Rev 2015;2015(10):CD008202.
21. Castro-Rodriguez JA, Custovic A, Ducharme FM. Treatment of asthma in young children: evidence-based recommendations. Asthma Res Pract 2016;2:5.
22. 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;53(12):1670-7.
23. FDA requires Boxed Warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. Risks may include suicidal thoughts or actions. Last updated 3-4-2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-boxed-warning-about-serious-mental-health-side-effects-asthma-and-allergy-drug.
24. Haarman MG, van Hunsel F, de Vries TW. Adverse drug reactions of montelukast in children and adults. Pharmacol Res Perspect 2017;5(5):e00341.
25. BTS/SIGN British Guideline on the Management of Asthma. Revised edition published July 2019 https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma.
26. National Asthma Education and Prevention Program. Expert Panel Report 4 (EPR-4) Working Group, 2018. Available from: https://www.nhlbi.nih.gov/about/advisory-and-peer-review-committees/national-asthma-education-and-prevention-program-coordinating/EPR4-working-group.
27. National Asthma Education and Prevention Program. Expert Panel Report III: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Institutes of Health; National Heart, Lung, and Blood Institute; 2007. NIH Publication No. 07-4051.
28. Jackson DJ. Emerging issues in pediatric asthma: gaps in EPR-3 guidelines for infants and children. Curr Allergy Asthma Rep 2014;14(12):477.
29. Arakawa H, Hamasaki Y, Kohno Y, Ebisawa M, Kondo N, Nishima S, et al; Japanese Society of Pediatric Allergy and Clinical Immunology, The Japanese Society of Allergology. Japanese guidelines for childhood asthma 2017. Allergol Int 2017;66(2):190-204.
30. Booster GD, Oland AA, Bender BG. Treatment Adherence in Young Children with Asthma. Immunol Allergy Clin North Am 2019;39(2):233-42.
31. Rehman N, Morais-Almeida M, Wu AC. Asthma across childhood: improving adherence to asthma management from early childhood to adolescence. J Allergy Clin Immunol Pract 2020;8(6):1802-7.
32. Dewalt DA, Dilling M, Rosenthal MS, Pignone MP. Low parental literacy is associated with worse asthma care measures in children. Ambul Pediatr 2007;7:25-31.
33. Mathioudakis AG, Custovic A, Deschildre A, Ducharme FM, Kalayci O, Murray C, et al. Research Priorities in Pediatric Asthma: Results of a Global Survey of Multiple Stakeholder Groups by the Pediatric Asthma in Real Life (PeARL) Think Tank. J Allergy Clin Immunol Pract 2020;8(6):1953-60.
34. Ruszczyński M, Ambrożej D, Adamiec A, Ryczaj K, Elenius V, Cavkaytar O, et al; EAACI Task Force on Clinical Practice Recommendations on Preschool Wheeze. Preschool wheezing and asthma in children: A systematic review of guidelines and quality appraisal with the AGREE II instrument. Pediatr Allergy Immunol 2020 Aug 20. doi: 10.1111/pai.13334. Online ahead of print.
35. Hossny E, Rosario N, Lee BW, Singh M, El-Ghoneimy D, Soh JY, Le Souef P. The use of inhaled corticosteroids in pediatric asthma: update. World Allergy Organ J 2016; 9:26.
36. Kalayci O, Abdelateef H, Pozo Beltrán CF, El-Sayed ZA, Gómez RM, Hossny E, et al. Challenges and choices in the pharmacological treatment of non-severe pediatric asthma: A commentary for the practicing physician. World Allergy Organ J 2019;12(9):100054.
37. Kuprys-Lipinska I, Kolacinska-Flont M, Kuna P. New approach to intermittent and mild asthma therapy: evolution or revolution in the GINA guidelines? Clin Transl Allergy 2020;10:19.
38. Holguin F, Cardet JC, Chung KF, Diver S, Ferreira DS, Fitzpatrick A, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J 2020;55(1):1900588.
39. MacGillivray ME, Flavin MP. Canadian paediatric asthma action plans and their correlation with current consensus guidelines. Paediatr Child Health 2014;19(7):362-6.
40. Papadopoulos NG1, Arakawa H, Carlsen KH, Custovic A, Gern J, Lemanske R, et al. International consensus on (ICON) pediatric asthma. Allergy 2012;67(8):976-97.
41. Baranova L, Garcia AN, Yusuf OM, Pitrez PMC, Pohunek P, Pozo Beltrán CF, et al; Pediatric Asthma in Real Life Collaborators. Impact of COVID-19 on pediatric asthma: practice adjustments and disease burden. J Allergy Clin Immunol Pract 2020;8(8):2592-9.
42. Papadopoulos NG, Custovic A, Deschildre A, Mathioudakis AG, Phipatanakul W, Wong G, et al; Pediatric Asthma in Real Life Collaborators. Impact of COVID-19 on Pediatric Asthma: Practice Adjustments and Disease Burden. J Allergy Clin Immunol Pract 2020;8(8):2592-9.
43. Kabesch M. Shielding against SARS-CoV-2 infection is not justified in children with severe asthma. Pediatr Allergy Immunol 2020 Aug 5;10.1111/pai.13327. doi: 10.1111/pai.13327. Online ahead of print.
44. Hossny E, El-Owaidy R, Abdel Raouf B, Aboajela S. Health-related quality of life assessment using EQ-5D-Y questionnaire in a group of Egyptian asthmatic children. Egypt J Pediatr Allergy Immunol 2020;18(1):25-34.
45. Meltzer LJ, Pugliese CE. Sleep in young children with asthma and their parents. J Child Health Care 2017;21(3):301-11.