New Guidelines for Managing Asthma in Children

Educational Objectives

The goal of this program is to improve asthma management using guideline recommendations. After hearing and assimilating this program, the clinician will be better able to:

1. Develop a strategy for asthma management based on Global Initiative for Asthma guidelines.
2. Compare the efficacy of various therapies for asthma management.

Summary

Introduction: consider using long-acting bronchodilators (LABs) and inhaled corticosteroids (ICS) for asthma rescue and control; consider using inhaled steroids even in patients with mild asthma (as needed and not daily); there has been increased focus on immunomodulators for severe asthma (effective but expensive)

Global Initiative for Asthma (GINA) guidelines: are revised yearly in European countries; recommendations are changed based on data obtained in the previous year; GINA guidelines for patients >12 yr of age are available free as slides and full text; guidelines recommend initiation of low-dose ICS-formoterol as needed in the initial stage; data are available only for formoterol and not for any other LABs; if as-needed is ineffective, consider scheduled maintenance ICS-formoterol with as-needed; guidelines recommend using immunomodulators and other interventions at step 5; clinicians significantly focus on asthma diagnosis as it is a difficult diagnosis in patients <5 yr of age; consider the presence of comorbidities and check if the risk factors can be treated; short-acting bronchodilators (SABs) are dangerous; all bronchodilators downregulate receptors, making the patient less responsive to bronchodilators if required in crisis

National Heart, Lung, and Blood Institute (NHLBI) guidelines 2020: still used drugs like theophylline and nedocromil; NHLBI guidelines recommend LABs as-needed and ICS at step 3; these are off-label in the United States; Bateman et al (2018) reported the effectiveness of a combination of as-needed budesonide and formoterol in mild asthma is similar to taking steroid all the time and reduces the lifetime steroid load; children are prescribed significant amounts of steroids; steroids cause long-term effects; one goal is to reduce steroid exposure without increasing asthma-associated deaths; the budesonide-formoterol combination is started as-needed, then tapered up to maintenance and relief; once the combination becomes ineffective, refer to an asthma specialist; because of the unavailability of specialists in many places, GINA guidelines do not mention specific experts for the referral

Guidelines for ages 6 to 11 yr: in the GINA guidelines, step 1 includes low-dose ICS whenever SABs are administered; anti-inflammatory medications are required to treat asthma; step 2 is daily low-dose ICS; long-acting β-agonists (LABAs) are added to ICS at step 3; NHLBI guidelines are similar; it recommends as-needed low-dose ICS-formoterol (off-label use); maintenance and reliever therapy (MART) is an option in patients 5 to 11 yr of age; it involves initiating with a single puff and titrating to 2 puffs during step-up; patients with severe asthma may require 2 puffs from the start; MART data for the budesonide-formoterol combination are favorable; maximum dose is 8 inhalations/day of low-dose budesonide-formoterol, and only severe cases require that many; avoid using an ICS-LABA combination with any other medications as it may lead to arrhythmia

Choice of steroids: fluticasone is reportedly more potent than budesonide and causes more systemic side effects; newer steroids (eg, ciclesonide, mometasone) may or may not be helpful; terms of insurance providers also affect the choice of steroids

Asthma management in children ≤5 yr of age: diagnosis is a challenge in this age group; wheezing is common in pediatric patients with cold; rule out other causes of wheezing (eg, anatomic abnormalities); consider medical history and asthma predictive index for assessment; there is limited evidence for daily controller; consider daily low-dose ICS as giving a LAB to young children could be dangerous because of dosing; National Institutes of Health guidelines recommend use of LABs at step 4, but GINA does not; 2022 GINA guidelines recommended using LABs but removed the recommendation because of too many adverse effects

Efficacy of as-needed steroids: Zeiger et al (2011) administered high-dose budesonide (1 mg) twice daily (the standard dose is 0.5 mg once or twice daily) and found no difference in outcomes between the standard daily dose vs high dose when sick; intermittent inhaled steroids were not inferior to daily dosing; parental preference is a major factor; parents usually do not administer ICS to asymptomatic children regardless of instructions

Side effects of corticosteroids: ICS are the mainstay of asthma treatment; however, adverse effects include thrush, growth delay with high doses, reduced bone density in adults, cataracts, and increased body mass index (BMI); in a study in 2000, the Childhood Asthma Management Program Research group compared the effect of budesonide vs nedocromil vs placebo on growth velocity in children and reported a 1.1-cm difference in growth velocity in the budesonide group at 1 yr; however, at the end of the study (4 yr), growth velocity was the same in all groups; a study reported high risk for fractures with oral corticosteroids (OCS) in children, with boys having more fractures than girls; Yao et al (2021) reported that a single dose of OCS increased risk for gastrointestinal bleeding, sepsis, pneumonia, and glaucoma in children; Kunøe et al (2021) reported a significant association between ICS exposure and BMI at 6 yr of age in children with cumulative ICS dose higher than that from ≥10 wk of standard treatment; dual energy X-ray absorptiometry scan showed a trend of association between ICS exposure and increased android body fat; these findings did not normalize after stopping ICS; OCS vs ICS — 2 puffs twice daily of fluticasone 44 μg for 1 yr provides 16 mg systemic steroid; a single steroid burst provides 200 mg of steroid; controlling asthma through ICS may be a better choice

Long-acting bronchodilators: last ≥3 times longer than SABs; they provide immediate relief; because they are currently only administered with ICS, they provide symptomatic relief and disease treatment; previously, they carried a boxed warning because of a study suggesting increased asthma deaths; the boxed warning was later removed in 2017 with the condition that they are combined with ICS; they are used as off-label for rescue in the United States

Leukotriene antagonists: have no proven benefits when administered as-needed or daily, except in a small group of patients with a specific genotype; the CLIC study (Szefler et al [2005]) reported that the only method to determine patient responsiveness is to evaluate the leukotriene levels in urine; the boxed warning includes behavior and mood changes, agitation, aggression, hostility, attention problems, depression, disorientation, anxiety, hallucination, and suicidal thoughts and actions; the speaker does not prescribe montelukast

Other therapies: anti-immunoglobulin (Ig) E antibody is an expensive treatment; criteria for using omalizumab is high IgE; most interleukin (IL) inhibitors are older; dupilumab is approved for asthma in ages ≥6 yr and blocks IL-4 and IL-13 but is expensive and may cause anaphylactic reactions; tiotropium is a newer drug that works through cyclic guanosine monophosphate unlike albuterol and salmeterol, which work through cyclic adenosine monophosphate; an unusual delivery device restricts its use; avoid using the combination of fluticasone, umeclidinium, and vilanterol (Trelegy Ellipta) as it is contraindicated in individuals <18 yr of age and has several side effects

Barriers to following guidelines: challenges include level of adherence to as-needed instructions, guideline awareness in the emergency department, scope of insurance coverage, and most inhalers not fitting in the criteria of asthma drug caps; separate inhalers increase the risk of using only the SABs

Readings

Bateman ED, Reddel HK, O’Byrne PM, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018;378(20):1877-1887. doi:10.1056/NEJMoa1715275; Bogart M, Germain G, Laliberté F, et al. Real-world study of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol on asthma control in the US. J Asthma Allergy. 2023;16:1309-1322. Published 2023 Dec 1. doi:10.2147/JAA.S424055; Childhood Asthma Management Program Research Group, Szefler S, Weiss S, et al. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med. 2000;343(15):1054-1063. doi:10.1056/NEJM200010123431501; Kelly HW, Van Natta ML, Covar RA, et al. 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;122(1):e53-e61. doi:10.1542/peds.2007-3381; Kunøe A, Sevelsted A, Chawes BL, et al. Associations between inhaled corticosteroid use in the first 6 years of life and obesity-related traits. Am J RespirCrit Care Med. 2021;204(6):642-650. doi:10.1164/rccm.202009-3537OC; Levy ML, BacharierLB, Bateman E, et al. Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update. NPJ Prim Care Respir Med. 2023;33(1):7. Published 2023 Feb 8. doi:10.1038/s41533-023-00330-1; SzeflerSJ, Phillips BR, Martinez FD, et al. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005;115(2):233-242. doi:10.1016/j.jaci.2004.11.014; Yao TC, Wang JY, Chang SM, et al. Association of oral corticosteroid bursts with severe adverse events in children [published correction appears in JAMAP ediatr. 2021 Jul 1;175(7):751. doi: 10.1001/jamapediatrics.2021.1760.]. JAMA Pediatr. 2021;175(7):723-729. doi:10.1001/jamapediatrics.2021.0433; Zeiger RS, Mauger D, BacharierLB, et al. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med. 2011;365(21):1990-2001. doi:10.1056/NEJMoa1104647.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Ackerman's lecture includes information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Ackerman was recorded at the Aloha Update: Pediatrics 2024, held October 26 to November 1, 2024, in Maui, HI, and presented by Children’s Hospital Los Angeles Medical Group. For information on future CME activities from this presenter, please visit https://www.chla.org/chla-medical-group. Audio Digest thanks Dr. Ackerman and the Children’s Hospital Los Angeles Medical Group for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

PD711701

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.