State-of-the-Art Pediatrics

New Asthma Guidelines: OK, Now What Am I Supposed to Do With This Inhaler?

Author: Jade Tam-Williams, MD, FAAP | Pulmonary & Sleep Medicine

Column Editor: Amita Amonker, MD, FAAP | Pediatric Hospitalist | Assistant Professor of Pediatrics, UMKC School of Medicine 

One of the many life-changing events that occurred in 2020 was the publication of the United States National Heart, Lung, and Blood Institute’s highly anticipated Focused Updates to the Asthma Management Guidelines by the Expert Panel Report-4 (EPR-4) Working Group.¹ In the document, the EPR-4 Working Group provided 19 recommendations focusing on six key topic areas using systematic reviews with data available prior to 2016: 1) intermittent inhaled corticosteroids (ICSs), 2) long-acting muscarinic antagonists (LAMAs), 3) indoor allergy relief, 4) immunotherapy in the treatment of allergic asthma, 5) fractional exhaled nitric oxide (FeNO) testing, and 6) bronchial thermoplasty. The EPR-4 update did not change the definition of asthma, asthma severity, control, or steps in treatment management. Another commonly referenced document for asthma management is Global Strategy for Asthma Management and Prevention, a report published annually by the Global Initiative for Asthma (GINA).² The GINA report reflects data from before 2020 and mainly targets primary care health care providers. GINA aims to provide global strategies to reduce asthma prevalence, morbidity and mortality. In this article, we focus predominantly on the use of ICS in both of these new management guidelines and the deciding factors around new options for treatment.

Since 2019, GINA has no longer recommended the use of short-acting beta-agonists (SABAs, e.g., albuterol) alone for those aged 12 and older as a risk-reduction strategy, recommending the addition of ICS at all severity levels, whether as a daily controller or as needed (PRN) with a reliever therapy. The EPR-4 report provided several recommendations on the use of ICS in children with different severity levels. For children with intermittent viral-triggered asthma under the age of 4 years, the panel recommended a seven- to 10-day course of daily ICS along with SABA PRN. The report recommended no particular guidance on low-, medium- or high-dose ICS, but the EPR-4 references the MIST trial using 1 mg of budesonide twice a day at onset of symptoms.³ In this regimen, an asthma action plan is recommended with clear instructions on when to start ICS, emphasizing the goal of avoiding oral corticosteroids as well as offering recommendations for routine monitoring of height due to possible effects on growth.

Children over age 12, with mild persistent asthma, have the usual option of daily ICS with SABA PRN, as well as the use of concomitant ICS and SABA together intermittently. In a concomitant plan, patients are recommended to take an ICS along with SABA (e.g., “Whenever you take your albuterol, take your Flovent.”) Those who may not be as adherent to daily ICS may benefit from this plan, but for those patients or families that have either too low or too high a perception of symptoms, this plan may lead to undertreatment or overtreatment with ICS. Currently, this plan requires two different inhalers, but a combination ICS/albuterol inhaler will likely be available in the future.

This recommendation may seem to conflict with the EPR-4’s other recommendation against increasing of ICS dosing with symptoms or changes in peak flow. The panel provided a conditional recommendation with low certainty against the doubling, quadrupling or quintupling of the regular daily dose with changing symptoms. In particular, this recommendation is targeted to patients 4 years and older with mild to moderate persistent asthma who are likely adherent to their daily ICS. It is important to recognize that though the recommendation is intended for the same severity level of patients (mild-moderate persistent), it is the lack of data on significant reduction in severity of exacerbations and quality of life weighed against concerns about growth, especially for the children who are adherent to daily medication, that led to this recommendation.

For those over the age of 4 with moderate to severe persistent asthma, EPR-4’s recommended treatment is now a single inhaler with ICS and formoterol, aka Single Maintenance and Reliever Therapy (SMART). In this plan, a patient is given one inhaler to use as both daily controller and as needed rescue inhaler. This strong recommendation has a high degree of certainty for those over age 12 and moderate certainty for those between 4 and 11. The GINA report also recommends that this plan start at age 6 in moderate to severe persistent asthmatics. The ICS/formoterol combination inhalers available in our local market are budesonide/formoterol (Symbicort) and mometasone/formoterol (Dulera); this plan is for only these two combination inhalers. For all other combination controller inhalers (e.g., Advair, Breo, Wixela), the rescue inhaler is a SABA. It is important to note that if a patient is presently well controlled on a non-formoterol containing combination inhaler, there is no need to change to an ICS/formoterol plan. But if a patient is not well controlled, the recommendation is to trial an ICS/formoterol prior to switching to a higher step in inhaled corticosteroid dosing. For example, if a patient is poorly controlled on Advair 115/21 two puffs BID, consider switching to Symbicort 80/4.5 two puffs BID with two puffs PRN up to maximum dosing per day in yellow zone prior to switching to Advair 230/21. It is critical to ensure patients and families know the maximum number of puffs per day to use. Using the standard formulation of 4.5 mcg of formoterol per puffs, between 4 and 11 years of age, the maximum dosing is eight puffs per day and over 12 years of age the maximum dosing is 12 puffs per day.

The benefits of this plan are simplifying the number of inhalers a patient has, giving families control over administration of medications, and minimizing inhaled steroid exposure during non-asthma seasons for patients. This plan is best for patients who need minimal ICS in green zone, but also need a quick ramp up of ICS in yellow zone. Example patient instructions could say: “Use one to two puffs once or twice a day in green zone; increase to two puffs four times a day in yellow zone” or “One to two puffs as needed up to eight puffs per day in yellow zone.” However, this plan would not be good for patients who are over- or under-perceivers of their asthma symptoms, as they may be exposed to more ICS than necessary, and under-perceivers may not act quickly enough to prevent worsening. A practical limitation to this plan can be cost, especially if insurance will not cover multiple inhalers in a month, and particularly if patients require a baseline of two puffs twice a day in their green zone. In addition, parents express fear of losing the more expensive ICS/formoterol inhaler to schools or child care or misplaced gym bags. Other difficulties to address in clinic with families include methods for keeping track of puffs and the need to stockpile medications.

Inhaled corticosteroids have long been the cornerstone of asthma care. But due to the fluctuating nature of asthma symptoms, fear of steroid side effects, and fear of dependency, families often resist the medical recommendations to use ICSs. What remains true is that ICSs decrease frequency and severity of exacerbations, improving quality of life, but now with this new guidance we have more options to offer families on how to implement them in their lives. Our pediatricians are challenged to provide the best counsel for each of our families. Therefore, we must have a strong understanding of a patient’s asthma severity, triggers, perception of disease, and ability to adhere and implement any treatment plan to guide our choice of treatment plan.

References: 

1. Cloutier MM, Baptist AP, Blake KV, et al; 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). 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;146(6):1217-1270. PMID: 33280709; PMCID: PMC7924476. doi:10.1016/j.jaci.2020.10.003
2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2022. www.ginasthma.org
3. 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;365(21):1990-2001. PMID: 22111718; PMCID: PMC3247621. doi:10.1056/NEJMoa1104647