The Journal of Allergy and Clinical Immunology: In Practice
Original ArticleA Pragmatic Trial of Symptom-Based Inhaled Corticosteroid Use in African-American Children with Mild Asthma
Introduction
Asthma guidelines have recommended daily use of inhaled corticosteroids (ICS) for persistent asthma for the past 3 decades.1, 2 However, adherence to daily asthma therapy remains low despite efforts,3 and concerns for side effects from ICS (such as growth effect4 and long-term steroid-induced complications5) negatively affect adherence.6, 7 Moreover, the cost of asthma therapy is a major concern of the urban minority family.7, 8 Reflecting this behavior and belief of the patients and families, primary care providers (PCPs) often elect not to recommend daily ICS to patients with persistent asthma,9 especially those with mild disease.10 These ongoing obstacles to guideline-based asthma management have led to consideration of alternative, nondaily strategies.
Intermittent, symptom-based adjustment (SBA) of ICS is a patient-centered strategy in which the dose of ICS is determined by the patient's rescue inhaler needs. Daily ICS is not used, but rather ICS is delivered whenever a short-acting β-agonist (SABA, albuterol) or a quick-onset long-acting β-agonist (LABA, formoterol) is used to treat symptoms. SBA of ICS with SABA was shown to be effective in controlling asthma and preventing exacerbation both in adults and in children with mild persistent asthma.11, 12, 13 The most recent update of the Global Initiative of Asthma published in April 2019 now recommends this strategy as one of the options for step 1 and step 2 therapy for the first time.14 Similarly, SBA of ICS combined with a LABA (budesonide + formoterol) has been recently shown to deliver better asthma control than SABA alone and resulted in a similar rate of asthma exacerbation compared with daily dose of budesonide + formoterol in patients with mild asthma.15, 16 These studies have consistently shown that patients using SBA were exposed to a lower dose of ICS compared with daily therapy11, 12, 13 and associated with less adverse growth effect.13
However, these previous studies were conducted in a controlled clinical trial setting, which is often different from usual clinical practice. Thus, there is a need to evaluate the SBA in a real-life, primary care setting, especially now that SBA is added to the Global Initiative of Asthma recommendation as a treatment option for mild asthma that is highly prevalent in the primary care practices.
We conducted our study in African-American children, a population in which provider-based guideline-directed adjustment (PBA) asthma care (current standard of care) has been inconsistently implemented.17, 18 Adherence to daily ICS is low,19 and African Americans have concerns regarding the adverse effects of daily ICS.7, 20, 21 We hypothesized that the SBA strategy might be better accepted in this population, because the patient or caregiver can initiate therapy at the onset of symptoms (self-management) without direct guidance by the PCP to adjust the ICS dose. Therefore, we evaluated the effectiveness of ICS use by SBA compared with PBA by a pragmatic trial in African-American children with mild asthma at PCP offices in the community.
Section snippets
Study design and participants
This study was a randomized, open-label, 2-arm, pragmatic trial in African-American children with mild asthma under the care of 12 participating PCPs in Saint Louis, MO (Clinicaltrials.gov: NCT02298205). We included African-American children, aged 6 to 17 years, under the care of the participating PCP with (1) physician-diagnosed asthma by the participant's PCP, (2) prescribed low-dose ICS, leukotriene receptor antagonist, or low-dose ICS plus LABA (for 12- to 17-year-olds), (3)
Demographic characteristics of participants
Of 1825 potential participants, 311 attended the first visit, and 206 participants were randomized (PBA n = 103, SBA n = 103) between March 2015 and October 2016 (Figure 1). There were significantly more females in the SBA group (P = .02). Otherwise, the participant characteristics were similar between groups (Table I). Both groups received similar number of phone-based education calls during run-in (PBA: 3.4 ± 0.6 calls vs SBA: 3.3 ± 0.6 calls; P = .46). A total of 179 participants completed
Discussion
In this pragmatic trial conducted in the primary care setting, SBA of ICS with SABA among African-American children with well-controlled mild asthma at study entry was similar in effectiveness and safety to PBA over 1 year. SBA of ICS resulted in similar level of asthma control as PBA with almost one-fourth of the exposure to ICS. The mean difference in asthma control between groups was much smaller than the reported minimally important difference,27, 29 indicating that there is little
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Cited by (45)
“As-Needed” Inhaled Corticosteroids for Patients With Asthma
2023, Journal of Allergy and Clinical Immunology: In PracticeThe ICS/Formoterol Reliever Therapy Regimen in Asthma: A Review
2023, Journal of Allergy and Clinical Immunology: In PracticeAs-Needed Use of Short-Acting β<inf>2</inf>-Agonists Alone Versus As-Needed Use of Short-Acting β<inf>2</inf>-Agonists Plus Inhaled Corticosteroids in Pediatric Patients With Mild Intermittent (Step 1) Asthma: A Cost-Effectiveness Analysis
2022, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :These challenges include the learned overuse or over-reliance on SABAs and underuse of ICS, which typically occurs in patients with poor adherence to ICS therapy; parents’ and caregivers’ safety concerns regarding regular use of ICS; the long-standing recommendation in the initial phase of the stepwise asthma management to use SABA alone on an as-needed basis during times of acute illness instead of an anti-inflammatory medication such as an ICS, despite evidence showing the presence of underlying airway inflammation of asthma even in patients with infrequent or recent-onset asthma symptoms; the highly variable activity level of pediatric asthma; the adjustments in medications occurring after a review of symptoms in a previous period of time rather than from the first onset of symptoms;20 and other factors that have been associated with suboptimal adherence to inhaled controller therapy, such as the typical episodic nature of pediatric asthma, a lack of perceived necessity (especially in patients with infrequent symptoms), and perceived and actual side effects.7 The results of the present study are in good agreement with previously published studies in the literature reporting not only the efficacy but also the cost-effectiveness of the use of ICS on an intermittent or as-needed basis.9,10,21-29 The use of ICS on an intermittent or as-needed basis does not refer to a single strategy, but rather includes heterogeneous strategies with different criteria for initiating ICS therapy (at the first sign of an upper respiratory tract infection, when signs and symptoms of an AE are already evident, or when a SABA is needed), with or without ICS use during stable periods of the disease.
Global Initiative for Asthma Strategy 2021. Executive Summary and Rationale for Key Changes
2022, Archivos de BronconeumologiaCitation Excerpt :In children, before stepping up, consider trying other controller options at the same step. Rationale: The addition of as-needed concomitant ICS + SABA as an antiinflammatory reliever in Step 1 for children was based on evidence from two studies in which children and adolescents were stepped down from maintenance ICS to as-needed ICS plus SABA in separate inhalers44,45 and because of likely nonadherence with daily ICS by children with infrequent symptoms. For Step 2, there is much more evidence for the safety and effectiveness of maintenance low-dose ICS, but in the real world, ICS adherence is extremely low.
Revisiting Mild Asthma: Current Knowledge and Future Needs
2022, ChestCitation Excerpt :It showed that as-needed beclomethasone with as-needed SABAs was more effective than SABA monotherapy at reducing exacerbations and achieved similar asthma control as daily ICS with lower ICS exposure. Furthermore, in a pragmatic study in specific populations, such as Black children with mild asthma,78 as-needed ICS plus SABAs treatment resulted in similar asthma control and asthma-related event rates compared with daily ICS treatment with one-fourth of the dose of ICS exposure. The implementation of as-needed low-dose ICS taken whenever SABAs are taken is recommended as step 1 for patients on track 2 per GINA 202116 in patients 12 years of age or older and step 1 for children 6 to 11 years of age.
Research reported in this work was funded through a Patient-Centered Outcomes Research Institute (PCORI) award (AS-1307-05588). The statements presented in this work are solely the responsibility of the authors and do not necessarily represent the views of the PCORI, its Board of Governors, or its Methodology Committee.
Conflicts of interest: K. Sumino reports university grant funding from the National Institutes of Health (NIH), the American Lung Association, and the Patient-Centered Outcomes Research Institute (PCORI) and personal fee from Teva. L. B. Bacharier reports grants from the NIH; personal fees from GlaxoSmithKline, Genentech/Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, AstraZeneca, WebMD/Medscape, Sanofi/Regeneron, Vectura, and Circassia; and research support from Sanofi and Vectura. M. Castro receives university grant funding from the NIH, the American Lung Association, and PCORI; receives pharmaceutical grant funding from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and sanofi-aventis; is a consultant for Aviragen, Boston Scientific, Genentech, Nuvaira, Neutronic, Therabron, Theravance, Vectura, 4D Pharma, VIDA, Mallinckrodt, Teva, and Sanofi-Aventis; is a speaker for Astra-Zeneca, Boehringer Ingelheim, Boston Scientific, Genentech, Regeneron, Sanofi, and Teva; and receives royalties from Elsevier. The rest of the authors declare that they have no relevant conflicts of interest.