The RAMER Reviews: As-needed Albuterol-Budesonide in Mild Asthma: The BUTARA Trial

 

Written by: Rozalina Suleymanova, DO; Edited by: Brian Smith, DO, MA, MMSc-Med

 

Background:

Let’s talk about the type of rescue inhalers we send for asthmatic patients in the setting of the emergency department. These are patients that come in with an exacerbation due to a viral illness or seasonal allergies, get better with some nebulizer treatments in the ED, and get discharged with a prescription for a short-acting beta agonist (SABA) rescue inhaler and instructions to follow up with their primary doctors outpatient. But are these rescue inhalers really doing any “rescuing?” 

The Global Initiative of Asthma (GINA) defines the severity of asthma based on the level of treatment required to maintain control of symptoms and to prevent exacerbations, rather than on symptom frequency. Mild asthma, for example, is defined as asthma well-controlled with low intensity treatment consisting of as-needed inhaled corticosteroid plus a short acting beta agonist (SABA). It affects between 50-70% of patients with a diagnosis of asthma. Moreover, these patients have as high as a 30% risk of severe exacerbation, which is defined as an acute worsening of symptoms resulting in ≥3 days’ use of a systemic glucocorticoid, an ED or urgent care visit warranting systemic glucocorticoids, hospitalization due to asthma, or death. It seems that a SABA rescue inhaler alone in patients with mild asthma does not adequately address airway inflammation, which prompted the GINA guidelines to be revised to include an inhaled corticosteroid in addition to a bronchodilator. 

This clinical trial published in July 2025 therefore supports the new change in guidelines by presenting results to suggest patients with mild asthma might benefit from a rescue inhaler that is a combination SABA-steroid.

Quick review of the pathophysiology of asthma before we delve into the study, there are multiple modalities in which we can treat asthma. We can stimulate bronchodilation with beta agonists, cause smooth muscle relaxation with anti-muscarinics, and decrease the production of mucus as well as generalized inflammation with leukotriene receptor antagonists, like montelukast.Quick review of the pathophysiology of asthma before we delve into the study, there are multiple modalities in which we can treat asthma. We can stimulate bronchodilation with beta agonists, cause smooth muscle relaxation with anti-muscarinics, and decrease the production of mucus as well as generalized inflammation with leukotriene receptor antagonists, like montelukast.

The Study:

Study type: decentralized, randomized, event-driven clinical trial 


Study question: whether adding a steroid, such as budesonide, to a beta agonist rescue inhaler reduces the risk of severe asthma exacerbation. In particular, authors investigated the efficacy and safety of an as-needed combination albuterol-budesonide inhaler versus an as-needed albuterol alone inhaler. 

Selection criteria: participants ≥12 years of age being treated for mild uncontrolled asthma with either a low-dose inhaled corticosteroid or leukotriene receptor antagonist. Participants were recruited largely via social media, as well as with the use of artificial intelligence to identify eligible participants. 

Intervention: one participant group that received PRN albuterol-budesonide (180 μg/160 μg per dose), second participant group received PRN albuterol (180 μg per dose) only

Duration: 52 weeks

Primary endpoint: time to first severe asthma exacerbation (on-treatment efficacy population)


Secondary endpoints: time to first severe exacerbation (intention-to-treat population)

Results:

As shown in the highlighted column, there were statistically significant findings of higher rates of severe exacerbation in the on-treatment and intention to treat groups, annual exacerbation rate, and systemic corticosteroid use in the group treated with albuterol inhaler alone compared to the participants who received a combination albuterol and steroid inhaler. While the on-treatment efficacy group is useful because it demonstrates the maximum potential benefit of a treatment if used as prescribed, intention to treat is a more realistic report of treatment use in the general public as it accounts for possible non-adherence. Nevertheless, both these populations show significantly reduced rates of the above endpoints when treated with combination SABA and steroid inhaler.  

The study certainly has its strengths, some of which include a large sample size of about 2500 participants, all of who were matched for sex, ethnicity, age, possible comorbid atopic conditions, and years of asthma diagnosis, to name a few. Contrarily, some limitations the authors reported include a lack of children and adolescent participants, essentially making it harder to apply the study’s findings to these age groups. It was also event-driven, which means the study was not based on a fixed timeline and was instead stopped when there was an already obvious difference in endpoints of the two treatment groups. The nature of this type of study may exaggerate efficacy, as well as limit any evidence for other secondary outcomes had the study continued longer. 

What does this mean for your practice in the ED? Consider changing what you prescribe as a rescue inhaler for your patients with asthma exacerbation in order to decrease the rate of asthma exacerbations, as well as systemic corticosteroid use. Remember these are generally going to be adult patients older than 18 years who have uncontrolled mild asthma.

 
 

References: 

  1. LaForce C, Albers F, Danilewicz A, Jeynes-Ellis A, Kraft M, Panettieri RA Jr, Rees R, Bardsley S, Dunsire L, Harrison T, Sobande O, Surujbally R, Trudo F, Cappelletti C, Papi A, Beasley R, Chipps BE, Israel E, Pandya H, Clancy M, Bacharier LB; BATURA Investigators. As-Needed Albuterol-Budesonide in Mild Asthma. N Engl J Med. 2025 Jul 10;393(2):113-124. doi: 10.1056/NEJMoa2504544. Epub 2025 May 19. PMID: 40388330. 

  2. Mosnaim G. Asthma in Adults. N Engl J Med. 2023 Sep 14;389(11):1023-1031. doi: 10.1056/NEJMcp2304871. PMID: 37703556. 

  3. Mohan A, Lugogo NL, Hanania NA, Reddel HK, Akuthota P, O'Byrne PM, Guilbert T, Papi A, Price D, Jenkins CR, Kraft M, Bacharier LB, Boulet LP, Yawn BP, Pleasants R, Lazarus SC, Beasley R, Gauvreau G, Israel E, Schneider-Futschik EK, Yorgancioglu A, Martinez F, Moore W, Sumino K. Questions in Mild Asthma: An Official American Thoracic Society Research Statement. Am J Respir Crit Care Med. 2023 Jun 1;207(11):e77-e96. doi: 10.1164/rccm.202304-0642ST. PMID: 37260227; PMCID: PMC10263130. 

  4. 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, Blake KV, Brooks EG, Bryant-Stephens T, DiMango E, Dixon AE, Elward KS, Hartert T, Krishnan JA, Lemanske RF Jr, Ouellette DR, Pace WD, Schatz M, Skolnik NS, Stout JW, Teach SJ, Umscheid CA, Walsh CG. 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):1217-1270. doi: 10.1016/j.jaci.2020.10.003. Erratum in: J Allergy Clin Immunol. 2021 Apr;147(4):1528-1530. doi: 10.1016/j.jaci.2021.02.010. PMID: 33280709; PMCID: PMC7924476.

 
Booth EM