Reference - N Engl J Med. 2025 Jul 10;393(2):113-124
Practice Point: For patients with uncontrolled mild asthma, as-needed use of an albuterol-budesonide combination inhaler may reduce severe exacerbations and systemic steroid exposure compared to albuterol alone.
EBM Pearl: When interpreting trial results, be cautious of high dropout rates, as they may mask adverse effects or overstate benefits, impacting how reliably the findings apply to your patients.
Mild asthma is the deceptively tame cousin in the asthma family. It wheezes just enough to annoy, rarely lands in the ICU, and often gets brushed aside with a puff or two of albuterol. However, it turns out that “mild” doesn’t necessarily mean harmless, as this group accounts for nearly 30% of asthma exacerbations, often requiring a visit to urgent care centers. Patients with mild asthma often get by with just a rescue inhaler, assuming their condition is under control. But that assumption can be misleading. Prior studies such as the DENALI trial and MANDALA trial focused on patients with moderate-to-severe asthma, but neither looked exclusively at patients with uncontrolled mild asthma whether or not they were receiving maintenance therapy. Enter the BATURA trial, a phase 3b, randomized, double-blind study that asked whether an as-needed combination of albuterol and budesonide could do more than just relieve symptoms—could it actually prevent severe exacerbations in this population?
In the trial, 2,516 patients (mostly adults) with uncontrolled mild asthma were randomized to receive pressurized metered-dose inhalers of either combination albuterol/budesonide or albuterol alone. At baseline, patients used a short-acting beta agonist (SABA) as needed with or without a maintenance low-dose inhaled glucocorticoid or leukotriene-receptor antagonist. Over 12-52 weeks, patients using the combination therapy experienced a lower incidence of first severe exacerbations: 5.1% vs. 9.1% in the on-treatment analysis and 5.3% vs. 9.4% in the modified intention-to-treat analysis. The annualized rate of severe exacerbations was cut in half significantly (0.15 vs. 0.32), and exposure to systemic glucocorticoids was significantly reduced (23.2 mg/year vs. 61.9 mg/year). Possibly most satisfying for those wary of systemic steroids, the average cumulative prednisone dose was reduced by a whopping 63%.
Importantly, there wasn’t a trade-off between inflammation control and safety. Patients appeared to receive the benefit of anti-inflammatory rescue therapy without the long-term daily inhaled corticosteroid exposure or the risks of high-dose systemic steroids. The adverse event profile looked similar between groups, and the trial was stopped early due to clear efficacy in favor of the combination treatment. These findings suggest that adding an inhaled corticosteroid to rescue therapy can meaningfully reduce asthma-related risks in those with mild disease.
Impressive? Perhaps. However, before we exhale in relief, at least one concern deserves some attention: the impact of attrition bias on the internal validity of the observed treatment benefit. Nearly 30% of participants did not complete the trial, with 19.2% never having taken one puff of their inhaler. Sixty percent of participants were recruited via social media, which may have contributed to the high loss to follow-up. Either way, while the trial may have been stopped early for the achieved efficacy, duplication of these data may be warranted before declaring it practice-changing.
Still, the real takeaway here isn’t just about numbers. The BATURA trial challenges the notion that controller therapy must be daily to be effective. It suggests that patients with mild asthma, often left to self-manage with albuterol, might do better when we add a little steroid in with their SABA. Mild asthma may never look the same again. And for patients reaching for their rescue inhalers, it may finally mean getting more than just short-term relief. They might be preventing their next trip to urgent care.
For more information, see the topic Asthma in Adults and Adolescents in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Rich Lamkin, MPH, MPAS, PA-C, Clinical Writer at DynaMed. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Dan Randall, MD, MPH, FACP, Senior Deputy Editor at DynaMed; Gayle Sulik, PhD, Senior Medical Editor and Team Lead for Palliative Care at DynaMed; McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed; Matthew Lavoie, Senior Medical Copyeditor, BA, at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.