Mild Asthma, Major Upgrade – Albuterol Plus Budesonide May Soon Replace Albuterol Alone in Asthma Inhalers

Key Takeaways

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.

EBM Focus Article

Mild asthma is the deceptively tame cousin in the asthma family. It wheezes just enough to annoy, rarely lands in the intensive care unit, 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 percent 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 moderate-to-severe asthma, and 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 prevent severe exacerbations in this population? This trial randomized 2,516 patients (mostly adults) with uncontrolled mild asthma to either a) pressurized metered-dose inhalers of either combination albuterol/budesonide or b) 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 to 52 weeks, patients using the combination therapy experienced a lower incidence of first severe exacerbation: 5.1 percent vs. 9.1 percent in the on-treatment analysis and 5.3 percent vs. 9.4 percent in the modified intention-to-treat analysis. The annualized rate of severe exacerbations was cut in half (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 percent!

Importantly, there was no 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 also 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 asthma.

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 percent of patients did not complete the trial, with 19.2 percent never having taken one puff of their inhaler. Sixty percent 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.