Adding a steroid to the asthma rescue puff meant fewer severe attacks

On 19 October 2026 the Journal of Asthma published a systematic review and meta-analysis of randomised trials of albuterol-budesonide, an inhaler that combines a fast-acting bronchodilator with an inhaled corticosteroid and is used as needed, when symptoms flare. The authors pooled three randomised controlled trials with 6,134 participants aged 12 and over and compared the combination with albuterol alone or standard reliever therapy. They rated the certainty of each result with the GRADE approach.

The blue inhaler opens the airways but leaves the inflammation alone

Albuterol is a short-acting β2-agonist, a bronchodilator. As the authors of the MANDALA trial put it in The New England Journal of Medicine in 2022, people rely on such rescue therapy as symptoms worsen, yet it does not address the worsening inflammation and leaves them at risk of severe exacerbations. The idea behind the combination is simple: every time a person reaches for relief, they also inhale an anti-inflammatory steroid.

Fewer severe attacks across the three trials

In the pooled analysis, the risk of a first severe exacerbation was lower with albuterol-budesonide than with the comparator: hazard ratio 0.72 (95% CI 0.58 to 0.89). The number of severe exacerbations (relative risk 0.64; 95% CI 0.49 to 0.82) and their annual rate (relative risk 0.68; 95% CI 0.51 to 0.89) were also lower. Lung function at week 12, measured as FEV1, was on average 80 mL higher (95% CI 46 to 114), and yearly exposure to systemic corticosteroids was lower. Adverse events were similar in both groups (relative risk 0.99; 95% CI 0.94 to 1.04).

The authors rated the certainty of evidence as moderate for the risk and annual rate of severe exacerbations and for systemic steroid exposure, low for the number of exacerbations and for FEV1, and high for adverse events.

The two large trials behind the idea

The meta-analysis brings no new patients; it re-analyses trials that have already been published. The two largest randomised trials of this inhaler were funded by the companies developing it. MANDALA (NEJM, 2022) randomised 3,132 people with uncontrolled moderate-to-severe asthma who continued their usual inhaled-steroid maintenance treatment; 97% were 12 or older. With one of the two combination formulations tested, the risk of a severe exacerbation was 26% lower than with albuterol alone (hazard ratio 0.74; 95% CI 0.62 to 0.89). With the other formulation the difference did not reach statistical significance (hazard ratio 0.84; 95% CI 0.71 to 1.00). MANDALA was funded by Avillion.

BATURA (NEJM, 2025) was a fully virtual, decentralised trial that randomised 2,516 people aged 12 and over whose mild asthma was uncontrolled, for up to 52 weeks; 97.2% of the analysed participants were adults, and three quarters used only a short-acting reliever at the start. It was stopped early for efficacy at a prespecified interim analysis. A severe exacerbation occurred in 5.1% of participants on albuterol-budesonide and 9.1% on albuterol (hazard ratio 0.53; 95% CI 0.39 to 0.73). BATURA was funded by Bond Avillion 2 Development and AstraZeneca.

Why three trials are not the last word

A pooled estimate from three trials is only as broad as those trials. The authors themselves point to the small number of studies and to heterogeneity for some outcomes. The abstract does not name a funder for the meta-analysis, and the large trials it draws on were sponsored by the companies developing the inhaler. The participants were adolescents and adults: in the US the combination has been approved since January 2023, and its label covers asthma in people 18 and older, not children.

Its abstract reports no comparison with the other way of giving a steroid with every reliever puff: an inhaler of budesonide with formoterol, a fast- and long-acting bronchodilator. In the SYGMA 1 trial (NEJM, 2018) of 3,849 people aged 12 and over with mild asthma, the annual rate of severe exacerbations was 0.07 with as-needed budesonide-formoterol versus 0.20 with a short-acting reliever alone.

If you manage asthma with a reliever alone, or reach for it often, it is worth asking your doctor whether a reliever that contains an inhaled steroid fits your asthma. Discuss any change of inhaler with your doctor first.

This material is for information only and does not replace a consultation with a doctor. Nothing in it is a recommendation to start, stop or change treatment.

Sources

• Ul Abideen Z, et al. Safety and Efficacy of Albuterol-Budesonide Versus Albuterol Alone in Asthma: A GRADE-assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Asthma. 2026. PMID 42895787

• Papi A, et al. Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma (MANDALA). N Engl J Med. 2022. PMID 35569035

• LaForce C, et al. As-Needed Albuterol-Budesonide in Mild Asthma (BATURA). N Engl J Med. 2025. PMID 40388330

• O'Byrne PM, et al. Inhaled Combined Budesonide-Formoterol as Needed in Mild Asthma (SYGMA 1). N Engl J Med. 2018. PMID 29768149

• US Food and Drug Administration. Drugs@FDA: Airsupra (albuterol and budesonide), NDA 214070. accessdata.fda.gov