Findings from a trial comparing the real-world effectiveness of asthma inhalers could reshape how children with asthma are treated.
In the first randomized controlled trial to investigate a 2-in-1 inhaler as the sole reliever therapy for children aged 5 to 15, an international team found the combined treatment more effective than salbutamol, the current standard for asthma symptom relief in children, with no additional safety concerns.
The results show that using a single 2-in-1 anti-inflammatory reliever inhaler – which combines the inhaled corticosteroid (ICS) budesonide and the fast-acting bronchodilator formoterol – reduced children’s asthma attacks by an average of 45%, compared to the widely-used salbutamol inhaler.
Asthma attacks in children can be life-threatening, and reducing their frequency and severity is a public health priority.
The 2-in-1 budesonide-formoterol inhaler is widely recommended as the preferred reliever treatment for adults, but children are still usually prescribed salbutamol.
Researchers say the findings, published on Sept.27 in The Lancet, provide the evidence needed to align children’s global asthma guidelines with those for adults, potentially benefiting millions of children worldwide with mild-to-moderate asthma.
The CARE study (Children’s anti-inflammatory REliever) was designed and led by the medical Research Institute of New Zealand (MRINZ), in collaboration with Imperial College london, University of Otago Wellington, Starship Children’s Hospital, and the University of Auckland.It recruited 360 children across New Zealand who were then randomly assigned to receive either budesonide-formoterol or salbutamol for on-demand symptom relief.
The year-long trial revealed a lower rate of asthma attacks with the budesonide-formoterol reliever than with salbutamol (0.23 versus 0.41 per participant per year). This means that for every 100 children with mild asthma who switch from salbutamol to a 2-in-1 budesonide-formoterol inhaler, there would be 18 fewer asthma attacks per year. Importantly, the study also confirmed the safety of the combined-inhaler approach, with no significant differences in children’s growth, lung function, or asthma control between the two groups.
Dr.Lee Hatter, lead author of the study and Senior Clinical Research Fellow at MRINZ, said, “This is a key step in addressing the evidence gap that exists between asthma management in adults and children. For the first time, we have demonstrated that the budesonide-formoterol 2-in-1 inhaler, used as needed for symptom relief, can considerably reduce asthma attacks in children with mild asthma. This evidence-based treatment could lead to improved asthma outcomes for children worldwide.”
Professor Richard Beasley,Director of MRINZ and senior author of the study,said,“Implementing these findings could be transformative for asthma management on a global scale. The evidence that budesonide-formoterol is more effective than salbutamol in preventing asthma attacks in children with mild asthma has the potential to redefine the global standard of asthma management.”
The burden of asthma is substantial for the estimated 113 million children and adolescents with asthma worldwide. This latest study builds on previous research in adults led by MRINZ researchers – which shaped international asthma treatment guidelines – and contributed to the recommended use of the 2-in-1 ICS-formoterol reliever inhaler as the preferred reliever treatment for adults with asthma globally.
Incorporating the CARE study’s findings into global asthma treatment strategies could help reduce disparities in care and ensure more children access effective, evidence-based treatments.
Researchers say global health organizations have long advocated for child-targeted asthma interventions,and their findings provide crucial evidence to support those efforts.
However, the authors acknowledge some limitations of the clinical trial. It was undertaken during the COVID-19 pandemic, and stringent public health measures and fewer circulating respiratory viruses contributed to the lower-than-predicted rate of severe asthma attacks. The authors also acknowledge challenges with identifying asthma attacks in children and the potential bias from a lack of blinding of the randomized treatments. they maintain, however, that the study’s findings are generalizable to clinical practise due to its pragmatic, real-world design.
Professor Andrew Bush, from imperial College London, senior respiratory pediatrician and co-author of the CARE study, said, “Having an asthma attack can be very scary for children and their parents. I’m so pleased that we’ve been able to prove that an inhaler that significantly reduces attacks – already a game-changer for adults – is safe for children with mild asthma too. We believe this will transform asthma care worldwide and are excited to be building on this work with the CARE UK study.”
Professor Helen Reddel, Chair of the Science Committee of the Global Initiative for Asthma (GINA), commented on the global importance of the study, stating it fills a critically significant gap in asthma management. Professor Reddel said, “Asthma attacks have a profound impact on children’s physical, social, and emotional development, and their prevention is a high priority for asthma care. It is indeed in childhood, too, that lifelong habits are established, particularly reliance on traditional medications like salbutamol that only relieve symptoms and don’t prevent asthma attacks.”
Professor Bob Hancox, Medical Director of the New Zealand Asthma and Respiratory Foundation, said, “This is a very critically important study for children with mild asthma. We have known for some time that 2-in-1 budesonide/formoterol inhalers are better than the traditional reliever treatment in adults, but this had not been tested in children. This research shows that this 2-in-1 inhaler is effective and safe for children as young as 5. This information will help to reduce the burden of asthma for many children,and both they and their families will breathe easier because of it.”
Study key points:
- The CARE study is the first randomized controlled trial comparing ICS-formoterol anti-inflammatory reliever inhaler treatment with salbutamol reliever inhaler treatment in children aged five to 15 years with asthma.
- budesonide-formoterol demonstrated a significant reduction in asthma attacks, with a 45% decrease in the rate of attacks compared to salbutamol (0.23 vs. 0.41 attacks per participant per year; relative rate 0.55, 95% CI 0.35-0.86, p=0.01).
- These findings are consistent with established benefits seen in adults, where ICS-formoterol has become the preferred reliever treatment for asthma management.
- The study found no safety concerns regarding the use of a combined inhaled steroid treatment in children,with no adverse effects on growth or lung function.
- This study provides compelling evidence that switching from a salbutamol reliever inhaler to a budesonide-formoterol reliever inhaler can help prevent asthma attacks in children with mild asthma as young as five, which could lead to a potential shift in asthma treatment globally.
The study was made possible by the generous support of the Health Research Council of New Zealand, Cure Kids (New Zealand), and the Barbara Basham Medical charitable Trust managed by Perpetual Guardian. Symbicort Rapihalers for the trial were provided by AstraZeneca.