A groundbreaking clinical trial has demonstrated that a combination inhaler can dramatically reduce asthma attacks in children, potentially transforming pediatric asthma care worldwide. The CARE study, published in The Lancet, found that a budesonide-formoterol combination inhaler reduced asthma attacks by 45% compared to salbutamol, the current standard treatment for children.
Trial Design and Results
The CARE study (Children's Anti-inflammatory REliever) was the first randomized controlled trial to investigate the use of a 2-in-1 inhaler as sole reliever therapy for children aged 5 to 15. 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, the trial recruited 360 children across New Zealand.
Participants were randomly assigned to receive either budesonide-formoterol or salbutamol for on-demand symptom relief over a 52-week period. The budesonide-formoterol reliever resulted in significantly lower rates of asthma attacks compared to salbutamol, with rates of 0.23 versus 0.41 per participant per year (relative rate 0.55, 95% CI 0.35–0.86, p=0.01).
"This means that for every 100 children with mild asthma who are switched from salbutamol to a 2-in-1 budesonide-formoterol inhaler, there would be 18 fewer asthma attacks per year," according to the study findings.
Safety Profile Confirmed
The study confirmed the safety of the combined-inhaler approach, with no significant differences in children's growth, lung function, or asthma control between the two treatment groups. This addresses a critical concern about using inhaled corticosteroids in pediatric populations.
Dr. Lee Hatter, lead author of the study and Senior Clinical Research Fellow at MRINZ, stated: "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 significantly reduce asthma attacks in children with mild asthma."
Global Impact Potential
The 2-in-1 budesonide-formoterol inhaler is widely recommended as the preferred reliever treatment for adults, but children are still usually prescribed salbutamol. The burden of asthma affects an estimated 113 million children and adolescents worldwide, making these findings particularly significant.
Professor Richard Beasley, Director of MRINZ and senior author of the study, emphasized the global implications: "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."
Professor Helen Reddel, Chair of the Science Committee of the Global Initiative for Asthma (GINA), commented on the study's significance: "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 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."
Clinical Implications
Professor Andrew Bush from Imperial College London, senior respiratory paediatrician and co-author of the CARE study, highlighted the clinical significance: "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."
The study builds on previous research in adults led by MRINZ researchers that 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 worldwide.
Study Limitations and Future Directions
The authors acknowledged some limitations of the clinical trial. It was conducted during the COVID-19 pandemic, when stringent public health measures and fewer circulating respiratory viruses contributed to lower than predicted rates of severe asthma attacks. The researchers also noted challenges with identifying asthma attacks in children and potential bias from the lack of blinding of randomized treatments. However, they emphasized that the study's findings are generalizable to clinical practice due to its pragmatic, real-world design.
Professor Bob Hancox, Medical Director of the New Zealand Asthma and Respiratory Foundation, concluded: "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."
The study was supported by the Health Research Council of New Zealand, Cure Kids (New Zealand), and the Barbara Basham Medical Charitable Trust, with Symbicort Rapihalers provided by AstraZeneca.
