A groundbreaking clinical trial, recently published in The Lancet, heralds a potential paradigm shift in pediatric asthma management worldwide. For decades, salbutamol inhalers have been the cornerstone of asthma symptom relief for children aged five to fifteen, despite increasingly compelling evidence supporting alternative treatments in adults. This new study, termed the CARE (Children’s Anti-inflammatory REliever) trial, is the first randomized controlled investigation to directly compare the effectiveness of a budesonide-formoterol 2-in-1 inhaler against traditional salbutamol as the sole reliever therapy in children with mild asthma.

Asthma remains a prevalent chronic respiratory condition affecting an estimated 113 million children and adolescents globally, imposing significant physical, psychological, and social burdens. Acute exacerbations or asthma attacks, characterized by worsening airway inflammation and bronchoconstriction, can impose life-threatening risks in pediatric populations. Preventing such episodes and improving long-term lung function preservation are pivotal goals of asthma treatment. The CARE trial’s innovative scope addresses a critical gap in clinical evidence regarding the utility and safety of anti-inflammatory combined inhalers in younger patients, where historically treatment guidelines have lagged behind those for adults.

Over the course of a year-long study involving 360 children recruited from multiple centers in New Zealand, participants were randomized to receive either the combined inhaler containing the inhaled corticosteroid (ICS) budesonide and the rapid-onset bronchodilator formoterol or the conventional fast-acting beta-2 agonist, salbutamol. This open-label, multicenter design aimed to reflect pragmatic, real-world usage conditions, thereby enhancing the reliability and generalizability of the findings. By assessing asthma attack rates per participant annually, researchers could directly quantify the clinical impact of these distinct reliever therapies.

Results revealed a striking 45% reduction in asthma attacks for children using the budesonide-formoterol inhaler compared to those on salbutamol, with respective attack rates of 0.23 versus 0.41 per child per year. Such a pronounced decline signals a major enhancement in disease control and potentially a decreased burden on emergency healthcare services. Importantly, the study reported no additional safety concerns associated with the combined ICS and bronchodilator treatment, dispelling longstanding reservations about the effects of corticosteroids on growth and lung function in young children.

The underlying pharmacological rationale for these outcomes lies in the dual-action nature of the budesonide-formoterol inhaler. Budesonide, a potent inhaled corticosteroid, exerts anti-inflammatory effects that mitigate airway hyperresponsiveness, a hallmark of asthma pathophysiology. Concurrently, formoterol promptly relaxes bronchial smooth muscle, providing rapid symptomatic relief. This contrasts with salbutamol, which is a bronchodilator lacking intrinsic anti-inflammatory properties, thus only addressing symptoms without modifying underlying disease mechanisms. The integration of anti-inflammatory and bronchodilatory effects in a single inhaler shifts the therapeutic paradigm toward both immediate relief and long-term exacerbation prevention.

Asthma management guidelines have long recommended the budesonide-formoterol combination as preferred reliever therapy in adults, reflecting accumulating evidence affirming its superior efficacy and safety profile. Yet, despite these advances, pediatric recommendations have traditionally favored salbutamol due to a historical paucity of direct evidence in children. The CARE study decisively bridges this evidence gap, providing robust data to inform global guideline revisions that could harmonize treatment approaches across age groups, ultimately benefiting millions of children globally who suffer from mild to moderate asthma.

Experts involved in the trial underscore its public health significance. Dr. Lee Hatter, the study’s lead author, emphasized the transformative potential of adopting budesonide-formoterol reliever inhalers in pediatric asthma care, highlighting the successful demonstration of both efficacy and safety in this vulnerable population. Such shifts not only promise fewer asthma attacks but also improved quality of life, reduced school absences, and diminished parental anxiety caused by unpredictable exacerbations. The capacity to consolidate symptom relief and inflammation control into a single inhaler simplifies management protocols, potentially enhancing medication adherence among children and caregivers alike.

Nonetheless, the researchers acknowledge certain limitations associated with the trial. Conducted during the COVID-19 pandemic, the study period coincided with widespread public health interventions that significantly curtailed the circulation of common respiratory viruses known to trigger asthma attacks. This ambient reduction in exacerbation risk may have attenuated the absolute rate of severe attacks observed. Furthermore, the open-label design, while reflecting real-world treatment, means that participants and healthcare providers were not blinded to the intervention, introducing potential biases in symptom reporting and clinical decision-making. However, the pragmatic methodological choices strengthen the applicability of findings to routine clinical practice.

Global asthma authorities have hailed the CARE trial as a landmark contribution. Professor Helen Reddel, Chair of the Global Initiative for Asthma’s Science Committee, remarked on the critical need to transform pediatric asthma care in alignment with emerging evidence, emphasizing the lifelong implications of early asthma control. Preventing attacks in childhood not only safeguards physical health but also reduces the socioeconomic detriments associated with chronic respiratory illness. The anticipated harmonization of guidelines to incorporate budesonide-formoterol as the frontline reliever could mitigate disparities in asthma outcomes and ensure more equitable access to optimal therapies worldwide.

The trial’s findings resonate strongly within the clinical and patient communities. Professor Bob Hancox, Medical Director of the New Zealand Asthma and Respiratory Foundation, highlighted the importance of translating this robust evidence into practice, reassuring caregivers about the safety and enhanced efficacy of the 2-in-1 inhaler. This is expected to catalyze a shift in prescribing habits and asthma management strategies, reducing the personal and societal burden of asthma exacerbations. The ongoing CARE UK study, a sister trial designed to replicate and expand on these findings within a different healthcare setting, is poised to further consolidate the evidence base.

Pharmaceutical support was instrumental in facilitating the trial, with the provision of Symbicort Rapihalers, the budesonide-formoterol inhaler, by AstraZeneca. Funding from key organizations such as the Health Research Council of New Zealand and Cure Kids underscored the importance of independent, investigator-led research addressing pediatric respiratory health. The international collaboration among leading research institutes, including Imperial College London and the University of Otago Wellington, demonstrates a multidisciplinary commitment to advancing evidence-based asthma care.

This landmark research not only challenges the status quo but also charts a course for more effective, integrated asthma management strategies in children. By conclusively showing that combined anti-inflammatory and bronchodilator reliever therapy significantly reduces asthma attacks without compromising safety, the CARE trial broadens therapeutic horizons. Its implications extend beyond clinical practice, shaping policy dialogues, global health initiatives, and future research directions aimed at safeguarding the respiratory health of children worldwide.

Subject of Research: People

Article Title: Budesonide-formoterol versus salbutamol as reliever therapy in children with mild asthma (CARE): a 52-week, open-label, multicentre, superiority, randomised controlled trial

News Publication Date: 28-Sep-2025

Web References: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00861-X/fulltext

Keywords: Human health, asthma, pediatric asthma, budesonide, formoterol, salbutamol, inhalers, randomized controlled trial