Eli, a nine-year-old, presents with mild asthma. Most days she’s fine, managing her wheeze with her blue inhaler as needed, but every so often a cough or sniffle turns into a flare that worries her parents about a looming attack. You want to prevent her next severe asthma attack, but what do you do?||
Do you stick with Short-acting Beta-2 Agonist (SABA)-only relievers, or is there something better? Could this alternative be an inhaled steroid? How will potential steroid exposure affect her? How do you balance preventing attacks with over-medicalising a child who is mostly well?
The Children’s Anti-inflammatory Reliever (CARE) study set out to answer exactly this question, comparing as-needed budesonide–formoterol with standard salbutamol in children like her over a full year.
Hatter L, Holliday M, Oldfield K, Kearns C, Barry T, Black M, Bruce P, Colman A, Dickinson E, Eathorne A, Harwood M. Budesonide–formoterol versus salbutamol as reliever therapy in children with mild asthma (CARE): a 52-week, open-label, multicentre, superiority, randomised controlled trial. The Lancet. 2025 Oct 4;406(10511):1473-83.
For years, adolescents and adults with mild asthma have been nudged away from the trusty blue inhaler and towards Inhaled Corticosteroid (ICS)–formoterol for reliever therapy. The rationale? Each puff of ICS during early flare-ups reduces airway inflammation before it worsens. The result is fewer attacks.
But what about younger kids?
Until now, we’ve had no paediatric Randomised Controlled Trial (RCT) evidence for ICS-formoterol reliever therapy in children under 12. Guidelines for kids have therefore lagged a step behind the adult evidence, even though asthma remains one of the most common reasons children turn up in EDs and urgent care, causing considerable morbidity as well as risk of death. This is even so in children with supposedly ‘mild’ disease!
Enter the CARE study.
This large, pragmatic New Zealand trial gives us the evidence we’ve been waiting for: Can budesonide–formoterol (Symbicort Rapihaler) used only as needed outperform salbutamol in children with mild asthma?
Spoiler: Yes. Quite definitively.
What did the CARE study do?
The CARE trial was a 52-week, open-label, multi-centre, superiority RCT in children aged 5–15 years who were using SABA only for asthma.
360 kids were randomised to:
- Budesonide–formoterol 50/3 μg (two puffs as needed)- 179 kids (50%) or
- Salbutamol 100 μg (two puffs as needed)- 181 kids (50%)
Both groups escalated treatment if a severe attack occurred—mirroring real-life management. The primary outcome was simple:
How many asthma attacks per child per year?
(moderate = needing urgent review; severe = needing steroids)
What did they find?
45% fewer asthma attacks with budesonide–formoterol
Kids on budesonide–formoterol had 0.23 attacks/year compared to 0.41 attacks/year on salbutamol (relative rate 0.55, p=0.012)
In real terms:
| Outcome | Budesonide–formoterol | Salbutamol | p-value |
| ≥1 attack | 17% | 32% | 0.0060 |
| ≥1 severe attack | 9% | 15% | 0.086 |
| Time to first attack | Longer | Shorter | 0.0010 |
The effects were consistent in sensitivity analyses.
Who benefited the most?
There were some interesting subgroup signals:
- Older kids (12–15 years): bigger benefit
- Boys: bigger benefit than girls
- High FeNO (Fractional Exhaled Nitric Oxide): markedly bigger benefit—suggesting ICS responsiveness
BUT these subgroup analyses are exploratory. The key message remains: All children benefitted.
Kids also tended to stay on Step 1 treatment in the Symbicort group—meaning they required fewer treatment escalations.
What didn’t change?
Despite fewer attacks, everything else basically stayed the same:
- FEV₁ (Forced Expiratory Volume in 1 second) – no difference
- ACQ (Asthma Control Questionnaire) scores – no difference
- FeNO – no meaningful change
- Growth – no difference (critical for parents and clinicians alike)
- Adverse events – similar across groups
- Serious adverse events – rare and unrelated to study drugs
Why does this matter?
Many severe asthma outcomes occur in kids labelled as having “mild” asthma who are relying on SABAs.
A SABA-only strategy treats bronchospasm—not the underlying inflammation that’s about to escalate. That’s where ICS-formoterol shines: every puff delivers both bronchodilation and anti-inflammatory action at the moment it matters most.
CARE now extends the evidence for adults and adolescents to the 5–15 age group.
This is big!
How does this fit with what we already know?
Previous key trials (SYGMA, Novel START) showed:
- 60–77% fewer severe attacks with ICS–ICS-formoterol in adults and teens
- Safety comparable to SABA
- Benefits mainly in terms of attack prevention
CARE mirrors this pattern in children.
The study also used pMDIs (Pressurised Metered-Dose Inhaler) with a spacer, which is more relevant to younger children in real-world settings than Turbohaler devices in adult trials.
Limitations?
A few:
- Open-label design (pragmatic for real world)
- Fewer severe attacks than expected (COVID-era respiratory virus suppression)
- ICS dose lighter than adult trials (appropriate for age but maybe less protective)
- Medication usage couldn’t be tracked by dose counters
Still, the real-world design makes findings highly applicable to everyday practice.
CASP (Critical Appraisal Skills Programme) checklist for cohort RCTs – How good was the paper?
Did the study address a clearly formulated research question?
Yes
Was the assignment of participants to interventions randomised?
Yes — children were randomly assigned to either budesonide–formoterol or salbutamol.
Were all participants who entered the study accounted for at its conclusion?
Mostly—nearly all children were followed for the full 52 weeks, although some dropouts were not fully detailed.
Were the participants, investigators and analysts ‘blind’ to the intervention they were given?
No — the CARE study was open-label, so participants, clinicians, and outcome assessors all knew which inhaler was being used.
Were the study groups similar at the start of the randomised controlled trial?
Yes — baseline characteristics were similar, so the groups were well balanced from the start.
Apart from the experimental intervention, did each study group receive the same level of care (that is, were they treated equally)?
Yes — aside from the reliever inhaler, both groups received standard asthma care, so treatment was otherwise the same.
Were the effects of the intervention reported comprehensively?
Yes — the study reported asthma attacks, safety, and adverse events, giving a clear picture of the intervention’s effects.
Was the precision of the estimate of the intervention or treatment effect reported?
Yes — effect sizes were reported with confidence intervals and p-values, showing both magnitude and precision of the benefit.
Do the benefits of the experimental intervention outweigh the harms and costs?
Yes — as-needed budesonide–formoterol nearly halved asthma attacks without increasing adverse events, making the benefits clearly outweigh the risks.
Can the results be applied to your local population/in your context?
Yes — the study population mirrors children with mild asthma in most paediatric settings, so the findings are highly relevant and applicable
Would the experimental intervention provide greater value to the people in your care than any of the existing interventions?
Yes — using as-needed budesonide–formoterol could prevent more asthma attacks than standard salbutamol relievers, offering clear added value for children with mild asthma.
So… should we switch children to ICS-formoterol reliever therapy?
Based on CARE:
Safe: Similar adverse event and growth profile
More effective: Fewer attacks, delayed time to attacks
Simpler: One inhaler, used only when needed
Guideline-aligned with emerging global recommendations
The study supports replacing SABA-only treatment with as-needed ICS-formoterol in children with mild asthma, just as we already do for adults and adolescents.
Bottom line
For children aged 5–15 with mild asthma, reaching for a blue inhaler alone is no longer the best option.
Budesonide–formoterol as-needed reduces asthma attacks by nearly half, with no additional safety concerns.
This is a practice-changing trial—and one that finally provides paediatric clinicians with data to align with adult guidelines that have long recommended these approaches.
