As new trial findings show significant reductions in paediatric asthma attacks from a budesonide-formoterol 2-in-1 reliever therapy, Professor Andy Bush speaks to Saša Janković about the system reforms needed to bring paediatric asthma outcomes in line with adult care.

‘Data is what you need to drive treatment,’ says Professor Andy Bush, consultant paediatric chest physician at Royal Brompton Hospital and professor of paediatrics and paediatric respirology at the National Heart and Lung Institute at Imperial College London. This is his response to the results of a recent trial showing the life-changing effects that 2-in-1 asthma inhalers can have on children living with asthma.

The year-long Children’s Anti-inflammatory Reliever trial, known as CARE, 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 aged between five and 15 years across New Zealand who had asthma and were using short-acting β2-agonist (SABA) reliever monotherapy.

They were randomly assigned to receive either budesonide-formoterol or continue to receive salbutamol inhalers for on-demand symptom relief.

Combining the inhaled corticosteroid budesonide and the fast-acting bronchodilator formoterol, the 2-in-1 inhaler is already widely recommended as the preferred reliever treatment for adults and young people aged 12 years and over, but, until now, had not been investigated in a randomised controlled trial in children.

A meeting with New Zealand respiratory researcher Professor Richard Beasley – whose work had helped uncover the link between asthma deaths and reliever overuse – led to Professor Bush’s involvement in the design and launch of the New Zealand trial.

Their results showed that the budesonide-formoterol reliever resulted in a lower rate of asthma attacks in children than the salbutamol reliever, with rates of 0.23 versus 0.41 per participant per year. This means that for every 100 children with mild asthma who switched from salbutamol to a 2-in-1 budesonide-formoterol inhaler, there would be 18 fewer asthma attacks per year.

Redefining paediatric asthma management

‘The UK had a history of persistently poor childhood asthma outcomes, with a child dying of asthma every month. Repeated inquests were highlighting the same issues over and over again of children not being given enough of their inhaled steroid preventer and taking too much of the blue reliever,’ Professor Bush explains. ‘The adult data on combination inhalers were already very solid, with meta-analyses involving thousands of patients, but paediatric evidence was lacking, leaving clinicians to tell parents that a treatment “works for an adult, and I’m sure it’ll work for your little child”, which was wholly unsatisfactory.’

CARE sought to change this and showed that all asthma attacks were reduced by this combined approach to therapy. Professor Bush notes that the study demonstrated reassuring safety data. This confirms previous studies in older children and adults and that ‘those using the combined inhaler actually took less steroid than the ones taking it regularly, and when the team examined growth, they found no effect on growth in those using the combination regimen’, he says.

As a result, Professor Bush believes this evidence has the potential to redefine the global standard of asthma management for children.

Current UK guidance still advises salbutamol as needed at the first step for younger children, followed by regular low dose inhaled steroids plus salbutamol. ‘NICE could not consider the CARE data because they had not yet been published,’ he explains, ‘but based on the emerging evidence the combined approach is the preferred and safest option for any child of five and over who’s got asthma.’

Expanding clinician awareness

Although personally well-versed in the latest results thanks to his involvement with the research, Professor Bush acknowledges that widespread understanding of budesonide-formoterol in paediatric asthma will take time.

‘My focus is solely on respiratory disease, but primary care clinicians must cover a whole range of things over the whole age range, which means new asthma paradigms are not always adopted quickly,’ he says, ‘plus changing ingrained practice is challenging for both clinicians and families, since many have spent years being told that regular twice-daily steroids are essential.’

Professor Bush’s hope is that the emerging evidence means clinicians can ‘red card the blue inhaler’ and allow practice in children to ‘catch up’ with the treatment that adults already receive.

In a bid to bring this knowledge even closer to home, Professor Bush is also involved in the CARE UK trial, led by his Royal Brompton colleague Professor Louise Fleming.

This will assess the budesonide-formoterol inhaler in 1,300 children between the ages of six and 11 years. The study is actively recruiting across all levels of disease severity and aims to deliver definitive evidence on the effectiveness of replacing SABA reliever monotherapy with a budesonide–formoterol combination inhaler in children already using regular preventer inhalers. In other words, a more severe group than those in the existing CARE study.

Key priorities

Alongside this important treatment shift, Professor Bush says there are several other areas where paediatric asthma care requires urgent attention.

‘A key priority is better recognition that frequent reliever use is a red flag,’ he says. ‘This is often overlooked in practice, but this failure to act on warning signs contributes directly to preventable morbidity and mortality.’

The Lancet asthma commission, co-chaired by Professor Bush, advises that clinicians should ‘view an asthma attack as “a never event”, and attacks should never drift into a cycle of one-off urgent care encounters. Instead, every child should have a clear point of clinical responsibility and appropriate follow-up’.

On diagnosis, he describes a ‘bonkers’ mismatch between expectations for asthma and other conditions. ‘NICE guidance stresses the need for objective testing, yet many services lack the capacity to deliver it, and this is not good enough,’ he says. ‘We need diagnostic hubs so that children receive robust testing and are not placed on lifelong treatment without clear evidence.’

Professor Bush also stresses that pharmacists remain a largely untapped asset in improving asthma care. ‘Pharmacists are a greatly underused resource in asthma management. For example, if someone comes into the community pharmacy regularly for a blue inhaler, the pharmacist could say “actually, there’s a better approach than this”, and advise the patient to contact their GP,’ he says. ‘Wise clinicians pay a lot of attention to pharmacists, because they are highly trained, highly skilled professionals, and they should be more deeply embedded in children’s asthma pathways as part of routine multidisciplinary care.’

Transforming paediatric asthma management

Longer term, Professor Bush has ambitious hopes for transforming paediatric asthma management, beginning with a shift in mindset across the system. ‘Although asthma is common, there has been a tendency to treat it as straightforward when, in reality, outcomes in the UK remain awful,’ he says. ‘Getting the basics right should be non-negotiable and every professional involved in asthma care should have appropriate training to make sure that asthma reviews are never treated as simply a tick box exercise.’

Raising expectations among families is just as important, he says. ‘Parents should feel empowered to insist on competent care, with clear lines of responsibility and proper follow-up after any attack, as well as continuity of care so that families don’t have a new face at every encounter, with no one owning the long-term picture,’ he maintains.

Above all, Professor Bush stresses that asthma attacks must be seen as preventable events. ‘An asthma attack is a sign of failure of management of a chronic condition,’ he says. ‘This requires system level investment in diagnosis and monitoring, so we have a future where asthma care is consistently competent, proactive and evidence based, where attacks are rare, and where children receive the standard of care parents reasonably expect.’

Put simply, he concludes: ‘We can’t accept second best for children.’