FeNO-based risk scale identifies patients at risk of asthma attack

A prototype risk scale for asthma attack has been developed by UK researchers that, if validated, could herald a new era of trait-based disease management.

The Oxford University team used data from more than 220,000 patients to design a risk scale potentially able to predict asthma attacks that may be prevented with anti-inflammatory therapy.

The OxfoRd Asthma attack Risk sCaLE (ORACLE) is based on two key markers of type II inflammation – blood eosinophils and fractional exhaled nitric oxide (FeNO) – which predict the risk of asthma exacerbations.

“The prototype ORACLE centres our attention on biomarkers which are easily measured in primary care and are both prognostic and theragnostic. Hence, raised inflammatory biomarkers identify patients who are at higher risk of asthma attacks,” said Dr Simon Couillard, a Clinical Research Fellow at the Respiratory Medicine Unit, Nuffield Department of Medicine.

“Importantly, these inflammation-driven asthma attacks are avoidable, as their inflammation is known to respond beautifully to anti-inflammatory therapy. Conversely, a patient with low biomarkers can be reassured that their asthma attack risk is low and that they are unlikely to benefit from more intense anti-inflammatory therapy.

“We hope this prototype will stimulate the development of a definitive scale, which is suitable for use across the range of clinical practice and capable of delivering an improvement in key outcomes,” he told the limbic

The scale is in the form of a chart with cells that represent the predicted annual asthma attack rate for a given scenario if treatment remains unchanged. It shows predicted asthma attack rates of 0.06 to 2.60 per year, comparable to observed attack rates in the trial control.


Dr Couillard and co-authors concluded that “a risk scale based on this prototype could facilitate better treatment decisions by doctors and patients by providing a framework for a preventive, treatable, trait-based management”, but also highlighted that the prototype needs refining and that several assumptions were made.

These include observed inconsistencies in the relationship between FeNO and the risk of asthma attacks in the mild asthma population;  a likely reflection of small sample size, but could also be due to other factors, such as a difference in the mechanism of asthma attacks.

“It is also important that the scale is refined using individual patient data from large and well-characterised populations,” they said, in the paper published online in Thorax.

Dr Couillard confirmed to the limbic that research on this is already underway. “We have begun work to refine and to validate the scale using individual participant data from clinical trials and real-world cohorts. This will take time and, notably, many different cohorts to work with. Indeed, it has been suggested that a robust scale should be validated in up to 50 different cohorts!”

He also said the team is keen to revisit the traditional predictors of asthma attacks in a manner which corrects for inflammatory biomarkers. “For example, is low lung function the result of long-standing inflammation which also causes recurrent asthma attacks, or is lung function an independent predictor of asthma attacks? The same stands for other conventional risk factors such as previous intensive care for asthma, high symptom burden, obesity, etc.”

Further data is currently under review showing how ORACLE also predicts the benefits of type-2 targeted therapy observed in clinical trial populations in asthma, which should also help to validate the scale’s use for clinical practice, Dr Couillard noted.

Speaking to the limbic, Dr Hitasha Rupani, a respiratory physician and Chair of the British Thoracic Society’s Asthma Specialty Advisory Group (SAG), who was not involved in the study, agreed that once the risk scale is validated it should become embedded in primary care pathways, in a similar way to those for cardiovascular risk.

“Currently there is a big move to get FeNO into primary care, and most other clinical risk factors should already be accessible to GPs. I think [the risk scale] will very easily translated into primary care electronic systems, which will support earlier referrals to secondary care.”

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