Blood eosinophils may herald a new era of precision medicine in COPD

Blood eosinophil counts are a ‘beautiful predictor’ of COPD exacerbations and the likelihood that inhaled corticosteroids could prevent them, a leading international expert says.

Speaking at a symposium in Melbourne Professor Ian Pavord, Professor of Respiratory Medicine at the University of Oxford in the UK, said there was mounting excitement over the potential of blood eosinophils as both a diagnostic and theragnostic biomarker for people living with COPD.

“It’s time for a new approach to airway disease, toward identifying treatable traits and moving away from labels that have been such a problem for us in developing new treatments,” Professor Pavord told delegates attending the Respiratory Insights Forum hosted by A. Menarini.

“For the first time in airway disease, we will be offering more precision medicine, with the right treatment for the right patient at the right time, and better outcomes”.

COPD was a complex, heterogeneous disease with a limited armoury of treatments, Professor Pavord said. It was therefore best to focus on two clear aspects of disease that could be easily identified and modified: air flow limitation (recorded with spirometry) and eosinophilic airway inflammation.

Blood eosinophil information was routinely collected during full blood counts but was not usually taken into consideration. However it was a “beautiful predictor” that was associated with the risk of exacerbations and the likelihood that inhaled corticosteroids (ICS) could prevent them, he said.

Blood eosinophils a standout marker

Two major patterns of airway inflammation in COPD have been identified since the late 1980s, when the induced sputum technique highlighted the role of both eosinophils and neutrophils.

However induced sputum was not a technique that could be routinely performed in clinical practice, especially in primary care, and it was not until recently that Dr Mona Bafadhel from Oxford University’s Nuffield Department of Medicine investigated various measures in the blood and sputum discovered that the standout marker of a raised sputum eosinophil count was the blood eosinophil count.

Several studies have shown that a blood eosinophil count ≥2% (150 cells/µL) is an accurate marker of eosinophillic airway inflammation. Patients with <2% do not have this pattern of inflammation and will not respond to ICS. “It was a remarkably robust cut off point – and it is repeatable,” Professor Pavord said.

A Dutch study in 1999 (Hospers et al), looked at blood eosinophil counts above the median and found the relative risk of death from COPD was nearly 5 times higher in these patients. Another meta-analysis looking at the use of steroids in acute lung attacks in COPD compared prednisolone with placebo.

It found that there was no benefit of prednisolone in those who had a baseline blood eosinophil count of <2%. In contrast those with higher blood eosinophil counts responded well to prednisolone, with a six-fold reduction in treatment failure rate.

Professor Pavord said 45% of COPD patients never had eosinophil airway inflammation and therefore did not have characteristics that would respond to steroids.

“It’s essential we are aware when we make a label that we are not identifying pathology. However, it is important to do this because of the consistent and close relationship between the blood eosinophil count and response to ICS,” he said.

Implications for treatment?

Even though the majority of COPD patients in primary care are receiving triple therapy, there are studies questioning the value of ICS. An analysis of the WISDOM trial has shown that withdrawing ICS increased exacerbations in patients with elevated blood eosinophil counts, but was possible in the majority of patients who had blood eosinophil levels <4% or 300 cells/µL.

With concern over costs, the risks of pneumonia and the availability of attractive alternatives such as LAMA/LABA, which could achieve good outcomes, blood eosinophil counts could help to stratify those patients for whom the benefits of ICS would outweigh the risks, Professor Pavord said.

“There’s a feeling it’s time to change the way we use ICS from a risk-directed strategy to a strategy where treatment is given to those who have the relevant steroid responsive inflammation,” he said.

“ICS is a rational choice if your biomarker tells you the patient might have the right biology, and can alter the progression of the disease if given to the right patients. Blood eosinophil count is also a marker of who will do badly if you choose to withdraw ICS,” Professor Pavord said.

“If the patient clearly has a high blood eosinophil count then there will be a great deal of benefit with treatment which will outweigh the risks of pneumonia. But if <2%, the benefits of treatment will be low and the risks will outweigh the benefits, so don’t treat”.

The way forward

The FLAME study showed that LAMA/LABA was better than LABA/ICS to prevent exacerbations regardless of blood eosinophil count, but Professor Pavord felt it was likely that there was a role for ICS on top of LAMA/LABA in patients selected on the basis of blood eosinophil count.

He cautioned that it was important to interpret a low blood eosinophil count in context, as prednisolone could confound the results. It was better to rely on counts taken in earlier blood tests rather than those recorded during hospitalisation, he said.

However, the fact remains that blood eosinophils appear to be a good predictor of response to ICS that was very closely linked to treatment.

“In the blood eosinophil count we will have a useful and important biomarker. It tells us about risk of exacerbation, risk of pneumonia and the likely response to ICS, and ultimately should be incorporated into the GOLD criteria,” he said.


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