COPD

Are blood eosinophils a biomarker of response to ICS?

Thursday, 19 May 2016


Research suggests that a minority of patients with COPD have elevated numbers of blood eosinophils that might predict a response to treatment with inhaled corticosteroids. We caught up with Peter Calverley, a Professor of Respiratory Medicine at the University of Liverpool and a senior investigator in the WISDOM study to get his view on on the topic.

What we learnt from WISDOM

The primary outcome of the study, published in 2014, was that exacerbation rates did not increase when inhaled corticosteroids were withdrawn in patients with severe COPD who were also using dual bronchodilator therapy.

The finding came as a “surprise” said Professor Calverley: “There was also no difference in exacerbation rates in a range of conventional subgroup analyses including age, gender, current or former smoking status, BMI, presence of chronic bronchitis or GOLD stage,” he told the limbic.

Professor Calverley’s initial view that ICS withdrawal would be detrimental has now been given some support by the post hoc analysis of WISDOM presented here at the American Thoracic Society’s annual scientific meeting here in San Francisco.

It showed that exacerbations were more common after ceasing ICS in patients with blood eosinophil counts of 4% or more (about 300 cells/mL).

However, only 19% of the patients in the study had this higher count. In addition, WISDOM enrolled patients with severe or very severe COPD (FEV1 <50% or less) and a history of exacerbations.

“The total WISDOM population might reflect only 10% of all patients with COPD, but a higher proportion of those seen by specialists,” Professor Calverley says.

Are blood eosinophils a biomarker of ICS response?

Although there is growing evidence that elevated blood eosinophils are a biomarker of ICS response, little is known about the potential biological mechanisms for any link.

“In fact, we don’t have a clue,” Professor Calverley says. “There are no associations between blood and sputum eosinophil numbers, nor between blood eosinophils and asthma-like symptoms in COPD patients.

“Empirical findings like our latest analysis don’t help us understand the process. Although there are a number of theories, the whole area remains astonishingly under-researched.

“Perhaps blood eosinophil numbers don’t tell us anything about the patient’s COPD, but instead are just a biomarker of steroid responsiveness.”

A small decline in lung function was observed after ICS withdrawal in WISDOM, but it needs to be interpreted cautiously, Professor Calverley says. “Daily FEV1 measurements in a subset of patients showed that the change occurred during a brief window of a few weeks, and did not progress.”

Making practical decisions

In the absence of data from prospective trials on ICS responsiveness, and while the debate continues, Professor Calverley says clinicians need to make practical decisions about treating their patients.

“As a general rule, patients with COPD do better with a long-acting bronchodilator than an ICS, and I would usually prefer a LAMA rather than a LABA as the first option,” Professor Calverley says.

“If the patient needs further symptomatic relief, the choice is between adding a second bronchodilator or adding an ICS.”

The FLAME study, published during ATS in the New England Journal of Medicine, showed that dual LABA/LAMA treatment was superior to a LABA/ICS combination in preventing exacerbations.

“The FLAME results support my view that there is a minority of COPD patients in whom I would add an ICS rather than a second bronchodilator,” he says. “They include patients with a past history of asthma, or a blood eosinophil count higher than about 300 cells/mL.”

Many questions about the role of blood eosinophils remain unanswered, including the thresholds that define a likely response to ICS, and whether the threshold should be adjusted in, for example, patients with a history of frequent exacerbations.

Panel discussion reflects lack of clarity

A panel discussion held during ATS reflected the lack of clarity around the role of blood eosinophils. Dr Fernando Martinez (University of Michigan), Professor Peter Barnes (Imperial College, London), Dr Antonio Anzueto (University of Texas, San Antonio) and Dr Don Mahler (Dartmouth, New Hampshire) debated the role of eosinophil counts as a biomarker of response, and highlighted the need for a prospective controlled trial to resolve the issue.

They emphasised that such a biomarker would have two important roles: to identify COPD patients in whom ICS may be a valuable addition to existing treatment, and those already being treated in whom ICS therapy might safely be withdrawn.

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