Blood Eosinophils May Help Guide COPD Therapy

By Reuters Staff

October 30, 2018

NEW YORK (Reuters Health) - Blood eosinophil concentrations can help guide initial management of chronic obstructive pulmonary disease (COPD), new research suggests.

For patients with high blood eosinophil concentrations (>4%) or counts (>300 cells/uL), a long-acting beta2 agonist with an inhaled corticosteroid is more effective than a long-acting muscarinic antagonist inhaler "and should be preferred for such eosinophilic patients," the researchers say in The Lancet Respiratory Medicine, online October 17.

Long-acting beta2 agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are recommended as initial maintenance treatment for COPD, with almost all LABAs dispensed in fixed combination with inhaled corticosteroids (LABA-ICS), note Dr. Samy Suissa from Jewish General Hospital and McGill University in Montreal, Canada, and colleagues.

They compared the apparent effectiveness and safety of initiating LABA-ICS versus LAMA treatment as a function of blood eosinophilia, a potential biomarker of ICS effectiveness, in a real-world setting.

Using the U.K. Clinical Practice Research Datalink, they selected two large matched groups of patients with COPD: 12,366 who initiated treatment with LAMA (mainly tiotropium) and 12,366 who initiated treatment with LABA-ICS (>60% fluticasone). Nearly all participants had a history of smoking; 33% of the LAMA cohort and 44% of the LABA-ICS cohort had asthma.

In the first year of treatment, there was no between-group difference in the risk of COPD exacerbations (hazard ratio with LABA-ICS vs. LAMA initiation, 0.95; 95% confidence interval, 0.90 to 1.01). There was also no difference in COPD flares by treatment in patients with blood eosinophil concentrations of <2% or 2% to 4% of white blood cell count.

Conversely, in patients with eosinophil concentrations >4% (or eosinophil counts of >300 cells/uL), initial treatment with LABA-ICS was more effective than LAMAs in guarding against disease flare (HR, 0.79; 95% CI, 0.70 to 0.88), particularly in patients with frequent exacerbations.

The LABA-ICS cohort had an increased risk of pneumonia (HR, 1.37; 95% CI: 1.17 to 1.60) and was similar across all eosinophil concentrations.

"Blood eosinophil concentrations can be important precision medicine guides in the selection of the optimal initial inhaler for the maintenance treatment of COPD," write Dr. Suissa and colleagues. "Because of the increased risk of pneumonia associated with the ICS component, initiation with a LAMA should be preferred in patients with blood eosinophil concentrations of less than 4%.”

The authors of a linked editorial say the results are "quite reassuring because they support the guidelines' recommendations of LABA-ICS and its efficacy and safety in patients with COPD who have frequent exacerbations. Furthermore, they show the relevance of blood eosinophilia, suggested so far only in randomized controlled trials comparing different combinations containing ICS. This outcome is even more interesting considering that the adherence to both treatments in the study was less than 50%."

But in an accompanying editorial, Dr. Leonardo Fabbri of the University of Ferrara in Italy and colleagues say the "suggestion to use eosinophils as a biomarker in treatment with LAMAs rather than LABA-ICS has limitations. The predictive value of blood eosinophil count for patients without a history of exacerbations (about 65% in the current study) is not sufficiently known and the reproducibility of blood eosinophils over time is limited (<50%)."

"The bottom line is that this interesting study provides important positive, clinically relevant information. However, because of its descriptive nature and limitations, the study cannot be used to make clinical recommendations but rather provides suggestions for future studies," the authors conclude.

The study was funded by the Canadian Institutes of Health Research and Canadian Foundation for Innovation.


Lancet Respir Med 2018.