Predictive biomarkers for type 2 airway inflammation in stable COPD: are we there yet?

Introduction
Chronic Obstructive Pulmonary Disease (COPD) is a common condition associated with significant morbidity and mortality. It is characterised by fixed airway obstruction due to an underlying inflammatory response to inhaled toxins. While this inflammation is usually neutrophilic of nature, it can be predominantly eosinophilic in a subgroup of patients. Blood eosinophil counts (BEC) and Fractional exhaled Nitric Oxide (FeNO) measurements are surrogate biomarkers for Type 2 airway inflammation. Over the past decade, BECs gained the interest of the research community as they can predict responsiveness to Inhaled Corticosteroids (ICS) in COPD patients at risk of exacerbations. Interest in FeNO within the context of COPD was recently rekindled by new evidence suggesting prognostic and theragnostic properties for this biomarker.

Aims
This research aimed to study the biomarkers of Type 2 inflammation in stable COPD patients. The primary objectives are: determining the prevalence of stable COPD patients with elevated blood eosinophil levels in Belgian primary care, examining the long-term and within-day stability of BECs and determining the within-day stability of FeNO.

Methods
A retrospective methodology was employed to assess the prevalence of elevated BECs (based on BEC GOLD thresholds of 100 and 300 cells/μL) and the long-term stability of BECs in Belgian primary care. Descriptive statistics and the Coefficient of Variation (CoV) were used for this purpose. Within-day stability of BECs and FeNO measurements were prospectively determined in an outpatient setting and expressed as CoV and Intra-class correlation coefficient (ICC).

Results
The prevalence of stable COPD patients (n=89) in Belgian primary care presenting with BECs ≥100 and ≥300 cells/μL was 78% and 23%, respectively. Long-term variability of BECs demonstrated a mean (median) CoV of 46% (41%) in our population of stable COPD patients (n=98) over a mean (median) follow-up period of 9.5 (8.4) years. Higher variability was observed at higher BEC. The median within-day CoV (IQR) of BEC in our population (n=50) was 28% (17-38%) and the ICCabsolute agreement was 0.79 (CI 0.88-0.94). The median within-day CoV (IQR) of FeNO in our population (n=69) was 14% (8-22%) and the ICCabsolute agreement was 0.92 (CI 0.88-0.94).

Conclusions
Elevated BECs are prevalent in Belgian primary care and BECs can be variable over time in individual patients. The BEC within-day variability found in our research suggests that time of day needs to be considered when interpreting results. Conversely, FeNO demonstrated a good within-day stability, enhancing its potential as predictive biomarker.