Blood eosinophils in chronic obstructive pulmonary disease: A potential biomarker

The paper examines whether blood eosinophil counts (BEC) can serve as a clinically useful biomarker in chronic obstructive pulmonary disease (COPD). COPD exhibits heterogeneous phenotypes with differing clinical characteristics and treatment responses. A substantial subset of patients shows eosinophilic airway inflammation. Given inconsistent findings across studies regarding the prognostic and therapeutic implications of blood eosinophils, the authors synthesize recent evidence to provide insights into the role of eosinophils in COPD and their potential to guide individualized treatment, particularly inhaled corticosteroid (ICS) use.

The review summarizes evidence on: (1) Eosinophilic airway inflammation in COPD, including recruitment pathways (CCL11, CCL5; IL-5, IL-13) and T2 inflammatory profiles; (2) Stability of BEC over time in stable COPD and during exacerbations, noting better reproducibility at lower thresholds and variability at higher counts; (3) Associations between eosinophil levels and clinical characteristics such as symptoms, dyspnea, lung function, bacterial load, and pneumonia risk; (4) Predictive value of BEC for response to corticosteroids, both inhaled and systemic, with multiple RCTs and post-hoc analyses showing greater benefit with higher BEC; (5) Relationships between BEC and future exacerbations, highlighting conflicting findings across cohorts and trials; and (6) Emerging evidence that variability and persistence of eosinophilia (rather than single measurements) relate to outcomes including exacerbation risk and survival.

This is a narrative review synthesizing recent studies on blood eosinophils in COPD, including cohort studies, randomized controlled trials, post-hoc and pre-specified analyses, and real-world data. No formal systematic search strategy, inclusion/exclusion criteria, or meta-analytic methods are reported.

- Prevalence: Approximately 20%–40% of stable COPD patients exhibit airway eosinophilic inflammation; about 28% of acute exacerbations are associated with sputum eosinophilia. In China, eosinophilic airway inflammation during acute exacerbation was reported in 38.04% of patients, and over 40% of inpatients had BEC ≥ 2%. - Biology: Eosinophilic COPD features T2 inflammation involving IL-5 and IL-13 pathways, suggesting potential therapeutic targets. - Stability: BEC shows within-patient stability over a year in stable COPD, with greater variability at higher counts (≥300 cells/µL) and better reproducibility at lower thresholds (100–150 cells/µL). During hospitalization for exacerbations, discordance of 35.6% was observed among those admitted with BEC ≥ 300 cells/µL between admission and discharge. - Clinical characteristics: Persistently higher eosinophil levels are associated with higher FEV1% predicted, fewer symptoms, and lower dyspnea/BODE indices. Lower eosinophil levels correlate with increased pneumonia risk and higher bacterial load (e.g., S. pneumoniae, M. catarrhalis, H. influenzae) during exacerbations. Low BEC is linked to increased pneumonia risk with ICS therapy. - Corticosteroid response: Higher BEC predicts greater benefit from ICS-containing regimens in reducing exacerbations, with effects observed at thresholds as low as ≥100 cells/µL and increasing with higher counts (e.g., ≥300 cells/µL). Eosinophil-guided systemic corticosteroid strategies during exacerbations can reduce steroid exposure without compromising outcomes, and eosinophilic exacerbations show faster symptom recovery and fewer treatment failures. - Exacerbation risk prediction: Evidence is mixed. Some cohorts show increased exacerbations with BEC ≥150 or ≥300 cells/µL, while others (e.g., SPIROMICS, CHAIN/BODE, pooled RCT analyses) find no significant relationship. Guidelines caution against using a single BEC to predict exacerbation risk. - Variability matters: High variability in BEC among stable COPD patients associates with more frequent exacerbations. In hospitalized AECOPD, persistently high BEC across admission correlates with higher moderate-to-severe exacerbation risk post-discharge, whereas persistently low BEC is associated with poorer survival. Multiple measurements (at least two) help stratify risk.

The synthesis indicates that blood eosinophils capture a biologically meaningful eosinophilic/T2 phenotype in COPD, which is associated with lower airway bacterial burden and enhanced responsiveness to corticosteroids. While a single BEC may not reliably predict future exacerbations across all populations, consistent patterns emerge: higher BEC identifies patients more likely to benefit from ICS, and dynamic features—persistence or variability of eosinophilia—better relate to outcomes than isolated measurements. These insights support using BEC to personalize therapy (notably ICS initiation or continuation) and to frame prognosis when serial measurements are available. The findings align with guidance recommending ICS for patients with frequent exacerbations and higher BEC, while recognizing uncertainty in using BEC alone as an exacerbation predictor. The role of eosinophils in T2 pathways also opens opportunities for targeted interventions in eosinophilic COPD.

Blood eosinophils represent a promising biomarker in COPD, reflecting a T2 inflammatory phenotype and predicting improved response to corticosteroid therapy. Although results are inconsistent regarding single BEC measures and future exacerbation risk, considering persistence and variability of eosinophilia enhances prognostic value. Clinically, BEC can guide ICS use, and eosinophil-guided systemic steroid strategies may optimize treatment during exacerbations. Future research should standardize thresholds, clarify temporal dynamics of BEC during stability and exacerbations, evaluate integration with other biomarkers and microbiologic profiles, and test targeted anti–T2 therapies in eosinophilic COPD.

- Narrative review without systematic search or meta-analysis, increasing risk of selection bias. - Heterogeneity across cited studies in design, populations, BEC thresholds (e.g., 100, 150, 300 cells/µL), measurement timing, and treatments limit comparability. - Conflicting results regarding BEC as a predictor of exacerbation risk reduce certainty of conclusions based on single measurements. - Limited data on intra-exacerbation BEC stability and its longitudinal implications; need for more prospective validation of variability-based risk stratification. - Potential confounding by ICS and other therapies on BEC and outcomes across observational datasets.