The Role of Neutrophil PD-L1 Expression in Acute Exacerbation of COPD

Background and Objective

The elevation of neutrophil-lymphocyte ratio (NLR) has been shown to be critically involved in unfavorable outcomes among patients with chronic obstructive pulmonary disease (COPD). While the mechanism underlying the changes of NLR during COPD progression remains unclarified.

Methods

In this prospective observational study from June to December 2024, we included 14 patients with acute exacerbation, 27 with stable conditions, and 9 controls. Blood samples were collected for neutrophil isolation, and the CD15 ⁺ CD274 ⁺ neutrophil ratio was measured using flow cytometry. We also recorded and analyzed smoking history, pulmonary function test results, and blood routine test data.

Results

The ratio of CD15 ⁺ CD274 ⁺ neutrophils was notably higher in patients with COPD compared to healthy controls and was even more elevated in those experiencing acute exacerbations of COPD (AECOPD) than in patients with stable COPD. This increased ratio was positively correlated with NLR but negatively correlated with FEV1% (FEV1 percentage of the predicted value). The CD15 ⁺ CD274 ⁺ neutrophil percentage is a powerful biomarker for predicting AECOPD (AUC 0.894; 95% CI 0.8–0.989). A ratio above 3.273 (odds ratio 1.386; 95% CI 1.016–1.891; P=0.039) independently predicts AECOPD.

Conclusion

The increased ratio of CD15 ⁺ CD274 ⁺ neutrophil serves as an independent risk factor in predicting the incidence of AECOPD, which might be due to disrupting NLR and worsening FEV1%. Elevated PD-L1(programmed death ligand 1, CD274 ⁺ ) on neutrophils might also be a potential therapeutic target for reversing immune dysfunction and poor outcomes of patients with COPD.

Key messages

What is already known on this topic – An increased neutrophil-lymphocyte ratio (NLR) is linked to poor outcomes in COPD patients, though the reasons for NLR changes during COPD progression are still unclear.

What this study adds – Higher level of CD15 ⁺ CD274 ⁺ (PD-L1) neutrophil, showing a positive correlation with NLR and a negative correlation with FEV1%, serves as a strong biomarker for predicting AECOPD.

How this study might affect research, practice or policy – Elevated CD15 ⁺ CD274 ⁺ neutrophil may indicate COPD progression by suppressing lymphocyte activity, causing abnormal NLR changes. Targeting elevated PD-L1 on neutrophils may improve immune function and outcomes in COPD patients.