Association Between anti-PD-1/PD-L1 Immune Checkpoint Inhibitors and Type 2 Airway Inflammation in Patients with Lung...

Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have revolutionized lung cancer therapy, but immune-mediated complications are a growing concern, and their impact on type 2 inflammation and chronic airway disease remains unclear. Corticosteroids, standard for eosinophilic airway diseases, are detrimental in anti-PD-1/PD-L1-treated patients.

We investigated the effect of ICIs on blood eosinophil counts (BEC), chronic airway disease development and exacerbations in a real-world cohort.

This retrospective study analyzed clinical, biological, and imaging data from 127 consecutive patients treated with PD-1/PD-L1 inhibitors for non-small cell lung cancer. BEC, lung function, comorbid asthma or COPD, frequency of exacerbations, corticosteroid use werecollected. ROC curves identified eosinophil thresholds predictive of exacerbation risk.

Half of the patients had COPD (n=47) or asthma (n=13), one third newly diagnosed, and 11 (8.7%) exacerbated on treatment, 9 of them frequently (≥2/year). BEC increased significantly during ICI, more so among exacerbators (p=0.0013). Pre-treatment BEC >275 cells/mm³ was associated with exacerbation onset, while on-treatment values >345 cells/mm³ offered better prediction (AUC 0.73, 67% sensitivity; 83% specificity). In multivariable analysis, exacerbations were negatively associated with 10% increase in FEV1 (OR=0.70; 95%CI=0.46-0.99) and positively associated with concomitant systemic corticosteroid use (OR=10.34; 95%CI=1.81-69.27), and on-treatment eosinophil rise (OR=1.15; 95%CI=1.01-1.36 per 10² cells/mm³).

ICIs may unmask or amplify underlying T2 airway inflammation. A raised eosinophil count is a specific but weakly predictive signal that should prompt surveillance rather than be over-interpreted, whereas a low count is reassuring.