Reduced Serum sRAGE Levels Identify COPD and Reflect Disease Severity: Findings from a Cross-Sectional Study in India

Background: Chronic Obstructive Pulmonary Disease (COPD) remains a leading cause of morbidity and mortality worldwide, particularly in low- and middle-income countries (LMICs), where both tobacco and biomass smoke exposure are major risk factors. While spirometry is the diagnostic gold standard, reliable non-invasive biomarkers are needed for early detection and disease monitoring. The soluble receptor for advanced glycation end-products (sRAGE), a circulating decoy receptor with anti-inflammatory activity, has shown potential in this context. Methods: In this prospective, exposure-stratified, cross-sectional study, 150 adults were enrolled into four groups of 25 each-tobacco-smoke COPD, male tobacco-exposed controls, biomass-smoke COPD, and female biomass-exposed controls-along with 50 healthy controls (25 males, 25 females). Participants underwent clinical evaluation, spirometry, and serum sRAGE quantification (ELISA). Systemic inflammation was assessed using neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Correlation and receiver operating characteristic (ROC) analyses determined diagnostic performance. Results: Serum sRAGE levels were significantly lower in tobacco-induced (545 ng/mL) and biomass-induced COPD (540 ng/mL) versus controls (1207-1462 ng/mL; p < 0.001). sRAGE correlated positively with FEV₁, FVC, and FEV₁/FVC (r = 0.54-0.75, p < 0.001), and negatively with CAT, mMRC, and SGRQ-C. ROC analysis showed excellent discrimination (AUC = 0.990; 94% sensitivity; 96% specificity at 946 ng/mL cutoff). Conclusions: Serum sRAGE is a robust, non-invasive biomarker for COPD diagnosis and severity assessment across exposure phenotypes. Its integration into clinical practice may enhance early detection and risk stratification, particularly in LMICs.