A serum cytokine-derived integrated inflammatory profile score (IIPS) links systemic inflammation to symptom burden and severity in COPD

Background Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic inflammatory syndrome in which forced expiratory volume in 1 s expressed as a percentage of predicted value (FEV1% predicted) may dissociate from patient-reported symptom burden. This study evaluated an Integrated Inflammatory Profile Score (IIPS) as a potential biological correlate for a more holistic assessment of stable COPD. Methods Serum concentrations of 11 cytokines were measured in 62 patients with stable COPD. The IIPS was derived using automated linear modeling with forward stepwise selection guided by the corrected Akaike information criterion (AICc). Associations of the IIPS with COPD Assessment Test (CAT) scores were compared with those of FEV1% predicted. Results The optimized IIPS, comprising interferon-gamma (IFN-γ), interleukin-2 (IL-2), and interleukin-10 (IL-10), was significantly associated with FEV1% predicted (R 2 = 0.1867, p = 0.0005) and outperformed the individual cytokines in discriminating spirometric severity (area under the receiver operating characteristic curve (AUC) = 0.7381). For symptom burden, FEV1% predicted showed greater explanatory power for exertional domains, particularly breathlessness (R 2 = 0.0832) and activities (R 2 = 0.1280). By contrast, the IIPS showed numerically stronger trend-level associations for sleep (R 2 = 0.0519, p = 0.0750) and energy (R 2 = 0.0511, p = 0.0773), although these associations did not reach conventional statistical significance. Conclusion The IIPS reflects Global Initiative for Chronic Obstructive Lung Disease (GOLD)-defined physiological severity more effectively than any single cytokine measured in this study. Its associations with patient-reported systemic symptoms were modest and exploratory, suggesting that integrated inflammatory profiling may complement spirometry in characterizing COPD burden but requires external and longitudinal validation before clinical application.