Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disorder characterized by irreversible airflow limitation and respiratory muscle dysfunction. Bioactive lipid mediators such as prostaglandins, leukotrienes, and specialized pro-resolving mediators (SPMs) play critical roles in regulating inflammation, yet their relationship with diaphragmatic performance in COPD remains poorly understood. This case-control study investigated the association between circulating lipid mediators and diaphragmatic function in 40 male COPD patients and 40 age- and sex-matched healthy controls. All participants underwent clinical assessment, spirometry, C-reactive protein (CRP) measurement, blood sampling for lipid mediator profiling-including polyunsaturated fatty acid (PUFA)-derived metabolites-and diaphragmatic ultrasound evaluation of excursion and thickening fraction (TF). COPD patients exhibited significantly impaired diaphragmatic function and elevated pro-inflammatory lipid mediators compared with controls. Receiver operating characteristic (ROC) analysis identified Prostaglandin E2 (PGE₂) (area under the curve [AUC] = 0.826), Thromboxane B2 (TXB₂) (AUC = 0.832), and Leukotriene B4 (LTB₄) (AUC = 0.737) as strong diagnostic biomarkers for COPD. Among SPMs, RvD1 correlated positively with diaphragmatic excursion (r = .62) and TF (r = .58), Lipoxin A4 (LXA₄) correlated with Forced Expiratory Volume in one second (FEV₁) (r = .66), and Protectin DX (PDX) showed an inverse association with the COPD Assessment Test (CAT) score (r = -.54). Leukotriene E4 (LTE₄) and Leukotriene D4 (LTD₄) were negatively associated with diaphragmatic performance, while CRP levels inversely correlated with ultrasound parameters. Diaphragmatic TF demonstrated high sensitivity (90%) and specificity (92%) in predicting severe exacerbations. These findings suggest that lipid mediator imbalance contributes to diaphragmatic dysfunction in COPD and that combining lipidomic profiling with diaphragmatic ultrasound may offer a promising approach for assessing systemic inflammation and respiratory muscle performance in male COPD patients.