High-coverage Lipidomics Analysis Reveals Biomarkers for Diagnosis of Acute Exacerbation of Chronic Obstructive Pulmonary Disease With Two Traditional Chinese Medicine Syndromes

BackgroundTraditional Chinese medicine (TCM) is distinguished by syndrome differentiation. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading cause of morbidity and mortality in COPD management. Previous studies have proved that AECOPD can be characterized as 2 TCM syndromes, and systematic dialectical treatment showed better curative effect than conventional therapy. However, detecting the progression from the stable stage to acute exacerbation of COPD with different TCM syndromes mainly depends on doctors’ judgment of clinical symptoms, and there is no biomarker that can be used for auxiliary clinical diagnosis. This study conducted a high-coverage lipidomics to find biomarker for the early diagnosis of AECOPD with 2 TCM syndromes.MethodsSerum samples from COPD patients (n=82) and healthy subjects (n=29) were collected and analyzed. Patients with COPD were divided into stable COPD (SCOPD) and AECOPD groups, with the latter comprising TCM syndromes: phlegm–heat congesting lung (PH-CL) and phlegm-damp amassing in the lung (PD-AL). High-coverage lipidomics profiling of 913 lipids belonging to 19 subclasses was carried out by liquid chromatography–quadrupole orbitrap mass spectrometry.ResultsWe performed 4 cross-comparisons to characterize metabolic disturbances associated with the progression of stable COPD to AECOPD—ie, SCOPD vs healthy subjects, AECOPD vs SCOPD, PH-CL-AECOPD vs SCOPD, and PD-AL-AECOPD vs SCOPD. We identified 86 lipids with differential abundance among groups. Lipids that were altered from the stable stage of disease to AECOPD included sphingolipids, ether-containing glycerophospholipids, phosphatidylglycerols, and glycerol lipids. Three panels of lipid biomarkers specific to AECOPD, two TCM syndromes of AECOPD vs SCOPD yielded areas under the receiver operating characteristic curve of 0.788, 0.921 and 0.920, respectively, with sensitivity of 77.5%, 80.7% and 91.3%, respectively, and specificity of 75.8%, 97.0% and 87.9%, respectively.ConclusionsDifferences in lipid metabolism may underlie AECOPD and its TCM syndromes, and can serve as biomarkers for early diagnosis.