Objective ·To investigate the value of the T-cell mitochondrial damage index (MDI) in risk prediction for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods ·A total of 100 patients with chronic obstructive pulmonary disease (COPD) who attended the Department of Respiratory Medicine, Jinhua Municipal Central Hospital, from May 2023 to December 2024 were enrolled. According to the post-bronchodilator percentage of predicted forced expiratory volume in 1 second (FEV₁%pred), they were divided into the moderate COPD group (50%≤FEV₁%pred<80%, n=50) and the severe COPD group (30%≤FEV₁%pred<50%, n=50). Additionally, 50 healthy individuals who underwent physical examinations during the same period were included as the healthy control group. Baseline characteristics of all subjects (including general clinical data and laboratory indicators) were collected. Flow cytometry was used to detect and compare the MDI of peripheral blood T cells and their subsets (CD3⁺, CD3⁺CD4⁺, and CD3⁺CD8⁺) in the three groups. The patients with COPD were followed up for 6 months, and were classified into the acute exacerbation (AE) group and the non-AE group according to whether AE occurred during follow-up. Differences in baseline characteristics between the two groups were compared. LASSO regression was used to screen baseline predictors of AECOPD. Univariable and multivariable Logistic regression models were used to establish a predictive model for AECOPD risk, and the performance of the model was validated using the receiver operating characteristic (ROC) curve, calibration curve, and five-fold cross-validation. Results ·The abnormal rates of MDI in T cells and their subsets were higher in patients with COPD than in the healthy control group. Among them, the abnormal rate of CD3⁺CD8⁺ T-cell MDI in the severe COPD group was significantly higher than that in the moderate COPD group and the healthy control group (both P<0.05). After 6 months of follow-up, 46 patients with COPD developed AE. Compared with the non-AE group, the patients in the AE group had lower FEV₁ levels (P<0.001), and higher COPD assessment tests (CAT) scores (P<0.001). Moreover, there were statistically significant differences in the categorical distribution of MDI injury grades in T cells and their subsets between the two groups (all P<0.001), with a higher proportion of mild-to-severe injury observed in the AE group. LASSO regression identified four baseline predictors: CD3⁺ T-cell MDI, CD3⁺CD8⁺ T-cell MDI, FEV₁, and CAT score. The area under the curve (AUC) of the AECOPD risk prediction model constructed based on these four variables was 0.848 (95%CI 0.772—0.923, P<0.001), with a sensitivity of 70.0% and a specificity of 81.0%. The calibration curve showed good model fit (P=0.136), and in the five-fold cross-validation, the accuracies of the training set and validation set was 0.80±0.03 and 0.82±0.06, respectively. Conclusion ·The AECOPD risk prediction model constructed based on CD3⁺ T-cell MDI, CD3⁺CD8⁺ T-cell MDI, FEV₁, and CAT score has good predictive value and may provide a reference for early clinical intervention.