Irisin, BMI, and SII as Predictors of Frequent Acute Exacerbations in COPD: Development of a Predictive Nomogram.

OBJECTIVE: Frequent acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with poor prognosis, but objective and easily applicable predictors remain limited. This study aimed to investigate the association of Irisin, body mass index (BMI), and systemic immune-inflammation index (SII) with frequent acute exacerbations in COPD and to develop a predictive nomogram. METHODS: This single-center retrospective-prospective observational study included 96 patients hospitalized with acute exacerbation of COPD (AECOPD) between March 2023 and March 2025. Frequent exacerbation was defined as ≥2 acute exacerbations or ≥1 hospitalization for AECOPD within one year. Patients were classified into the frequent exacerbation group (n=34) and non-frequent exacerbation group (n=62). Clinical data and serum Irisin levels were collected. Group comparisons, correlation analysis, univariate and multivariable logistic regression analyses were performed, and a nomogram was developed. Model performance was evaluated using receiver operating characteristic (ROC) analysis, calibration curve, bootstrap internal validation, and decision curve analysis. RESULTS: Compared with the non-frequent exacerbation group, the frequent exacerbation group had lower Irisin and BMI levels and higher white blood cell count, neutrophil count, and SII. Multivariable logistic regression showed that Irisin (OR=0.981, 95% CI: 0.974-0.989) and BMI (OR=0.980, 95% CI: 0.963-0.998) were independently associated with a lower risk of frequent exacerbations, whereas lnSII (OR=1.117, 95% CI: 1.012-1.234) was associated with a higher risk. The combined model yielded an area under the ROC curve of 0.856 (95% CI: 0.780-0.933), showing better discrimination than Irisin alone. Calibration and decision curve analyses suggested favorable internal performance. CONCLUSION: Irisin, BMI, and SII were associated with frequent acute exacerbations in COPD. The combined nomogram may provide a preliminary reference for risk stratification, but external validation is required before clinical application.