Abstract: Objective To investigate the expression of serum progranulin (PGRN), hypoxia inducible factor-1 (HIF)-1α and hypersensitive C-reactive protein/albumin ratio (HCAR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their value in predicting acute re-exacerbation.Methods A total of AECOPD 60 patients who were treated in the People's Hospital of Jiawang from January 2021 to June 2022 were selected as an experimental group. Meanwhile, 30 healthy subjects who underwent physical examination were selected as a control group. Then, their peripheral blood samples (2 ml per person) were collected, and the levels of serum PGRN and HIF-1α were measured. The demographic data and arterial blood gas analysis and blood routine results were collected, while the levels of hypersensitive C-reactive protein (hsCRP) and albumin (ALB) were recorded to calculate HCAR. After discharge, all the subjects were regularly followed-up. Based on the presence of acute re-exacerbation within 180 days, they were divided into two groups:an acute re-exacerbation group and a non-acute re-exacerbation group. The correlation between each variable and acute re-exacerbation was determined through univariate logistic regression analysis. A receiver operating characteristic curve (ROC) was plotted to evaluate the value of PGRN and HIF-1α in predicting acute re-exacerbation.Results The concentrations of serum PGRN and HIF-1α and HCAR in the AECOPD group was obviously higher than those in the control group (P<0.05). The concentrations of serum PGRN and HIF-1α and HCAR in AECOPD patients with respiratory failure were obviously higher than those without respiratory failure (P<0.05). Univariate logistic regression analysis suggested that serum PGRN and HIF-1α were the risk factors of AECOPD acute re-exacerbation. The ROC analysis showed that the area under the curve of serum PGRN combined with HIF-1α was 0.84, which was statistically higher than that of serum HIF-1α (0.68, P<0.05), but without statistical difference compared with serum PGRN, with an AUC of 0.71.Conclusions Serum PGRN, HIF-1α and HCAR can reflect the severity of AECOPD patients. The combined use of serum PGRN and HIF-1α has higher specificity in predicting acute re-exacerbation in AECOPD patients.