Objective To explore the association between plasma IgG and acute exacerbation (AE) or death risk in patients with chronic obstructive pulmonary disease (COPD). Methods A total of 262 COPD patients treated in our hospital from February 2018 to February 2020 were recruited in our study. All patients were divided into AE≥2 group and AE≤1 group according to AE frequency during follow-up of 1 year. Basic data and laboratory data such as IgG, IgA and IgM of two groups were comparatively analyzed. Univariate analysis and COX regression were performed to analyze the related factors of frequency of AE≥2 times in 1 year. Depicting restricted cubic spline was performed to analyze the relation between IgG and AE by R software. All patients were also divided into high IgG group, low IgG group, high IgA group and low IgA group based on median of patients’ baseline plasma IgG and IgA level, depicting survival curve by Kaplan-Meier to analyse differences between the groups with different IgG or IgA level in the risk of AE and death respectively. ResultsFinally, there were 14 patients lost to follow-up and 248 cases were included (AE≤1 group contained 154 cases, AE≥2 group contained 94 cases) until February 28, 2021. Age and COPD Assessment Test (CAT) scores in the AE≥2 group were higher than those in the AE≤1 group; Albumin, IgG and IgA level in the AE≥2 group were lower than those in the AE≤1 group; Neutrophil to lymphocyte ratio (NLR) in the AE≥2 group was higher than that in the AE≤1 group (all P<0.05). There were 99 and 114 cases of AE in the high IgG and low IgG groups respectively within 1 year. Kaplan Meier survival analysis showed that risk of AE in the high IgG group and high IgA group were lower than that in the low IgG group and the low IgA group (log rank χ2=23.791, 67.153, both P=0.000). Risk of death in the high IgG group was lower than that in the low IgG group (log rank χ2=6.214, P=0.013), there was no statistically difference in the risk of death in the high IgA group compared to the low IgA group (log rank χ2=2.400, P=0.121). Multivariate Cox regression analysis showed that CAT score (HR=1.096, P=0.001) and NLR (HR=2.061, P=0.000) were independent risk factors of frequency of AE≥2 times in 1 year for COPD patients, albumin (HR=0.921, P=0.006) and IgG (HR=0.572, P=0.000）were the independent protective factors. Restricted cubic spline analysis showed that combining the COX regression model, after adjusting for IgA, albumin, NLR and other variables, there was non-linear relationship between IgG level and AE (P=0.000).Conclusion Plasma IgG level is related to AE in COPD patients, and may become a reliable predictor of acute exacerbation risk in the future.