Abstract： Objective:To investigate the relationship of serum cyclooxygenase-2(COX-2)and alpha 2-macroglobulin(α2-MG)levels with acute respiratory failure in elderly lung cancer patients after pneumonectomy.Methods:This study was a cohort study, from May 2019 to May 2021, a total of 108 elderly patients with lung cancer who were admitted to the department of Thoracic Surgery of Liaocheng Third People′s Hospital were selected, including 68 males and 40 females, aged(72.15±13.15)years old, ranging from 60 to 85 years old.According to whether acute respiratory failure occurred after pneumonectomy, the patients were divided into failure group( n=21)and non-failure group( n=87).Using the tendentious scoring matching model, 20 patients who matched successfully in the failure group were the matched failure group, and 20 patients who matched successfully in the non-failure group were the matched non-failure group.Immediately after the operation, the patient′s peripheral venous blood was collected, and the serum COX-2 and α2-MG level were determined, the relationship between serum COX-2 and α2-MG levels and acute respiratory failure was analyzed. Results:Before the propensity score match, there was a statistically significant difference in the range of lung resection between the failure group and the non-failure group( P>0.05).After the propensity score match, there was no statistically significant difference between the two groups in gender, age, body mass index, range of lung resection, tumor diameter, pathological classification, preoperative history of respiratory diseases, and smoking history( P<0.05).Serum COX-2 level in matched failure group immediately after operation[(146.99 ± 36.52)μg/ml] was significantly higher than that of matched non-failure group[(121.14 ± 30.15)μg/ ml], α2-MG[(126.59±23.65)μg/ml] was significantly lower than that of matched non-failure group[(269.64 ± 29.68)μg/ml], the difference was statistically significant( P<0.05).The results of describing the subject′s work characteristic curve(ROC)showed that COX-2 and α2-MG has certain value in predicting acute respiratory failure after pneumonectomy for lung cancer in the elderly.COX-2 combined α2-MG application can effectively improve the efficiency when applied alone. Conclusions:COX-2 and α2-MG levels are of great significance in predicting the acute respiratory failure in elderly lung cancer patients after pneumonectomy.