〔Abstract〕 Objective To explore the application value of combined detection of fractional exhaled nitric oxide at an exhaled airflow rate of 50 mL·s-1 (FeNO₅₀) and alveolar exhaled nitric oxide (CaNO) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with glucocorticoids. Methods Prospective enrollment of 62 AECOPD patients admitted to the Department of Respiratory and Critical Care Medicine at Shenzhen Second People's Hospital from June 1, 2021 to May 31, 2023. They were categorized into four groups based on their FeNO₅₀ and CaNO levels upon admission (Group I: FeNO₅₀ < 25 ppb, CaNO ≤ 5 ppb; Group II: FeNO₅₀ ≥ 25 ppb, CaNO ≤ 5 ppb; Group III: FeNO₅₀ < 25 ppb, CaNO > 5 ppb; Group IV: FeNO50 ≥ 25 ppb, CaNO > 5 ppb). All patients received treatment with systemic glucocorticoids. The levels of FeNO₅₀, CaNO, peripheral blood eosinophils (EOS), pulmonary function [(forced expiratory volume in the first second (FEV1)], and chronic obstructive pulmonary disease assessment test (CAT) scores were measured at admission and discharge. Pearson correlation analysis was conducted to examine the relationship between EOS, FeNO₅₀, and CaNO. The improvement in FEV1 and CAT scores before and after treatment was compared among the 4 groups. Furthermore, the predictive value of FeNO₅₀, CaNO, and EOS on lung function improvement after treatment was assessed using receiver operating characteristic curve (ROC). Results There were no significant differences in age, sex, body mass index (BMI), smoking history and normal symptoms among all groups (P > 0.05). Pearson analysis showed that there was a positive correlation between EOS and FeNO₅₀ (r = 0.521, P < 0.05). After treatment, the improvement value of EOS was positively correlated with that of FeNO₅₀ (r = 0.472, P < 0.05). After systemic glucocorticoid treatment, there were statistically significant differences in FEV1 improvement and CAT score improvement among the 4 groups (P < 0.001; P = 0.002). Compared with the other three groups, the improvement of FEV1 in group IV was more obvious, and the difference was statistically significant (P < 0.05); the improvement of CAT scores in group III and IV were more obvious than those in the other two groups, and the differences were statistically significant (P < 0.05). No significant predictive value of EOS, FeNO₅₀ and CaNO was observed in the area under ROC curve for the significant improvement of lung function in patients with AECOPD after treatment. Conclusion The combined detection of FeNO₅₀ + CaNO has a certain predictive effect on the efficacy of systemic glucocorticoid in AECOPD patients. Patients with both elevated FeNO₅₀ and CaNO have more obvious improvement in lung function after systemic glucocorticoid treatment, while patients with elevated CANO have more obvious improvement in symptoms after treatment. However, the sample size needs to be expanded for further verification.