Abstract: Objective To explore the clinical effect of nebulized acetylcysteine inhalation combined with bronchoscopy in treating elderly patients with severe ventilator-associated pneumonia (VAP). Methods From January 2016 to December 2017, 80 elderly patients with severe VAP who were hospitalized in Zhejiang Hospital were divided into acetylcysteine+ bronchoscopy group [24 males and 16 females, aged (78±7) years] and bronchoscopy group [26 males and 14 females, aged (80±7) years]using random number table for a prospective cohort study. Patients in bronchoscopy group were treated with bronchoscopy in addition to conventional supportive care of symptoms. Patients in acetylcysteine+ bronchoscopy group received nebulized acetylcysteine inhalation therapy on the basis of the treatment given to patients in bronchoscopy group. Patients in both groups received treatment continuously for 7 days. The simplified clinical pulmonary infection score (CPIS) in both groups was assessed before and after treatment. Venous blood of 10 mL was collected before and after treatment to detect leukocyte count, serum C-reactive protein, and procalcitonin. Arterial blood of 1 mL was collected before and after treatment to detect partial arterial oxygen pressure (PaO₂), partial arterial carbon dioxide pressure (PaCO₂), oxygenation index. The inhalation platform pressure (Pplat), dynamic lung compliance (Cdyn), airway resistance, work of breathing, time of antibiotic use, and time of mechanical ventilation of patients in two groups were recorded before and after treatment. Data were statistically analyzed with chi-square test and t test. Results (1) The simplified CPIS, leukocyte count, serum C-reactive protein, and procalcitonin of patients in acetylcysteine+ bronchoscopy group were significantly lower than those in bronchoscopy group after treatment (t=2.32, 2.15, 6.08, 7.12, P<0.05 or P<0.01). The simplified CPIS, leukocyte count, serum C-reactive protein, and procalcitonin of patients in acetylcysteine+ bronchoscopy group and bronchoscopy group after treatment were significantly lower than those before treatment (t=13.76, 13.60, 12.70, 8.32, 11.44, 14.28, 9.48, 9.50, P<0.01). (2) Compared with bronchoscopy group, patients in acetylcysteine+ bronchoscopy group had significantly higher PaO₂ and oxygenation index (t=4.14, 2.55, P<0.05 or P<0.01) but significantly lower PaCO₂ (t=4.36, P<0.01) after treatment. The PaO₂ and oxygenation index of patients in acetylcysteine+ bronchoscopy group after treatment were significantly higher than those before treatment (t=10.90, 43.72, P<0.01). The PaO₂ and oxygenation index of patients in bronchoscopy group after treatment were also significantly higher than those before treatment (t=6.55, 43.03, P<0.01). The PaCO₂ of patients in both groups after treatment were significantly lower than those before treatment (t=21.54, 21.92, P<0.01). (3) The Cdyn of patients in acetylcysteine+ bronchoscopy group after treatment was significantly higher than that in bronchoscopy group (t=5.41, P<0.01), and Pplat, airway resistance, and work of breathing were significantly lower than those in bronchoscopy group (t=2.18, 5.46, 2.49, P<0.05 or P<0.01). The Cdyn of patients in both groups after treatment were significantly higher than those before treatment (t=16.10, 10.90, P<0.01), and Pplat, airway resistance, and work of breathing were significantly lower than those before treatment (t=21.18, 11.13, 9.32, 15.50, 5.17, 5.97, P<0.01). (4)The time of mechanical ventilation and antibiotic usage of patients in acetylcysteine+ bronchoscopy group were (6.9±1.9)and (8.7±2.8) d, respectively, which were significantly shorter than (10.1±2.2) and (11.6±3.5) d in bronchoscopy group (t=6.85, 4.09, P<0.01). Conclusions Nebulized acetylcysteine inhalation combined with bronchoscopy can significantly control the degree of lung infection in elderly patients with severe VAP, improve patients′ respiratory mechanics parameter and blood gas analysis indicator, and shorten the time for mechanical ventilation and antibiotic usage.