Introduction

According to the Global Cancer Statistics 2020, lung cancer is the second most common cancer and has the highest mortality rate among cancers.1 To date, surgical resection, particularly video-assisted thoracoscopic surgery, remains an effective and safe treatment for patients with lung cancer. However, postoperative pneumonia (POP), the most common pulmonary complication following lung cancer surgery, poses significant challenges to patient recovery.2,3 The incidence of POP in lung cancer patients ranges from 2% to 25%.4–7 Research has shown that POP can significantly extend hospital stays, increase healthcare costs, and even raise perioperative mortality rates.4,8 Therefore, identifying the risk factors associated with POP among lung cancer patients is essential for predicting its occurrence in the early stages.

Recent literature has reported that diabetes is associated with surgical complications, including POP. For instance, López-de-Andrés et al found that between 2001 and 2015, patients with type 2 diabetes (T2DM) exhibited a 21% higher incidence of POP compared to nondiabetic patients.9 In 2019, Ma et al further demonstrated that the incidence of POP in patients with T2DM was 3.2%, while only 1.7% of patients without T2DM developed POP.10 Additionally, two studies indicated that T2DM is an independent risk factor for POP in orthopedic surgery.11,12 Although these studies highlight the significant impact of diabetes on POP, it remains uncertain whether T2DM increases the risk of POP in patients undergoing video-assisted thoracoscopic surgery (VATS).

Thus, this study was to investigate the association between T2DM and POP after VATS, and further explore the risk factors involved in POP in patients without T2DM.

MethodsSubjects

We performed this retrospective cohort study and obtained the ethic approval from Clinical Research Ethics Committee of the Second Hospital of Fujian Medical University (No. 2023496) on 28 July 2023. All patients undergoing VATS were from the Second Hospital of Fujian Medical University between January 2019 and December 2023. The inclusion criteria were listed as follows: 1) patients undergoing VATS due to the pathology diagnosis of lung cancer, 2) over 18 years old. The exclusion criteria: 1) patients diagnosed with pneumonia before surgery, 2) patients were diagnosed with other types of diabetes instead of T2DM, 3) pregnancy, 4) patients who underwent bilateral pulmonary resection, 5) patients who admitted to ICU after surgery and 6) patients with missing data.

Classification of Pneumonia and Diabetic Type

Pneumonia and diabetic types were determined via the codes of International Classification of Diseases-10 (ICD-10) classifications for hospital admissions. In order to distinguish POP from preoperative pneumonia, we recorded the diagnosis time of pneumonia. The preoperative pneumonia is that patients is diagnosed with pneumonia at the time of hospital admission or before surgery. In addition, the codes of T2DM were included in the study. The codes of other types of diabetes were excluded.

Data Collection

All data were extracted and obtained from our Hospital Information System. The following sociodemographic variables were collected: age, sex, height, weight, hospital length of stay (LOS), ASA and hospital cost. Collected clinical data included: preoperative blood glucose level of patients with T2DM, comorbidity, tumor characteristics, chemoradiotherapy, and perioperative transfusion.

Statistical Analyses

All analyses were performed using the R software version 4.3.1. Numerical variables were expressed as mean ± standard deviation (SD). Comparisons were performed between groups using Student’t test and Analysis of Variance (ANOVA). Categorical data were compared via chi-square test. The multivariate logistic regression analysis was performed to analyze characteristic variables to obtain the independent risk factors involved in POP. P<0.05 was considered statistically significant.

Results

We initially screened 518 patients who underwent VATS from January 2019 and December 2023. After data collection, 42 patients were removed from the final analysis: 25 patients were diagnosed with preoperative pneumonia via CT; 11 patients required bilateral pulmonary resection; 4 patients admitted to ICU after surgery; 2 patients had missing data. Finally, a total of 476 patients were included into the current study. Among these patients, 73 patients (15.3%) had POP (Table 1). We next explored the risk factors of POP via logistic analysis. In the unadjusted logistic analysis, sex (crude odds ratio [OR] = 0.27, 95% confidence interval [CI] = 0.15–0.46, P<0.001), age (crude odds ratio [OR] =  1.03, 95% confidence interval [CI] =  1–1.05, P=0.04), hospital stays (crude odds ratio [OR] =  1.04, 95% confidence interval [CI] =  1–1.07, P=0.04), diabetes (crude odds ratio [OR] =  2.55, 95% confidence interval [CI] =  1.54–4.26, P<0.001), ASA (crude odds ratio [OR] =  2.41, 95% confidence interval [CI] =  1.00–5.46, P=0.041), and location (crude odds ratio [OR] =  0.75, 95% confidence interval [CI] =  0.61–0.9, P=0.003) were associated with the risk of POP during VATS (Table 2). In the multiple logistic analysis, diabetes was independently associated with the risk of POP (adjusted OR = 2.07, 95% CI = 1.13–3.86, P=0.019), after adjusting for sex, age, hospital stay, ASA, and tumor location (Figure 1). In addition, correlation analysis was conducted between diabetes and the risk of POP. The results demonstrated a positive correlation between them, implying that diabetes may play a role in promoting the occurrence of POP during VATS (cor=0.17, P<0.001; Figure 2).

Table 1 Clinical Characteristics of Included 476 Patients

Table 2 Univariate Analysis Results Related to Postoperative Pneumonia

Figure 1 Multiple logistic regression models based on 476 patients underwent video-assisted thoracoscopic surgery.

Figure 2 Correlation between diabetes and postoperative pneumonia. ***P<0.001.

We further investigated the risk factors associated with POP in patients with T2DM. In this study, 182 patients were diagnosed with T2DM. The incidence of POP was demonstrated more higher among male patients than female in T2DM populations (76.19% and 23.81%, p=0.006) (Table 3). The positive rate of P63 in patients with T2DM with POP was 9.52%, which was higher than that of patients with T2DM without POP (P<0.001) (Table 3). Additionally, 34.29% of patients with T2DM without POP received chemoradiotherapy, surpass the patients with T2DM with POP (30.95%, P=0.027) (Table 3). Importantly, we evaluated the effect of preoperative blood glucose control on the occurrence of POP in patients with T2DM. We divided patients with T2DM into low-glucose group and high-glucose group according to the median preoperative blood glucose level. We found that POP was demonstrated more frequently among patients in high-glucose group than patients in low-glucose group (25.3% and 13.2%, p=0.039). Subsequently, we screened the independent risk indicators for predicating the probability of POP in patients with T2DM by using logistic analysis. The results demonstrated that sex, P63 and tumor location were involved in the occurrence of POP for patients with T2DM (Table 4). Importantly, sex and tumor location were independent predicators, after adjusting confounding variables (Figure 3).

Table 3 Clinical Characteristics of Included 182 Diabetes Patients

Table 4 Univariate Analysis Results Related to Postoperative Pneumonia in 182 Diabetes Patients

Figure 3 Multiple logistic regression models based on 182 type 2 diabetes patients underwent video-assisted thoracoscopic surgery.

Discussion

In this study, we found a higher prevalence of hospitalization due to POP in patients with T2DM undergoing VATS compared to patients without this comorbidity. Additionally, we demonstrated that a higher incidence rate of POP in patients with T2DM was observed among male patients, those with positive P53, and those who had not received chemoradiotherapy. Importantly, effective preoperative blood glucose control can significantly reduce the incidence rate of POP in patients with T2DM.

Numerous studies have reported an association between T2DM and the risk of POP. In an observational analysis involving patients who underwent total joint arthroplasty (including total hip arthroplasty and total knee arthroplasty), diabetes mellitus was identified as an independent risk factor for POP.13 Additionally, a previous study using data from the American College of Surgeons National Surgical Quality Improvement Program found a greater risk of POP in patients with diabetes undergoing lumbar fusion surgeries compared to those without this condition.12 One underlying explanation is that diabetes-induced immunosuppression may increase susceptibility to POP.14 Following coronary artery bypass grafting, diabetes is associated with a 1.26-fold increased risk of POP.15 In a retrospective study of 555 patients who underwent elective hepatectomy, Pessaux et al identified several independent risk factors for POP, including diabetes.16 Importantly, they also provided potential explanations for the mechanisms that may promote the occurrence of POP, primarily due to significant changes in immune cell function, vascular permeability, and bacterial proliferation. In 2019, a study utilized the Spanish National Hospital Discharge Database to analyze the temporal trends, demographic and clinical characteristics, and hospital mortality rates of POP among patients with T2DM in Spain from 2001 to 2015. The study found that T2DM is significantly associated with an increased risk of POP, but it did not influence in-hospital mortality.9 Subsequently, the researchers proposed several possible explanations for this association between T2DM and POP, including the rising complexity and rates of surgeries, as well as increases in mean age and the prevalence of concomitant conditions. In contrast, a Chinese retrospective study involving 43,174 inpatients who underwent surgery found that patients with T2DM are more susceptible to POP, and that the mortality rate significantly increases when patients with T2DM are concurrently diagnosed with POP.10

In our study, we observed a significant increase in the incidence of POP in patients with T2DM undergoing VATS after adjusting for potential confounding factors. Subsequently, we explored the underlying risk factors for POP in T2DM patients using logistic analysis and identified two independent risk factors: sex and tumor location. In a retrospective cohort study involving 1208 patients aged ≥ 65 years who underwent hip fracture surgery from 2005 to 2021, male sex (OR, 3.01; P = 0.017) was identified as a significant risk factor for postoperative aspiration pneumonia.17 A previous study analyzing 1495 geriatric patients (>65 years) who underwent intertrochanteric fracture surgery from a prospective hip fracture database found that male sex (OR = 2.13; P = 0.017) was an independent risk factor for the incidence of POP.18 Similarly, we observed a higher incidence of POP in male patients with T2DM compared to female patients (76.19% vs 23.81%). This phenomenon may be attributed to the fact that, when compared to women, a greater proportion of men are smokers, which adversely affects their respiratory health. Additionally, tumor location was also found to be correlated with POP, a relationship that has not been previously reported.

Our study has several limitations. First, it was a single-center, retrospective analysis. Multicenter studies should be conducted to further investigate the incidence of and risk factors for POP within 30 days or even 1 year following VATS to validate our findings. Second, some factors or diseases, such as Parkinson’s disease and dementia, which could contribute to an increased incidence of POP, were not included in our study. Third, the severity scores of pneumonia were not assessed in our analysis.

In summary, patients with T2DM who underwent VATS exhibit a higher incidence of POP compared to those without this condition. Additionally, male gender and tumor location are independent risk factors for POP in patients with T2DM. Therefore, perioperative management should be improved and optimized for male patients with T2DM to enhance patient safety.

Data Confidentiality Statement

All of data involve in patients’ privacy and thus the authors do not have permission to share data.

Ethical Approval

This study complied with the Declaration of Helsinki and was approved by Ethics Committee of the Second Affiliated Hospital of Fujian Medical University (approval number: 2023496). Informed consent was waived by the ethics committee of the Second Affiliated Hospital of Fujian Medical University.

Acknowledgments

Xue-E Su and Yu-Shen Yang share first authorship.

Funding

This work was supported by grants from the Natural Science Foundation of Fujian Province (2020J01227), Medical Innovation Science and Technology Project of Fujian Province (2020CXA047), Joint funds for the innovation of science and technology, Fujian province(2023Y9244), and the Fujian Provincial Clinical Key Specialty Construction Project (No. HLZDZK202307).

Disclosure

No potential conflict of interest was reported by the author(s).

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