Identifying risk factors and pathogens in postoperative pneumonia after lung surgery for cancer: a retrospective cohort study

Introduction

Postoperative pneumonia (PoP) is a significant challenge in thoracic surgery, with reported incidence rates ranging from 1.5% to 12% following lung resections (1-4). This variability in reported rates highlights the complex nature of this complication influenced by patient-specific and surgical factors.

Moreover, PoP has been associated with serious complications such as bronchopleural fistula which can further exacerbate the patient’s clinical course. Respiratory failure, dysphagia, and pulmonary aspiration are also well-documented postoperative complications that can lead to life-threatening consequences if not promptly recognized and managed (1-4).

By understanding the risk factors and employing effective prevention strategies, healthcare providers can work to reduce the burden of PoP and improve patient outcomes following lung resections.

The objectives of this study were to determine the frequency of PoP following surgery for lung cancer, to compare postoperative results between patients who develop PoP and those who do not, and to pinpoint dependable risk factors for PoP in patients after lung cancer surgery. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-169/rc) (5).

Methods

Patient selection

Adult patients (≥18 years of age) admitted to the Thoracic Surgery Unit of IRCCS Humanitas Research Hospital (Rozzano, Milan, Italy) affected by primary lung neoplasia and admitted for lung cancer surgery (i.e., segmentectomy, lobectomy, bilobectomy, or pneumonectomy) between 2017 and 2019 were eligible for inclusion. Exclusion criteria comprised lung atypical resections (e.g., wedge resections), human immunodeficiency virus (HIV) infection, a history of hematologic malignancy, and autoimmune diseases, due to their potential impact on immune function and infection risk. Wedge resections were excluded to ensure a homogeneous surgical cohort, as they are typically performed in patients with different clinical profiles and carry a lower risk of postoperative complications compared to anatomical resections.

All patients underwent a standardized preoperative assessment, including pulmonary function tests [forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lungs for carbon monoxide (DLCO)], arterial blood gas analysis, cardiac evaluation [electrocardiogram (ECG) and echocardiography when indicated], routine laboratory testing, and imaging studies such as contrast-enhanced computed tomography (CT) and positron emission tomography (PET)-CT scans. Performance status was evaluated using both the Eastern Cooperative Oncology Group (ECOG) and American Society of Anesthesiologists (ASA) scoring systems.

A chest X-ray was performed on all patients on the first postoperative day to assess for immediate complications, such as pneumothorax, atelectasis, or pulmonary infiltrates. Additional chest X-rays were ordered if the patient exhibited signs or symptoms of respiratory distress or if there was clinical suspicion of complications like pneumonia. Routine blood tests were performed on the first postoperative day, including a complete blood count (CBC) and C-reactive protein (CRP) levels, to monitor for signs of infection or inflammation. If the patient showed symptoms indicative of infection, further tests were conducted, such as blood cultures, procalcitonin (PCT), and tests to assess liver and renal function.

All data were extracted from our hospital’s database. Basic demographic information including age, sex, comorbidities, smoking status, preoperative measurement of lung function (FEV1 and DLCO), surgical approach [open thoracotomy, video-assisted thoracoscopic surgery (VATS) or RATS], type of surgery (segmentectomy, lobectomy, bilobectomy, or pneumonectomy), histological findings [adenocarcinoma (ADC), squamous cell carcinoma (SCC), other types], tumor stage, and neoadjuvant chemotherapy (nCT) were retrospectively reviewed from the records. Postoperative outcomes included chest drainage duration, length of postoperative hospital stay, complications, and 30-day mortality.

Laboratory examinations were recorded, including serum PCT, CRP, and blood neutrophil count. PCT values above 0.5 ng/mL and CRP values above 10 mg/L were defined as positive values in the patients. Patients suspected of PoP underwent bronchoscopy with bronchoalveolar lavage (BAL) as part of the routine diagnostic work-up.

BAL was performed following standard institutional protocols. BAL was carried out using a flexible bronchoscope under local anesthesia and mild sedation. The procedure involved instillation of 100–150 mL of sterile saline (divided into aliquots of 20–30 mL) into the segmental bronchus of the most radiologically affected area, followed by gentle aspiration. The retrieved fluid was sent for microbiological analysis, including Gram stain and culture.

Outcome

The primary endpoint was the occurrence of PoP between 72 h after admission and postoperative day 7. Secondary endpoints encompassed perioperative mortality, defined as any death occurring within 30 days of the surgical procedure as well as the analysis of risk factors for PoP.

Definition of postoperative pneumonia

The diagnostic criteria for PoP at IRCCS Humanitas Research Hospital (Rozzano, Milan, Italy) aligned with the variable definitions of the European Society of Thoracic Surgery and the Society of Thoracic Surgeons (6). To receive a PoP diagnosis, patients had to meet at least one chest radiological pattern (such as new pulmonary infiltrates, consolidation, or opacity), combined with at least one inflammatory markers (such as fever >38 ℃ or abnormal leukocyte count <4×10⁹/L or ≥12×10⁹/L), or at least two respiratory symptoms among sputum production, new onset, or aggravated cough, dyspnea.

Statistical analysis

Shapiro-Wilk test and Skewness and Kurtosis test were used to assess whether variables were normally distributed. Normally distributed continuous variables were described as mean ± standard deviation (SD) and compared by the two-tailed Student’s t-test. Non-normally distributed data were presented as median (interquartile range) and compared by the Mann-Whitney U-test. Categorical variables are reported as counts and percentages and analyzed using either Pearson’s chi-squared test or Fisher’s exact test, as appropriate.

Logistic regression with a backward method was employed to identify independent predictors of PoP. Variables with P<0.1 in univariate analysis were included in a backward stepwise multivariate logistic regression model. Model calibration was evaluated using the Hosmer-Lemeshow test, with a non-significant result considered indicative of good fit. A P value <0.05 was considered statistically significant. Analyses were performed using Stata 18.0 (Stata Corp., College Station, TX, USA).

The study was approved by the institutional ethics committee CET Lombardia 5 (No. 41/25) of IRCCS Humanitas. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. All patients signed an informed consent upon hospital admission that permits the use of anonymized clinical data for retrospective research purposes.

Results

Study population

A total of 737 patients [male: 60.7%, mean (SD) age: 67.8 (9.4) years] were enrolled, see Table 1. The most common comorbidity was hypertension (32.3%); the preoperative lung function showed a mean DLCO% of 76.4%±19.2% and mean FEV1%_predicted of 88.7%±20.2%. Lobectomy was performed in 78.6% of cases, with open thoracotomy being the preferred approach in 57.9% of cases. Most cases were adenocarcinoma (71.2%), followed by squamous cell carcinoma (18.6%) with predominantly early stages (I–II; 72.7%) over the advanced (III–IVA; 27.3%). Only patients with stage IV disease limited to a solitary metastasis (e.g., brain, adrenal) underwent surgery, following multidisciplinary discussion (MDT) discussion and with curative intent.

The mean in-hospital stay was 7.9±6.8 days, and the mean chest tube duration was 5.9±4.6 days. Postoperative complications included persistent air leaks (10.0%), perioperative anemia (5.9%), atrial fibrillation (8.0%) and bronchial stump insufficiency (0.9%), see Table 2.

In total, 79 (10.7%) patients developed PoP, see Table 1. According to Clavien-Dindo classification, most cases were classified as Grade II (antibiotic therapy required), while 14 patients (23%) required intensive care unit (ICU) management, qualifying as Grade IV.

Risk factors for PoP

Patient-specific risk factors

The univariate analysis proved smoking habit, low DLCO and FEV1%, chronic obstructive pulmonary disease (COPD), asthma, diabetes, high ASA score, neoadjuvant chemotherapy, advanced (III–IV) cancer stage, and histology of squamous cell carcinoma to be predictors of PoP (Table 3). At the multivariate analysis, only COPD and asthma, higher ASA scores, and advanced-stage cancer were independent risk factors for PoP (Table 4).

Surgical risk factors

The univariate analysis proved longer operative time, open thoracotomy approach (vs. mini-invasive), and the positioning of two chest tubes (vs. one) at the end of the surgical procedure to be predictors of postoperative pneumonitis (Table 3). At the multivariate analysis, only the open thoracotomy approach and the conversion from VATS or RATS to the open thoracotomy were independent risk factors for PoP (Table 4). Moreover, although not significant, when analyzing the type of pulmonary resections, bilobectomy was the one more correlated with the occurrence of PoP (21.0%) when compared with lobectomy (10.2%), segmentectomy (7.8%) and pneumonectomy (14.5%). The final model showed adequate calibration with the Hosmer-Lemeshow test (P=0.76).

Postoperative outcomes

When considering the postoperative outcomes, patients who developed PoP had significantly higher rates of respiratory failure requiring either ICU stay and intubation/tracheostomy, reintervention, longer in-hospital stay, and longer chest tube duration (Table 2). Additionally, 6 (7.6%) patients with PoP required rehospitalization within 30 days after discharge. There was no in-hospital mortality in the PoP cohort.

Pneumonia management and outcomes

Out of the total 79 patients affected by PoP, 69 (87.3%) underwent a bronchoscopy to perform a BAL (Table 4). In 29 (36.7%) cases, BAL did not show the presence of any pathogen. Among the remaining 40 patients, the most frequently encountered pathogens were Escherichia coli (E. coli) (11.4%) and Pseudomonas aeruginosa (8.9%), see Table 5. Patients who developed PoP had a mean CRP v-max of 22.1±7.8 mg/L and a mean PCT v-max of 1.4±1.3 ng/mL (Table 6). All 79 patients initially received empiric antibiotic therapy with levofloxacin, either alone or in combination with piperacillin/tazobactam. In cases where BAL showed the presence of a pathogen, antibiotic therapy was changed in 14 (17.7%) patients based on the results of the antibiogram. Following appropriate antibiotic therapy (according to culture and antibiogram), 45 (57.0%) patients experienced complete resolution, 23 (29.1%) partial resolution, 12 (15.2%) required re-hospitalization, and 1 (1.3%) patient died due to PoP. A detailed analysis on the outcomes of pneumonitis caused by specific pathogens has been added as Table S1. The mean length of stay (LOS) ranged from 9.0 days for methicillin-susceptible Staphylococcus aureus (MSSA) to 25.0 days for mixed infections with Gram-negative, Gram-positive, Streptococcus pneumoniae, and Candida albicans. The 30-day readmission rate varied from 0.0% for several pathogens, including E. coli, Corynebacterium spp, and Pseudomonas aeruginosa, to a maximum of 50.0% in cases with MSSA. Outcome distribution also varied by pathogen. Complete resolution was observed in 100.0% of cases with Corynebacterium spp, Staphylococcus aureus, and MSSA. Partial resolution was most frequent in MRSA (100.0%) and Serratia (66.7%). Cases of recurrence or infection aggravation were reported in infections involving E. coli, Pseudomonas aeruginosa, Gram-negative bacteria, and mixed infections. Mortality (20.0%) was reported only in patients with Candida albicans. No statistically significant differences were found in LOS (P=0.39) or 30-day readmission rates (P=0.46) across pathogens.

Discussion

PoP is a significant challenge in thoracic surgery, with reported incidence rates ranging from 1.5% to 10% following lung resections (1-4). This variability in reported rates highlights the complex nature of this complication, influenced by patient-specific and surgical factors.

The underlying lung pathology of the patient and their comorbidities are primary contributing factors to PoP. Patients with COPD are particularly vulnerable to postoperative pulmonary complications. A retrospective study conducted by Licker et al. (7) analyzed the impact of COPD, considering data from 1,222 patients over 15 years. The incidence of respiratory complications was closely related to lung function measured preoperatively. An adverse respiratory event occurred in 10% of patients with normal pulmonary function, 25% of patients with moderate COPD, and 27% of patients with severe COPD (P<0.001). An FEV1 cutoff value of 60% of the predicted value was used.

Smoking is a well-established risk factor for PoP (8-11). Mason et al. (10) reported that pulmonary complications were significantly more frequent in current or former smokers compared to never-smokers. The risk decreases with longer abstinence, becoming comparable to never-smokers after more than 8 weeks (8). Smoking promotes a pro-inflammatory pulmonary environment, increasing susceptibility to infections. Similarly, type 2 diabetes mellitus (T2DM) has been associated with a higher incidence of PoP and in-hospital mortality, as shown in a large study by Ma et al. (12), which suggested that chronic dysmetabolism and immune dysfunction in T2DM may underlie this association (13).

Asthma also emerged as an independent risk factor for PoP in our cohort. Although less frequently discussed in the literature compared to COPD, asthma may contribute to postoperative respiratory complications through mechanisms such as bronchial hyperreactivity, chronic airway inflammation, and impaired mucociliary clearance. These factors may increase susceptibility to infection and compromise pulmonary recovery after lung resection (14). Moreover, a high ASA physical status score was strongly associated with the occurrence of PoP. The ASA score reflects the overall burden of systemic disease and functional reserve, both of which are critical determinants of postoperative resilience. Patients with ASA III–IV typically present with multiple comorbidities and reduced physiologic reserve, placing them at greater risk for pulmonary complications and prolonged recovery (14,15). These findings underscore the value of ASA classification as a simple, yet effective, tool in preoperative risk stratification.

In our study, surgical factors, such as the extent of the resection and the surgical approach, also proved to matter. Bilobectomy is associated with increased mortality and short-term morbidity compared to lobectomy; the overall morbidity for bilobectomy is estimated at 50%, with inferior bilobectomy related to a higher rate of complications than superior bilobectomy (16,17). This difference is commonly associated with the significant discrepancy created between the volume of the pleural cavity and the residual pulmonary lobe immediately after surgery, leading to more pulmonary and pleural complications. Also in this study, although the multivariate analysis did not show a significant correlation between bilobectomy/pneumonectomy vs. lobectomy/segmentectomy, the incidence of pneumonia in the first category was higher. It has been proven that as the cancer stage advances, the risk of PoP complications increases. A study of 2,105 patients who underwent lung resection for cancer by Shiono et al. (18) found that the adjusted odds ratio (OR) for PoP was 2.23 [95% confidence interval (CI): 1.27–3.92] for cancer stages ≥ III compared to stages I/II. Similarly, Busch et al. (19) demonstrated that extended lung resections were linked to pulmonary complications, with a significant increase in major pulmonary complications in patients who had undergone induction chemotherapy. The incidence of pneumonia after induction therapy was found to be 13%, consistent with the results of Martin et al. (20). Furthermore, a recent retrospective analysis of 52,982 anatomic lung resections in the European Society of Thoracic Surgeons (ESTS) database by Brunelli et al. (21) revealed that neoadjuvant treatment remained significantly associated with cardiopulmonary complications (P<0.0001), with a higher incidence of PoP (6.5% vs. 8.3%, P=0.004) after matching patients who underwent lobectomy for lung cancer.

Our multivariate analysis has demonstrated the significant impact of the surgical approach on the eventual development of postoperative pulmonary complications. This association has been consistently supported by previous studies (20-26). Notably, a recent meta-analysis by Francis et al. (22) comparing the outcomes of open thoracotomy, VATS, and RATS for segmentectomy revealed that VATS is associated with a substantial >0.5-fold reduction in the risk of postoperative pneumonia compared to open thoracotomy (OR =0.42; 95% CI: 0.26–0.68). Furthermore, Cao et al. (23) found in their meta-analysis that VATS lobectomies were linked to significantly fewer complications, including prolonged air leak, pneumonia, and atrial arrhythmias, compared to open thoracotomy, as well as a shorter duration of hospitalization. The mininvasive approach causes minimal trauma to the chest wall leading to less pain and preserved muscle function compared to traditional open surgery, resulting in better breathing and coughing. Additionally, it is believed that reducing the overall inflammatory response would help maintain immune function, potentially providing better protection against infections compared to open surgery. Despite the advantages of mininvasive lung resections, PoP remains a significant issue. A survey conducted at Beijing General Hospital, involving more than 1,500 patients who underwent VATS resections for lung cancer, found an overall PoP incidence of 9.15% (24). Among factors linked to the procedure, a longer surgery duration and the intraoperative use of colloids were strongly associated with an increased risk of PoP. Huang et al. also reported a notable readmission rate of 19.8% for PoP following VATS lobectomy, even within the context of an enhanced recovery after surgery (ERAS) program (23-26). In our cohort, we analyzed the impact of specific pathogens identified via BAL on clinical outcomes. Although patients infected with Candida albicans or mixed flora (e.g., Streptococcus pneumoniae + Candida) tended to experience prolonged hospital stays and higher rates of ICU admission, these differences were not statistically significant when compared across pathogen types. Patients with E. coli had comparatively better outcomes. However, due to the small number of patients in each subgroup, our findings should be interpreted with caution and warrant confirmation in larger studies.

Conversion from minimally invasive approaches (VATS or RATS) to thoracotomy was observed in 54 patients (7.3%) in our cohort. Among them, the incidence of postoperative pneumonia was 14.8% This finding aligns with previous reports highlighting conversion as a marker of surgical complexity and increased postoperative morbidity (27). Potential reasons include longer operative time, increased manipulation of lung parenchyma, blood loss, and the stress of unplanned procedural shift, all of which may contribute to impaired pulmonary function and infection risk.

To reduce the risk of PoP, a comprehensive strategy is crucial. This includes the use of corticosteroids, antibiotics, and regional anesthesia techniques, as well as adopting noninvasive ventilation methods in the perioperative care of patients undergoing lung resections. Additionally, selecting the most appropriate surgical approach and determining the extent of resection for each patient—while considering any comorbidities that may increase the risk of PoP—is critical for the surgeon’s decision-making process.

By identifying risk factors and applying effective prevention measures, healthcare providers can help lower the incidence of PoP, improve patient outcomes after lung resections, and significantly reduce the duration of chest tube placement, hospital stay, and the need for reintervention. These efforts also lead to substantial cost savings for the healthcare system. Remarkably, our cohort experienced no in-hospital mortality among patients with PoP. This outcome contrasts with previous studies reporting mortality rates ranging from 4.6% to 8.6%, especially in patients with type 2 diabetes or after complex surgeries and neoadjuvant treatments (12,18,19). We believe this result reflects the effectiveness of our structured management pathways, including early diagnosis through routine BAL, prompt antibiotic tailoring, and standardized perioperative care. Despite including high-risk patients, such as those with COPD, advanced-stage cancer, or undergoing thoracotomy, these coordinated efforts may have prevented the progression of PoP to fatal outcomes. One important factor to think about is the choice to exclude patients with autoimmune diseases from our study group. This decision was based on the potential impact of immune dysregulation and the common use of immunosuppressive treatments in these patients could raise the risk of postoperative infections, like pneumonia. While excluding these patients helped maintain a more homogeneous study population, it also limits the generalizability of our findings to this subgroup. Future studies specifically addressing postoperative outcomes in patients with autoimmune disease would be valuable to guide more tailored perioperative strategies.

This study has several limitations. First, its retrospective design introduces potential biases, such as selection bias and unmeasured confounders. While the large cohort and single-center setting provide valuable insights, the findings may not be fully generalizable to other populations or healthcare systems.

Second, the reliance on standard diagnostic criteria for PoP may have led to some misclassification, particularly for mild or atypical cases. Additionally, certain factors such as nutritional status, and preexisting infections were not assessed, potentially limiting our understanding of PoP risk.

An additional limitation of our study is the absence of a structured prehabilitation program for patients undergoing lung resection. Several studies have demonstrated that preoperative rehabilitation can enhance exercise capacity and pulmonary function, thereby decreasing the incidence of postoperative pulmonary complications (28). For instance, a meta-analysis by Li et al. reported that patients who underwent preoperative rehabilitation had a reduced incidence of postoperative pulmonary complications (OR =0.44; 95% CI: 0.27–0.71), along with a shorter hospital stay and improved exercise capacity.

Future multicenter prospective studies with broader criteria and long-term follow-up are needed to validate these findings and explore the prolonged effects of PoP.

Conclusions

Pneumonia following major lung resection for non-small cell lung cancer (NSCLC) occurs with a notable frequency, often resulting in complicated management and extended hospital stays. Several preoperative and postoperative factors have been identified as significant risk contributors. To reduce the risk of this complication and enhance patient outcomes, attention should be directed toward modifiable factors that can be adjusted or controlled.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-169/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-169/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-169/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-169/coif). E.B. has received honoraria from AB Medica SpA. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by the institutional ethics committee CET Lombardia 5 (No. 41/25) of IRCCS Humanitas. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. All patients signed an informed consent upon hospital admission that permits the use of anonymized clinical data for retrospective research purposes.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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