Risk factors for cough after pulmonary resection in patients with non-small cell lung cancer: a systematic review and meta-analysis

Introduction

Background

Lung cancer remains the leading cause of cancer-related mortality worldwide, with a persistently poor prognosis despite advances in therapeutic modalities (1,2). Surgical resection is the cornerstone of curative treatment for early-stage non-small cell lung cancer (NSCLC) and selected benign lung tumors (3). However, postoperative complications can arise even after successful surgery, significantly affecting patients’ recovery and long-term outcomes (4). One such complication, postoperative cough after pulmonary resection (CAP), is particularly concerning. It affects approximately 25% of long-term survivors who undergo pulmonary resection for NSCLC, contributing to a substantial decline in quality of life (5-7). The incidence of CAP has been reported in over 50% of patients within the first year post-surgery, and around 18% continue to suffer from persistent cough five years after surgery (8).

Rationale and knowledge gap

CAP is characterized by a dry cough lasting no less than two weeks after pulmonary resection, excluding conditions such as nasal drip syndrome, bronchial asthma, or the use of angiotensin-converting enzyme inhibitors (ACEIs). Imaging, such as chest X-ray, typically reveals no apparent abnormalities (6). This chronic cough can extend well beyond the normal recovery period, leading to a wide range of physical and psychological consequences. Patients with severe CAP may experience vomiting, chest pain, rib fractures, and a notable decrease in their overall quality of life (9,10). Despite its frequency and impact, CAP is often under-recognized and inadequately treated, underscoring the need for a clearer understanding of its risk factors to develop more effective preventive strategies. With advances in early detection of lung cancer, the number of lung resections continues to rise, making the issue of postoperative cough increasingly important in thoracic surgery and postoperative care (11). Although enhanced recovery after surgery (ERAS) protocols have been widely adopted to mitigate complications such as chronic postoperative cough and improve overall patient outcomes (12,13), existing research often focuses on isolated variables, lacks comprehensive analysis, or fails to account for interactions between multiple factors. No prior systematic review and meta-analysis have synthesized these findings to provide a holistic understanding of the risk factors associated with CAP.

Objective

Therefore, this study aims to systematically review and conduct a meta-analysis to identify the risk factors contributing to CAP following lung resection. By synthesizing the available evidence, evaluating the relative impact of surgical and perioperative factors, this research seeks to provide clinicians with evidence-based medicine evidence on the etiology and predictors of CAP, which will inform future practice and help optimize postoperative care protocols, particularly within the ERAS framework, to further enhance recovery and quality of life for patients after lung resection. We present this article in accordance with the PRISMA and MOOSE reporting checklists (14,15) (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2222/rc).

Methods

The protocol for this study was pre-registered on the INPLASY platform (registration number: INPLASY2024100081) and can be accessed online at https://inplasy.com (10.37766/inplasy2024.10.0081).

Databases and search strategy

A comprehensive literature search was conducted using three major databases: PubMed, Embase, and the Cochrane Library, covering publications up to October 1, 2024. The search strategy included Medical Subject Headings (MeSH) such as “Lung Neoplasms”, “Cough”, and “Thoracic Surgical Procedures”, along with relevant free text terms. These terms were strategically combined using Boolean operators (“AND” and “OR”) to maximize the search scope. Detailed search strategies for each database are provided in Table S1. All identified articles were independently reviewed by two authors (Z.L. and R.L.), who cross-checked the results. Then, Z.Z., Y.W., S.Z., H.L. et al. worked independently and extracted the target data from the screened studies. Additionally, the reference lists of the excluded studies were manually screened to identify any additional relevant, non-duplicate studies. Discrepancies between the reviewers were resolved through discussion.

Study selection and criteria

The criteria for selecting studies encompassed the following: (I) research involving adult individuals who had undergone either selective thoracoscopic or open pulmonary resections (which include wedge resection, segmentectomy, and lobectomy); (II) studies that included subgroups with CAP and no cough after pulmonary resection (NCAP); (III) studies reporting at least one relevant outcome of interest (detailed below); and (IV) studies written in English.

Exclusion criteria were as follows: (I) ineligible article types such as case reports, reviews, conference abstracts, and non-comparative studies; (II) studies that did not report outcomes of interest; (III) studies involving non-human participants; and (IV) studies written in languages other than English.

Data collection

Two independent reviewers (Z.L. and R.L.) screened eligible studies and extracted relevant data using predefined forms. Any discrepancies were resolved through discussion to reach a consensus. The following data were extracted from each study: (I) publication details: authors, publication year, and country; (II) experimental details: study design, period, and research methods; (III) demographic details: sample size, age, and gender; and (IV) outcome details: duration of anesthesia, duration of surgery, type of surgical procedure, surgical site, extent of resection, and detailed postoperative complications. The authors were not contacted for unpublished data.

Quality assessment

The quality of the cohort studies was evaluated using the Newcastle-Ottawa Scale (NOS) (16), with studies scoring 6 or higher being deemed suitable for inclusion in the meta-analysis. For randomized controlled trials (RCTs), the Cochrane risk of bias tool was employed (17). Given the nature of postoperative complications like coughing, blinding patients and staff is often impractical. However, studies that did not report blinding were considered to have a high risk of performance bias. Quality assessments were conducted independently by two investigators (ZL and RL), with any disagreements resolved through consensus.

Statistical analysis

Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes to assess the effects of postoperative complications. For continuous data, mean differences (MDs) with 95% CI were used to summarize the results. The results were presented by forest plot. For individual studies, medians and quartiles were used to characterize data on continuous variables. We transformed medians and quartiles into means and standard deviations and then analyzed them according to the data transformation tools of Luo et al., Shi et al., and Wan et al. (18-21). Heterogeneity among studies was evaluated using the Cochrane’s Q test and I² statistic, with I²>50% indicating substantial heterogeneity (22). A two-sided P<0.05 was considered statistically significant. To account for potential bias, random-effects models were applied to calculate pooled effect sizes. Sensitivity analyses were conducted to assess the stability of the results by sequentially omitting individual studies to evaluate their impact on the pooled estimates. And publication bias was visualized using funnel plots and combined with Egger’s test to detect the significance of the bias, if P<0.05 of Egger’s test, it indicated the existence of significant publication bias. All statistical analyses were performed using Review Manager (RevMan version 5.3; The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) and Stata software (version 15.0; StataCorp LLC, College Station, TX, USA).

Results

Literature search

A flowchart outlining the search process is presented in Figure 1. A total of 4,526 potential articles were identified, including 905 from PubMed, 3,301 from Embase, and 320 from the Cochrane Library. Furthermore, conducting manual reviews of the reference lists uncovered 8 pertinent studies. Following the elimination of duplicates and the evaluation of titles, abstracts, and complete texts, a total of 9 articles were ultimately included in our meta-analysis.

Figure 1 PRISMA flow diagram of literature retrieval. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Characteristics of the included studies

Baseline characteristics of each eligible study are summarized in Table 1, with characteristics of the patients in the Table 2 and perioperative outcomes detailed in Tables 3,4. This meta-analysis involved 6 retrospective cohort studies (RCSs), 2 prospective cohort studies (PCSs), and 1 RCT. The studies were conducted in 2 different countries between 1992 and 2022, with sample sizes ranging from 70 to 901. A total of 2,751 patients were included in the meta-analysis, of which 826 were assigned to the CAP group and 1,925 to the NCAP group. Most participants were from China (n=2,681; 97.5%), followed by 70 patients from Japan (2.5%).

Quality assessment results

The quality of the included studies was assessed using the NOS for cohort studies and the Cochrane risk of bias tool for RCT, and the assessment was presented in Table S2 and Figure S1. All cohort studies scored higher than 6 on the NOS, indicating acceptable quality, while the RCT displayed a high risk of performance and detection bias due to the nature of the interventions, though no other significant biases were detected. Publication bias is represented using a funnel plot and presented in Figures S2,S3.

This meta-analysis incorporated a total of 9 studies that evaluated various patient demographics, clinical characteristics, surgical techniques, and perioperative factors that may influence the occurrence of CAP. These analyses identified several significant risk factors for CAP, including the operative site, extent of lung resection, mediastinal lymph node dissection, the duration of surgery and anesthesia, and gastroesophageal reflux disease (GERD). We categorized the different types of risk factors into continuous variables (Table 5) and dichotomous variables (Table 6). These findings underscore the complexity of postoperative cough in patients undergoing lung resection and emphasize the importance of careful perioperative planning and management to mitigate these risks.

Risk factor analysis

Demographic characteristics

Nine studies examined the impact of gender on postoperative cough, showing no statistically significant difference between the CAP and NCAP groups (OR =1.15; 95% CI: 0.84–1.56; P=0.38), though with significant heterogeneity (I²=61%; P=0.009), as shown in Figure 2A. No publication bias was found using Egger’s test (P=0.76). Similarly, Age, a continuum variable, was assessed in 9 studies (2 of these studies were expressed as dichotomous variables and they were excluded), with no significant difference found between groups (MD =−0.67; 95% CI: −1.62 to 0.29; P=0.17), and no observed heterogeneity (I²=0%; P=0.70), as shown in Figure 2B. No publication bias was found using Egger’s test (P=0.13).

Figure 2 Meta-analysis of risk factors in the CAP and NCAP groups. (A) Gender; (B) age; (C) smoking history. CAP, cough after pulmonary resection; CI, confidence interval; IV, inverse-variance weighting; M-H, Mantel-Haenszel; NCAP, no cough after pulmonary resection; SD, standard deviation.

Preoperative smoking status

The role of smoking history was reported in 9 studies, showing no significant difference between groups (OR =1.07; 95% CI: 0.71–1.61; P=0.76), but with marked heterogeneity (I²=75%; P<0.001), as shown in Figure 2C. No publication bias was found using Egger’s test (P=0.28).

Operative site distribution

The operative site was found to significantly influence CAP, with higher incidence following right-sided lung surgery compared to left-sided surgery (OR =1.55; 95% CI: 1.14–2.12; P=0.006), and considerable heterogeneity (I²=61%; P=0.01), as shown in Figure 3A. No publication bias was found using Egger’s test (P=0.17).

Figure 3 Meta-analysis of risk factors in the CAP and NCAP groups. (A) Operative site; (B) extent of excision; (C) mediastinal LN resection. CAP, cough after pulmonary resection; CI, confidence interval; IV, inverse-variance weighting; LN, lymphatic node; M-H, Mantel-Haenszel; NCAP, no cough after pulmonary resection.

Classification of lung resection scope

The extent of lung resection also had a significant impact, with CAP incidence being higher after lobectomy compared to sublobar resection (OR =2.27; 95% CI: 1.62–3.19; P<0.001), again with significant heterogeneity (I²=61%; P=0.02), as shown in Figure 3B. No publication bias was found using Egger’s test (P=0.36).

Mediastinal lymph node dissection

Mediastinal lymph node dissection was evaluated in 5 studies, with results showing a significantly higher CAP incidence in patients who underwent the procedure (OR =3.87; 95% CI: 2.17–6.88; P<0.001), with significant heterogeneity (I²=75%; P=0.003), as shown in Figure 3C. No publication bias was found using Egger’s test (P=0.48).

Duration of surgery and anesthesia

Duration of surgery was assessed in 3 studies, revealing a statistically significant association with CAP incidence (MD =16.17; 95% CI: 3.07–29.26; P=0.02), with moderate heterogeneity (I²=52%; P=0.13), as shown in Figure 4A. No publication bias was found using Egger’s test (P=0.46). Likewise, 4 studies showed a statistically significant effect of anesthesia duration on the development of CAP (MD =19.94; 95% CI: 12.76–27.13; P<0.001), and there is no heterogeneity (I²=0%; P=0.62), as shown in Figure 4B. No publication bias was found using Egger’s test (P=0.68).

Figure 4 Meta-analysis of risk factors in the CAP and NCAP groups. (A) Duration of operation; (B) duration of anesthesia; (C) blood loss; (D) pathology (adenocarcinoma vs. squamous carcinoma). CAP, cough after pulmonary resection; CI, confidence interval; IV, inverse-variance weighting; M-H, Mantel-Haenszel; NCAP, no cough after pulmonary resection; SD, standard deviation.

Analysis of intraoperative blood loss

Intraoperative blood loss was analyzed in 3 studies, with no significant impact on CAP incidence (MD =7.81; 95% CI: −15.19 to 30.80; P=0.51), although high heterogeneity was observed (I²=81%; P=0.005), as shown in Figure 4C. No publication bias was found using Egger’s test (P=0.14).

Classification of pathological types

Pathological type was examined in 4 studies. As shown in Figure 4D, no significant difference was found in the incidence of CAP when comparing adenocarcinoma to squamous cell carcinoma (OR =1.13; 95% CI: 0.49–2.63; P=0.78). It is not surprise to see that a higher CAP incidence in malignant lesions compared to benign ones, but the results were not statistically significant (OR =2.90; 95% CI: 0.98–8.56; P=0.050) with heterogeneity (I²=84%; P=0.002), as shown in Figure 5A. Similarly, there is no significant difference in the incidence of CAP when comparing non-stage I (stage II/IIIa) to stage I malignancies (OR =1.28; 95% CI: 0.70–2.32; P=0.42; Figure 5B). Heterogeneity was present in both results. No publication bias was found using Egger’s test (P=0.69).

Figure 5 Meta-analysis of risk factors in the CAP and NCAP groups. (A) Pathology (malignant vs. benign); (B) pathological stage; (C) duration of drainage; (D) GERD. CAP, cough after pulmonary resection; CI, confidence interval; GERD, gastroesophageal reflux disease; IV, inverse-variance weighting; M-H, Mantel-Haenszel; NCAP, no cough after pulmonary resection; SD, standard deviation.

Postoperative drainage tube indwelling time

Lastly, drainage duration was evaluated in 2 studies, with no significant difference in CAP incidence based on the duration of drainage (MD =0.13; 95% CI: −0.52 to 0.77; P=0.70), though significant heterogeneity was present (I²=76%; P=0.04), as shown in Figure 5C.

Correlation analysis of GERD

GERD was evaluated in 3 studies. For the diagnosis of GERD, questionnaire was used instead of upper gastrointestinal endoscopy (Table S3). The analysis showed a statistically significant impact on CAP (OR =4.96; 95% CI: 2.05–12.02; P<0.001), though with substantial heterogeneity (I²=71%; P=0.03), as shown in Figure 5D. No publication bias was found using Egger’s test (P=0.65). In all of these studies, the investigators used questionnaires to assess the presence of GERD in their patients. Questionnaires are more convenient and feasible than using upper gastrointestinal endoscopy to diagnose GERD, although this loses some accuracy.

Sensitivity analysis

To assess the robustness and reliability of the results, sensitivity analyses were performed by sequentially removing individual studies and reanalyzing the data. This approach allowed us to evaluate the impact of each study on the overall findings and identify any outliers or studies with disproportionate influence on the pooled estimates, as shown in Figures S4,S5.

For the primary outcomes, including the associations between surgical factors (operative site, extent of resection, mediastinal lymph node dissection) and CAP, the sensitivity analyses showed consistent results, with no significant changes in the direction or magnitude of the effect sizes after removing individual studies. In contrast, some of the factors with higher heterogeneity, such as the role of GERD and the duration of surgery, showed slight variations in effect sizes when specific studies were excluded. However, these changes did not significantly alter the overall findings or the statistical significance of the associations. The sensitivity analysis thus confirmed that the results of this meta-analysis are robust and that the observed associations are unlikely to be driven by individual studies.

Furthermore, funnel plots were visually inspected to assess the presence of publication bias, as shown in Figures S2,S3. No clear asymmetry was observed, indicating that publication bias was unlikely to significantly impact the results. These findings strengthen the reliability of the conclusions drawn from this meta-analysis.

Discussion

Key findings

Cough and pain remain the most common complications after pulmonary resection (7,31), and despite the popularity of minimally invasive surgery that has greatly reduced complications (2,32), CAP is still a problem that bothers clinicians and patients, and finding the causes of CAP and effectively preventing it has become a hurdle that thoracic surgeons urgently need to overcome. Currently, there is no meta-analysis to comprehensively compare the factors influencing the occurrence of CAP; therefore, we conducted a systematic review and meta-analysis on the topic, summarizing 9 studies from previous investigators and identifying six risk factors with the aim of providing evidence-based medicine evidence to reduce the incidence of clinical CAP.

In this study, we found that the generation of CAP was mainly related to surgical factors, such as operative site (reflecting tumor location), size of surgical resection (reflecting tumor size), whether mediastinal lymph nodes were cleared or not, length of surgery or anesthesia and GERD. While these factors were significant, variables such as gender, age, smoking history, surgical blood loss, drainage duration, and pathological stage, etc. did not show a significant independent association with CAP in this analysis. These findings suggest that while certain patient characteristics may influence respiratory health, they do not independently determine postoperative cough risk.

Comparison with similar researches

This study provides a comprehensive analysis of CAP in NSCLC patients, addressing multiple risk factors such as surgery type, anesthesia duration, and GERD. Unlike previous studies that focused on isolated factors, the meta-analysis integrates these variables to offer a holistic view of their combined impact on CAP. Notably, it highlights the significant role of GERD, which has been underexplored in the context of postoperative complications. This work expands on existing literature by systematically assessing the interplay of surgical factors and GERD, providing new insights that can inform surgical planning and postoperative care.

Heterogeneity analysis

We analyzed the heterogeneity of this study for the following possible reasons: (I) study design: variations between retrospective and prospective studies can introduce biases and influence results; (II) patient population: differences in sample size and patient characteristics, such as disease stage and age, can affect outcomes; (III) postoperative management: variability in how CAP is defined, assessed, and managed across studies contributes to heterogeneity; (IV) surgical techniques: differences in lung resection types, anesthesia duration and postoperative care protocols may impact CAP development; (V) statistical methods: discrepancies in statistical approaches, such as multivariate versus univariate analysis, can lead to differing results; (VI) geographic variability: healthcare quality and practices vary across regions, influencing recovery and complication rates.

Review processes analysis

(I) Subjectivity in reviewer’s interpretation: reviewers may have different interpretations of the study’s methodology and results. (II) Quality of studies included: the included studies in the meta-analysis vary in quality. (III) Data reporting and availability: Incomplete data reporting for some studies.

Explanations of findings

Gender, age, and smoking history

Gender did not emerge as a significant risk factor for CAP, aligning with findings from studies by Xie et al. (29) and Pan et al. (24). However, this contradicts research by Lin et al. (23). In a recent review (33), there was a significant gender difference in the proportion of patients with chronic cough, and they found that female patients with NSCLC were more likely to have CAP after pulmonary resection than males, which may be related to hormonal influences and the high sensitivity of the female viscera, as well as the hypersensitivity of airway afferents to the somatosensory cortex (34-36). Narrower airways in females may also lead to greater mechanical stimulation during tracheal intubation and tracheal blockage, contributing to respiratory symptoms. Unfortunately, a study showing that long-term chronic cough is more detrimental to the health-related quality of life of female patients (37), reminds us of the need to pay attention to CAP in female patients in our clinical work and to provide timely interventions for those with severe symptoms. Moreover, age is not an independent risk factor for CAP. Interestingly, a history of smoking did not independently correlate with CAP development, probably because certain components of cigarettes inhibit the sensitivity of C-fibers associated with the cough reflex (38,39). The presence of postoperative cough symptoms in a relatively small number of nonsmoking patients was not sufficient to draw a conclusion, whereas patients with postoperative cough symptoms in combination with a history of smoking were more inclined to blame their coughing on their previous history of smoking, and therefore seldom sought specialized medical advice to address the problem, leading to some bias in postoperative follow-up.

Operative site and extent of excision

In terms of surgery, patients who underwent lobectomy were more likely to develop CAP. The incidence of postoperative cough was significantly higher after right-sided lung surgery, especially after right upper lobectomy, whereas it was similar after other lobectomies (23,24,28). This may be due to the greater extent of dissection required for lobectomy, the greater physiologic changes and stresses on the body caused by the surgery, and the greater inflammation and trauma. The relatively complex deconstructive features of the upper lobe of the right lung, such as greater volume, a more vertical right bronchus, and closer proximity to the vagus nerve, increase the likelihood of tissue irritation during surgery, leading to a higher incidence of CAP. This is supported by the studies of Lu et al. (26) and Ueda et al. (40). After upper lobectomy, the remaining lung lobes and diaphragm are displaced upward, and the remaining ipsilateral bronchioles appear distorted. These kinks lead to angulation of the bronchus, causing airway constriction or obstruction and inducing cough (26,40,41). In addition, the vagus nerve is inextricably linked to the cough reflex. C-fibers, the main subtype of the vagus nerve distributed over the bronchopulmonary, are receptors for a cough reflex, mainly in the trachea, the tracheal bulge, and the tracheobronchial bifurcation, which reflexively elicits a protective cough when stimulated (23,25,42). It has been noted that after partial or complete resection of the upper lobe of the right lung, a relatively large number of C-fibers are exposed to a sterile inflammation that allows abnormal activation of the C-fibers and thus produces an irritating cough for a certain period of time (43,44). Based on our results, the difference in CAP incidence rate by surgical site may be a difference brought about by different lung lobectomies, which needs to be further verified.

Mediastinal lymph node dissection

Mediastinal lymph node dissection involves the freeing and removal of lymphatic tissue, which is crucial for the accurate staging of lung cancer and one of the important risk factors for CAP (23,24,27,28,30). There are abundant nerves in the vicinity of the mediastinum. Among them, the pulmonary vagus nerve mainly enters the lungs along the trachea and bronchus through the mediastinum. Mediastinal lymph node dissection may damage the vagus nerve and its branches and cause CAP (23,25,42). Patients who undergo pulmonary resection without lymph node clearance have less postoperative coughing symptoms. After lymph node dissection, the C-fibers are in a state of sterile inflammation, leading to abnormal activation of cough receptors and triggering cough. This result is also supported by the study of Huang et al. (45), who concluded that the cavity left after mediastinal lymph node dissection stimulates cough receptors and successfully reduced the incidence of CAP using adipose tissue autografts to fill the residual cavity. Besides, Lin et al. (23) concluded that among all mediastinal lymph node stations, resection of subcarinal lymph nodes and lower paratracheal lymph nodes was an independent risk factor for CAP. In the literature included in this study, there are fewer studies that differentiate between different sites of mediastinal lymph node dissection and further research is needed.

Duration of operation and anesthesia

Longer surgery times imply increased manipulation of tissue, increased blood loss, and a more pronounced inflammatory response, all of which can lead to increased postoperative complications. In addition, the patient’s cardiorespiratory burden is increased during anesthesia, and changes in blood pressure and heart rate can produce indirect stimulation of the airway (46). At present, the mainstream anesthesia for lung surgery is still tracheal intubation general anesthesia, and both the texture of the tracheal tube itself and the damage caused to the mucous membranes of the airway and vocal folds during the operation can stimulate the cough receptors distributed there (46), and CAP will occur. Pan et al. (24) and Chen et al. (46) all believe that the use of anesthesia with preservation of spontaneous respiration can reduce the occurrence of CAP. Therefore, reducing the operating time and using less invasive anesthesia may be an important way to reduce postoperative cough.

Pathological type and other factors

Patients undergoing surgery for malignant lung lesions exhibited a higher incidence of CAP compared to those with benign conditions, possibly due to the need for comprehensive mediastinal lymph node dissection. However, there was no significant difference between adenocarcinoma and squamous cell carcinoma regarding CAP risk, suggesting that tumor pathology itself may not be a major determinant. Similarly, our analysis did not find an association between postoperative drainage duration and CAP, which could be due to the suppression of cough reflex by drainage-related discomfort. Besides, some patients develop postoperative GERD, which is often caused by a significant decrease in intrathoracic pressure, a relative increase in abdominal pressure, and an elevation of the diaphragm after massive lung resection, and the reflux of corrosive digestive juices causes damage to the larynx and vocal cords, stimulating the development of cough. This is consistent with the findings of Irwin et al. (47), who confirmed the association of GERD with CAP by 24-hour esophageal PH monitoring. In addition to the above factors, changes in the morphology of the residual bronchial tree, the development of bronchial kinks, and the length of the bronchial stump after lung surgery can alter the original airflow dynamics of the airway, resulting in changes in local airway pressure and increasing the sensitivity of the cough reflex (26). Factors such as whether the bronchial artery is preserved or not, and the sutures of the tracheal stump have also been demonstrated in relevant studies to be associated with the production of CAP (26,48).

Implications and actions needed

This study emphasizes the critical role of surgical and perioperative factors in the development of CAP in patients with NSCLC. The findings emphasize the need for tailored surgical planning and careful perioperative management to reduce the incidence of CAP and improve recovery outcomes.

Next steps should include: (I) improved clinical management: focus on optimizing surgical techniques, managing anesthesia duration, and addressing GERD during the perioperative period to mitigate CAP risk; (II) further research: conduct prospective studies to validate the identified risk factors and explore targeted interventions to prevent CAP, including GERD management and strategies to reduce surgical trauma; (III) implementation of ERAS protocols: integrate these findings into ERAS protocols to refine postoperative care and reduce complications.

Strengths and limitations

This study has several strengths, a comprehensive analysis, integration of data from several studies, and a robust assessment of CAP risk factors. In conclusion, this meta-analysis identifies key surgical and perioperative factors associated with post-pulmonary resection cough, emphasizing the need for careful surgical planning and perioperative management to reduce the risk of CAP and improve patient prognosis. However, the study has some limitations, such as low number of randomized controlled studies included, heterogeneity among the studies, the preponderance of studies conducted in China, and potential bias inherent in the retrospective study design. These limitations suggest that although the results of the study provide valuable insights, caution is needed when interpreting them, and further research is needed to validate the results in different populations and clinical settings. Future studies should focus on addressing these limitations by including more diverse populations, standardizing protocols, and exploring targeted interventions to reduce CAP risk.

Conclusions

The study concludes that CAP is influenced by a combination of patient-related, surgical, and anesthetic factors, and that several key surgical and perioperative factors significantly contribute to the development of CAP in NSCLC patients. These factors include right-sided lung surgery, lobectomy, mediastinal lymph node dissection, prolonged surgery and anesthesia durations, and postoperative GERD. The findings highlight the importance of careful surgical planning and perioperative management to minimize CAP risk and improve recovery. By addressing these risk factors, particularly GERD, clinicians can better manage postoperative outcomes, ultimately enhancing patient recovery and quality of life following pulmonary resection.

Acknowledgments

We acknowledge all the authors whose papers have been included in this meta-analysis for their work, which made this analysis possible. We also appreciate the assistance of proofreader and editor for their help in manuscript editing and review.

Footnote

Reporting Checklist: The authors have completed the PRISMA and MOOSE reporting checklists. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2222/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2222/prf

Funding: This work was supported by Taishan Scholar Program of Shandong Province (No. TS201712087) and Natural Science Foundation of Shandong Province (No. ZR2021LSW006).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2222/coif). The 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.

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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