Our study shows that NTB is a strong predictor of postoperative immediate pneumothorax in CT-TPLB. Specifically, we report a novel non-linear relationship between NTB distance and postoperative immediate pneumothorax, with a crucial inflection point at 8mm. For NTB ≤ 8mm, each 1mm increase correlates with a 26% decrease in pneumothorax risk (OR = 0.74, 95% CI: 0.66–0.81). However, NTB > 8mm show no significant association with postoperative immediate pneumothorax (P-value > 0.05), suggesting that severity of NTB does not influence the risk beyond this point. Therefore, a NTB of 8 mm is a useful indicator to predict postoperative immediate pneumothorax in adult patients with CT-TPLB. In clinical practice, these findings can be used to identify high-risk patients who may benefit from specialized care.
Patient undergoing CT-TPLB are prone to pneumothorax due to various factors, such as patient-related (age, BMI, emphysematous lungs, bulla), lesion and operation related (position, needle diameter, fissure crossed, multiple pleural punctures, lesion size, transpulmonary length, operator experience) 19,20.
It has been demonstrated that patients with NTB show a reduced risk of pneumothorax. Prior research indicated that NTB act as a protective factor against pneumothorax 10. This suggests that identifying NTB may have a predictive value for pneumothorax incidents in patients CT-TPLB. The relationship between NTB and postoperative pneumothorax prevalence has been studied. Recent research found that NTB can contribute to a lower likelihood of pneumothorax 12. Our study in line with the above studies, but these studies failed to quantitative analysis of the relationship between NTB and pneumothorax.
Building on observations of NTB is against post biopsy pneumothorax occurrence, it appears plausible that creating an artificial along-needle track bleeding could serve as a valuable measure to reduce the incidence of pneumothorax and other complications. This strategy involves the intentional injection of patch materials along the biopsy track during needle withdrawal to simulate the protective effect of NTB. A ground-breaking study by Ronald McCartney 21 validated this idea in both patient and animal models, demonstrating that pneumothorax could be virtually eliminated as a procedural complication via a lung patch technique. But the injection width of patch materials is few reported.
Massimo De Filippo et al. 10 along with Vittorio Sabatino et al. 11 use 6 mm as the cut-off value for classifying NTB, In their study, compared to NTB < 6mm, the higher NTB group (NTB > 6mm) reduced pneumothorax, It means that a certain amount of NTB will reduce postoperative pneumothorax. Based on our research result the inflection point of NTB is 8mm, which is inconsistent with the previous research. In our study, we initially performed linear regression on the adjusted model and considered the comprehensively confounder. Subsequently, we established an association using curve fitting and found a clinical saturation effect and a meaningful inflection point. Further, a sensitivity analysis of trend test in the linear model demonstrated that curve fitting was better than linear fitting to explain the association between NTB and postoperative immediate pneumothorax. So, the cut-off value of NTB in our study derived through strict statistical inference, rather than arbitrarily defined.
Furthermore, this optimal cut-off value is great clinical significance, due to help predict the occurrence of postoperative pneumothorax and providing reference to guide effective biopsy track sealing with various path materials22–25, especially for autologous blood seal.
The mechanism of NTB reducing the occurrence of pneumothorax remain unclear, however, several factors might provide a plausible explanation. (1) Self-sealing Effect: along needle track alveolar presence of blood products might serve as a natural self-sealing agent, effectively preventing or reducing air-leak into pleural cavity21. (2) Induction of Clotting: hemorrhage along the needle path could initiate clotting, resulting in a patch-like formation that may limit airflow from the airspace to the pleural space10. (3) Altered Ventilation: the presence of blood products within the alveolar space could lead to a reduction in ventilation, subsequently decreasing the flow of air from the airspace to the pleural space and reduce the risk of pneumothorax. (4) Promotion of Pleural Adhesion: blood accumulation on the pleural surface might stimulate the adhesion between the visceral and parietal pleura, thus preventing the formation of air pockets that could lead to pneumothorax. (5) Increased Airway Pressure: blood in the alveolar space could increase airway pressure. This increased pressure might counteract the forces causing air to leak from the lungs, thereby reducing the occurrence of pneumothorax. (6) Altering Lung Compliance: Pulmonary hemorrhage may change the lung compliance. Reduced lung compliance means the lungs are less likely to overexpand and cause an air leak, thus reducing the risk of pneumothorax. While these proposed mechanisms offer some insights into the relationship between NTB and reduced pneumothorax incidence, further research are needed for definitive evidence.
Our study has some strengths as follows: (1) To the best of our knowledge, this is the first study to observe and quantify the association between NTB and postoperative immediate pneumothorax using confounder adjusted multiple models. (2) We found a nonlinear relationship between them, and an optimal inflection point was identified. Thus, our study has greater clinical significance, which previous studies have not investigated. (3) We used sensitivity analysis to test the robustness of our findings. (4) Try our best to offer plausible mechanisms for the protective effect of NTB.
Our research has limitations: Firstly, this was a retrospective study, lack of a prospective evaluation and the absence of long-term follow-up in patients who developed NTB, further validation in prospective studies should be considered. Secondly, due to the observational nature, residual or unmeasured confounding factors might interfere with the results. however, we computed the E-value to quantify the potential influence of unmeasured confounders and conclude that they were unlikely to influence the findings. Thirdly, we couldn't quantify pneumothorax volume. We categorized patients into pneumothorax and no pneumothorax groups following the CT scanner, and thus the delayed pneumothorax was assessed mostly by X-ray. This might not achieve accurate grouping or underestimate delayed pneumothorax rate, and we failed to analyze the association between NTB and delayed pneumothorax because only 10 patients were detected. Fourthly, being a single-center study from China, our findings may not be generalizable to other settings. Lastly, we didn't measure NTP volume or consider other types of pulmonary hemorrhage (such as lesion perilesional bleeding, hemoptysis), focusing on NTB, the relationship between other types of pulmonary hemorrhage and pneumothorax needs further study. Despite these potential limitations, our study was the first to reveal NTB associated with immediate pneumothorax risk in a nonlinear relationship with different regression models, and the conclusions postulated remain credible.