Impact of fiberoptic bronchoscopy on systemic inflammatory markers and outcomes in neonatal patients with respiratory conditions

Introduction

Fiberoptic bronchoscopy has evolved as a pivotal tool in the diagnosis and management of respiratory conditions in neonatal populations, providing critical insights into airway anomalies and therapeutic interventions such as bronchoalveolar lavage (BAL) (1). As technology advances, its role for both diagnostic and therapeutic purposes is continually expanding, particularly in complex cases involving congenital and acquired neonatal respiratory pathologies (2,3). This study leverages a retrospective analysis approach to examine the clinical characteristics and outcomes of neonates undergoing bronchoscopy and evaluates the effects of this intervention on respiratory and systemic health parameters.

Neonatal respiratory disorders, such as congenital lung malformations, pneumonia, and bronchopneumonia, pose considerable diagnostic and therapeutic challenges (4,5). Bronchoscopy can aid in confirming diagnoses and in performing direct therapeutic actions (6). Although its local effects on airway patency are well described, the procedure’s systemic effects—particularly on inflammatory and metabolic responses—remain underexplored.

Recent studies have begun to investigate the broader physiological implications of respiratory interventions, including their impact on systemic inflammation and metabolic status (7-9). Inflammatory markers such as the systemic immune-inflammation index (SII) (10) have been used to predict outcomes in pneumonia and post-operative conditions (11,12). However, their relevance in neonatal lung diseases and their dynamic changes following bronchoscopy are still unclear.

The present study, conducted at Anhui Provincial Children’s Hospital, includes data from January 2019 to December 2022 and focuses on the dual role of fiberoptic bronchoscopy. By assessing changes in physiological and biochemical markers, we aimed to explore not only respiratory improvements but also systemic inflammatory resolution. We further investigated whether changes in systemic inflammatory markers, especially SII, were associated with bilirubin metabolism and the risk of neonatal hyperbilirubinemia—a novel hypothesis that connects respiratory intervention with systemic metabolic processes. We further investigated whether changes in systemic inflammatory resolution.

This study contributes to our understanding of bronchoscopy’s broader impact on neonatal health and proposes a potential utility for SII as a predictor of complications beyond the pulmonary system. The findings may inform individualized treatment strategies and enhance clinical decision-making in neonatal respiratory medicine. We present this article in accordance with the STARD reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-81/rc).

Methods

Study design

This study utilizes a retrospective analysis approach to explore the clinical characteristics and outcomes of neonatal patients undergoing fiberoptic bronchoscopy. Additionally, it examines the effects of fiberoptic bronchoscopy treatment on respiratory and systemic health parameters. The study sample includes 38 neonates from a larger cohort with respiratory conditions treated at Anhui Provincial Children’s Hospital between January 2019 and December 2022. All patients were neonates (≤28 days of age), including both preterm and full-term infants. Only neonates who met the clinical indications for bronchoscopy and had complete laboratory data pre- and post-procedure were included. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board (IRB) of Anhui Provincial Children’s Hospital (No. ahslyy20206) and informed consent was obtained from the parents or legal guardians of all participating subjects. All patient data were anonymized.

Patient selection criteria

Inclusion criteria were: (I) respiratory tract damage from prolonged intubation or unexplained extubation difficulty; (II) recurrent stridor suggestive of congenital airway anomalies; (III) suspected tracheoesophageal fistula; (IV) treatment-resistant atelectasis or recurrent infections requiring BAL (BAL criteria: BAL was indicated in cases of suspected mucus plugging, segmental atelectasis, or persistent pulmonary infiltrates despite empirical treatment); and (V) need for diagnostic clarification in severe respiratory distress. Exclusion criteria included: severe cardiopulmonary failure, multiorgan dysfunction, coagulopathy (platelet count <50×10⁹/L), pulmonary hypertension, body weight <2,000 g, or incomplete records. Criteria for BAL included radiographic evidence of mucus plugging, persistent lung opacity, or failed response to conventional therapy.

Data collection

Clinical and demographic data included gestational age, birth weight, age at bronchoscopy, gender, diagnosis, birth history, and bronchoscopic findings. Laboratory parameters, including arterial blood gas, complete blood count, and inflammatory markers, including C-reactive protein (CRP), neutrophils, lymphocytes, SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-platelet ratio (NPR), were collected within 12 hours prior to the procedure and repeated within 12 hours post-procedure. Only one paired result set per patient was used in the final analysis. Definitions (11,13): SII = (neutrophil × platelet)/lymphocyte; hyperbilirubinemia = total serum bilirubin >221 µmol/L (12.9 mg/dL).

Diagnostic and therapeutic protocol

Bronchoscopy was conducted using an Olympus XP260 fiberoptic bronchoscope (Tokyo, Japan), and the procedure adhered to the American Thoracic Society (ATS) guidelines for neonatal flexible bronchoscopy (14,15). The procedure was typically performed bedside under local anesthesia (2% lidocaine), premedication with atropine (0.01 mg/kg), and midazolam if required. Vital signs were monitored throughout. The procedure was typically performed bedside under local anesthesia (2% lidocaine), premedication with atropine (0.01 mg/kg), and midazolam if required. Vital signs were monitored throughout. Procedure indications included unresolved respiratory symptoms, suspicion of anatomical anomalies, and mucus obstruction. Alveolar lavage (3–4 times with 1–2 mL saline) was performed as needed. Continuous monitoring and emergency preparedness were ensured. Oxygen saturation (SO₂) <85% (term) or <90% (preterm) led to immediate procedure cessation and resuscitative measures. Patients were monitored for at least 24 hours post-procedure. Post-procedure, children were kept under electrocardiogram (ECG) monitoring for 24 hours in the neonatal intensive care unit, with vigilant observation for fever, respiratory difficulties, or blood-tinged secretions, and timely management of potential complications like worsening pulmonary infections or pneumothorax (16-18).

Evaluating the impact of fiberoptic bronchoscopy

The primary outcomes focused on improvements in blood gas parameters such as partial pressure of oxygen (PO₂) and SO₂, indicative of enhanced respiratory function post-treatment. Secondary outcomes included evaluating changes in inflammatory markers, such as CRP, NLR, PLR, NPR, and SII. Electrolytes (Na⁺, K⁺) and lactate were also recorded to assess systemic impact.

Risk assessment for hyperbilirubinemia

Logistic regression was used to assess the association between evaluated inflammatory markers (e.g., SII >500), demographic factors (e.g., sex, age >15 days), and hyperbilirubinemia. Receiver operating characteristic (ROC) curves evaluated the predictive value of inflammatory markers, and area under the curve (AUC) was calculated.

Statistical analysis

All statistical results were obtained using R version 3.5.3, and figures were created using GraphPad Prism. Descriptive statistics were applied to baseline data, employing medians and interquartile ranges (IQRs) for continuous variables and frequencies with percentages for categorical data. The Chi-squared test or Fisher’s exact test was used for categorical comparisons where appropriate. For comparisons of clinical and laboratory parameters before and after bronchoscopy, only one pre- and one post-procedure value per patient were used. Paired statistical tests were applied: the Wilcoxon signed-rank test for non-normally distributed variables and the paired t-test for normally distributed variables. A P value <0.05 was considered statistically significant. A multivariate linear regression model was used to explore the relationship between bicarbonate levels (as the dependent variable) and inflammatory markers, including neutrophil count, white blood cell count (WBC), CRP, and SII, before and after bronchoscopy.

Results

Clinical characteristics and outcomes of neonatal patients undergoing bronchoscopy

A total of 38 neonates were included in this study. The most common diagnosis was pneumonia (81.6%), followed by bronchopneumonia (10.5%). The median age at bronchoscopy was 13 days (IQR, 3–23.5 days), and 81.6% were male. Most patients underwent bronchoscopy for both diagnostic and therapeutic purposes (94.7%), with dyspnea (57.9%) and stridor (15.8%) being the most frequent indications. About one-third of the patients were premature, and 47.4% were delivered via cesarean section. Computed tomography (CT) findings were consistent with pneumonia in half of the patients, while bronchoscopy revealed airway inflammation in nearly 90% of cases. No patients required intubation or escalation of care post-procedure. All bronchoscopy procedures were conducted without endotracheal intubation. Of the 38 neonates, 35 were transferred to general pediatric wards and discharged after a median of 5 days post-procedure; three were referred to higher-level pediatric centers for advanced care.

Although rare, other findings included laryngomalacia (5.3%), inflammatory stenosis, and tracheal O-type stenosis. These findings suggest that bronchoscopy is a valuable diagnostic tool not only for common infectious pathologies but also for identifying congenital or structural anomalies. Regarding clinical outcomes, 92.1% of the patients were discharged after treatment, and 7.9% were transferred for further management, with no deaths or procedure-related severe adverse events reported. Table 1 provides a detailed summary of patient characteristics, clinical presentations, and outcomes.

Changes in blood gas parameters before and after bronchoscopy

Among the 38 patients, blood gas analyses were conducted both before and after bronchoscopy, resulting in a total of 76 paired data points. After treatment, significant improvements were seen in oxygenation. PO₂ increased from a median of 57.6 to 97.9 mmHg (P<0.001), and SO₂ increased from 94.9% to 98.9% (P<0.001), indicating improved gas exchange. In addition, lactate levels decreased significantly (from 2.15 to 1.30 mmol/L, P<0.001), suggesting better tissue oxygenation and perfusion.

Other blood gas parameters such as pH, partial pressure of carbon dioxide (PCO₂), HCO₃⁻, and base excess did not change significantly, indicating that acid-base homeostasis was maintained. These results imply that bronchoscopy, likely by clearing airway obstructions and reducing inflammation, can quickly improve respiratory function and metabolic status in affected neonates. Interestingly, a significant drop in serum sodium and potassium levels was observed post-procedure (P=0.04 and P=0.01, respectively), which might be related to saline lavage or temporary fluid shifts. Table 2 shows the full comparison of blood gas and metabolic parameters before and after the intervention.

Hematological and inflammatory marker changes before and after bronchoscopy

Post-bronchoscopy measurements revealed notable changes in systemic inflammatory markers. Neutrophil counts decreased significantly, while lymphocyte percentage increased, leading to a decrease in NLR. The SII, which integrates neutrophil, lymphocyte, and platelet counts, decreased from 463.60 to 333.69 (P<0.001). CRP, a widely used inflammatory marker, also decreased significantly from 0.90 to 0.10 mg/L (P=0.006). These changes support the hypothesis that fiberoptic bronchoscopy contributes to the reduction of systemic inflammation, possibly through removal of airway secretions and improved ventilation. There were no significant changes in other markers such as PLR, NPR, red blood cell count (RBC), hemoglobin, or total leukocytes, suggesting that the inflammatory modulation was more specific rather than global hematologic suppression. Table 3 details these hematologic changes.

Relationship between inflammatory markers and bicarbonate levels

To further explore the physiological impact of inflammation, we conducted a multivariate linear regression analysis with HCO₃⁻ as the dependent variable and inflammatory markers as predictors. Before bronchoscopy, neutrophil count and WBC were significantly associated with bicarbonate levels (Figure 1A), suggesting that inflammation may be linked to disturbances in acid-base regulation. The model explained 30.2% of the variance. However, after bronchoscopy, this association disappeared (R²=0.024), and none of the inflammatory variables significantly predicted bicarbonate levels (Figure 1B). This finding implies that bronchoscopy may help stabilize systemic physiology by resolving inflammatory processes that otherwise affect metabolic regulation.

Figure 1 Multivariate regression of HCO₃⁻ levels with inflammatory markers. (A) Multivariate linear regression analysis of HCO₃⁻ levels against inflammatory markers, including neutrophil count, SII, WBC, and CRP, in neonates with pulmonary disease before fiberoptic bronchoscopy treatment. The regression model accounts for 30.2% of the variance (R²=0.302). Significant associations are identified for neutrophil count (b1=−2.0588, P=0.009) and WBC (b3=1.5663, P=0.002), with respective confidence intervals (−3.5732, −0.5444) and (0.6148, 2.5178) indicating statistical significance. The heatmap on the right shows the parameter covariance of the corresponding regression equation. (B) Post-treatment multivariate linear regression analysis of HCO₃⁻ levels with the same markers reveals a low explained variance (R²=0.024). No associations reached statistical significance (P>0.05). The reduction in R² suggests that inflammatory markers had less predictive power after treatment, potentially reflecting clinical improvement and resolution of systemic inflammation. The heatmap on the right shows the parameter covariance of the corresponding regression equation. CRP, C-reactive protein; SII, systemic immune-inflammation index; WBC, white blood cell count.

Correlation between bilirubin and inflammatory markers

Given the relatively high prevalence of hyperbilirubinemia in neonates with pulmonary conditions, we further investigated the relationship between bilirubin levels and inflammatory indices. As shown in Figure 2, SII significantly decreased after bronchoscopy. Among the various inflammatory ratios assessed (NLR, PLR, NPR, CRP), only SII showed a statistically significant positive correlation with total bilirubin levels (R=0.3887, P=0.02). This novel finding may reflect a common immunometabolic pathway linking systemic inflammation with bilirubin metabolism, potentially mediated by oxidative stress or macrophage activity. Although preliminary, this association provides a rationale for future studies into inflammation-mediated neonatal hyperbilirubinemia.

Figure 2 SII and bilirubin correlation with inflammatory markers. (A) SII levels measured before and after fiberoptic bronchoscopy treatment show a significant reduction post-intervention in neonates with pulmonary disease, suggesting an improvement in the inflammatory state. (B-E) No significant linear correlation exists between bilirubin levels and variables such as the NLR, NPR, PLR, and CRP. (F) A positive linear correlation between bilirubin levels and SII is observed, with a R of 0.3887 and significance level P=0.02, highlighting a notable relationship. Each data point in this figure represents a single patient’s value before or after bronchoscopy. No averaging across multiple time points was applied. CRP, C-reactive protein; NLR, neutrophil-to-lymphocyte ratio; NPR, neutrophil-to-platelet ratio; PLR, platelet-to-lymphocyte ratio; SII, systemic immune-inflammation index.

Assessing risk factors and predictive markers for neonatal hyperbilirubinemia

Logistic regression analysis identified two independent predictors for neonatal hyperbilirubinemia: SII >500 [odds ratio (OR) =34.3; 95% confidence interval (CI): 4.1–285.5; P<0.001] and male sex (OR =14.8; 95% CI: 1.0–215.1; P<0.05). Age and CRP were not significant in the model (Figure 3A). To further assess diagnostic accuracy, we performed ROC curve analysis. SII demonstrated the highest diagnostic value with an AUC of 0.9091 (95% CI: 0.8–1), outperforming NLR, PLR, NPR, and CRP (Figure 3B). These findings suggest that SII could serve as a reliable marker for identifying neonates at risk of hyperbilirubinemia in clinical practice, especially in the context of pulmonary disease.

Figure 3 Logistic regression analysis on factors affecting neonatal hyperbilirubinemia and predictive value of inflammatory markers. (A) Logistic regression analysis explores the relationship between neonatal hyperbilirubinemia and variables such as SII >500, male sex, CRP ≥0.5 mg/L, and age >15 days. The analysis identifies significant associations for SII >500 (OR =34.3; 95% CI: 4.1, 285.5) and male sex (OR =14.8; 95% CI: 1.0, 215.1) with increased hyperbilirubinemia risk. (B) The predictive capability of inflammatory markers (SII, NLR, NPR, PLR, CRP) for neonatal hyperbilirubinemia is assessed using ROC curve analysis. The AUC for SII (0.9091; 95% CI: 0.8, 1) suggests high prognostic value. Significant differences in predictive capabilities are evident between several ROC comparisons, especially between ROC1 (SII) and other markers, indicating varying diagnostic effectiveness. AUC, area under the curve; CI, confidence interval; CRP, C-reactive protein; NLR, neutrophil-to-lymphocyte ratio; NPR, neutrophil-to-platelet ratio; PLR, platelet-to-lymphocyte ratio; OR, odds ratio; ROC, receiver operating characteristic; SII, systemic immune-inflammation index.

Discussion

The current study provides a comprehensive analysis of the application and outcomes of fiberoptic bronchoscopy in neonatal patients with respiratory conditions, focusing particularly on systemic health parameters and inflammatory markers. Previous literature extensively documents the utility of bronchoscopy in diagnosing and managing neonatal respiratory disorders, underlining its importance in cases of congenital and acquired anomalies (19,20). Although the study only analyzed 38 neonates from a smaller sample, this group represented a highly selected population with complete, high-quality data and clear clinical indications for bronchoscopy. This limits generalizability but enhances internal validity. Our findings reaffirm the dual diagnostic and therapeutic role of bronchoscopy, similar to previous studies, demonstrating significant improvements in oxygenation (21,22). In this study, we report for the first time the changes in the SII in neonates with lung disease undergoing fiberoptic bronchoscopy treatment.

The majority of neonates in our study underwent bronchoscopy due to dyspnea and were later confirmed to have bronchial inflammation or pneumonia. This finding supports the view that respiratory symptoms often correlate with inflammatory airway changes, which bronchoscopy can effectively visualize and treat. Notably, the study period overlapped with the COVID-19 pandemic. Although maternal COVID-19 infection could plausibly affect neonatal respiratory status, maternal infection data were not consistently documented in the medical records and thus could not be included in our analysis. The application of neonatal fiberoptic bronchoscopy, particularly for both diagnostic and therapeutic purposes, is well-acknowledged (23,24). However, there has been limited exploration into its effects on systemic health parameters such as inflammatory markers and metabolic function, which are increasingly recognized as crucial components influencing treatment outcomes (25). The significant reduction in inflammatory markers post-bronchoscopy observed in this study is consistent with recent reports suggesting that respiratory interventions can modulate systemic inflammatory responses (26-28). This study’s pivotal contribution lies in quantifying these changes and proposing SII as a potential predictor for complications like hyperbilirubinemia, expanding the scope of bronchoscopy’s impact beyond localized respiratory improvements.

The observed efficacy of bronchoscopy in improving respiratory parameters parallels prior investigations (29). Moreover, the reduction in acute inflammation markers such as CRP indicates bronchoscopy’s therapeutic benefits in airway disease management. Despite these similarities, our study uniquely emphasizes bronchoscopy’s systemic implications, as illustrated by significant improvements in metabolic stress indicated by lactate levels, which few studies have comprehensively addressed. We also acknowledge that selecting bicarbonate as the outcome variable in the regression model has limitations, particularly in neonates and especially in premature infants, who may exhibit lower bicarbonate levels due to renal immaturity. This may introduce variability unrelated to systemic inflammation. Although lactate is a relevant marker of tissue hypoxia and metabolic stress, its distribution in our dataset was highly skewed, with several extreme values that would have required transformation or exclusion. Therefore, we opted to model HCO₃⁻, while interpreting the results conservatively. Electrolyte changes observed post-procedure, particularly reductions in sodium and potassium, may be attributed to dilutional effects caused by BAL fluid or minor post-intervention shifts in fluid compartments. However, these changes were within clinical tolerance and did not require intervention. Unlike prior studies where the focus remained on direct respiratory effects, our research highlights the broader physiological implications of bronchoscopy, investigating shifts in systemic inflammatory indices. The significant positive correlation found between SII and bilirubin levels suggests an interlinked mechanism that has not been extensively reported in neonatal literature. This novel association may be attributed to bronchoscopy’s potential interventions in innate immune pathways, warranting further exploration. Another notable finding is the low explanatory power (R²=0.024) of inflammatory markers for HCO₃⁻ levels post-treatment, compared to pre-treatment (R²=0.302), which may reflect clinical resolution of inflammation and reduced metabolic stress. This shift further supports the therapeutic benefit of bronchoscopy in this population. One of the primary strengths of our study is the rigorous analysis of pre- and post-bronchoscopic parameters, which robustly establishes the therapeutic benefits of the procedure across multiple domains—anatomical, respiratory, and systemic. The use of ROC curves to assess biomarker efficiency enhances the statistical rigor of our findings, underscoring SII’s potential utility in clinical settings for predicting neonatal complications such as hyperbilirubinemia.

The study’s retrospective design, while offering broad insights, inherently limits causal interpretation. Future prospective studies could confirm these observations, providing greater clarity on the underlying mechanisms of systemic changes post-bronchoscopy. The small sample size may have influenced the generalizability of our findings; thus, subsequent research with larger cohorts is necessary to validate and expand upon these results. Additionally, while our focus on inflammatory markers is novel, integrating genetic and environmental factors could further delineate bronchoscopy’s multifaceted impact. Finally, exploring long-term outcomes post-treatment, particularly concerning systemic health, would offer valuable insights into bronchoscopy’s sustained efficacy and potential adverse effects.

Conclusions

In conclusion, our study highlights the multifaceted benefits of fiberoptic bronchoscopy in neonates, including improved oxygenation, reduced systemic inflammation, and potential metabolic stabilization. The association between SII and bilirubin levels provides new insight into inflammation-mediated hyperbilirubinemia, positioning SII as a promising biomarker for both disease monitoring and risk stratification. These findings support the broader application of bronchoscopy in neonatal respiratory care and underscore the need for further investigation into its systemic effects.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-81/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-81/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-81/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-81/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. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board (IRB) of Anhui Provincial Children’s Hospital (No. ahslyy20206) and informed consent was obtained from the parents or legal guardians of all participating subjects.

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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