Endoluminal approaches to postoperative air leaks

Introduction

Background

Postoperative air leaks are a common complication following thoracic surgery, occurring in up to 50% of patients after pulmonary resection (1). Although most (80%) air leaks present on postoperative day 1 and resolve by day 5 (2), prolonged air leak (PAL)—defined as an air leak lasting more than 5 days—develops in 8–10% of patients undergoing lobectomy, with higher rates after lung volume reduction surgery (3) and among those with emphysema (4).

Patients who develop PAL are 8.5 times more likely to develop empyema [odds ratio (OR) =8.5, P<0.001], 7.5 times more likely to require additional chest tube placement for pneumothorax (OR =7.5, P<0.001), 4 times more likely to require an unplanned return to the operating room (OR =4, P<0.001), and twice as likely to be readmitted within 30 days (OR =2, P=0.009). PAL also prolongs hospitalization by a median of 5 days [relative effect 5.04 days, 95% confidence interval (CI): 3.77–6.30, P<0.001] but may continue for weeks to months (95% CI: 3.77–6.30, P<0.001) (5). It also imposes a substantial economic burden, with USA data demonstrating more than $11,000 in incremental hospital expenditures per affected patient (6).

Rationale and knowledge gap

The natural history of PAL is unpredictable—while some air leaks resolve spontaneously with observation alone, others persist for weeks to months. When observation alone is insufficient, conservative management strategies, such as continued chest tube drainage, suction modulation, outpatient Heimlich valve placement, and chemical pleurodesis, may be employed. However, the effectiveness of these approaches is variable. Intervention beyond conservative management is considered when the harm from complications, such as empyema, pneumonia, or restricted mobility, begin to outweigh procedural risks. Surgical re-exploration remains first-line therapy for tracheal or bronchial fistula, stump dehiscence, empyema, significant tissue necrosis, or large central defects. Patients who are poor surgical candidates or have small bronchopleural or alveolopleural fistulae may benefit from endoluminal bronchoscopic therapies, which have emerged as a minimally invasive alternative. The indication, timing, technique, and effectiveness of these endoluminal bronchoscopic interventions remain poorly defined and are the focus of this chapter.

Objective

This chapter reviews the pretest probability, defining, grading, and localizing strategies for PALs before shifting specifically to contemporary endoluminal treatment options utilized when surgical options are no longer being considered. Surgical management, including measures to reduce the chance of postoperative air leak and surgical interventions when persistent postoperative air leaks manifest, is addressed in the accompanying surgical chapters.

Pretest probability of PALs

Risk factors & preoperative PAL risk prediction models

Several patient-level and procedure-related characteristics are associated with increased PAL risk, as summarized in Table 1 (3-4,7-8).

These variables form the basis of several preoperative prediction tools. Comparative evaluation of three commonly used models—the index of persistent air leak (IPAL) score, the Gilbert score, and the prolonged air leak score (PALS) from The Society of Thoracic Surgeons General Thoracic Surgery Database (STS-GTSD)—suggests each offers distinct clinical utility across different decision thresholds (9). IPAL demonstrates the greatest net benefit at lower predicted risk thresholds (≤0.12), the Gilbert score performs best within a narrow midrange (0.12–0.16), and PALS provides more consistent utility across typical clinical thresholds (0.16–0.28) (9). Table 2 (7,10-14) summarizes the performance characteristics of these models and two additional models used in clinical practice.

Intra- and early postoperative risk assessment

Intraoperative quantification of air leak flow—calculated as the difference between inspired and expired tidal volumes using standardized ventilator settings [tidal volume 8 mL/kg, respiratory rate 10, positive end-expiratory pressure (PEEP) 5 cm H₂O]—offers a reproducible measure. An intraoperative air leak flow exceeding 500 mL/min is associated with markedly longer postoperative leak duration (mean 10.1 vs. 1.5 days, P<0.001) (15).

Omura et al. (16) is a single-center retrospective study that developed the postoperative PAL prediction score (PPALS), incorporating four predictors measured within the first 3 postoperative hours: preoperative forced expiratory volume in 1 second (FEV₁) <60%, additional negative pressure (ANP) <1 cm H₂O, air leak flow >20 mL/min, and pleural adhesions. The ANP is the difference between the suction pressure set by the surgeon and the actual pressure detected by a transducer. PAL rates increase from 1.7% for PPALS 0 to 46.7% for PPALS 3 [area under the curve (AUC) =0.823; 95% CI: 0.718–0.929], though the model has not undergone external validation.

Limitations

Discriminatory performance of these models is moderate (AUC 0.69–0.82). Negative predictive values average approximately 91%, but positive predictive values are low (~19%). The models are derived from retrospective datasets, have undergone limited external validation, and do not predict the mechanism of PAL. Additionally, there is no evidence that model-guided management improves outcomes.

Clinical application

Risk prediction tools may help counsel patients, identify individuals who may benefit from intraoperative preventive measures, standardize clinical trial eligibility, and prompt earlier multidisciplinary discussions regarding intervention. Selection of a specific scoring system should be guided by institutional preference, data availability, and the clinical decision threshold.

Takeaway points

There are multiple PAL prediction models and intraoperative assessments (intraoperative air leak, PPALS) that should be used based on data availability and clinical decision thresholds, primarily to facilitate early multidisciplinary discussion regarding possible additional monitoring and interventions needed.

Defining and grading air leak

Postoperative air leaks can be described along three dimensions: temporal definitions, physiologic classifications, and severity grading systems. Together, these frameworks help clinicians interpret the clinical significance of an air leak and guide subsequent decision-making.

Temporal definition

Postoperative air leaks arise from communication between the airways or alveoli and the pleural space (17). Resolution depends on visceral pleural healing and adequate re-expansion of the remaining lung to achieve pleural apposition (1) and sealing of microscopic parenchymal defects (18). Approximately 59–73% of expiratory-only air leaks resolve within 12–36 hours when chest tubes are converted from suction to water seal (19). The likelihood of spontaneous cessation peaks between postoperative days 3 and 7, making postoperative day 5 the widely accepted threshold for defining PAL (2).

Physiologic classification: drainage-dependent vs. drainage-independent air leak

A proposed framework distinguishes drainage-dependent PAL (DDPAL) from drainage-independent PAL (DIPAL) (20).

Physiologic basis

After anatomical lung resection, incomplete expansion may create a lung-thoracic cavity size mismatch, particularly after upper lobectomy, where the exposed lower lobe apex assumes a “bullet shape” (21). The resulting geometric curvature produces focal stress amplification and higher regional pleural pressure gradients—22.6 cmH₂O after upper lobectomy vs. 11.5 cmH₂O after lower lobectomy (22). The pressure gradient created by applied suction draws air through small visceral pleural defects, defining DDPAL (20). Clinically, DDPAL is associated with shorter hospital stay (6.9 vs. 11 days) and lower re-exploration rates (6% vs. 100%) compared with DIPAL, though evidence is limited (20).

In contrast, DIPAL reflects a true fistula persisting regardless of pleural pressure dynamics (20), typically due to a larger parenchymal defect, impaired tissue healing, or ongoing tissue destruction. One area of research concerns an elevated pleural CO₂ concentration (≥6%), which is hypothesized to inhibit alveolar epithelial cell proliferation. Alveolar gas contains approximately 5% CO₂ (partial pressure of ~40 mmHg). The presence of a fistula from the alveoli to the pleura allows CO₂ concentration in the pleura to rise. Every 1% increase in pleural CO₂ is associated with a 9-hour delay in air leak resolution and a 10-fold increase in odds of PAL (23). Patients who were treated with supplemental oxygen and extra-pleural suction had faster air leak resolution (3.4±1.1 vs. 6.0±1.2 days, P<0.001) (23), likely due to the same mechanism of standard pneumothorax treatment with nitrogen washout and drainage. Pleural CO₂ measurement is purely investigational as it requires infrared spectroscopy-based analyzers, which is not widely available.

Diagnostic options: pleural manometry vs. tube clamping trial

Pleural pressure measurement can be performed using (I) Water manometer system (24) comprised of a simple U-tube system connected to the chest tube, to estimate mean values, (II) an electronic transducer system (24) that allows precise measurement of instantaneous pleural pressure or (III) using a continuous epidural catheter method (25) passed through the drainage tube into the pleural space and connected to an electronic transducer with real-time calculation and display of pleural pressure. Pleural pressure is measured after chest tubes are clamped for 20 minutes. DDPAL is diagnosed if the end-expiratory pleural pressure plateaus and the patient remains clinically stable and without respiratory symptoms. Despite its physiologic rationale, pleural manometry to distinguish DDPAL from DIPAL is not widely utilized. The Society of Thoracic Surgeons (STS) Expert Consensus Document [2024] (26), European consensus recommendations [2025] (27), and Delphi consensus study [2022] (28) do not recommend pleural manometry as a diagnostic tool.

A simple tube-clamping trial on postoperative day 5 serves as a pragmatic method to assess drainage dependence. A randomized non-inferiority trial (29) of 95 patients found that clamping at higher air leak rates (60–80 mL/min) was as safe as clamping at minimal rates (0–20 mL/min), with shorter lengths of stay (13.5 vs. 16.5 days, P=0.02) and drainage duration (10 vs. 12 days, P=0.007). Notably, up to 10% of patients with no visible leak failed clamping, supporting a timing-based rather than leak-based approach.

Severity grading system

Higher air leak severity is associated with longer leak duration. In the original Cerfolio series (19), median air leak duration increased from approximately 2 days for grade 1 leaks to 7 days for grade 4 continuous leaks, supporting the prognostic value of severity grading. However, severity alone has not been consistently validated as a predictor of the need for intervention.

Methods of severity classification

Qualitative (analog) grading is based on visual observation of bubbling patterns in the water seal chamber and is thus limited by subjectivity and interobserver variability. The earliest widely adopted standardized classification was introduced by Cerfolio et al. in 1998 (19) and has since been adopted into a graded system summarized in Table 3.

Quantitative (digital) grading involves electronic pleural drainage systems equipped with flow sensors that directly and continuously measure air passage through the drainage circuit, typically reported in milliliters per minute (mL/min). A 2022 international working group (28) proposed digital severity categories: mild (<100 mL/min), moderate (100–400 mL/min), and severe (>400 mL/min). No digital grading system has been prospectively validated against clinical outcomes.

Mori et al. (30) found a strong correlation (R=0.85, P<0.001) between analog visual assessment levels and digital flow measurements. Analog assessment of leaks occurring during coughing only correlated with digital values of 2.4 mL/min (level 0) to 48.6 mL/min (level 1), whereas a continuous leak correlated with a digital value of 405.3 mL/min (level 3).

Benefits and limitations of severity grading

Table 4 summarizes the meta-analyses (31-35) comparing analog and digital chest drainage systems. Analog grading systems are universally available, require no specialized equipment, and are familiar to all thoracic surgical teams. However, they are inherently limited by subjectivity, interobserver variability, and lack of standardization between institutions. Analog assessment provides only categorical severity estimates (e.g., expiratory vs. continuous leak) and cannot capture trends over time, making it difficult to establish reproducible criteria for chest tube removal or to identify patients whose leak trajectory predicts failure of conservative management.

Digital systems address several of these limitations by providing objective, continuous airflow quantification. Meta-analyses consistently demonstrate modest reductions in chest tube duration (~0.5–0.7 days) and hospital length of stay (LOS) (~0.8–1.0 days) with digital systems (31-35). These benefits likely stem from standardized documentation, continuous monitoring for air leak resolution (commonly defined as <20 mL/min sustained for ≥6 hours) (36), facilitation of protocol-driven chest tube removal, and earlier identification of high-risk leak trajectories (with flows ≥100 mL/min frequently identified as a predictor of PAL).

Despite these advantages, important limitations of digital systems must be acknowledged. No universally validated intervention thresholds exist; commonly used values (20, 40, 80, or 100 mL/min) are consensus-derived and have not been shown to reliably predict failure of conservative management, need for bronchoscopic or surgical intervention, development of empyema, or readmission risk. Airflow magnitude does not equate to fistula severity—measurements are influenced by chest tube size, suction settings, pleural pressure, lung expansion, tube position, and patient respiratory effort. Consequently, a large measured air leak does not necessarily indicate a large fistula requiring surgical repair. The strongest evidence for digital drainage is limited to process outcomes (chest tube duration, LOS), with little data regarding mortality, empyema prevention, reoperation rates, or long-term outcomes. Comparisons across studies are further hampered by heterogeneous definitions of PAL (>5 vs. >7 days) and air leak resolution criteria.

In summary, both analog and digital grading systems inform clinical decision-making, but neither has been prospectively validated to predict the need for intervention, reoperation, or long-term outcomes. Clinical decisions should integrate severity grading with imaging findings, patient symptoms, degree of lung expansion, infection status, and operative risk.

Takeaway points

• Temporal definition: PAL is defined as an air leak persisting beyond postoperative day 5, after which spontaneous resolution becomes increasingly unlikely.
• Physiologic classification: DDPAL is driven by pressure gradients from applied suction; DIPAL reflects a true fistula. A tube clamping trial at postoperative day 5—regardless of leak magnitude—is the most practical method to distinguish the two.
• Severity grading system: analog (Cerfolio) classification is universally available but subjective; digital systems provide objective quantification but lack validated intervention thresholds. Neither has been prospectively validated to predict the need for intervention. Digital vs. analog: meta-analyses show digital systems modestly reduce chest tube duration (~0.5–0.7 days) and LOS (~0.8–1.0 days), but do not reduce PAL incidence or predict need for reoperation.

Localizing the air leak

Alveolar-pleural fistula (APF) vs. bronchopleural fistula (BPF)

BPF typically involves larger, central airways with identifiable defects. Direct visualization via bronchoscopy combined with standard computed tomography (CT) imaging is usually sufficient for BPF localization. In one series of 24 patients with confirmed BPF, multidetector CT (MDCT) demonstrated direct radiographic evidence in only 58% (37).

APF arises from peripheral parenchymal leaks not visible on routine airway inspection or standard CT imaging. Localization requires functional techniques capable of identifying active airflow at the alveolar level. From a practical standpoint, bronchoscopic balloon occlusion testing remains the most accessible and widely employed method for APF localization.

Clinical assessment

Physical examination findings provide limited anatomic precision for air leak localization. Subcutaneous emphysema (SE) occurs in approximately 6% of patients following pulmonary resection (38). The distribution of SE reflects the chest tube insertion site and regional fascial planes rather than the proximity of the parenchymal leak. Iatrogenic factors such as poor chest tube placement, tube blockage, and side-port migration should be excluded before attributing emphysema to a parenchymal source. Recalcitrant SE—persisting despite adequate pleural drainage—typically occurs when the leaking lung becomes partially adherent to the intercostal space previously traversed by the chest tube (38). Risk factors include FEV₁ <50%, active air leak, previous ipsilateral thoracotomy, and lobectomy as the index operation.

Imaging modalities

Conventional CT demonstrates good sensitivity for central BPF but performs poorly for peripheral APF. Advanced CT post-processing techniques—including multiplanar reconstructions, virtual bronchoscopy, and minimum-intensity projections—can improve detection of subtle fistulae. Dynamic high-resolution CT obtained during saline instillation via the chest tube while the patient vocalizes may demonstrate active air leakage; in a series of 11 patients with spontaneous pneumothorax, this technique correctly identified surgically confirmed leak sites in all cases (39). Dynamic 320-detector-row CT allowed real-time visualization of air movement and successfully localized the responsible bulla in 8 of 10 patients (40).

Among nuclear medicine techniques, Technegas single-photon emission CT (SPECT)/CT successfully localized the leak in 18 of 20 patients (90%) in the largest reported series of postoperative persistent air leaks (41). Radioaerosol ventilation scintigraphy using technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) demonstrated a sensitivity of 78% and specificity of 100% in a cohort of 28 patients (42). Despite their diagnostic performance, nuclear medicine techniques remain limited by availability, logistical complexity, and radiation exposure.

Bronchoscopic localization techniques

Although general anesthesia is frequently utilized, testing and valve placement can be done under conscious sedation with potential advantages including preservation of spontaneous ventilation, avoidance of general anesthesia, shorter recovery time, and potentially improved localization of air leaks.

Balloon occlusion testing

Sequential balloon occlusion is the most widely used bronchoscopic localization technique (43). Using a negative localization strategy, airways are sequentially occluded from proximal (lobar) to distal (segmental or subsegmental) levels until complete cessation or substantial reduction in air leak is noted. In the largest published series of 40 patients, balloon occlusion successfully localized the responsible bronchus in 34 cases (85%) (44). A recognized limitation is collateral ventilation through interalveolar and bronchial pathways (pores of Kohn, canals of Lambert, channels of Martin), which may sustain airflow to the fistula despite correct balloon positioning, potentially leading to mislocalization.

End-tidal CO₂ (ETCO₂) monitoring

ETCO₂ monitoring during sequential balloon occlusion has been proposed as an adjunctive method. Occlusion of the responsible bronchus redirects expiratory flow back through the central airway, producing a detectable rise in ETCO₂. However, this approach remains poorly validated, with only a single study describing its use and no established thresholds for the expected magnitude of ETCO₂ change (45).

Transbronchoscopic oxygen insufflation with digital monitoring

This positive localization strategy insufflates low-flow oxygen (1–2 L/min) through the bronchoscope wedged in candidate subsegmental bronchi, monitoring for a corresponding increase in air leak volume on the chest drainage system. A single case report (46) demonstrated successful localization using this technique. This approach remains investigational.

Intraoperative localization techniques

When re-exploration surgery is planned, other techniques can be utilized to localize the leak.

Water submersion test

The conventional method involves flooding the operative field with warm saline and ventilating the lung to identify sites of active bubbling on the visceral pleural surface. While widely used, this technique has a reported detection rate of approximately 75% (47) and may miss small or intermittent leaks. A video-assisted thoracoscopic surgery (VATS)-adapted modification (48) uses low-pressure intrathoracic CO₂ insufflation (3–5 mmHg) under two-lung ventilation to maintain the operative space, allowing direct visualization of air leak sites on the lung surface without requiring single-lung isolation. In a series of 22 patients with persistent air leaks, this technique identified the leak site in all but one patient.

Dye instillation

Instillation of dyes (e.g., methylene blue) or saline into the airway via bronchoscopy with concurrent thoracoscopic or open visualization of the pleural surface can localize air leaks by identifying sites of dye egress or active bubbling (43).

Indocyanine green (ICG) fluorescence imaging

Aerosolized ICG administered into the airway and observed with a near-infrared camera during VATS or thoracotomy represents a newer approach. In a study of 61 patients, the ICG sealing test achieved a detection rate of 98% compared with 75% for the conventional water submersion test (P=0.001), identifying 13 additional leak sites missed by standard methods (47). The technique allows prolonged observation of the lung in a collapsed state and is well-suited for minimally invasive surgery.

Takeaway points

BPF involves central airways and is typically identifiable by bronchoscopy or CT imaging. APF arises from peripheral parenchyma and generally requires functional localization techniques. Conventional CT has moderate sensitivity for BPF but limited utility for APF. Functional imaging (Technegas SPECT/CT, dynamic CT) offers superior localization but is constrained by availability. Sequential balloon occlusion is the most practical localization technique, but collateral ventilation may result in incomplete leak suppression and potential mislocalization. Intraoperatively, ICG fluorescence imaging may offer superior detection rates compared with conventional water submersion testing.

Endoluminal intervention

Mechanism of action

The unifying principle of endoluminal interventions is to reduce or eliminate the transpulmonary pressure gradient driving airflow from the airway into the pleural space, permitting healing of fistulous connection. Endoluminal strategies can be grouped into three mechanistic categories (43):

• Airflow reduction (one-way valves): block inspiratory airflow while allowing expiratory airflow and secretion drainage.
• Complete bronchial occlusion (spigots, plugs): fully occlude the airway lumen, eliminating both inspiratory and expiratory airflow. Does not permit distal secretion drainage.
• Direct defect sealing (fibrin glue, cyanoacrylate, hydrogel): physically obliterate the fistulous tract or coat the defect surface.

With discrete identifiable defects, BPFs may be amenable to direct sealing or complete occlusion. APFs, representing diffuse peripheral disruptions, are generally better suited to one-way valves. Substantial overlap exists in practice, and device selection is guided by fistula size, location, collateral ventilation, and patient-specific factors.

Devices

Endobronchial valves (EBVs)

One-way EBVs are the most extensively studied endoluminal intervention for persistent air leak (49). After localizing the airway with the balloon occlusion test—which is used to size the target airway, too—placement of the self-expanding valve is performed under direct visualization via flexible bronchoscopy. Proper positioning is confirmed by visualization of circumferential apposition to the airway wall.

Valve types and design

Two self-expanding, silicone-covered nitinol framework valve systems (50) are currently available in the USA:

• Zephyr^® Endobronchial Valve (Pulmonx Corporation): a “duckbill” valve sized to fit within the bronchial lumen, relying on circumferential contact for retention. Available in 4.0, 4.0-LP, 5.5, and 5.5-LP sizes (51).
• Spiration^® Valve System (Olympus Corporation): an “umbrella-shaped” valve with expandable struts and distal anchors. Available in 5, 6, 7, and 9 mm sizes (51).

Although the Spiration device is technically classified as an intrabronchial valve (IBV), both devices are commonly referred to as EBVs in the literature. For clarity, the term EBV is used generically in this chapter, with specific device distinctions made where relevant. Of note, only the Spiration Valve System received a Humanitarian Device Exemption (HDE) specifically for PALs following lobectomy, segmentectomy, or lung volume reduction surgery (43,52).

Number of valves

The number of valves required varies depending on airway anatomy and the number of segments contributing to the air leak. In a multicenter series by Travaline et al., between one and nine valves were placed per patient across 40 patients treated at 17 international sites (53).

Efficacy

No randomized controlled trials have been conducted for this indication; the best available evidence derives from observational studies synthesized in systematic reviews and meta-analyses as summarized in Table 5 (54-56). The most comprehensive meta-analysis (Damaraju et al., 2024) (54) included 28 observational studies comprising 2,472 patients and reported a pooled success rate of 82% (95% CI: 75–88%; 95% prediction interval). Subgroup analyses demonstrated higher success rates with IBVs compared with EBVs (84% vs. 72%), though this did not remain significant on meta-regression.

Duration of placement

Valves are generally temporary, with removal planned after leak resolution. Optimal conditions (no collateral ventilation with complete lobar occlusion) achieve median resolution in 3–4.5 days (57,58), while collateral ventilation delays resolution to a median of 17.5 days (58). Elective removal at 3 weeks after implantation has been safely performed (57). Valves may remain in situ if removal poses risks or if there are potential benefits from underlying emphysema.

Safety and complications

The overall complication rate is approximately 9% (54), with no procedure-related mortality reported in major series (51). Reported complications include:

• Granulation tissue formation at the valve site (most common);
• Valve migration or expectoration, particularly in lower-lobe placements (24% dislocation rate with the 9-mm Spiration valve in one series) (59);
• Hypoxemia due to ventilation–perfusion mismatch, most relevant in patients with limited pulmonary reserve (54-56).

Endobronchial Watanabe spigots (EWS)

EWS are radiopaque silicone bronchial plugs with multiple studs functioning as friction anchors, designed for complete mechanical occlusion of affected airways (60). Three sizes are available (5 mm × 8.5 mm, 6 mm × 10.5 mm, 7 mm × 12.5 mm). Unlike one-way valves, EWS fully seal the airway lumen, preventing distal secretion drainage—a trade-off that increases post-obstructive infection risk but may provide more durable airflow interruption. EWS are widely used in Asia, but are not approved in the USA.

Deployment and removal

Under direct visualization, the spigot is deployed and seated within the target bronchus until stable fixation is achieved. In a Japanese case series (60) of 63 bronchial occlusions, the medium-sized spigot was used most frequently, with an average of 4.4 spigots per case. Spigots are typically removed within 2–4 weeks after air leak resolution.

Efficacy

Reported success rates range from approximately 29% to over 60% as monotherapy (61-63). A small single-center study reported 75% success for postoperative pulmonary fistulas (61). Adjunctive treatments—including chemical pleurodesis or additional spigot placement—are frequently required. Observational data suggest that prior surgical intervention before EWS placement may be associated with worse outcomes, including higher in-hospital mortality or the need for subsequent surgical repair following bronchial occlusion (62).

Safety and complications

Pneumonia has been reported in approximately 3.3–5.5% of patients (60,63). Migration is uncommon, with sporadic reports of displacement into the central airway or pleural cavity (64). The evidence base consists predominantly of case reports and single-center series, mostly from Asian populations.

Sealants

Sealants aim to directly close the defect by forming a physical or chemical barrier. They are most effective for small, well-defined fistulae and are frequently used as adjunctive therapy with occlusive devices. Adequate pleural drainage and infection control remain prerequisites before considering these therapies.

Fibrin glue

Fibrin glue is a two-component biologic sealant (fibrinogen and thrombin) that polymerizes within minutes, forming a stable fibrin clot. It is highly biocompatible, elicits minimal inflammatory response, and undergoes biodegradation within 2–4 weeks. Reported success rates range from 70–100% in small case series (65-67), with higher success in the smallest defects. Key limitations include low tensile strength and rapid biodegradation, making it most suitable for adjunctive therapy after partial reduction with a valve or other device, with currently insufficient evidence of efficacy when used first.

Cyanoacrylate adhesives

N-butyl-2-cyanoacrylate (NBCA) polymerizes rapidly on contact with tissue moisture, forming a rigid seal. It induces a dense localized inflammatory response. Cyanoacrylate has been used most successfully for BPF measuring 4–8 mm, with definitive closure in 71% in one series of seven patients (68). For larger or more chronic defects, cyanoacrylate has been combined with polyvinyl alcohol sponge plugs, which serve as a scaffold to improve adhesive retention. Risks include airway obstruction from adhesive migration and thermal injury from exothermic polymerization.

Polyethylene glycol (PEG)-based hydrogel sealants

Two liquid components that rapidly polymerize and crosslink with exposure to moisture form a flexible, biocompatible hydrogel designed for gradual degradation. In a series of 22 patients with APF, PEG hydrogel achieved complete air leak resolution in 86%, with chest tube removal a mean of 4.3 days after final application. Material migration was reported in 2 of 22 patients (69).

Selection of sealant type should be individualized:

• Fibrin glue: small defects requiring a temporary, biocompatible seal.
• Cyanoacrylate: small-to-moderate defects requiring durable, permanent closure.
• PEG hydrogel: moderate defects where a flexible, temporary seal with minimal tissue reaction is preferred.

Autologous blood patch (ABP) therapy

ABP therapy uses a patient’s own blood to promote fistula closure through clot formation, mechanical sealing, and localized inflammatory response. ABP may be delivered intrapleurally via chest tube or endobronchially targeting specific airways. Adequate pleural drainage and infection control remain prerequisites.

Intrapleural instillation

Instillation of autologous blood through an existing chest tube to coat the visceral pleural surface and seal sites of air leakage with volumes ranging from 50 to 200 mL. Systematic reviews demonstrate approximately 80–90% success rates with no clear dose–response relationship (70). One randomized controlled trial (RCT) in secondary spontaneous pneumothorax found equivalent success at 1.0 and 2.0 mL/kg (both 82%), compared with 27% at 0.5 mL/kg and 9% with placebo, suggesting a threshold effect rather than a linear dose dependency (71).

A large multicenter retrospective cohort (72) (510 patients, propensity-matched to 109 per group) demonstrated that ABP was associated with shorter time to chest tube removal (8.12 vs. 9.30 days, P=0.004) and reduced hospital LOS (10 vs. 11 days, P=0.045) compared with conservative management. The Shackcloth randomized trial (73) (n=20) showed ABP significantly shortened the median time to chest drain removal (6.5 vs. 12 days, P<0.001) and hospital discharge (8 vs. 13.5 days, P<0.001). Complication rates are generally low, with transient fever the most common adverse effect.

Endobronchial instillation

Data specifically addressing postoperative air leaks are limited. A randomized controlled trial (74) of 150 patients with secondary spontaneous pneumothorax demonstrated significantly higher pneumothorax resolution at 14 days (82%) with segmental instillation of autologous blood (20–30 mL per segment) combined with thrombin solution, compared with chest tube drainage alone (60%, P=0.008). Temporary hemoptysis was commonly observed following the procedure, but the incidence of chest pain, cough, fever, and infection was similar between the treatment and control groups. Extrapolation to the postoperative setting should be performed cautiously.

Limitations

The evidence base is limited by heterogeneity in technique, timing, and dosing. Intrapleural instillation may be less effective or technically challenging in patients with large-volume air leaks who remain suction dependent, as adequate dwell time and pleural apposition may be difficult to achieve. Key evidence gaps include standardized dosing strategies, clarification of optimal timing relative to postoperative day and air leak physiology, and direct comparisons between intrapleural and endobronchial delivery routes.

Emerging and experimental therapies

Several emerging approaches remain experimental or preclinical and cannot be recommended for routine clinical use yet.

Autologous platelet-rich plasma (PRP)

Prepared from the patient’s own blood, centrifuged to concentrate plate and endogenous growth factors that promote fistula healing and activating the concentrate into a gel, which is then injected around the fistula during bronchoscopy. A single case series (75) of three patients with tracheobronchial fistulae reported successful healing after submucosal PRP injection. No RCTs or comparative studies exist.

Bioengineered endoluminal devices

Silk-elastin sponges promoted airway epithelium regeneration in a canine model (76). Bio-three-dimensional (3D) printed cellular plugs are composed of mesenchymal stem cells combined with endothelial cells that achieved bronchial closure in a rat model (77). Self-fused powder adhesives are a poly(amino acid)-based microgel that demonstrate strong tissue adhesion with antibacterial properties in animal models (78).

Bioengineered surgical sealants

Alginate and gelatin-based hydrogels achieved sustained pleural wound repair for up to one month in rat and porcine models (79). Lung-mimetic hydrofoam sealants replicate alveolar-like porous architecture with lung-specific viscoelastic properties that have been able to rapidly seal air leaks while preserving baseline lung mechanics in rat and swine models (80).

Limitations and future directions

Current evidence supporting endoluminal interventions derives primarily from observational studies, case series, and expert consensus, with a lack of randomized comparative trials. Definitions of treatment success remain heterogeneous, and severity thresholds are consensus-based. Future priorities include comparative trials between surgery and endoluminal therapy, comparative trials between endoluminal options, standardized outcome definitions, investigation of the benefit of digital drainage analytics, and clinical translation of bioengineered closure systems.

With careful patient selection, physiological classification, accurate localization, and appropriate device matching, endoluminal therapies represent an integral component of modern postoperative thoracic care—offering minimally invasive alternatives that may reduce morbidity and shorten hospitalization in appropriately selected patients.

Takeaway points

All endoluminal interventions work by reducing or eliminating the transpulmonary pressure gradient driving air across the fistula. Three mechanistic categories exist: one-way valves reduce airflow, spigots/plugs completely occlude airways, and sealants directly seal defects. Device selection is guided by local device availability, fistula type (BPF vs. APF), size, location, and patient factors. EBVs are the most extensively studied and most efficacious. The Spiration Valve System is the only device with an on-label FDA indication for persistent air leak. Intrapleural ABP is a low-cost, bedside-accessible option (~80–90% success) with a threshold effect at ~1 mL/kg. No single modality is universally effective, and interventions are frequently combined in practice. Table 6 provides a summary and comparison of Endoscopic Interventions.

Conclusions

Postoperative air leaks affect approximately 50% of patients after pulmonary resection, with 8–10% progressing to PAL beyond postoperative day 5. The clinical consequences are substantial, including an 8.5-fold increase in empyema risk and an average 5-day prolongation of hospitalization.

Figure 1 synthesizes the evidence into a comprehensive management algorithm. Preoperative risk models (IPAL, Gilbert, PALS) and intraoperative air leak quantification identify high-risk patients early. However, digital drainage systems lack prospectively validated thresholds, and prediction models demonstrate only moderate discrimination with low positive predictive values. Neither has been shown in prospective trials to improve patient outcomes. These tools should be viewed as aids to risk stratification and to multidisciplinary discussion rather than definitive determinants of intervention timing.

Figure 1 Persistent air leak evaluation and treatment. BPF, bronchopleural fistula; CT, computed tomography; DDPAL, drainage-dependent prolonged air leak; DIPAL, drainage-independent prolonged air leak; EBV, endobronchial valve; EtCO₂, end-tidal CO₂; NM, nuclear medicine.

On postoperative day 5, a tube-clamping trial distinguishes DDPAL from DIPAL. Clamping can be performed based on timing rather than waiting for leak diminution, as higher-flow clamping (60–80 mL/min) is non-inferior to minimal-flow clamping and shortens hospital stay.

Patients who fail clamping undergo flexible bronchoscopy, which serves as the pivotal diagnostic and therapeutic step. Direct visualization of bronchial stump dehiscence establishes BPF and directs care toward surgical revision or bronchial stenting. When airway inspection is unremarkable, sequential balloon occlusion testing attempts functional localization. Results of localization, combined with fistula size and anatomy, guide surgical intervention or device selection in non-surgical candidates: EBVs or spigots for localized segmental leaks, and sealants or ABP for small or distal defects. Reassessment within 24–72 hours allows iterative escalation or combination therapy.

Although endoluminal therapies are generally less invasive than surgery, cumulative procedural risk may increase with multiple bronchoscopic interventions. Persistent leaks despite initial endoluminal therapy should prompt reassessment of surgical candidacy rather than indefinite escalation of bronchoscopic interventions.

Acknowledgments

None.

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Roman V. Petrov and Andrei I. Gritsiuta) for the series “Complications in Anatomical Lung Resection: A Comprehensive Surgical Perspective” published in Journal of Thoracic Disease. The article has undergone external peer review.

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1067/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1067/coif). The series “Complications in Anatomical Lung Resection: A Comprehensive Surgical Perspective” was commissioned by the editorial office without any funding or sponsorship. The authors have no other 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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