Abstract
Background:
Giant emphysematous bulla (GEB) is a form of emphysematous lung destruction and patients experience progressive dyspnea and decline in quality of life. Conventional surgical reduction is not available for all patients, especially those in poor condition, and a less invasive approach is needed.
Objectives:
This study aimed to evaluate the feasibility and preliminary clinical outcomes of medical thoracoscopic bulla volume reduction for GEB.
Design:
Single-center retrospective observational study.
Methods:
A total of 35 GEB patients who underwent medical thoracoscopic bulla volume reduction were retrospectively analyzed. Preoperative and postoperative clinical data and chest computed tomography were collected. The feasibility of the technique was evaluated by radiological changes (bullae volume and diameter) and postoperative complications. Improvement in dyspnea was assessed using the modified Medical Research Council (mMRC) dyspnea scale. Accessible six-minute walk distance (6MWD) and spirometry test follow-up data were analyzed to assess preliminary clinical functional improvement.
Results:
The targeted bulla volume was 1183.8 ± 636.7 mL preoperatively and decreased to 169.2 ± 237.2 mL postoperatively, representing an 87.7 ± 17.1% decrease compared to the baseline. A total of 91.4% (32/35) of the patients achieved more than 50% volume reduction relative to baseline, and the diameter of the targeted bulla also showed a significant decrease (p < 0.0001). Nine subcutaneous emphysema cases and one thoracic infection case were reported as postoperative complications. In the overall population, the mMRC score decreased by 1.2 ± 0.6 points at the 6-month follow-up. Available follow-up data on 6MWD and spirometry tests also showed improvement.
Conclusion:
Medical thoracoscopic bulla volume reduction may represent a feasible and less invasive therapeutic option for patients with GEB and demonstrated preliminary clinical outcomes.
Plain language summary
Giant emphysematous bullae are large air spaces that form in the lungs when lung tissue is destroyed. These bullae take up space inside the chest and press on the healthy parts of the lung, making it hard for patients to breathe. The usual treatment is surgery to remove the bullae, but many patients are too sick or have other health problems that make surgery too risky. In this study, we tested a less invasive procedure using a medical thoracoscope, which is a small camera and tool inserted through a small cut in the chest wall. The goal was to shrink the bullae and improve breathing. We treated 35 patients who could not have traditional surgery. After the procedure, the size of the bullae decreased by nearly 88 percent on average. Most patients felt less short of breath six months later. The most common side effect was air under the skin, which got better with treatment. The average time to stop air leakage from the lung was about four days, and the chest tube was removed after about seven days. We also looked at lung function and walking distance in patients who had available follow-up data. Both showed improvement. This procedure may be a good option for patients with large lung bullae who are not healthy enough for standard surgery.
Introduction
Giant emphysematous bulla (GEB) represents a form of emphysematous lung destruction when one or more bullae enlarge to the extent that they occupy more than one-third. 1 Because of the alveolar destruction, these bullae lack an alveolar–capillary interface and act as a space-occupying lesion compressing normal lung parenchyma. 2 During the respiratory cycle, these easily distensible bullae are preferentially filled during inspiration, resulting in air trapping and progressive bulla expansion.2,3
Surgical resection (open thoracotomy or video-assisted thoracic surgery) remains the conventional treatment for symptomatic giant emphysematous bullae, but its applicability is often limited in high-risk patients with poor cardiopulmonary reserve and multiple comorbidities.4,5 Moreover, postoperative complications following giant bullectomy are not uncommon, including prolonged air leak, atrial fibrillation, postoperative mechanical ventilation, and pneumonia. 2 Compared to conventional surgery, medical thoracoscopy (MT) is a less invasive approach and also offers the advantage of direct visualization. In this study, we aimed to investigate the feasibility and preliminary clinical outcomes of the medical thoracoscopic bulla volume reduction for GEB.
Methods
Study design
This was a retrospective analysis of GEB patients who underwent medical thoracoscopic bulla volume reduction in West China Hospital of Sichuan University from May 2022 to May 2025. Written procedural consent for medical thoracoscopic treatment was obtained from all patients before the operation as part of routine clinical practice. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. 6 The completed STROBE checklist is provided as Supplemental Table 1.
Inclusion criteria were (1) age ⩾40 and ⩽85 years; (2) the target pulmonary bulla occupying more than one-third of the hemithorax confirmed by chest computed tomography (CT); (3) a well-defined boundary between the bulla and surrounding lung tissue; and (4) patients considered unsuitable for surgical intervention because of impaired cardiopulmonary reserve or who declined surgical treatment. Exclusion criteria included patients with active pulmonary infection, severe pulmonary hypertension, severe heart failure (New York Heart Association class IV), bronchiectasis, asthma, a history of myocardial infarction within 6 months before operation, as well as patients who were current smokers within the preceding 6 months.
Device
Semi-rigid Medical Thoracoscope (LTF 240, OLYMPUS), electrocautery knife (KD-31C-1, OLYMPUS), electrosurgical unit (VIO 200D, ERBE), argon plasma coagulator (APC2, ERBE), APC probe (20132-221, ERBE), trocar (179301, Covidien), pressure extension tube (YCGH×2.03, SCW Medicath Ltd.), and human fibrin sealant kit (Shanghai RAAS Blood Products Co., Ltd.)
Medical thoracoscopic bulla volume reduction procedure
Building on previous studies on MT treatment for GEB, we developed the following technical procedures.7,8 Within 48 h before surgery, a catheter (8–14 F) was placed into the pulmonary bulla under CT guidance to establish an artificial pneumothorax, allowing us to observe pleural adhesions within the pleural cavity. MT procedure was performed while maintaining spontaneous respiration. Intravenous dexmedetomidine and sufentanil were used for sedation and analgesia. A dose of 5–10 ml of 2% lidocaine was administered for local anesthesia. The surgical site was selected on the chest wall, corresponding to the center of the pulmonary bulla on the chest CT, and avoided areas of pleural adhesion. A 1.0 cm incision was made following disinfection and draping. The subcutaneous and muscle layers were bluntly dissected with vascular forceps to access the pleural cavity, after which the trocar was inserted. A medical thoracoscope was then introduced through the trocar cannula into the pleural cavity.
After entering the pleural cavity, adhesions between the target pulmonary bulla and the pleura, mediastinum, or diaphragm were carefully dissected using an electrocautery knife (power 55 W). The medical thoracoscopic adhesiolysis procedure is illustrated in Figure 1. After adhesiolysis, the targeted bulla was then grasped with a Kelly clamp and gently retracted out of the thoracic cavity through the trocar cannula. Human fibrin sealant (8–20 mL) was sprayed into the interior of the bulla through a pressure extension tube, which was clamped for 3–5 min. The surface of the bulla was subsequently cauterized using APC (power 30–35 W) until it turned yellowish-brown (2–3 s per site), to ensure sustained collapse and loss of elasticity without overcauterization or rupture. Finally, an even layer of human fibrin sealant (2 mL) was sprayed over the surface of the bulla. The patient was instructed to cough, or manual ventilation was performed using a bag-valve-mask to assess re-expansion of the pulmonary bulla. If re-expansion occurred, additional human fibrin sealant was sprayed into the bulla, and argon plasma cauterization was repeated as necessary. If the bulla failed to re-expand, the procedure was terminated, and a chest drainage tube was placed.
Medical thoracoscopic dissection of adhesions using an electrocautery knife. (a) The targeted pulmonary bulla (the white arrow). (b) Adhesions between the bulla and the parietal pleura (the white arrow). (c) Dissection of adhesions with an electrocautery knife (the black arrow), with the red arrow indicating the parietal pleura. (d) Complete release of adhesions.
Postoperative monitoring
After operation, bronchoscopic sputum aspiration, prophylactic anti-infective therapy, and analgesic treatment were administered. A chest X-ray (posteroanterior view) was performed 4–12 h later to evaluate lung re-expansion. If the lung failed to re-expand, suction was applied through a water-seal system at 5 mmHg. The chest tube was clamped shut for 24 h after stopping air leak. The chest tube was removed if chest X-ray confirmed no pneumothorax. The time to air leak cessation and the time to chest tube removal were recorded for each person. Complications including subcutaneous emphysema, thoracic infection, vasovagal reaction, intrapleural hemorrhage, and bronchopleural fistula were documented.
Study outcomes
To assess the feasibility of this technique, we investigated radiographic changes in pulmonary bullae and collected complications postoperatively. Volume and diameter of the targeted bullae were measured with the Lungpro software (Hangzhou Broncus Medical, China). The CT scan taken within 2 weeks postoperatively was compared with the preoperative CT scan. The relative reduction in the volume of bullae was expressed as (preoperative volume − postoperative volume) divided by the preoperative volume. Technical success was defined as a relative reduction of more than 50% in the targeted bulla volume compared with baseline. Safety was assessed based on postoperative chest tube monitoring and procedure-related complications. Preliminary clinical outcomes included dyspnea assessment using the modified Medical Research Council (mMRC) scale at baseline and follow-up. Additionally, available 6-minute walking distance (6MWD) and spirometry test results at 6 months postoperatively were included in the exploratory analysis of clinical outcomes.
Statistical analysis
Continuous variables were summarized as means and SDs. Categorical variables were summarized as frequencies and percentages. Paired comparisons of pre- and postoperation continuous measurements were performed using the paired t-test or Wilcoxon signed-rank test, depending on sample size and distribution. Mean differences with 95% confidence intervals (CIs) were calculated for exploratory functional outcomes. All statistical analyses were performed with GraphPad Prism 10 (GraphPad Software, San Diego, CA, USA) and SPSS version 25 (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.
Results
Baseline characteristic
A total of 35 patients were analyzed in the study. The specific reasons for patients being considered unsuitable for surgical intervention are summarized in Supplemental Table 2. The mean age of the population was 62.1 ± 8.2 years, with a mean body mass index of 21.4 ± 3.2 kg/m2 and a mean smoking history of 36.7 ± 24.0 pack-years. The main symptoms reported were cough (100%, 35/35), expectoration (97.1%, 34/35), and dyspnea (97.1%, 34/35). Dyspnea was grade 0 or 1 in five patients (14.3%, 5/35) and grades 2, 3, or 5 in thirty patients (85.7%, 30/35). Comorbidities include chronic obstructive pulmonary disease (COPD; 100%, 35/35), hypertension (34.3%, 12/35), diabetes (8.6%, 3/35), coronary heart disease (11.4%, 4/35), cor pulmonale (14.3%, 5/35), hyperlipidemia (5.7%, 2/35), and lung cancer (2.9%, 1/35). Pleural adhesions were identified in 80% of patients under MT. The baseline characteristics are summarized in Table 1.
Baseline characteristics of included patients.
BMI, body mass index; mMRC dyspnea scale, modified Medical Research Council dyspnea scale.
Feasibility and safety of the technique
Medical thoracoscopic bulla volume reduction was successfully performed in all patients. In the study population, the preoperative targeted bulla volume was 1183.8 ± 636.7 mL, and the postoperative pulmonary bulla volume was 169.2 ± 237.2 mL. The volume of postoperative target pulmonary bullae decreased by 87.7 ± 17.1% compared to pre-operation measurements (p < 0.0001). Overall, 91.4% of them (32/35) achieved more than 50% volume reduction. The decrease in lung bullae for the other three patients was 29.2%, 47.5%, and 48.8%, respectively. The overall population’s preoperative target lung bulla diameter was 17.1 ± 5.8 cm and the postoperative diameter was 5.4 ± 4.7 cm; the improvement was statistically significant (p < 0.0001). Changes in bulla volume and diameter for each patient before and after the operation are shown in Figure 2. We present a preoperative and postoperative CT comparison for one patient in Figure 3, and his intraoperative MT procedure in Figure 4. The 81-year-old patient had a preoperative targeted bulla volume of 826 mL, which decreased to 0 mL postoperatively, achieving complete bulla volume reduction.
Individual changes in the targeted bullae diameter (a) and the targeted bullae diameter (b).
A case’s postprocessing computed tomography imaging before (a) and after (b) the operation. The green areas indicate the targeted bulla (the red arrowheads), which completely resolved after intervention.
A case’s medical thoracoscopic imaging of the procedure. (a, b) The targeted bulla (the white arrow) under the medical thoracoscopy. (c) The targeted bulla (the white arrow) was grasped with a Kelly clamp (the black arrow) and gently retracted through the trocar cannula (the red asterisk), followed by fibrin sealant injection into the bulla through a pressure extension tube (the red arrow). (d) The targeted bulla shrank (the white arrowhead) after intervention.
The overall mean time to air leak cessation was 4.4 ± 3.2 days and the mean time to chest tube removal was 6.8 ± 4.2 days. The most common postoperative complication was subcutaneous emphysema 34.3% (12/35). For moderate-to-severe subcutaneous emphysema, negative pressure was applied through the chest tube. No events of vasovagal reaction or pleural hemorrhage were observed. Postoperative monitoring parameters were summarized in Table 2. The 30-day postoperative survival rate was 97.1% (34/35), and the cause of the death case was lung cancer progression.
Postoperative monitoring of the chest tube and complications.
Symptom and exploratory clinical functional improvement analysis
At the 6-month follow-up, the mMRC score decreased by 1.2 ± 0.6 points in the overall population. Of all patients, 32 (91.4%) reported relief from dyspnea, with 10 improving by 2 points and the remaining by 1 point. Twenty-one patients with available 6-month postoperative 6MWD data and seven patients with spirometry data were analyzed. The mean improvement in 6MWD at 6 months after surgery was 211.8 ± 132.5 (p < 0.0001, 95% CI: 151.4–272.1), compared with baseline. The improvement was 188.1 ± 113.0 (p < 0.01, 95% CI: 83.7–292.6) mL in FEV1, 9.0 ± 4.0% (p < 0.001, 95% CI: 5.4–12.7%) in FEV1% Pred, 354.3 ± 573.5 (p = 0.3, 95% CI: –176.1–884.7) mL in FVC, 12.7 ± 12.3% (p = 0.03, 95% CI: 1.4–24.1%) in FVC% Pred. FEV1 and FEV1% Pred both reached statistical significance. Among FVC-related indices, FVC did not show a significant change, whereas FVC% Pred was achieved. The specific individual changes in 6MWD and spirometry tests before and 6 months postoperatively are shown in Figure 5.
Individual changes in 6-minute walk distance (a) and spirometry test (b) at 6 months postoperatively.
Discussion
For patients with GEB, bullectomy is a conventional but more invasive approach requiring general anesthesia. Surgical resection involving a large volume of emphysematous lung tissue may increase the risk of postoperative pneumothorax and the formation of new bullae. 5 Considering that most patients have comorbidities and limited residual functional lung parenchyma, rendering them unable to tolerate surgery, we aimed to develop a novel medical thoracoscopic approach and evaluate its feasibility and functional improvement.
In this study, we aimed to treat GEB with the medical thoracoscopic bulla volume reduction technique. The postprocessing imaging software confirmed that this technique successfully reduced bullae volume, with nine patients achieving complete reduction of bullae. The main postoperative complications reported were subcutaneous emphysema (12/35, 34.3%) and thoracic infection (1/35, 2.9%), confirming the acceptable safety profile of this technique. Regarding symptom improvement, 91.4% of patients experienced relief from dyspnea, with no patients showing worsening symptoms. Among those without improvement, one patient had a baseline mMRC grade of 0 and two had grade 2, suggesting that improvement may not have been observed due to the mild nature of their symptoms. In the exploratory functional analysis, patients showed a mean improvement of 188 mL in FEV1 and 212 m in 6MWD at 6 months postoperatively. In comparison, previous surgical studies of giant emphysematous bullae reported a mean FEV1 improvement of approximately 700 mL and a mean 6MWD improvement of approximately 113 m after surgical bullectomy. 2 The less pronounced improvement in FEV1 in our study, compared with surgical resection, may be because our patients were surgically unfit with poorer general condition, lower baseline FEV1, and the presence of comorbidities may have partly limited the observed improvement. For FVC, our study showed a trend toward improvement without statistical significance, which is consistent with findings from surgical studies, where the main improvement following bullectomy is primarily observed in FEV1.2,9,10
Several interventional approaches to treat GEB have been explored gradually. Bronchoscopic strategies include sclerosing agents and endobronchial valves to prevent bulla expansion. In a study by Santini et al., they evaluated the efficacy of endobronchial treatment with one-way valves for GEB in nine surgically unfit patients, showing an improvement of around 800mL in FEV1 and 138m in 6MWD at 6 months follow-up, but the effect of bronchoscopic occlusion is limited on GEB with interlobar collateral ventilation.11,12 Besides, one-way valve placement can be associated with complications including pneumothorax, bleeding, pneumonia, and valve dislodgement. 13 CT-guided percutaneous bulla drainage was first introduced by Takizawa et al., and expanded by Wang et al., aiming to achieve collapse of the bullae mainly through intra-bulla negative pressure drainage.14,15 Of the complications of percutaneous drainage, prolonged air leak is the most concerning one. We hypothesize that this may be attributable to incomplete closure of the multiple collateral ventilation channels between bullae and airways. Simply relying on negative pressure suction without blocking the gas source within the bullae is insufficient to completely collapse them, and leads to prolonged air leak. Additionally, in some cases, adhesions are present between the bullae and the pleura, which restrain the bullae from collapsing. In our study, we attempted to first dissect the adhesions contacting the pulmonary bullae under direct visualization with the MT, then inject fibrin sealant into the bullae to seal the gas-supplying pores, and clamp the bullae to expel residual gas. Subsequently, APC was applied to cauterize the surface of the pulmonary bulla to induce surface stiffening, followed by spraying fibrin sealant to seal potential residual defects on the bulla surface, thereby achieving bulla volume reduction. The median duration of chest tube drainage reported in our study was 5.5 days; the only case beyond 14 days was removed on day 16. Our technique targets precise GEB intervention and mitigates the risk of prolonged air leak after operation, with outcomes confirming its feasibility and preliminary functional improvements.
There are some limitations in this study. Since postoperative follow-up examinations are not mandatory, the available postoperative data on exercise capacity assessments and pulmonary function are limited. Additionally, some high-risk patients underwent only spirometry preoperatively, data for residual volume and diffusion capacity for carbon monoxide are also missing in certain cases, thus, we did not conduct further analysis. In addition, due to the retrospective study design, health-related quality of life assessment was lacking. We consider this study may provide evidence for the technique of the medical thoracoscopic bulla volume reduction for GEB, serving as a foundation for subsequent prospective studies to explore its further efficacy and safety.
Conclusion
Medical thoracoscopic bulla volume reduction may be considered as a feasible and less invasive alternative to surgical resection, while its further efficacy warrants validation in a larger prospective study.
Supplemental Material
sj-doc-1-tar-10.1177_17534666261465491 – Supplemental material for Feasibility and preliminary clinical outcomes of medical thoracoscopic bulla volume reduction for giant emphysematous bulla
Supplemental material, sj-doc-1-tar-10.1177_17534666261465491 for Feasibility and preliminary clinical outcomes of medical thoracoscopic bulla volume reduction for giant emphysematous bulla by Rui Xu, Xinmiao Du, Ling Zuo, Jingyu Shi, Yongxiao Luo, Tao Zhang, Dan Liu and Kaige Wang in Therapeutic Advances in Respiratory Disease
Supplemental Material
sj-docx-1-tar-10.1177_17534666261465491 – Supplemental material for Feasibility and preliminary clinical outcomes of medical thoracoscopic bulla volume reduction for giant emphysematous bulla
Supplemental material, sj-docx-1-tar-10.1177_17534666261465491 for Feasibility and preliminary clinical outcomes of medical thoracoscopic bulla volume reduction for giant emphysematous bulla by Rui Xu, Xinmiao Du, Ling Zuo, Jingyu Shi, Yongxiao Luo, Tao Zhang, Dan Liu and Kaige Wang in Therapeutic Advances in Respiratory Disease
Supplemental Material
sj-xlsx-1-tar-10.1177_17534666261465491 – Supplemental material for Feasibility and preliminary clinical outcomes of medical thoracoscopic bulla volume reduction for giant emphysematous bulla
Supplemental material, sj-xlsx-1-tar-10.1177_17534666261465491 for Feasibility and preliminary clinical outcomes of medical thoracoscopic bulla volume reduction for giant emphysematous bulla by Rui Xu, Xinmiao Du, Ling Zuo, Jingyu Shi, Yongxiao Luo, Tao Zhang, Dan Liu and Kaige Wang in Therapeutic Advances in Respiratory Disease
Footnotes
References
Supplementary Material
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