Lung volume reduction surgery by intra-bullous fibrin sealant application using thoracoscopy, an alternative in the management of vanishing lung syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Lung volume reduction surgery by intra-bullous fibrin sealant application using thoracoscopy, an alternative in the management of vanishing lung syndrome Ling Zuo, Kaige Wang, Weimin Li, Jingyu Shi, Fen Tan, Dan Liu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3972514/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 15 You are reading this latest preprint version Abstract Background: To investigate the efficacy of lung volume reduction surgery (LVRS) through the application of intra-bullous fibrin sealant using thoracoscopy in patients diagnosed with vanishing lung syndrome(VLS). Methods: A retrospective analysiswas conducted on the clinical data of patients with VLS who were admitted to the West China Hospital of Sichuan University between March 2022 and September 2023. Patients who met the inclusion criteria underwent LVRS and were followed up to evaluate the efficacy and safety of the technique. Results: A total of seven male patients were included, with a median age of 61 years. The patients' post-operative activity tolerance, as assessed by the chronic obstructive pulmonary disease assessment test (CAT) score and the 6-minute walk test (6-MWT), showed continuous significant improvement. Besides, five patients injected with at least 20 mL of fibrin sealant underwent successful reduction and received double-lumen endotracheal intubation while under anesthesia. The operation failed in two patients with fibrin sealant injection volume less than 12 mL. However, no significant postoperative complications were observed except for one patient with 20 mL pleural hemorrhage and a maximum of 28 days of postoperative air leakage. Conclusion: The application of intra-bullous fibrin sealant through thoracoscopy is a safe and effective approach for managing VLS, resulting in minimal wound and fewer complications. The success of this strategy depends on using dual lumen tracheal intubation to block lung ventilation and applying the appropriate amount of fibrin sealant. Retrospective trial registration: (Chinese Clinical Trial Center, registration number: ChiCTR2300078038, registered 2023-11-27) lung volume reduction surgery vanishing lung syndrome thoracoscopy intra-bullous fibrin sealant Figures Figure 1 Figure 2 Figure 3 Introduction Vanishing lung syndrome (VLS), also known as idiopathic giant bullous emphysema, typically manifests in the upper lobes. This condition predominantly affects young, slender male smokers [ 1 ] . In 1987, specific radiological criteria were proposed to diagnose VLS, include the presence of giant bullae in one or both upper lobes, occupying at least one third of the hemithorax. Consequently, normal lung function is compromised [ 2 ] . In addition, some patients may develop fatal pneumothorax [ 3 ] . The management of VLS varies in approach, ranging from conservative to surgical, based on the patients' comorbidities and suitability for surgical resection. Lung volume LVRS is the primary treatment for VLS. Surgical bullectomy, performed through Video-assisted thoracoscopic surgery (VATS) or thoracotomy, has gained acceptance in specific patient populations. Nevertheless, the utilization of surgical bullectomy remains restricted due to prolonged post-operative leakage, significant trauma, and high hospitalization costs [ 4 , 5 ] . Consequently, the management of VLS remains an ongoing challenge. In recent years, intra-bullous fibrin sealant has been employed to decrease the size of pulmonary bullae through percutaneous pulmonary bulla centesis [ 8 ] There are few studies on the safety and effectiveness of thoracoscopy combined with fibrin sealant for the management of VLS [ 6 , 7 ] . To investigate the efficacy of LVRS through the application of intra-bullous fibrin sealant using thoracoscopy in patients diagnosed with VLS, to guide clinical practice. Methods The clinical data of seven patients diagnosed with VLS between March 2022 and September 2023 at West China Hospital of Sichuan University were gathered. A retrospective analysis was performed to examine the overall condition, clinical features, treatment approaches, and patient outcomes. The inclusion criteria for our study were as follows: 1) Patients met the diagnostic criteria for VLS, which entails the presence of bullae occupying at least one-third of a hemithorax. 2) Patients were unable to undergo thoracic surgery due to intolerance. The exclusion criteria for this study were as follows: 1) Patients with respiratory failure who could not be weaned off mechanical ventilation were excluded. 2) Patients who refuse to undergo surgery will also be excluded from the study. Surgical methods The surgical methods employed in this study were as follows: 1) The adhesive joint was separated using thoracoscopy, and the bulla was fully freed. 2) The bulla was punctured, and fibrin sealant was injected into it through a puncture needle. The gas inside the bulla was aspirated, causing the bulla to collapse and close. 3) Oval forceps was used to clamp the bullae, ensuring complete occlusion and adhesion. 4) Water was injected into the thoracic cavity on the surgical side, and bilateral lung ventilation was restored to observe any air leakage. If there is any air leakage, repeat the above steps. Data collection Information on the overall condition, symptoms, chest high resolution CT (HRCT) findings were collected. Subsequently, all patients were monitored at 1 month, 3 months, and 6 months post-surgery, with activity tolerance assessed through the CAT score and 6-MWT. Method for estimating the volume of bullae The chest CT image data was evaluated through the post-processing workstation (3D Slicer) for measurement. The lung quantification software was employed to measure the horizontal axis image with a layer thickness of 1mm. The software automatically delineated the lung tissue and other tissues in the image, while some tissues were manually outlined. Pseudo color technology was utilized to visually present the target lung bullae and their relative proportion to the entire lung, along with the calculation of their volume. The threshold for measuring the volume of bullae was set at -1024 to -980HU. The threshold for emphysema was set at -980 to -910HU. Definition of successful LVRS The successful outcome of LVRS is defined as the absence of target lung bullae or the target lung bullae volume not exceeding one-third of its preoperative measurement, as observed in the chest imaging examination conducted three months after the procedure. Results A total of 11 individuals diagnosed with VLS were admitted to our hospital. Among them, one patient underwent VLRS through the surgical removal of pulmonary bullae. Two patients declined the surgical intervention, while one patient experienced respiratory failure and was unable to be disconnected from the ventilator. Eventually, seven patients were treated with LVRS via intra-bullous fibrin sealant application using thoracoscopy. The age range of the seven male patients included in the study was between 57 and 73 years, with a median age of 61 years. All patients were diagnosed with COPD and received standardized nebulized inhalation therapy. Six patients were classified as being in the stable phase (Case 1-6), while one patient (Case 7) was experiencing an acute exacerbation phase and undergoing intravenous glucocorticoid treatment. All patients had a history of smoking. The clinical symptoms observed in all patients included cough, expectoration, and dyspnea. The general condition of all patients is presented in Table 1. Laboratory examination results revealed that two patients had hemoglobin levels exceeding 160 g/L. Additionally, five patients suffered from chronic respiratory failure and required long-term home oxygen therapy. Case 7 specifically required high-flow oxygen therapy (Table 1). All patients' chest HRCT scans revealed bilateral diffuse emphysema, unilateral or bilateral giant pulmonary bullae, and compressibility atelectasis of lung tissue surrounding the bullae. As indicated in Table 2, five patients underwent successful LVRS. No major complications occurred during the surgical procedure, except for one patient with 20 mL of pleural hemorrhage and a maximum of 28 days of postoperative air leakage. Chest HRCT examination was conducted three months post-surgery. The size, diameter, and volume of the targeted pulmonary bullae significantly decreased, as demonstrated in Table 3. Patients were evaluated for 6-MWT at 1, 3, and 6 months postoperatively, showed improvement in activity tolerance (Figure. 1). Nevertheless, two patients experienced surgical failure. One patient (Case 5) was referred to thoracic surgery for LVRS and subsequently succumbed to tension pneumothorax two weeks after the procedure. Additionally, another patient (Case 7) was lost to follow-up after being discharged automatically. Table 1 Characteristics of 7 Hospitalized Patients with vanishing lung syndrome Patient Number Age ( y ) Gender Smoking history (y) Underlying disease Hemoglobin concentration (g/L) Pulmonary bulla position Current treatment plan P 1 61 M 30 COPD,Hypertension 166 Right middle lobe ICS+LABA P 2 64 M 28 COPD 140 Right middle lobe ICS+LABA+LAMA P 3 59 M 20 COPD,Diabetes 146 Right upper lobe ICS+LABA+LAMA P 4 57 M 31 COPD 124 Left upper lobe ICS+LABA+LAMA P 5 60 M 40 COPD 134 Right middle lobe ICS+LABA+LAMA P 6 64 M 38 COPD 162 Left upper lobe ICS+LABA P 7 73 M 40 COPD,Asthma,Lung cancer 126 Left upper lobe ICS+LABA+LAMA Cases 1-6 were diagnosed with stable phase COPD and received standardized nebulized inhalation therapy. Case 7 was in an acute exacerbation phase and receiving intravenous glucocorticoid treatment. Abbreviations: y: year; M: male; F: female, ICS: Inhaled Corticosteroids; LBAB: Long-Acting Beta-Agonist; LAMA: Long-acting muscarine anticholinergic; COPD: Chronic obstructive pulmonary disease. Table 2 Surgical methods and postoperative conditions of patients Patient Number Mode of anesthesia Operation time ( M ) fibrin sealant dose ( ml ) Postoperative negative pressure aspiration Postoperative air leakage time ( d ) Other complications Successful capacity reduction P 1 Double cavity intubation, general anesthesia 82 32 Yes 5 Subcutaneous emphysema Yes P 2 Double cavity intubation, general anesthesia 75 30 No 1 No Yes P 3 Double cavity intubation, general anesthesia 80 32 Yes 28 Pleural hemorrhage 20ml Yes P 4 Double cavity intubation, general anesthesia 90 28 Yes 10 No Yes P 5 Laryngeal mask, general anesthesia 70 12 Yes NA No Yes P 6 Double cavity intubation, general anesthesia 78 20 Yes 3 No Yes P 7 Local anesthesia 85 12 Yes NA No No Abbreviations: M: minutes; d: days Table 3 Assessment of bulla volume reduction effect in patients Patient 1 week before the reduction 3 months after volume reduction Number Bulla diameter ( cm ) Bulla volume of lung ( cm 3 ) CAT score 6-MWT (m) Bulla diameter ( cm ) Bulla volume of lung ( cm 3 ) CAT score P 1 21*13*16.9 2306.9 15 349 0*0*0 0 10 P 2 19*11.5*12.6 1398.6 18 309 7*4.8*3 48 12 P 3 11*10.6*19.7 1150 24 280 0*0*0 0 16 P 4 14*10*12.2 884 26 112 4*3*2 7.6 15 P 5 14.6*6.4*10.7 540.9 28 96 NA NA NA P 6 11*8.2*5.6 360.2 10 540 0*0*0 0 8 P 7 10*9*11.1 508.5 32 0 10*9*11.1 508.9 32 6-MWT,CAT score and size, diameter, and volume of the targeted pulmonary bullae were evaluated at one week before surgery and three months postoperatively. Abbreviations: CAT: Chronic Obstructive Pulmonary Disease Assessment Test; 6-MWT: 6-minute walk test Case presentation Case 1 A 61-year-old man was admitted to the hospital due to a persistent cough and expectoration lasting for 10 years, along with dyspnea persisting for 5 years. The dyspnea progressively worsened over the past 5 years, leading to a diagnosis of COPD. The patient received inhalation treatment with inhaled corticosteroids (ICS) and long-acting beta-agonist (LABA). Upon admission to our hospital, the blood routine examination revealed a white blood cell count of 4.6 x 10 9 /L, neutrophil count of 2.1 x 10 9 /L, and hemoglobin level of 166 g/L. Arterial blood gas analysis (without oxygen inhalation) demonstrated a pH of 7.46, PO 2 of 65 mmHg, and PCO 2 of 48 mmHg. Chest HRCT (Figure. 2a) revealed emphysema in both lungs, multiple pulmonary bullae, a prominent pulmonary bulla in the right lung, and surrounding compressibility atelectasis. The patient was diagnosed with COPD, VLS, and hypoxemia. The patient underwent thoracoscopy in conjunction with fibrin sealant application for LVRS. Intraoperatively, a large pulmonary bullous lesion was observed, resulting in ventilation obstruction on the affected lung side (Figure. 2b). Utilizing direct visualization provided by thoracoscopy, a puncture needle(MC1816/C1816A, Bard Peripheral Vasular, USA) was percutaneously inserted into the bullous lesion, followed by injection of 32 mL of fibrin adhesive. Postoperatively, the gas within the bullous lesion was aspirated to induce collapse(Figure. 2c). The bullous lesion was subsequently clamped using oval forceps for a duration of 10 minutes, leading to restoration of bilateral lung ventilation. After noting the lack of expansion in the bullous lesion, a thoracic drainage tube was inserted. Subsequently, a chest X-ray conducted on the first day following the surgical procedure revealed the presence of pneumothorax and atelectasis, prompting the addition of negative pressure suction. On the fifth day post-surgery, the leakage from the thoracic drainage tube ceased. Following a 24-hour period of clamping the drainage tube, a subsequent chest X-ray exhibited absorption of the pneumothorax, leading to the removal of the drainage tube. Lung function evaluation and a reexamination of the chest HRCT were conducted after a span of three months (Figure. 2d). Case 2 A 60 years old male was admitted due to a history of cough and phlegm persisting for 12 years, accompanied by dyspnea for the past 6 years. Six years ago, the patient experienced a gradual worsening of dyspnea and was subsequently diagnosed with COPD. As part of his treatment, he was prescribed an inhalation therapy consisting of "ICS + LABA + long-acting muscarine anticholinergic (LAMA)". An arterial blood gas analysis, conducted without the administration of supplemental oxygen, revealed the following results: pH of 7.46, PO 2 of 52 mmHg, and PCO 2 of 58 mmHg. Additionally, a chest HRCT scan (Figure. 3a) indicated the presence of emphysema, multiple bullae, and a giant bulla in both lungs, as well as compressibility atelectasis surrounding them. Consequently, the patient was diagnosed with COPD, VLS, and Type II respiratory failure. To address the volume of the right lung bulla, a thoracoscopy was performed in conjunction with the application of fibrin sealant. The patient underwent general anesthesia after the insertion of a laryngeal mask. During the surgical procedure, a 12 mL dose of fibrin adhesive was injected into the bulla, followed by the aspiration of gas within the bulla to induce its collapse (Figure. 3b). Postoperatively, thoracoscopic bullous atresia was observed on the affected side (Figure. 3c). The bulla was subsequently clamped using oval forceps for a duration of 10 minutes. After confirming that there was no expansion of the bulla, a thoracic drainage tube was inserted, indicating that the surgery was finished. A chest X-ray conducted one day post-surgery revealed pulmonary bullous occlusion. On the third day after the operation, the patient experienced sudden dyspnea and a decrease in oxygen saturation. A subsequent chest X-ray demonstrated the re-opening of the lung bulla (Figure. 3d). Following the placement of the chest tube in the second intercostal space of the right midclavicular line, the patient experienced an improvement in symptoms and was subsequently transferred to the thoracic surgery department for LVR. Unfortunately, the patient succumbed to tension pneumothorax two weeks after the operation. Discussion VATS has emerged as a preferred option for VLS patients due to its minimal invasiveness, rapid recovery, and reduced pain. Nevertheless, challenges persist, including prolonged postoperative air leakage and increased hospitalization costs [13] . Our study examined a cohort of seven middle-aged and elderly males with VLS who underwent LVRS through the application of intra-bullous fibrin sealant using thoracoscopy. These individuals had previously been diagnosed with COPD. Even the patients are under the standardized inhaled treatment, they are still worsening and have very poor activity tolerance. Five patients successfully underwent pulmonary bullous volume reduction surgery, resulting in a significant decrease in their CAT score. In recent years, the progress in respiratory intervention technology has led to the recommendation of endobronchial valve volume reduction for patients with advanced heterogeneous emphysema [14] . Several scholars have documented the effectiveness of endobronchial valve placement in reducing the volume of giant pulmonary bullae, although these findings are limited to case reports [15, 16] . Additionally, CT-guided percutaneous puncture drainage technology can be employed in patients with giant pulmonary bullae accompanied by intravesicular fluid or intravesicular infection [17, 18] . In previous research, certain scholars have successfully utilized a combination of endobronchial valve and percutaneous pulmonary bullous puncture techniques to reduce the size of patients suffering from giant pulmonary bullae. [19, 20] . In this study, we introduces a novel approach to volume reduction. Utilizing a thoracoscopy for direct visualization, fibrin adhesive is administered into the pulmonary bulla via a puncture needle. Subsequently, the bulla is clamped using oval forceps, leading to its closure and the subsequent achievement of a reduction in volume. Previously, certain scholars have employed fibrin adhesive as a therapeutic approach for managing refractory pneumothorax resulting from pulmonary bullous rupture, yielding specific outcomes [21, 22] . In this investigation, all five patients who achieved successful volume reduction underwent treatment with general anesthesia utilizing dual lumen tracheal intubation. This technique effectively obstructs ventilation in the affected lung, encompassing the targeted lung bulla, and subsequent administration of fibrin adhesive induces firm adhesion of the bulla wall within the lung. Hence, the achievement of successful volume reduction surgery may be contingent upon the complete occlusion of the affected lung. Furthermore, it is noteworthy that the injection volume of fibrin adhesive into the pulmonary bullae was considerably greater in the 5 patients who experienced successful volume reduction compared to the 2 patients who did not, suggesting that a minimal quantity of fibrin adhesive should be avoided. Nevertheless, the existing literature does not provide any substantiation regarding the appropriateness of selecting the dosage of fibrin adhesive based on the volume of pulmonary bullae. The optimal dosage of fibrin adhesive needs further research. The evaluation of the effectiveness of lung bullous volume reduction or emphysema volume reduction surgery in the past was mainly based on observing the patient's postoperative pulmonary function improvement status and symptom score [14, 23, 24] . This study is the first to use preoperative and postoperative changes in the volume of pulmonary bullae to evaluate the effect of volume reduction. The utilization of computer post-processing technology enables precise estimation of the volume of the targeted pulmonary bullae, thereby introducing a novel approach. This technology has been previously employed for preoperative morphological evaluation of volume reduction in pulmonary emphysema [25] . In conclusion, we find that LVRS through the application of intra-bullous fibrin sealant using thoracoscopy is safe and effective.It enhanced their activity tolerance without notable complications. Furthermore, using the change in volume of pulmonary bullae as an indicator to observe and assess the effectiveness of volume reduction surgery provides a more objective evaluation of surgical outcomes. Consequently, for VLS patients who are unable to tolerate or decline surgery removal of pulmonary bullae, this approach may be considered as a viable option for volume reduction therapy. Abbreviations CAT(Chronic Obstructive Pulmonary Disease Assessment Test), COPD (chronic obstructive pulmonary disease), HRCT (chest high resolution CT), LVRS (lung volume reduction surgery), 6-MWT (6-minute walk test), VLS (vanishing lung syndrome) Declarations Statement of Ethics The study was approved by the Biomedical Ethics Review Committee of the West China Hospital of Sichuan University (approval no.1636) and was conducted in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was waived by our Institutional Review Board because of the retrospective nature of our study. Data Availability Statement All data generated and analyzed during this study are included in this article. Further inquiries can be directed to corresponding author. Conflict of Interest Statement The authors have no conflicts of interest to declare. Funding The work is also supported by Sichuan University West China Hospital Clinical Incubation 1.3.5 Project (2022HXFH002). Author Contributions All authors have made substantive contributions to the preparation and writing of the manuscript. Fengming Luo, Dan Liu and Fen Tan conceptualized and designed the study, also approved the final manuscript. Ling Zuo and Kaige Wang drafted the initial manuscript, searched for bibliography, and revised the final manuscript. Jingyu Shi and Weimin Li were involved in critical revision of the manuscript. All authors approved the final version of the manuscript. Acknowledgments We thank all the participants and all the researchers and collaborators who participated in this study. The authors greatly appreciate Dr. Zhu Hui and Dr. Yang Sai (Department of Pulmonary and Critical Care Medicine, West China Hospital of Sichuan University, Sichuan, Chengdu, China) for their technical assistance. References Hoeper MM, Vonk-Noordegraaf A. 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Criner GJ, Sue R, Wright S, et al. A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE). Am J Respir Crit Care Med. 2018. 198(9): 1151-1164. Wan IY, Toma TP, Geddes DM, et al. Bronchoscopic lung volume reduction for end-stage emphysema: report on the first 98 patients. Chest. 2006. 129(3): 518-26. Liu F, Han P, Wang JJ, et al. Multislice spiral CT morphological evaluation before lung volume reduction surgery with volume rendering technique. Chinese Journal of Radiology. 2007 . Additional Declarations No competing interests reported. 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Luo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYBAC9gYQacDAwMfAwPgAyJRhYGDDr4XnAFQLUB0zkDLgIVILA1gdmwRxWth7D7+6UXDHrk0i+VjFx7Y/PPzsbQkMPyq24dbCcy7NOsfgWXKbRFrazZltBjySPccOMPacuY1Ti71EjplxjsHhZDYg4zYvUIvBjfQGZsY23Fp45N8gtBQTp0WCx/gxUIsdSAszREvaAfxaeIAqgVoS2HieJUvOOGcM8kvCQXx+4WE/Y/w5589he3725IMfPpTJyQFDzPDBjwrcWhgg0cGQ2IAsdACfeiBg/gAk7AkoGgWjYBSMgpEMACojTy7YYuMPAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Fengming","middleName":"","lastName":"Luo","suffix":""}],"badges":[],"createdAt":"2024-02-20 10:34:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3972514/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3972514/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52034640,"identity":"566d37d5-efde-4686-b21a-cf09f48912fa","added_by":"auto","created_at":"2024-03-05 16:50:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":110848,"visible":true,"origin":"","legend":"\u003cp\u003eResults of the 6-minute walk test (6-MWT) conducted on patients who underwent successful lung volume reduction surgery.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3972514/v1/0522fbd1b4a00a7d74e32de4.png"},{"id":52034642,"identity":"f4f68701-0e68-438b-84e4-01d08cf36dea","added_by":"auto","created_at":"2024-03-05 16:50:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":796630,"visible":true,"origin":"","legend":"\u003cp\u003eHigh-resolution computed tomography (HRCT) and medical thoracoscopic findings of one patient who underwent successful lung volume reduction surgery (LVRS). a) The axial images illustrate the pre-surgical chest HRCT of the patient, revealing bilateral emphysema, a large pulmonary bulla in the middle lobe of the right lung, compressed atelectasis in the surrounding lung tissue, and scattered pulmonary bullae in the left lung. b) Photograph illustrated the inflation of the target pulmonary bulla under medical thoracoscopy. c) Photograph illustrated the occlusion state of the pulmonary bulla after adhesion. d) HRCT image showing examination conducted 5 days after the vanishing lung syndrome procedure, demonstrating the absence of pulmonary bullae and the restoration of normal atelectasis in the surrounding lung tissue.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3972514/v1/a35d268fb1633123e4d87825.png"},{"id":52035284,"identity":"439c5cdf-770b-4f0f-bde8-6d0311ed8005","added_by":"auto","created_at":"2024-03-05 16:58:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":680793,"visible":true,"origin":"","legend":"\u003cp\u003eThe chest high-resolution computed tomography (HRCT) and medical thoracoscopic observations were performed on a patient who underwent successful lung volume reduction surgery. a) The axial depict the patient's chest HRCT prior to the volume reduction procedure. Bilateral emphysema is observed, with the presence of a large lung bulla in both the right middle lobe and left lower lobe (with the right middle lobe lung bulla being the specific target). Additionally, the surrounding lung tissue exhibits compressed atelectasis. b) Photograph illustrated the puncture needle puncturing the bulla through a puncture card and injecting adhesive. c) Photograph illustrated the injection of adhesive into the pulmonary bulla. d) Chest X-ray examination on the following day after volume reduction surgery reveals the absence of the right pulmonary bullae.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3972514/v1/b55c6588620784c9fdc81d77.png"},{"id":52036266,"identity":"7aa565ed-7a65-49a3-9561-9e68c335762b","added_by":"auto","created_at":"2024-03-05 17:06:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2566340,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3972514/v1/f2a08997-91c6-47e2-868f-be90a7faa744.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lung volume reduction surgery by intra-bullous fibrin sealant application using thoracoscopy, an alternative in the management of vanishing lung syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVanishing lung syndrome (VLS), also known as idiopathic giant bullous emphysema, typically manifests in the upper lobes. This condition predominantly affects young, slender male smokers \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. In 1987, specific radiological criteria were proposed to diagnose VLS, include the presence of giant bullae in one or both upper lobes, occupying at least one third of the hemithorax. Consequently, normal lung function is compromised \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. In addition, some patients may develop fatal pneumothorax\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe management of VLS varies in approach, ranging from conservative to surgical, based on the patients' comorbidities and suitability for surgical resection. Lung volume LVRS is the primary treatment for VLS. Surgical bullectomy, performed through Video-assisted thoracoscopic surgery (VATS) or thoracotomy, has gained acceptance in specific patient populations. Nevertheless, the utilization of surgical bullectomy remains restricted due to prolonged post-operative leakage, significant trauma, and high hospitalization costs\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Consequently, the management of VLS remains an ongoing challenge.\u003c/p\u003e \u003cp\u003eIn recent years, intra-bullous fibrin sealant has been employed to decrease the size of pulmonary bullae through percutaneous pulmonary bulla centesis\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003eThere are few studies on the safety and effectiveness of thoracoscopy combined with fibrin sealant for the management of VLS\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. To investigate the efficacy of LVRS through the application of intra-bullous fibrin sealant using thoracoscopy in patients diagnosed with VLS, to guide clinical practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe clinical data of seven patients diagnosed with VLS between March 2022 and September 2023 at West China Hospital of Sichuan University were gathered. A retrospective analysis was performed to examine the overall condition, clinical features, treatment approaches, and patient outcomes. The inclusion criteria for our study were as follows: 1) Patients met the diagnostic criteria for VLS, which entails the presence of bullae occupying at least one-third of a hemithorax. 2) Patients were unable to undergo thoracic surgery due to intolerance. The exclusion criteria for this study were as follows: 1) Patients with respiratory failure who could not be weaned off mechanical ventilation were excluded. 2) Patients who refuse to undergo surgery will also be excluded from the study.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSurgical methods\u003c/h2\u003e \u003cp\u003eThe surgical methods employed in this study were as follows: 1) The adhesive joint was separated using thoracoscopy, and the bulla was fully freed. 2) The bulla was punctured, and fibrin sealant was injected into it through a puncture needle. The gas inside the bulla was aspirated, causing the bulla to collapse and close. 3) Oval forceps was used to clamp the bullae, ensuring complete occlusion and adhesion. 4) Water was injected into the thoracic cavity on the surgical side, and bilateral lung ventilation was restored to observe any air leakage. If there is any air leakage, repeat the above steps.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eInformation on the overall condition, symptoms, chest high resolution CT (HRCT) findings were collected. Subsequently, all patients were monitored at 1 month, 3 months, and 6 months post-surgery, with activity tolerance assessed through the CAT score and 6-MWT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eMethod for estimating the volume of bullae\u003c/h2\u003e \u003cp\u003eThe chest CT image data was evaluated through the post-processing workstation (3D Slicer) for measurement. The lung quantification software was employed to measure the horizontal axis image with a layer thickness of 1mm. The software automatically delineated the lung tissue and other tissues in the image, while some tissues were manually outlined. Pseudo color technology was utilized to visually present the target lung bullae and their relative proportion to the entire lung, along with the calculation of their volume. The threshold for measuring the volume of bullae was set at -1024 to -980HU. The threshold for emphysema was set at -980 to -910HU.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eDefinition of successful LVRS\u003c/h2\u003e \u003cp\u003eThe successful outcome of LVRS is defined as the absence of target lung bullae or the target lung bullae volume not exceeding one-third of its preoperative measurement, as observed in the chest imaging examination conducted three months after the procedure.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 11 individuals diagnosed with VLS were admitted to our hospital. Among them, one patient underwent VLRS through the surgical removal of pulmonary bullae.\u0026nbsp;Two patients declined the surgical intervention, while one patient experienced respiratory failure and was unable to be disconnected from the ventilator. Eventually, seven patients were treated with LVRS via intra-bullous fibrin sealant application using thoracoscopy. The age range of the seven male patients included in the study was between 57 and 73 years, with a median age of 61 years. All patients were diagnosed with COPD and received standardized nebulized inhalation therapy. Six patients were classified as being in the stable phase (Case 1-6), while one patient (Case 7) was experiencing an acute exacerbation phase and undergoing intravenous glucocorticoid treatment. All patients had a history of smoking. The clinical symptoms observed in all patients included cough, expectoration, and dyspnea. The general condition of all patients is presented in Table 1. Laboratory examination results revealed that two patients had hemoglobin levels exceeding 160 g/L. Additionally, five patients suffered from chronic respiratory failure and required long-term home oxygen therapy. Case 7 specifically required high-flow oxygen therapy (Table 1). All patients\u0026apos; chest HRCT scans revealed bilateral diffuse emphysema, unilateral or bilateral giant pulmonary bullae, and compressibility atelectasis of lung tissue surrounding the bullae.\u003c/p\u003e\n\u003cp\u003eAs indicated in Table 2, five patients underwent successful LVRS. No major complications occurred during the surgical procedure, except for one patient with 20 mL of pleural hemorrhage and a maximum of 28 days of postoperative air leakage. Chest HRCT examination was conducted three months post-surgery. The size, diameter, and volume of the targeted pulmonary bullae significantly decreased, as demonstrated in Table 3. Patients were evaluated for 6-MWT at 1, 3, and 6 months postoperatively, showed improvement in activity tolerance (Figure. 1). Nevertheless, two patients experienced surgical failure. One patient (Case 5) was referred to thoracic surgery for LVRS and subsequently succumbed to tension pneumothorax two weeks after the procedure. Additionally, another patient (Case 7) was lost to follow-up after being discharged automatically.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Characteristics of 7 Hospitalized Patients with vanishing lung syndrome\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient Number\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.66721044045677%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ey\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.298531810766722%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking history\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(y)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnderlying disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.33442088091354%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemoglobin concentration\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(g/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary bulla position\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.43393148450245%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCurrent treatment plan\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003eP 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.66721044045677%\" valign=\"top\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.298531810766722%\" valign=\"top\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eCOPD,Hypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.33442088091354%\" valign=\"top\"\u003e\n \u003cp\u003e166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eRight middle lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.43393148450245%\" valign=\"top\"\u003e\n \u003cp\u003eICS+LABA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003eP 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.66721044045677%\" valign=\"top\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.298531810766722%\" valign=\"top\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.33442088091354%\" valign=\"top\"\u003e\n \u003cp\u003e140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eRight middle lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.43393148450245%\" valign=\"top\"\u003e\n \u003cp\u003eICS+LABA+LAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003eP 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.66721044045677%\" valign=\"top\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.298531810766722%\" valign=\"top\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eCOPD,Diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.33442088091354%\" valign=\"top\"\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eRight upper lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.43393148450245%\" valign=\"top\"\u003e\n \u003cp\u003eICS+LABA+LAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003eP 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.66721044045677%\" valign=\"top\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.298531810766722%\" valign=\"top\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.33442088091354%\" valign=\"top\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eLeft upper lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.43393148450245%\" valign=\"top\"\u003e\n \u003cp\u003eICS+LABA+LAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003eP 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.66721044045677%\" valign=\"top\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.298531810766722%\" valign=\"top\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.33442088091354%\" valign=\"top\"\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eRight middle lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.43393148450245%\" valign=\"top\"\u003e\n \u003cp\u003eICS+LABA+LAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003eP 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.66721044045677%\" valign=\"top\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.298531810766722%\" valign=\"top\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.33442088091354%\" valign=\"top\"\u003e\n \u003cp\u003e162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eLeft upper lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.43393148450245%\" valign=\"top\"\u003e\n \u003cp\u003eICS+LABA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003eP 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.66721044045677%\" valign=\"top\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.298531810766722%\" valign=\"top\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.766721044045678%\" valign=\"top\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eCOPD,Asthma,Lung cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.33442088091354%\" valign=\"top\"\u003e\n \u003cp\u003e126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.866231647634583%\" valign=\"top\"\u003e\n \u003cp\u003eLeft upper lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.43393148450245%\" valign=\"top\"\u003e\n \u003cp\u003eICS+LABA+LAMA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eCases 1-6 were diagnosed with stable phase COPD and received standardized nebulized inhalation therapy. Case 7 was in an acute exacerbation phase and receiving intravenous glucocorticoid treatment.\u003c/p\u003e\n\u003cp\u003eAbbreviations: y: year; M: male; F: female, ICS: Inhaled Corticosteroids; LBAB: Long-Acting Beta-Agonist; LAMA: Long-acting muscarine anticholinergic; COPD: Chronic obstructive pulmonary disease.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Surgical methods and postoperative conditions of patients\u003c/strong\u003e\u003cstrong\u003e\u003cu\u003e\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"648\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.35548686244204%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNumber\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.901081916537867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMode of anesthesia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.97372488408037%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOperation time\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eM\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.964451313755797%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003efibrin sealant dose\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eml\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.610510046367851%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative negative pressure aspiration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.528593508500773%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePostoperative air leakage time\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ed\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.146831530139103%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther complications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.519319938176197%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSuccessful capacity reduction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.35548686244204%\" valign=\"top\"\u003e\n \u003cp\u003eP 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.901081916537867%\" valign=\"top\"\u003e\n \u003cp\u003eDouble cavity intubation, general anesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.97372488408037%\" valign=\"top\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.964451313755797%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.610510046367851%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.528593508500773%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.146831530139103%\" valign=\"top\"\u003e\n \u003cp\u003eSubcutaneous emphysema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.519319938176197%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.35548686244204%\" valign=\"top\"\u003e\n \u003cp\u003eP 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.901081916537867%\" valign=\"top\"\u003e\n \u003cp\u003eDouble cavity intubation, general anesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.97372488408037%\" valign=\"top\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.964451313755797%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.610510046367851%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.528593508500773%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.146831530139103%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.519319938176197%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.35548686244204%\" valign=\"top\"\u003e\n \u003cp\u003eP 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.901081916537867%\" valign=\"top\"\u003e\n \u003cp\u003eDouble cavity intubation, general anesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.97372488408037%\" valign=\"top\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.964451313755797%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.610510046367851%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.528593508500773%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.146831530139103%\" valign=\"top\"\u003e\n \u003cp\u003ePleural hemorrhage 20ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.519319938176197%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.35548686244204%\" valign=\"top\"\u003e\n \u003cp\u003eP 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.901081916537867%\" valign=\"top\"\u003e\n \u003cp\u003eDouble cavity intubation, general anesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.97372488408037%\" valign=\"top\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.964451313755797%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.610510046367851%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.528593508500773%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.146831530139103%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.519319938176197%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.35548686244204%\" valign=\"top\"\u003e\n \u003cp\u003eP 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.901081916537867%\" valign=\"top\"\u003e\n \u003cp\u003eLaryngeal mask, general anesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.97372488408037%\" valign=\"top\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.964451313755797%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.610510046367851%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.528593508500773%\" valign=\"top\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.146831530139103%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.519319938176197%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.35548686244204%\" valign=\"top\"\u003e\n \u003cp\u003eP 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.901081916537867%\" valign=\"top\"\u003e\n \u003cp\u003eDouble cavity intubation, general anesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.97372488408037%\" valign=\"top\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.964451313755797%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.610510046367851%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.528593508500773%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.146831530139103%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.519319938176197%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.35548686244204%\" valign=\"top\"\u003e\n \u003cp\u003eP 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.901081916537867%\" valign=\"top\"\u003e\n \u003cp\u003eLocal anesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.97372488408037%\" valign=\"top\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.964451313755797%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.610510046367851%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.528593508500773%\" valign=\"top\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.146831530139103%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.519319938176197%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAbbreviations: M: minutes; d: days\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Assessment of bulla volume reduction effect in patients\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"650\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.46153846153846%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 week before the reduction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.23076923076923%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3 months after volume reduction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBulla diameter\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ecm\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.461538461538462%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBulla volume of lung\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ecm\u003csup\u003e3\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAT score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e6-MWT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(m)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBulla diameter\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ecm\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBulla volume of lung\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003ecm\u003csup\u003e3\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAT score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003eP 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e21*13*16.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.461538461538462%\" valign=\"top\"\u003e\n \u003cp\u003e2306.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e349\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e0*0*0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003eP 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e19*11.5*12.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.461538461538462%\" valign=\"top\"\u003e\n \u003cp\u003e1398.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e309\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e7*4.8*3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003eP 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e11*10.6*19.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.461538461538462%\" valign=\"top\"\u003e\n \u003cp\u003e1150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e0*0*0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003eP 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e14*10*12.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.461538461538462%\" valign=\"top\"\u003e\n \u003cp\u003e884\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e4*3*2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e7.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003eP 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e14.6*6.4*10.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.461538461538462%\" valign=\"top\"\u003e\n \u003cp\u003e540.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003eP 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e11*8.2*5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.461538461538462%\" valign=\"top\"\u003e\n \u003cp\u003e360.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e0*0*0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.307692307692308%\" valign=\"top\"\u003e\n \u003cp\u003eP 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e10*9*11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.461538461538462%\" valign=\"top\"\u003e\n \u003cp\u003e508.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.153846153846153%\" valign=\"top\"\u003e\n \u003cp\u003e10*9*11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e508.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.846153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e6-MWT,CAT score and size, diameter, and volume of the targeted pulmonary bullae were evaluated at one week before surgery and three months postoperatively. Abbreviations: CAT: Chronic Obstructive Pulmonary Disease Assessment Test; 6-MWT: 6-minute walk test\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003e\u003cstrong\u003eCase 1\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA 61-year-old man was admitted to the hospital due to a persistent cough and expectoration lasting for 10 years, along with dyspnea persisting for 5 years. The dyspnea progressively worsened over the past 5 years, leading to a diagnosis of COPD.\u0026nbsp;The patient received inhalation treatment with\u0026nbsp;inhaled corticosteroids (ICS)\u0026nbsp;and long-acting beta-agonist (LABA). Upon admission to our hospital, the blood routine examination revealed a white blood cell count of 4.6 x 10\u003csup\u003e9\u003c/sup\u003e /L, neutrophil count of 2.1 x 10\u003csup\u003e9\u003c/sup\u003e /L, and hemoglobin level of 166 g/L. Arterial blood gas analysis (without oxygen inhalation) demonstrated a pH of 7.46, PO\u003csub\u003e2\u003c/sub\u003e of 65 mmHg, and PCO\u003csub\u003e2\u003c/sub\u003e of 48 mmHg. Chest HRCT (Figure. 2a) revealed emphysema in both lungs, multiple pulmonary bullae, a prominent pulmonary bulla in the right lung, and surrounding compressibility atelectasis. The patient was diagnosed with COPD, VLS, and hypoxemia. The patient underwent thoracoscopy in conjunction with fibrin sealant application for LVRS. Intraoperatively, a large pulmonary bullous lesion was observed, resulting in ventilation obstruction on the affected lung side (Figure. 2b). Utilizing direct visualization provided by thoracoscopy, a puncture needle(MC1816/C1816A, Bard Peripheral Vasular, USA) was percutaneously inserted into the bullous lesion, followed by injection of 32 mL of fibrin adhesive. Postoperatively, the gas within the bullous lesion was aspirated to induce collapse(Figure. 2c). The bullous lesion was subsequently clamped using oval forceps for a duration of 10 minutes, leading to restoration of bilateral lung ventilation. After noting the lack of expansion in the bullous lesion, a thoracic drainage tube was inserted. Subsequently, a chest X-ray conducted on the first day following the surgical procedure revealed the presence of pneumothorax and atelectasis, prompting the addition of negative pressure suction. On the fifth day post-surgery, the leakage from the thoracic drainage tube ceased. Following a 24-hour period of clamping the drainage tube, a subsequent chest X-ray exhibited absorption of the pneumothorax, leading to the removal of the drainage tube. Lung function evaluation and a reexamination of the chest HRCT were conducted after a span of three months (Figure. 2d).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 2\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA 60 years old male was admitted due to a history of cough and phlegm persisting for 12 years, accompanied by dyspnea for the past 6 years. Six years ago, the patient experienced a gradual worsening of dyspnea and was subsequently diagnosed with COPD. As part of his treatment, he was prescribed an inhalation therapy consisting of \u0026quot;ICS + LABA +\u0026nbsp;long-acting muscarine anticholinergic (LAMA)\u0026quot;. An arterial blood gas analysis, conducted without the administration of supplemental oxygen, revealed the following results: pH of 7.46, PO\u003csub\u003e2\u003c/sub\u003e of 52 mmHg, and PCO\u003csub\u003e2\u003c/sub\u003e of 58 mmHg. Additionally, a chest HRCT scan (Figure. 3a) indicated the presence of emphysema, multiple bullae, and a giant bulla in both lungs, as well as compressibility atelectasis surrounding them. Consequently, the patient was diagnosed with COPD, VLS, and Type II respiratory failure. To address the volume of the right lung bulla, a thoracoscopy was performed in conjunction with the application of fibrin sealant. The patient underwent general anesthesia after the insertion of a laryngeal mask. During the surgical procedure, a 12 mL dose of fibrin adhesive was injected into the bulla, followed by the aspiration of gas within the bulla to induce its collapse (Figure. 3b). Postoperatively, thoracoscopic bullous atresia was observed on the affected side (Figure. 3c). The bulla was subsequently clamped using oval forceps for a duration of 10 minutes. After confirming that there was no expansion of the bulla, a thoracic drainage tube was inserted, indicating that the surgery was finished. A chest X-ray conducted one day post-surgery revealed pulmonary bullous occlusion. On the third day after the operation, the patient experienced sudden dyspnea and a decrease in oxygen saturation. A subsequent chest X-ray demonstrated the re-opening of the lung bulla (Figure. 3d). Following the placement of the chest tube in the second intercostal space of the right midclavicular line, the patient experienced an improvement in symptoms and was subsequently transferred to the thoracic surgery department for LVR. Unfortunately, the patient succumbed to tension pneumothorax two weeks after the operation.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eVATS has emerged as a preferred option for VLS patients due to its minimal invasiveness, rapid recovery, and reduced pain. Nevertheless, challenges persist, including prolonged postoperative air leakage and increased hospitalization costs\u0026nbsp;\u003csup\u003e[13]\u003c/sup\u003e. Our study examined a cohort of seven middle-aged and elderly males with VLS who underwent LVRS through the application of intra-bullous fibrin sealant using thoracoscopy. These individuals had previously been diagnosed with COPD. Even the patients are under the standardized inhaled treatment, they are still worsening and have very poor activity tolerance.\u0026nbsp;Five patients successfully underwent pulmonary bullous volume reduction surgery, resulting in a significant decrease in their CAT score.\u003c/p\u003e\n\u003cp\u003eIn recent years, the progress in respiratory intervention technology has led to the recommendation of endobronchial valve volume reduction for patients with advanced heterogeneous emphysema\u003csup\u003e[14]\u003c/sup\u003e. Several scholars have documented the effectiveness of endobronchial valve placement in reducing the volume of giant pulmonary bullae, although these findings are limited to case reports\u003csup\u003e[15, 16]\u003c/sup\u003e. Additionally, CT-guided percutaneous puncture drainage technology can be employed in patients with giant pulmonary bullae accompanied by intravesicular fluid or intravesicular infection\u003csup\u003e[17, 18]\u003c/sup\u003e. In previous research, certain scholars\u0026nbsp;have successfully utilized a combination of endobronchial valve and percutaneous pulmonary bullous puncture techniques to reduce the size of patients suffering from giant pulmonary bullae.\u003csup\u003e[19, 20]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn this study, we introduces a novel approach to volume reduction. Utilizing a thoracoscopy for direct visualization, fibrin adhesive is administered into the pulmonary bulla via a puncture needle. Subsequently, the bulla is clamped using oval forceps, leading to its closure and the subsequent achievement of a reduction in volume. Previously, certain scholars have employed fibrin adhesive as a therapeutic approach for managing refractory pneumothorax resulting from pulmonary bullous rupture, yielding specific outcomes\u003csup\u003e[21, 22]\u003c/sup\u003e. In this investigation, all five patients who achieved successful volume reduction underwent treatment with general anesthesia utilizing dual lumen tracheal intubation. This technique effectively obstructs ventilation in the affected lung, encompassing the targeted lung bulla, and subsequent administration of fibrin adhesive induces firm adhesion of the bulla wall within the lung. Hence, the achievement of successful volume reduction surgery may be contingent upon the complete occlusion of the affected lung. Furthermore, it is noteworthy that the injection volume of fibrin adhesive into the pulmonary bullae was considerably greater in the 5 patients who experienced successful volume reduction compared to the 2 patients who did not, suggesting that a minimal quantity of fibrin adhesive should be avoided. Nevertheless, the existing literature does not provide any substantiation regarding the appropriateness of selecting the dosage of fibrin adhesive based on the volume of pulmonary bullae. The optimal dosage of fibrin adhesive needs further research.\u003c/p\u003e\n\u003cp\u003eThe evaluation of the effectiveness of lung bullous volume reduction or emphysema volume reduction surgery in the past was mainly based on observing the patient\u0026apos;s postoperative pulmonary function improvement status and symptom score\u003csup\u003e[14, 23, 24]\u003c/sup\u003e. This study is the first to use preoperative and postoperative changes in the volume of pulmonary bullae to evaluate the effect of volume reduction.\u0026nbsp;The utilization of computer post-processing technology enables precise estimation of the volume of the targeted pulmonary bullae, thereby introducing a novel approach.\u0026nbsp;This technology has been previously employed for preoperative morphological evaluation of volume reduction in pulmonary emphysema\u003csup\u003e[25]\u003c/sup\u003e. In conclusion, we find that LVRS through the application of intra-bullous fibrin sealant using thoracoscopy is safe and effective.It enhanced their activity tolerance without notable complications. Furthermore, using the change in volume of pulmonary bullae as an indicator to observe and assess the effectiveness of volume reduction surgery provides a more objective evaluation of surgical outcomes. Consequently, for VLS patients who are unable to tolerate or decline surgery removal of pulmonary bullae, this approach may be considered as a viable option for volume reduction therapy.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCAT(Chronic Obstructive Pulmonary Disease Assessment Test), COPD (chronic obstructive pulmonary disease), HRCT (chest high resolution CT), LVRS (lung volume reduction surgery), 6-MWT (6-minute walk test), VLS (vanishing lung syndrome)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatement of Ethics\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Biomedical Ethics Review Committee of the West China Hospital of Sichuan University (approval no.1636) and was conducted in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was waived by our Institutional Review Board because of the retrospective nature of our study. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll data generated and analyzed during this study are included in this article. Further inquiries can be directed to corresponding author.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe work is also supported by Sichuan University West China Hospital Clinical Incubation 1.3.5 Project (2022HXFH002).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have made substantive contributions to the preparation and writing of the manuscript. Fengming Luo, Dan Liu and Fen Tan conceptualized and designed the study, also approved the final manuscript. Ling Zuo and Kaige Wang drafted the initial manuscript, searched for bibliography, and revised the final manuscript. Jingyu Shi and Weimin Li were involved in critical revision of the manuscript. All authors approved the final version of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the participants and all the researchers and collaborators who participated in this study. The authors greatly appreciate Dr. Zhu Hui and Dr. Yang Sai (Department of Pulmonary and Critical Care Medicine, West China Hospital of Sichuan University, Sichuan, Chengdu, China) for their technical assistance.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHoeper MM, Vonk-Noordegraaf A. Is there a vanishing pulmonary capillary syndrome. Lancet Respir Med. 2017. 5(9): 676-678.\u003c/li\u003e\n\u003cli\u003eLadizinski B, Sankey C. Images in clinical medicine. Vanishing lung syndrome. N Engl J Med. 2014. 370(9): e14.\u003c/li\u003e\n\u003cli\u003eYousaf MN, Chan NN, Janvier A. Vanishing Lung Syndrome: An Idiopathic Bullous Emphysema Mimicking Pneumothorax. Cureus. 2020. 12(8): e9596.\u003c/li\u003e\n\u003cli\u003eFishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003. 348(21): 2059-73.\u003c/li\u003e\n\u003cli\u003eCooper JD, Patterson GA, Sundaresan RS, et al. Results of 150 consecutive bilateral lung volume reduction procedures in patients with severe emphysema. J Thorac Cardiovasc Surg. 1996. 112(5): 1319-29; discussion 1329-30.\u003c/li\u003e\n\u003cli\u003eZhang H, Wang L, Ge CS, et al. [Efficacy and safety of giant emphysematous bulla volume reduction via medical thoracoscope]. Zhonghua Yi Xue Za Zhi. 2021. 101(30): 2370-2374.\u003c/li\u003e\n\u003cli\u003eZhang H, Xu WW, Chen CD, et al. [A prospective study of position selection combined with autologous blood intrathoracic infusion in the treatment of postoperative persistent air leakage with an unexpanded lung]. Zhonghua Jie He He Hu Xi Za Zhi. 2023. 46(4): 404-407.\u003c/li\u003e\n\u003cli\u003eLi WL, Li YH, Yang YB, Lv LH. Intrabullous Adhesion Pexia (IBAP) by Percutaneous Pulmonary Bulla Centesis: An Alternative for the Surgical Treatment of Giant Pulmonary Bulla (GPB). Can Respir J. 2018. 2018: 5806834.\u003c/li\u003e\n\u003cli\u003eSenbaklavaci O, Wisser W, Jandrasits O, Ozpeker C, Wolner E, Klepetko W. [Results of lung-volume reduction surgery in end-stage lung emphysema]. Chirurg. 1999. 70(8): 909-14.\u003c/li\u003e\n\u003cli\u003eWakabayashi A. Thoracoscopic laser pneumoplasty in the treatment of diffuse bullous emphysema. Ann Thorac Surg. 1995. 60(4): 936-42.\u003c/li\u003e\n\u003cli\u003eFischel RJ, McKenna RJ Jr. Bovine pericardium versus bovine collagen to buttress staples for lung reduction operations. Ann Thorac Surg. 1998. 65(1): 217-9.\u003c/li\u003e\n\u003cli\u003eNaunheim KS, Wood DE, Krasna MJ, et al. Predictors of operative mortality and cardiopulmonary morbidity in the National Emphysema Treatment Trial. J Thorac Cardiovasc Surg. 2006. 131(1): 43-53.\u003c/li\u003e\n\u003cli\u003eFur\u0026aacute;k J, P\u0026eacute;csy B, Ottlak\u0026aacute;n A, et al. [Results of the video-assisted thoracic surgery lobectomy at our department in the last five-year periode]. Magy Seb. 2016. 69(3): 100-4.\u003c/li\u003e\n\u003cli\u003eSciurba FC, Ernst A, Herth FJ, et al. A randomized study of endobronchial valves for advanced emphysema. N Engl J Med. 2010. 363(13): 1233-44.\u003c/li\u003e\n\u003cli\u003eLee EG, Rhee CK. Bronchoscopic lung volume reduction using an endobronchial valve to treat a huge emphysematous bullae: a case report. BMC Pulm Med. 2019. 19(1): 92.\u003c/li\u003e\n\u003cli\u003eHou G, Wang W, Wang QY, Kang J. Bronchoscopic bullectomy with a one-way endobronchial valve to treat a giant bulla in an emphysematic lung: a case report. Clin Respir J. 2016. 10(5): 657-60.\u003c/li\u003e\n\u003cli\u003eRead A, Parry-Jones W, Bhowmik A. Percutaneous drainage of a fluid-containing emphysematous bulla. BMJ Case Rep. 2021. 14(5).\u003c/li\u003e\n\u003cli\u003eKalra N, Aiyappan SK, Jindal SK, Khandelwal N. Image-guided percutaneous drainage of an emphysematous bulla with a fluid level. Indian J Radiol Imaging. 2010. 20(1): 34-6.\u003c/li\u003e\n\u003cli\u003eIm Y, Jeong BH, Park HY, Kim TS, Kim H. Expeditious Resolution of Giant Bullae with Endobronchial Valves and Percutaneous Catheter Insertion. Yonsei Med J. 2022. 63(2): 195-198.\u003c/li\u003e\n\u003cli\u003eGoud A, Krimsky W, Caldwel M, et al. Percutaneous Bullectomy in Conjunction with Endobronchial Valve Placement as an Alternative to Surgical Management of Giant Bullae. Respiration. 2016. 91(6): 523-6.\u003c/li\u003e\n\u003cli\u003eDrovandi L, Cianchi I, Pratesi S, Dani C. Fibrin glue pleurodesis for pneumothorax in extremely preterm infants: a case report and literature review. Ital J Pediatr. 2018. 44(1): 91.\u003c/li\u003e\n\u003cli\u003eTanaka A, Mishina T, Izumi H, et al. [Direct instillation of the fibrin glue into the ruptured bulla is an effective treatment for uncontrolled pneumothorax occurred from severe emphysematous bullae]. Kyobu Geka. 2011. 64(4): 286-90.\u003c/li\u003e\n\u003cli\u003eCriner GJ, Sue R, Wright S, et al. A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE). Am J Respir Crit Care Med. 2018. 198(9): 1151-1164.\u003c/li\u003e\n\u003cli\u003eWan IY, Toma TP, Geddes DM, et al. Bronchoscopic lung volume reduction for end-stage emphysema: report on the first 98 patients. Chest. 2006. 129(3): 518-26.\u003c/li\u003e\n\u003cli\u003eLiu F, Han P, Wang JJ, et al. Multislice spiral CT morphological evaluation before lung volume reduction surgery with volume rendering technique. Chinese Journal of Radiology. 2007 .\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"lung volume reduction surgery, vanishing lung syndrome, thoracoscopy, intra-bullous fibrin sealant","lastPublishedDoi":"10.21203/rs.3.rs-3972514/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3972514/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eTo investigate the efficacy of lung volume reduction surgery (LVRS) through the application of intra-bullous fibrin sealant using thoracoscopy in patients diagnosed with vanishing lung syndrome(VLS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A retrospective analysiswas conducted on the clinical data of patients with VLS who were admitted to the West China Hospital of Sichuan University between March 2022 and September 2023. Patients who met the inclusion criteria underwent LVRS and were followed up to evaluate the efficacy and safety of the technique.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A total of seven male patients were included, with a median age of 61 years. The patients' post-operative activity tolerance, as assessed by the chronic obstructive pulmonary disease assessment test (CAT) score and the 6-minute walk test (6-MWT), showed continuous significant improvement. Besides, five patients injected with at least 20 mL of fibrin sealant underwent successful reduction and received double-lumen endotracheal intubation while under anesthesia. The operation failed in two patients with fibrin sealant injection volume less than 12 mL. However, no significant postoperative complications were observed except for one patient with 20 mL pleural hemorrhage and a maximum of 28 days of postoperative air leakage.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe application of intra-bullous fibrin sealant through thoracoscopy is a safe and effective approach for managing VLS, resulting in minimal wound and fewer complications. The success of this strategy depends on using dual lumen tracheal intubation to block lung ventilation and applying the appropriate amount of fibrin sealant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRetrospective trial registration: \u003c/strong\u003e(Chinese Clinical Trial Center, registration number: ChiCTR2300078038, registered 2023-11-27)\u003c/p\u003e","manuscriptTitle":"Lung volume reduction surgery by intra-bullous fibrin sealant application using thoracoscopy, an alternative in the management of vanishing lung syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-05 16:50:49","doi":"10.21203/rs.3.rs-3972514/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-17T06:11:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-03T10:42:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-30T15:25:48+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-28T16:15:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"c86752bb-1d6c-490d-8797-84ac8115dc14","date":"2024-03-22T05:47:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0391799e-da26-4742-9b88-0960c41ac80e","date":"2024-03-21T16:18:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"c2ad3bb7-4227-4638-b046-14821827078f","date":"2024-03-20T11:07:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30f42446-4cc3-4cfb-8fbc-2f3749c57ceb","date":"2024-03-19T21:25:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-19T06:38:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0e5eec2d-e957-4c8d-ae1f-e453811b6d25","date":"2024-03-18T19:15:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-09T00:39:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-09T00:27:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-02-29T10:35:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-29T10:33:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2024-02-20T10:22:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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