Biological Lung Volume Reduction Research Articles

Bronchoscopic lung volume reduction by instillation of fibrinogen and thrombin in COPD patients with homogenous emphysema

BackgroundThe new endobronchial therapy called biological lung volume reduction (BioLVR) involves using a rapid polymerizing sealant to block off the most emphysematous portions of the lungs. The primary mechanism of action is resorption atelectasis, which is then followed by inflammation and remodeling of the airspace. The remodeling process will result in the formation of scars, leading to the contraction of the lung tissue. As a result, a decrease in functional lung volume is anticipated for a period of 6–8 weeks.ObjectiveAssessing the safety and effectiveness of bronchoscopic installation of (fibrinogen and thrombin) in COPD patients with homogeneous emphysema in terms of radiological, physiological, and quality of life outcomes.MethodsBetween December 2017 and December 2019, 40 COPD patients with homogeneous emphysema were studied using a fiber optic bronchoscope while they were awake but sedated. Tanta University Hospitals’ chest medicine department collaborated with the diagnostic radiology department of the Faculty of Medicine.ResultsAll the following parameters were reduced from their initial values: HRCT volumetry, RV/TLC, mMRC dyspnea scale, CAT score, 6MWT, FEV1, and the FEV1/FVC ratio at the first, third, and sixth months from the beginning (p = 0.001). One individual (0.025%) had pneumonia, whereas three individuals had COPD (0.075%). Using fibrin glue produced locally, biological lung volume reduction (Bio LVR) may be an effective treatment for advanced homogenous emphysema.ConclusionBy using locally prepared fibrin glue the biologic lung volume reduction (Bio LVR) may be a convenient method to treat advanced homogenous emphysema.

Endoscopic Lung Volume Reduction with Autologous Blood: What is the Evidence?

Biological lung volume reduction (BioLVR) is a novel and low-cost endobronchial treatment method aimed at reducing the volume of the target lung lobe using biological agents, including fibrin-based hydrogel, fibrinogen, and autologous blood (AB) with thrombin. BioLVR induces local inflammation, resulting in acute airway obstruction, resorption atelectasis, fibrosis, and finally tissue remodeling by contraction of the target lobe and reduction in the lung volume, similar to the application of hot water vapor and foam. In addition, patients with severe impairment in lung function and quality of life may refuses to undergo surgery, resulting in limited treatment options. In such complex clinical scenarios, BioLVR with AB appears to be a good therapeutic option. These treatment modalities resulted in favorable outcomes in patients with heterogeneous and bullous emphysema, pulmonary lymphangioleiomyomatosis, and giant bullous lesions. AB applications result in functional improvement, improvement in the quality of life, decrease in dyspnea scores, and reduction in the size of bullae. Based on the available evidence, application of AB for lung volume reduction is minimally invasive and well tolerated by patients. There was no incidence of pneumothorax or mortality. This review aimed to investigate the benefits, complications, and future perspectives of AB application as BioLVR in the treatment of hyperinflated lung diseases.

Status of and prospects for bronchoscopic lung volume reduction for patients with severe emphysema.

Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment for severe emphysema, providing treatment options for patients who are unable to undergo lung volume reduction surgery (LVRS) or lung transplantation. Current BLVR techniques include bronchoscopic volume reduction with valve implants, use of a lung volume reduction coil (LVRC), bronchoscopic thermal vapor ablation (BTVA), biological lung volume reduction (BioLVR), and use of airway bypass stents (ABS). To date, several randomized controlled trials of these bronchoscopic therapies have been conducted in patients with emphysema, and bronchoscopic volume reduction with valve implants remains the best approach thus far. Recent studies indicate that BLVR may be of great value in improving lung function, exercise capacity, and quality of life and that BLVR has the potential to replace conventional surgery for patients with severe emphysema. Optimal patient selection and the proper selection of the BLVR technique in accordance with patient characteristics are crucial to the success of BLVR. More multicenter, prospective, randomized controlled trials need to be conducted in the future to optimize the current selection strategy and evaluate the safety, efficiency, and long-term benefit of BLVR techniques.

In situ forming chitosan-based hydrogel as a lung sealant for biological lung volume reduction

Biological lung volume reduction (BLVR) using lung sealant has received more attention recently as a new non-surgical approach to emphysema treatment. Many tissue sealants have been studied but only a few have been proposed for BLVR. In this work, we prepared in situ forming chitosan-based hydrogels (CSG) using covalent cross-linking of chitosan and genipin in the cooperation of ionic interaction between chitosan and sodium orthophosphate hydrate (Na3PO4·12H2O) and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and rheological methods. CSG showed short gelation time (8min), high swelling ratio (>100%) and non-toxicity (3T3 mouse fibroblast cell viability >80%) under physiological conditions. The application of lung sealant for BLVR was tested in a Chinese dog and evaluated by chest computed tomography. After 3 weeks of the installation of CSG in bronchopulmonary segment, the gel formation was detected at a localized region of bronchi and the local atelectasis occurred. Our findings indicate that this chitosan-based hydrogel is a promising new candidate for use as a lung sealant for BLVR.

PULMONARY FUNCTION CHANGES AFTER BRONCHOSCOPIC BIOLOGICAL LUNG VOLUME REDUCTION THERAPY USING AUTOULOGOUS BLOOD

Background: Bronchoscopic lung volume reduction (BLVR) using biological agents is one of the new alternatives to lung volume reduction surgery. Objectives: To evaluate the potential efficacy of bronchoscopic biological lung volume reduction using autologous blood injection in pulmonary emphysema patients. Methods: 7 male patients were enrolled in the study. After determining the targeted emphysematous segment by high resolution computerized tomography (HRCT), 30 ml autologous blood was injected via balloon catheter over 10 to15 seconds into the targeted segment and left in position for 3-6 minutes allowing time for blood to coagulate. The bronchoscope was then repositioned at the following targeted segment. Changes in residual volume (RV), residual volume to total lung capacity ratio (RV/TLC), forced expiratory volume in one second (FEV1) and forced expiratory volume to forced vital capacity ratio (FEV1/FVC) were evaluated at 12-week post procedure as well as for complications. Results: At 12-week post procedure there was statistically significant reduction in RV/TLC (p = 0.038). FEV1 significantly increased (p = 0.018). In addition, there was significant improvement in FEV1/FVC % (p = 0.003). All cases tolerated the procedure with no mortality. There was one case that developed pneumonia at the same side of intervention, and two cases developed mild haemoptysis (blood streaked sputum). There was no life threatening complications e.g (pneumothorax, pulmonary embolism, cardiac ischaemia or myocardial infarction) occurred htoughout the study. Conclusion: Bronchoscopic lung volume reduction using autologous blood injection could be an effective, cheap and relatively safe method to treat advanced emphysema in comparison to other agents used in the clinical trials. Keywords: Emphysema; Bronchoscopy; Lung volume reduction.

Lung Volume Reduction Therapies for Advanced Emphysema: An Update

Observational and randomized studies provide convincing evidence that lung volume reduction surgery (LVRS) improves symptoms, lung function, exercise tolerance, and life span in well-defined subsets of patients with emphysema. Yet, in the face of an estimated 3 million patients with emphysema in the United States, < 15 LVRS operations are performed monthly under the aegis of Medicare, in part because of misleading reporting in lay and medical publications suggesting that the operation is associated with prohibitive risks and offers minimal benefits. Thus, a treatment with proven potential for palliating and prolonging life may be underutilized. In an attempt to lower risks and cost, several bronchoscopic strategies (bronchoscopic emphysema treatment [BET]) to reduce lung volume have been introduced. The following three methods have been tested in some depth: (1) unidirectional valves that allow exit but bar entry of gas to collapse targeted hyperinflated portions of the lung and reduce overall volume; (2) biologic lung volume reduction (BioLVR) that involves intrabronchial administration of a biocompatible complex to collapse, inflame, scar, and shrink the targeted emphysematous lung; and (3) airway bypass tract (ABT) or creation of stented nonanatomic pathways between hyperinflated pulmonary parenchyma and bronchial tree to decompress and reduce the volume of oversized lung. The results of pilot and randomized pivotal clinical trials suggest that the bronchoscopic strategies are associated with lower mortality and morbidity but are also less efficient than LVRS. Most bronchoscopic approaches improve quality-of-life measures without supportive physiologic or exercise tolerance benefits. Although there is promise of limited therapeutic influence, the available information is not sufficient to recommend use of bronchoscopic strategies for treating emphysema.

Biologic Lung Volume Reduction in Advanced Upper Lobe Emphysema: Phase 2 Results

Biologic Lung Volume Reduction in Advanced Upper Lobe Emphysema: Phase 2 Results

Biologic lung volume reduction therapy for advanced homogeneous emphysema

This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

Biologic Lung Volume Reduction in Advanced Upper Lobe Emphysema

Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling. Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema. Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life. After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (-6.4 +/- 9.3%; P = 0.002) and HD (-5.5 +/- 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P = 0.021; DeltaFVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life. BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).

Endobronchial Biologic Lung Volume Reduction (BLVR) Therapy for Unilateral Bullous Emphysema

Background Biologic lung volume reduction (BLVR) is an experimental endobronchial treatment for advanced emphysema that reduces lung volume by remodeling damaged areas of hyperinflated lung. This article summarizes the first experience using BLVR to treat unilateral bullous disease. Methods A 67-year-old man with very severe chronic obstructive pulmonary disease owing to advanced emphysema underwent BLVR at 8 right upper lobe (RUL) subsegmental sites during 2-treatment sessions 6 weeks apart. Response to therapy was assessed 6 weeks after initial treatment, and 6 and 12 weeks after the second treatment. Results Six weeks after initial BLVR treatment at 4 subsegments, small improvements in spirometry, dyspnea [Modified Medical Research Council Dyspnea (MRCD) score=−1 U change], and a 6-minute walk distance (6MWD=+76 m change) were observed. Improvements at 6 and 12 weeks after repeat treatment in FEV1 (+20.0%, +22.1%), FVC (+33.1%, +27.6%), DLco (+6.4%, +6.3%), RV/TLC ratio (−9.8%, −5.1%), MRCD (−1 U, −1 U), 6MWD (79 m, 77 m), and St George's Respiratory Questionnaire score (total score=−5.9 U, −2.2 U) were observed. Quantitative analysis of computed tomography imaging demonstrated a 357 mL reduction in RUL lung volume, and corresponding increases in volumes of adjacent, less damaged areas of lung tissue. Conclusions BLVR produced effective targeted lung volume reduction of a RUL bullous and improvements in spirometry, symptoms, exercise capacity, and diffusing capacity. This novel bronchoscopic technique may provide a safe alterative to bullectomy in selected patients.

Biological Lung Volume Reduction: A New Bronchoscopic Therapy for Advanced Emphysema

Biological lung volume reduction (BLVR) using biological reagents to remodel and shrink damaged regions of lung has previously been accomplished in sheep with experimental pulmonary emphysema. This report summarizes the initial clinical experience including a 3-month follow-up using this technique in humans.An open-label phase 1 trial designed to evaluate the safety of BLVR in patients with advanced heterogeneous emphysema enrolled six patients. Of these, three patients received unilateral treatment at two pulmonary subsegments (group 1) and three patients received unilateral treatment at four pulmonary subsegments (group 2). The incidence of adverse events and changes in pulmonary function test results, symptoms, and exercise capacity were evaluated.The mean (+/- SD) age of the six men enrolled in the study was 66 +/- 5.7 years (age range, 57 to 73 years). BLVR was well tolerated in both treatment groups and was not associated with any serious complications. All patients were discharged from the hospital on posttreatment day 1. Although the primary purpose of the study was to examine safety, improvements were observed in mean vital capacity (+7.2 +/- 9.5%; range, -2% to + 19%), mean residual volume (RV) [-7.8 +/- 8.5%; range, + 1% to -22%], mean RV/total lung capacity ratio (-6.6 +/- 4.7%; range, -1% to -15%), mean 6-min walk distance (+14.5 +/- 18.5%; range, 0 to + 51%), and in mean dyspnea score. On average, group 2 patients experienced greater benefit from BLVR than group 1 patients, suggesting a dose-response pattern.Preliminary results indicate that BLVR can be safe and may produce benefits in appropriately selected patients with advanced heterogeneous emphysema.