New insights in immunomodulation for intestinal transplantation.

Tolerance is the Holy Grail of solid organ transplantation (SOT) and remains its primary challenge since its inception. In this topic, the seminal contributions of Thomas Starzl at Pittsburgh University outlined foundational principles of graft acceptance and tolerance, with chimerism emerging as a pivotal factor. Immunologically, intestinal transplantation (ITx) poses a unique hurdle due to the inherent characteristics and functions of the small bowel, resulting in increased immunogenicity. This necessitates heavy immunosuppression (IS) while IS drugs side effects cause significant morbidity. In addition, current IS therapies fall short of inducing clinical tolerance and their discontinuation has been proven unattainable in most cases. This underscores the unfulfilled need for immunological modulation to safely reduce IS-related burdens. To address this challenge, the Leuven Immunomodulatory Protocol (LIP), introduced in 2000, incorporates various pro-tolerogenic interventions in both the donor to the recipient, with the aim of facilitating graft acceptance and improving outcome. This review seeks to provide an overview of the current understanding of tolerance in ITx and outline recent advances in this domain.

The nature of chronic rejection after lung transplantation: a murine orthotopic lung transplant study.

Introduction: Chronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation. Methods: 40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT. For timing and location of rejection, extra grafts were sacrificed at day 7, 35, 56 and investigated by ex vivo µCT or single cell RNA (scRNA) profiling. Results: Chronic rejection originated as innate inflammation around small arteries evolving toward adaptive organization with subsequent end-arterial fibrosis and obliterans. Subsequently, venous and pleural infiltration appeared, followed by airway related bronchiolar folding and rarely bronchiolitis obliterans was observed. Ex vivo µCT and scRNA profiling validated the time, location and sequence of events with endothelial destruction and activation as primary onset. Conclusion: Against the current belief, chronic rejection in lung transplantation may start as an arterial response, followed by responses in venules, pleura, and, only in the late stage, bronchioles, as may be seen in some but not all patients with CLAD.

Multilevel Analysis of the Neovascularization and Integration Process of a Nonvascularized Rectus Fascia Transplantation.

Background: Failure to close the abdominal wall after intestinal transplantation (ITx) or multivisceral Tx remains a surgical challenge. An attractive method is the use of nonvascularized rectus fascia (NVRF) in which both layers of the donor abdominal rectus fascia are used as an inlay patch without vascular anastomosis. How this graft integrates over time remains unknown. The study aims to provide a multilevel analysis of the neovascularization and integration process of the NVRF. Methods: Three NVRF-Tx were performed after ITx. Clinical, radiological, histological, and immunological data were analyzed to get insights into the neovascularization and integration process of the NVRF. Moreover, cryogenic contrast-enhanced microfocus computed tomography (microCT) analysis was used for detailed reconstruction of the vasculature in and around the NVRF (3-dimensional histology). Results: Two men (31- and 51-y-old) and 1 woman (49-y-old) underwent 2 multivisceral Tx and 1 combined liver-ITx, respectively. A CT scan showed contrast enhancement around the fascia graft at 5 days post-Tx. At 6 weeks, newly formed blood vessels were visualized around the graft with Doppler ultrasound. Biopsies at 2 weeks post-Tx revealed inflammation around the NVRF and early fibrosis. At 6 months, classical 2-dimensional histological analysis of a biopsy confirmed integration of the fascia graft with strong fibrotic reaction without signs of rejection. A cryogenic contrast-enhanced microCT scan of the same biopsy revealed the presence of microvasculature, enveloping and penetrating the donor fascia. Conclusions: We showed clinical, histological, and microCT evidence of the neovascularization and integration process of the NVRF after Tx.

Aerostasis to limit air leak following extended pleurectomy-decortication.

Extended pleurectomy-decortication is a cytoreductive surgical treatment for malignant pleural mesothelioma. Prolonged air leak remains a major postoperative challenge, lengthening hospital stay and increasing morbidity. In this video report, we present a stepwise approach for visceral decortication and introduce the concept of aerostasis by construction of an artificial neopleura. Our results suggest that improved aerostasis results in shortened air leak duration.

Abdominal Wall Closure in Intestinal and Multivisceral Transplantation: A State-Of-The-Art Review of Vascularized Abdominal Wall and Nonvascularized Rectus Fascia Transplantation.

Failure to close the abdomen after intestinal or multivisceral transplantation (Tx) remains a frequently occurring problem. Two attractive reconstruction methods, especially in large abdominal wall defects, are full-thickness abdominal wall vascularized composite allograft (AW-VCA) and nonvascularized rectus fascia (NVRF) Tx. This review compares surgical technique, immunology, integration, clinical experience, and indications of both techniques. In AW-VCA Tx, vascular anastomosis is required and the graft undergoes hypotrophy post-Tx. Furthermore, it has immunologic benefits and good clinical outcome. NVRF Tx is an easy technique without the need for vascular anastomosis. Moreover, a rapid integration and neovascularization occurs with excellent clinical outcome.

Controlled Hypothermic Storage for Lung Preservation: Leaving the Ice Age Behind.

Controlled hypothermic storage (CHS) is a recent advance in lung transplantation (LTx) allowing preservation at temperatures higher than those achieved with traditional ice storage. The mechanisms explaining the benefits of CHS compared to conventional static ice storage (SIS) remain unclear and clinical data on safety and feasibility of lung CHS are limited. Therefore, we aimed to provide a focus review on animal experiments, molecular mechanisms, CHS devices, current clinical experience, and potential future benefits of CHS. Rabbit, canine and porcine experiments showed superior lung physiology after prolonged storage at 10°C vs. ≤4°C. In recent molecular analyses of lung CHS, better protection of mitochondrial health and higher levels of antioxidative metabolites were observed. The acquired insights into the underlying mechanisms and development of CHS devices allowed clinical application and research using CHS for lung preservation. The initial findings are promising; however, further data collection and analysis are required to draw more robust conclusions. Extended lung preservation with CHS may provide benefits to both recipients and healthcare personnel. Reduced time pressure between procurement and transplantation introduces flexibility allowing better decision-making and overnight bridging by delaying transplantation to daytime without compromising outcome.

Multicentre retrospective analysis on pulmonary metastasectomy: an European perspective.

OBJECTIVES: To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS: Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS: A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25-75% = 1-2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS: Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice.

Extensive surgical resections for rare pleural neoplasms: a single-center experience with a yolk sac tumor and synovial sarcoma.

BACKGROUND: Pleural neoplasms are rare and can be subdivided into pleural metastasis and primary pleural neoplasms. Non-mesothelioma primary pleural neoplasms are a diverse group of extremely rare pathologies. CASE PRESENTATION: In this case series, we describe the presentation and management of two rare primary pleural neoplasms. A first case describes a primary pleural yolk sac tumor treated with neoadjuvant chemotherapy, extended pleurectomy decortication, and hyperthermic intrathoracic chemotherapy. In a second case we describe the management of a primary pleural synovial sarcoma by neoadjuvant chemotherapy and extrapleural pneumonectomy. A complete resection was obtained in both cases and the post-operative course was uncomplicated. No signs of tumor recurrence were noted during follow-up in the first patient. In the second patient a local recurrence was diagnosed 6 months after surgery. CONCLUSION: Neo-adjuvant chemotherapy followed by extensive thoracic surgery, including hyperthermic intrathoracic chemotherapy, is a feasible treatment strategy for non-mesothelioma primary pleural neoplasms, but careful follow-up is required.

Implementation of an enhanced recovery protocol for lung volume reduction surgery: an observational cohort study.

OBJECTIVES: Lung volume reduction surgery (LVRS) is an established therapeutic option for advanced emphysema. To improve patients' safety and reduce complications, an enhanced recovery protocol (ERP) was implemented. This study aims to describe and evaluate the short-term outcome of this ERP. METHODS: This retrospective single-centre study included all consecutive LVRS patients (1 January 2017 until 15 September 2020). An ERP for LVRS was implemented and stepwise optimised from 1 August 2019, it consisted of changes in pre-, peri- and postoperative care pathways. Patients were compared before and after implementation of ERP. Primary outcome was incidence of postoperative complications (Clavien-Dindo), and secondary outcomes included chest tube duration, incidence of prolonged air leak (PAL), length of stay (LOS) and 90-day mortality. Lung function and exercise capacity were evaluated at 3 and 6 months post-LVRS. RESULTS: Seventy-six LVRS patients were included (pre-ERP: n=41, ERP: n=35). The ERP cohort presented with lower incidence of postoperative complications (42% vs 83%, P=0.0002), shorter chest tube duration (4 vs 12 days, P<0.0001) with a lower incidence of PAL (21% vs 61%, P=0.0005) and shorter LOS (6 vs 14 days, P<0.0001). No in-hospital mortality occurred in the ERP cohort versus 4 pre-ERP. Postoperative forced expiratory volume in 1 s was higher in the ERP cohort compared to pre-ERP at 3 months (1.35 vs 1.02 l) and at 6 months (1.31 vs 1.01 l). CONCLUSIONS: Implementation of ERP as part of a comprehensive reconceptualisation towards LVRS, demonstrated fewer postoperative complications, including PAL, resulting in reduced LOS. Improved short-term functional outcomes were observed at 3 and 6 months.

Extended ischemic time (>15 hours) using controlled hypothermic storage in lung transplantation: A multicenter experience.

Static ice storage has long been the standard-of-care for lung preservation, although freezing injury limits ischemic time (IT). Controlled hypothermic storage (CHS) at elevated temperature could safely extend IT. This retrospective analysis assesses feasibility and safety of CHS with IT > 15 hours. Three lung transplant (LuTx) centers (April-October 2023) included demographics, storage details, IT, and short-term outcome from 13 LuTx recipients (8 male, 59 years old). Donor lungs were preserved in a portable CHS device at 7 (5-9.3)°C. Indication was overnight bridging and/or long-distance transport. IT of second-implanted lung was 17.3 (15.1-22) hours. LuTx were successful, 4/13 exhibited primary graft dysfunction grade 3 within 72 hours and 0/13 at 72 hours. Post-LuTx mechanical ventilation was 29 (7-442) hours. Intensive care unit stay was 9 (5-28) and hospital stay 30 (16-90) days. Four patients needed postoperative extracorporeal membrane oxygenation (ECMO). One patient died (day 7) following malpositioning of an ECMO cannula. This multicenter experience demonstrates the possibility of safely extending IT > 15 hours by CHS.

Ventilatory capacity in CLAD is driven by dysfunctional airway structure.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood. METHODS: A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Ex vivo whole lung µCT and tissue-core µCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014-2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions. FINDINGS: BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters. INTERPRETATION: Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted. FUNDING: This research was funded with the National research fund Flanders (G060322N), received by R.V.

Diagnosis and Management of Esophageal Fistulas After Lung Transplantation: A Case Series.

Background: Lung transplantations are highly complex procedures, often conducted in frail patients. Through the addition of immunosuppressants, healing can be compromised, primarily leading to the development of bronchopleural fistulas. Although esophageal fistulas (EFs) after lung transplantation remain rare, they are associated with significant morbidity. We aimed to investigate the clinical presentation, diagnostic approaches, and treatment strategies of EF after lung transplantation. Methods: All patients who developed EF after lung transplantation at the University Hospitals Leuven between January 2019 and March 2022 were retrospectively reviewed and the clinical presentations, diagnostic approaches, and treatment strategies were summarized. Results: Among 212 lung transplantation patients, 5 patients (2.4%) developed EF. Three patients were male and median age was 39 y (range, 34-63). Intraoperative circulatory support was required in 3 patients, with 2 needing continued support postoperatively. Bipolar energy devices were consistently used for mediastinal hemostasis. All EFs were right-sided. Median time to diagnosis was 28 d (range, 12-48) and 80% of EFs presented as recurrent respiratory infections or empyema. Diagnosis was made through computed tomography (n = 3) or esophagogastroscopy (n = 2). Surgical repair with muscle flap covering achieved an 80% success rate. All patients achieved complete resolution, with only 1 patient experiencing a fatal outcome during a complicated EF-related recovery. Conclusion: Although EF after lung transplantation remains rare, vigilance is crucial, particularly in cases of right-sided intrathoracic infection. Moreover, caution must be exercised when applying thermal energy in the mediastinal area to prevent EF development and mitigate the risk of major morbidity. Timely diagnosis and surgical intervention can yield favorable outcomes.

The Immunopathology of Pulmonary Rejection after Murine Lung Transplantation.

To improve outcomes following lung transplantation, it is essential to understand the immunological mechanisms that result in chronic graft failure. The associated clinical syndrome is termed chronic lung allograft dysfunction (CLAD), which is known to be induced by alloimmune-dependent (i.e., rejection) and alloimmune-independent factors (e.g., infections, reflux and environmental factors). We aimed to explore the alloimmune-related mechanism, i.e., pulmonary rejection. In this study, we use a murine orthotopic left lung transplant model using isografts and allografts (C57BL/6 or BALB/c as donors to C57BL/6 recipients), with daily immunosuppression (10 mg/kg cyclosporin A and 1.6 mg/kg methylprednisolone). Serial sacrifice was performed at days 1, 7 and 35 post-transplantation (n = 6 at each time point for each group). Left transplanted lungs were harvested, a single-cell suspension was made and absolute numbers of immune cells were quantified using multicolor flow cytometry. The rejection process followed the principles of a classic immune response, including innate but mainly adaptive immune cells. At day 7 following transplantation, the numbers of interstitial macrophages, monocytes, dendritic cells, NK cells, NKT cells, CD4+ T cells and CD8+ T and B cells were increased in allografts compared with isografts. Only dendritic cells and CD4+ T cells remained elevated at day 35 in allografts. Our study provides insights into the immunological mechanisms of true pulmonary rejection after murine lung transplantation. These results might be important in further research on diagnostic evaluation and treatment for CLAD.

Simultaneous Lung-abdominal Organ Procurement From Donation After Circulatory Death Donors Reduces Donor Hepatectomy Time.

BACKGROUND: Prolonged organ procurement time impairs the outcome of donation after circulatory death (DCD) and liver transplantation (LiT). Our transplant team developed a simultaneous, rather than sequential, lung-abdominal organ explantation strategy for DCD donation to prioritize liver procurement. We evaluated whether this change in strategy effectively reduced donor hepatectomy time (dHT), without affecting donor pneumonectomy time (dPT), and influenced LiT and lung transplantation outcome. METHODS: All lung-abdominal and abdominal-only transplant procedures between 2010 and 2020 were analyzed in this retrospective cohort study. Relationships were assessed between the year of transplant and dHT and dPT (univariate linear regression), 1-y patient and graft survival, primary graft dysfunction, and nonanastomotic biliary strictures (univariate logistic regression). RESULTS: Fifty-two lung-abdominal and 110 abdominal-only DCD procedures were analyzed. A significant decrease in dHT was noted in lung-abdominal (slope -1.14 [-2.14; -0.15], P = 0.026) but not in abdominal-only procedures; dPT did not increase. There were no significant associations between the year of transplant and nonanastomotic biliary strictures frequency, primary graft dysfunction incidence, 1-y patient, and graft survival. CONCLUSIONS: Simultaneous organ procurement in multiorgan lung-abdominal DCD procedures is feasible, and effectively shortened dHT without affecting lung transplantation outcome. No impact on LiT outcome was observed; however, larger multicenter studies are needed.

Computed tomography-based machine learning for donor lung screening before transplantation.

BACKGROUND: Assessment and selection of donor lungs remain largely subjective and experience based. Criteria to accept or decline lungs are poorly standardized and are not compliant with the current donor pool. Using ex vivo computed tomography (CT) images, we investigated the use of a CT-based machine learning algorithm for screening donor lungs before transplantation. METHODS: Clinical measures and ex situ CT scans were collected from 100 cases as part of a prospective clinical trial. Following procurement, donor lungs were inflated, placed on ice according to routine clinical practice, and imaged using a clinical CT scanner before transplantation while stored in the icebox. We trained and tested a supervised machine learning method called dictionary learning, which uses CT scans and learns specific image patterns and features pertaining to each class for a classification task. The results were evaluated with donor and recipient clinical measures. RESULTS: Of the 100 lung pairs donated, 70 were considered acceptable for transplantation (based on standard clinical assessment) before CT screening and were consequently implanted. The remaining 30 pairs were screened but not transplanted. Our machine learning algorithm was able to detect pulmonary abnormalities on the CT scans. Among the patients who received donor lungs, our algorithm identified recipients who had extended stays in the intensive care unit and were at 19 times higher risk of developing chronic lung allograft dysfunction within 2 years posttransplant. CONCLUSIONS: We have created a strategy to ex vivo screen donor lungs using a CT-based machine learning algorithm. As the use of suboptimal donor lungs rises, it is important to have in place objective techniques that will assist physicians in accurately screening donor lungs to identify recipients most at risk of posttransplant complications.

The value of point-of-care tests for the detection of SARS-CoV-2 RNA or antigen in bronchoalveolar lavage fluid.

BACKGROUND: Transmission of SARS-CoV-2 from donor to recipient is a clinically relevant risk for developing severe COVID-19 after lung transplantation (LTx). This risk of iatrogenic transmission can be reduced by timely detection of viral RNA or antigen in samples of bronchoalveolar lavage (BAL) fluid obtained at the time of lung procurement. We aimed to retrospectively evaluate the detection of SARS-CoV-2 RNA or antigen in BAL fluid samples using three point-of-care tests (POCTs). METHODS: BAL fluid samples came from patients hospitalized in an intensive care unit during the COVID-19 pandemic. These pandemic samples were scored as positive or negative for SARS-CoV-2 by a RT-qPCR comparator assay for orf1ab. Three commercially available POCTs were then evaluated: cobas SARS-CoV-2 & Influenza A/B assay with the cobas Liat RT-qPCR system (Roche Diagnostics), ID NOW COVID-19 and COVID-19 2.0 (Abbott), and SARS-CoV-2 Rapid Antigen Test (RAT) (Roche Diagnostics). Samples from the pre-pandemic era served as negative controls. RESULTS: We analyzed a total of 98 BAL fluid samples, each from a different patient: 58 positive pandemic samples (orf1ab Ct<38), 20 putatively negative pandemic samples (orf1ab Ct≥38), and 20 pre-pandemic samples. Univariate logistic regression shows that the probability of detection was highest for cobas Liat, followed by ID NOW, and then RAT. Of clinical relevance, cobas Liat detected SARS-CoV-2 RNA in 30 of the 31 positive pandemic samples that were collected within 10 days after RT-qPCR diagnosis of SARS-CoV-2 infection. None of the 20 pre-pandemic samples had a false-positive result for any POCT. CONCLUSIONS: POCTs enable the detection of SARS-CoV-2 RNA or antigen in BAL fluid samples and may provide additional information to decide if donor lungs are suitable for transplantation. Detection of respiratory pathogens with POCTs at the time of donor lung procurement is a potential strategy to increase safety in LTx by preventing iatrogenic transmission and severe postoperative infections.

Complications related to extracorporeal life support in lung transplantation: single-center analysis.

Background: Extracorporeal life support (ECLS) is not routinely used at our center during sequential single-lung transplantation (LTx), but is restricted to anticipate and overcome hemodynamic and respiratory problems occurring peri-operatively. In this retrospective descriptive cohort study, we aim to describe our single-center experience with ECLS in LTx, analyzing ECLS-related complications. Methods: All transplantations with peri-operative ECLS use [2010-2020] were retrospectively analyzed. Multi-organ and heart-lung transplantation were excluded. Demographics, support type and indications are described. Complications are categorized according to the underlying nature and type. Data are presented as median [interquartile range (IQR)]. Kaplan-Meier was used for survival analysis. Results: The overall use of ECLS was 22% (156/703 patients) with a mean age of 52 years (IQR, 36-59 years). Transplant indications in ECLS cohort were interstitial lung disease (38%; n=60), chronic obstructive pulmonary disease (COPD) (19%; n=29), cystic fibrosis (17%; n=26) and others (26%; n=41). Per indication, 94% (15/16) of pulmonary arterial hypertension patients required ECLS, whereas only 8% (29/382) of COPD patients did. In 16% (25/156) of supported patients, veno-venous extracorporeal membrane oxygenation was initiated, while 77% (120/156) required veno-arterial support, and 7% (11/156) cardiopulmonary bypass. Thirty-day mortality was 6% (9/156). Sixteen percent (25/156) of patients were bridged to transplantation on ECLS and 24% (37/156) required post-operative support. Main reasons to use ECLS were intra-operative hemodynamic instability (53%; n=82), ventilation/oxygenation problems (22%; n=34) and reperfusion edema (17%; n=26). Overall incidence of patients with at least one ECLS-related complication was 67% (n=104). Most common complications were hemothorax (25%; n=39), need for continuous renal replacement therapy (19%; n=30), and thromboembolism (14%; n=22). Conclusions: ECLS was required in 22% of LTxs, with a reported ECLS-related complication rate of 67%, of which the most common was hemothorax. Larger databases are needed to further analyze complications and develop tailored deployment strategies for ECLS-use in LTx.

Surgical and bronchoscopic pulmonary function-improving procedures in lung emphysema.

COPD is a highly prevalent, chronic and irreversible obstructive airway disease without curative treatment. Standard therapeutic strategies, both non-pharmacological and pharmacological, have only limited effects on lung function parameters of patients with severe disease. Despite optimal pharmacological treatment, many patients with severe COPD still have a high burden of dyspnoea and a poor quality of life. If these patients have severe lung emphysema, with hyperinflation as the driver of symptoms and exercise intolerance, lung volume reduction may be an effective treatment with a significant impact on lung function, exercise capacity and quality of life. Currently, different lung volume reduction approaches, both surgical and bronchoscopic, have shown encouraging results and have been implemented in COPD treatment recommendations. Nevertheless, choosing the optimal lung volume reduction strategy for an individual patient remains challenging. Moreover, there is still room for improving durability of effect and safety in all available procedures. Ongoing and innovative research is essential to push this field forwards. This review provides an overview of results and limitations of the current lung volume reduction options for patients with severe lung emphysema and hyperinflation.