Lung Volume Reduction Followed by Lung Transplantation in Emphysema-A Multicenter Matched Analysis.

Objective: The impact of previous lung volume reduction surgery (LVRS) or endoscopic lung volume reduction (ELVR) on lung transplantation (LuTX) remains unclear. This study assesses the risk of previous lung volume reduction on the outcome of a later LuTX. Methods: Patients suffering from emphysema who underwent bilateral LuTX were included in this multicenter analysis. Study groups were defined as: previous LVRS, previous ELVR, controls. Imbalances were corrected by coarsened exact matching for center, gender, age, diagnosis, and BMI. A comparative analysis of intraoperative characteristics, perioperative outcome and long-term survival was performed. Results: 615 patients were included (LVRS = 26; ELVR = 60). Compared to controls, LVRS patients had a higher rate of postoperative ECMO (15.4 vs. 3.9%; p = 0.006), whereas ELVR patients suffered more often from wound infections (8.9% vs. 2.5%; p = 0.018). Perioperative outcome, duration of ventilation, ICU stay, and hospital stay were comparable between groups. Bacterial colonization of the airway differed significantly between both LVR groups and controls in pre- and post-LuTX cultures. Survival was not impacted (1-/3-/5-year survival for LVRS: 92.3%/85.7%/77.1%; controls: 91.3%/82.4%/76.3%; p = 0.58 | ELVR: 93.1%/91%/91%; controls 91.2%/81.7%/75.3%; p = 0.17). Conclusion: Lung volume reduction does not impact short and long-time survival after bilateral LuTX. Due to differences in airway colonization after LVR, caution to prevent infectious complications is warranted.

Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation.

The existence of latent viral reservoirs (LVRs), also called latent cells, has long been an acknowledged stubborn hurdle for effective treatment of HIV-1/AIDS. This stable and heterogeneous reservoir, which mainly exists in resting memory CD4+ T cells, is not only resistant to highly active antiretroviral therapy (HAART) but cannot be detected by the immune system, leading to rapid drug resistance and viral rebound once antiviral treatment is interrupted. Accordingly, various functional cure strategies have been proposed to combat this barrier, among which one of the widely accepted and utilized protocols is the so-called 'shock-and-kill' regimen. The protocol begins with latency-reversing agents (LRAs), either alone or in combination, to reactivate the latent HIV-1 proviruses, then eliminates them by viral cytopathic mechanisms (e.g., currently available antiviral drugs) or by the immune killing function of the immune system (e.g., NK and CD8+ T cells). In this review, we focuse on the currently explored small molecular LRAs, with emphasis on their mechanism-directed drug targets, binding modes and structure-relationship activity (SAR) profiles, aiming to provide safer and more effective remedies for treating HIV-1 infection.

Comparison between the EQ-5D-3L and the SF-6D quality of life (QOL) questionnaires in patients with chronic obstructive pulmonary disease (COPD) undergoing lung volume reduction surgery (LVRS).

PURPOSE: Lung volume reduction surgery (LVRS) has been shown to improve lung function, but also improve the overall quality of life (QOL). The aim of this study is to compare two QOL questionnaires-EuroQol Questionnaire (EQ-5D-3L) and 36-item Short Form Health Survey (SF-36) in patients post-LVRS. METHODS: All patients undergoing LVRS for severe chronic obstructive pulmonary disease (COPD) at a single center of excellence were analyzed (n = 94). Baseline demographic and clinical outcomes were characterized. Both EQ-5D-3L and SF-36 questionnaires were administered to all patients at baseline (n = 94) and at the end of 1 year (n = 89) post-surgery. SF-36 was converted to Short Form six-dimensions (SF-6D) using standard algorithm. Correlation, discrimination, responsiveness and differences across the two questionnaires were examined. RESULTS: The mean age of patients enrolled in the cohort was 66 years. There was significant increase in forced expiratory volume (FEV1, 43%), forced vital capacity (FVC 46%), diffusion capacity (DLCO 15%), 6 min walk distance test (6MWD 21%) and a significant decrease in residual volume (RV 23%) at the end of 1-year follow-up. The overall mean utility index significantly improved for both SF-6D and EQ-5D-3L questionnaires at the end of follow-up (p = 0.0001). However, the magnitude of percentage increase was higher with EQ-5D-3L compared to SF-6D (32% vs. 13%). Stronger correlations confirmed convergent validity at the end of 1-year follow-up between similar domains. Both questionnaires failed to discriminate between different levels of disease severity post-LVRS in patients with severe COPD. CONCLUSIONS: Both questionnaires responded similarly in patients with COPD post-LVRS. Combining results from QOL questionnaire(s) along with symptoms of disease and history of exacerbation may be a possible solution for identifying disease severity in old and sick patients unwilling/unable to come to hospital for a pulmonary function test post-LVRS.

Lung Volume Reduction Surgery and Improvement of Endothelial Function and Blood Pressure in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

RATIONALE: Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Preliminary studies have shown that both airflow obstruction and systemic inflammation may contribute to endothelial dysfunction in COPD. Lung volume reduction surgery (LVRS) is a treatment option in selected patients with COPD with emphysema that improves breathing mechanics and lung function. OBJECTIVES: To determine the effect of LVRS on endothelial function and systemic inflammation. METHODS: We conducted a randomized controlled trial in 30 patients scheduled for LVRS. In the intervention group, immediate LVRS was performed after baseline evaluation followed by reassessment 3 months later. In the control group, reassessment followed 3 months after baseline evaluation, and thereafter LVRS was performed. MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were the treatment effect on endothelial function and systemic inflammation. In the LVRS group 14 patients completed the trial and 13 in the control group. LVRS led to a relative reduction in mean (SD) residual volume/total lung capacity of -12% (12%) and an increase in FEV1 of 29% (27%). Flow-mediated dilatation of the brachial artery increased in the intervention group as compared with the control group (+2.9%; 95% confidence interval, +2.1 to +3.6%; P < 0.001), whereas there was no significant change in systemic inflammation. A significant treatment effect on mean blood pressure was observed (-9.0 mm Hg; 95% confidence interval, -17.5 to -0.5; P = 0.039). CONCLUSIONS: Endothelial function and blood pressure are improved 3 months after LVRS in patients with severe COPD and emphysema. LVRS may therefore have beneficial effects on cardiovascular outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 01020344).

Relevance of pleural adhesions for short- and long-term outcomes after lung volume reduction surgery.

Objective: Pleural adhesions (PLAs) have been shown to be a possible risk factor for air leak after lung volume reduction surgery (LVRS), but the relevance of PLA for lung function outcome remains unclear. We analyzed our LVRS cohort for the influence of PLA on short-term (ie, prolonged air leak) and long-term outcomes. Methods: Retrospective observational cohort study with 187 consecutive patients who underwent LVRS from January 2016 to December 2019. PLA were defined as relevant if they were distributed extensively at the dorsal pleura; were present in at least at 2 areas, including the dorsal pleura; or present extensively at the mediastinal pleura. In patients with bilateral emphysema, bilateral LVRS was performed preferentially. The objectives were to quantify the association of PLA and rate of prolonged air leak (chest tube >7 days), and the association of PLA with postoperative exacerbations and with forced expiratory volume in 1 second 3 months postoperatively. The associations were quantified with odds ratios for binary outcomes, and with between-group differences for continuous outcomes. To account for missing observations, 100-fold multiple imputation was used. Results: PLAs were found in 46 of 187 patients (24.6%). There was a 32.6% rate of prolonged air leak (n = 61), mean chest tube time was 7.84 days. A total of 94 (50.3%) LVRSs were unilateral and 93 were bilateral. There was evidence for an association between PLA and the rate of prolonged air leak (odds ratio, 2.83; 95% CI, 1.36 to 5.89; P = .006). There was no evidence for an association between PLA and postoperative exacerbations (odds ratio, 1.11; 95% CI, 0.5 to 2.45; P = .79). There was no evidence for an association between PLA and forced expiratory volume in 1 second (estimate -1.52; 95% CI -5.67 to 2.63; P = .47). Both unilateral and bilateral LVRS showed significant postoperative improvements in forced expiratory volume in 1 second by 27% (8.43 units; 95% CI, 3.66-13.12; P = .0006) and by 28% (7.87 units; 95% CI, 4.68-11.06; P < .0001) and a reduction in residual volume of 15% (-33.9 units; 95% CI, -56.37 to -11.42; P = .003) and 15% (-34.9 units; 95% CI, -52.57 to -17.22; P = .0001), respectively. Conclusions: Patients should be aware of potential prolongation of hospitalization due to PLA. However, there might be no relevant influence of PLA on lung function outcomes.

Surgical and Interventional Approaches in COPD.

Many patients suffer from complaints of dyspnea, cough, and sputum production, clinical symptoms that hallmark the structural abnormalities that are present in patients with COPD. Although pharmacologic and non-pharmacologic medical therapies help reduce these symptoms, many of these symptoms, especially dyspnea, remain unchecked and contribute to the burden of disease in patients with COPD. Over the last 3 decades, several surgical and interventional treatments delivered via a bronchoscopic approach have been developed to complement medical therapies and show promise to improve patient outcomes. Surgical and interventional treatments target structural abnormalities of the airway and lung parenchyma that can be identified with a combination of imaging and physiological testing, factors that are key to select patients most likely to benefit from these treatments. This paper reviews surgical and bronchoscopic interventional treatment options for patients with emphysema and airways disorders.

Nonintubated versus Intubated Lung Volume Reduction Surgery in Patients with End-Stage Lung Emphysema and Hypercapnia.

Lung volume reduction surgery (LVRS) represents an important treatment option in carefully selected patients with end-stage lung emphysema. The aim of this study was to assess the efficacy and safety of nonintubated LVRS compared to intubated LVRS in patients with preoperative hypercapnia and lung emphysema. Between April 2019 and February 2021, n = 92 patients with end-stage lung emphysema and preoperative hypercapnia undergoing unilateral video-assisted thoracoscopic LVRS (VATS-LVRS) performed in epidural anesthesia and mild sedation (nonintubated, group 1) or conventional general anesthesia (intubated, control, group 2) were prospectively enrolled in this study. Data were retrospectively analyzed. In all patients, low-flow veno-venous extracorporeal lung support (low-flow VV ECLS) was applied as a bridge through LVRS. Ninety-day mortality was considered as the primary outcome. Secondary endpoints included: chest tube duration, hospital stay, intubation and conversion to general anesthesia. Intergroup analysis showed no significant difference between the baseline data and patients' demographics. N = 36 patients underwent nonintubated surgery. VATS-LVRS under general anesthesia was performed in n = 56 patients. The mean duration of postoperative VV ECLS support was 3 ± 1 day in group 1 compared to 4 ± 1 in group 2. The 90-day mortality rate was 3% in group 1 compared to 7% in group 2. In group 1, all chest tubes were removed 5 ± 1 day (range 4-32 days) and 8 ± 1 day (range 4-44 days) in the control group after the surgery (p < 0.02). Prolonged chest tube therapy (>8 days) was observed in n = 3 patients in group 1 and n = 11 patients in the control group. The mean ICU stay was 4 ± 1 days in group 1 compared to 8 ± 2 days in the control group (p = 0.04). The mean hospital stay was significantly shorter in the nonintubated group 1 (6 ± 2 days vs. 10 ± 4 days, p = 0.01). Conversion to general anesthesia was necessary in one patient due to severe pleural adhesions. Nonintubated VATS-LVRS in patients with end-stage lung emphysema and hypercapnia is effective and well tolerated. Compared to general anesthesia, a reduction in mortality, chest tube duration, ICU and hospital stay and lower rate of prolonged air leak was observed. VV ECLS increases intraoperative safety and mitigates postoperative complications in such "high-risk" patients.

A 64-year-Old patient assigned male at birth with COPD and worsening dyspnea while on estrogen and antiandrogen agents.

Among patients with COPD, ventilatory inefficiency in response to exercise can be due to respiratory muscle dysfunction or expiratory flow limitation causing air-trapping and dynamic hyperinflation. We discuss a case of severe ventilatory limitation in response to exercise due to reduced respiratory muscle mass in the setting of gender-affirming hormone therapy (GAHT), and how the interpretation of pulmonary function testing (PFT) and respiratory symptoms among transgender and gender diverse (TGD) patients can be influenced by GAHT.

Comparative outcomes of lung volume reduction surgery and lung transplantation: a systematic review and meta-analysis.

Background: Lung volume reduction (LVR) and lung transplantation (LTx) have been used in different populations of chronic obstructive pulmonary disease (COPD) patients. To date, comparative study of LVR and LTx has not been performed. We sought to address this gap by pooling the existing evidence in the literature. Methods: An electronic search was performed to identify all prospective studies on LVR and LTx published since 2000. Baseline characteristics, perioperative variables, and clinical outcomes were extracted and pooled for meta-analysis. Results: The analysis included 65 prospective studies comprising 3,671 patients [LTx: 15 studies (n=1,445), LVR: 50 studies (n=2,226)]. Mean age was 60 [95% confidence interval (CI): 58-62] years and comparable between the two groups. Females were 51% (95% CI: 30-71%) in the LTx group vs. 28% (95% CI: 21-36%) in LVR group (P=0.05). Baseline 6-minute walk test (6MWT) and pulmonary function tests were comparable except for the forced expiratory volume in 1 second (FEV1), which was lower in the LTx group [21.8% (95% CI: 16.8-26.7%) vs. 27.3% (95% CI: 25.5-29.2%), P=0.04]. Postoperatively, both groups experienced improved FEV1, however post-LTx FEV1 was significantly higher than post-LVR FEV1 [54.9% (95% CI: 41.4-68.4%) vs. 32.5% (95% CI: 30.1-34.8%), P<0.01]. 6MWT was also improved after both procedures [LTx: 212.9 (95% CI: 119.0-306.9) to 454.4 m (95% CI: 334.7-574.2), P<0.01; LVR: 286 (95% CI: 270.2-301.9) to 409.1 m (95% CI: 392.1-426.0), P<0.01], however, with no significant difference between the groups. Pooled survival over time showed no significant difference between the groups. Conclusions: LTx results in better FEV1 but otherwise has comparable outcomes to LVR.

The nodule in the emphysematous lung: an appeal for surgery in a lung volume reduction concept.

Background: Emphysema patients, who are candidates for lung volume reduction surgery (LVRS) usually present with an extensive smoking history and thus have an increased risk for lung. The incidence of pulmonary nodules in emphysematous lungs is high. We therefore aimed to analyse the incidence and histological findings of pulmonary nodules in our LVRS program. Methods: We conducted a retrospective review of all patients who underwent LVRS between 2016 and 2018. Data concerning preoperative workup, 30 days mortality and histopathological findings analysed. Results: Between 2016 and 2018, LVRS was performed in 66 patients. In 18 (27%) a nodule was found in the preoperative computed tomography (CT) scan. Histological findings revealed in two cases squamous cell lung cancer. In two other cases, histopathological findings revealed an anthracotic intrapulmonary lymph node. In eight cases, a tuberculoma was found with a positive culture in one case. The other six histopathological findings were hamartoma, granuloma or sequelae of pneumonia. Conclusions: Malignancy was found in 11.1% of patients presenting with a nodule in preoperative LVRS workup. The relative risk of lung cancer in emphysema patients is increased and if LVRS criteria are fulfilled surgical resection of a pulmonary nodule is a meaningful way to verify the histology.

Advances in Surgical and Mechanical Management of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality in the United States, behind cardiovascular and malignant disorders. As the understanding of the pathogenesis has evolved, it led to targeting mechanical aspects of the disease to improve patient symptoms and quality of life. Modern management of COPD offers a variety of mechanical and surgical treatments for patients with advanced disease who do not achieve benefit from medical therapy alone. These treatments include therapies aimed at lung volume reduction, through surgical or bronchoscopic techniques. While these techniques are established and have proven benefit, others are still under development. Herein we discuss these techniques, aimed at improving clinician recognition of patients that may benefit from these interventions.

Impact of the type of initial intervention on the outcomes of lung volume reduction for emphysema: a propensity matched study.

Background: The type of initial intervention i.e., endobronchial valve (EBV) implantation or lung volume reduction surgery (LVRS) to be offered as initial intervention remains vague in the treatment of emphysema-chronic obstructive pulmonary disease (COPD) patients. Aim of the present study was to compare the outcomes of EBV with that of LVRS in emphysema patients who could have both offered as an initial intervention. Methods: The outcomes of 44 EBV patients were retrospectively compared to the outcomes of 44 matched LVRS patients (matched for age, gender, performance status, body mass index (BMI), lung functions, comorbidities and exercise tolerance, matching tolerance 0.2) treated in a single institute within a 5-year period. The median follow-up was 32 months (maximum duration 84 months). Results: Mean age was 61.91±9.48 years and 55 (62.5%) were male. Postoperative morbidity was similar but length of stay (LOS) was longer in the LVRS group (median 10 vs. 6 days, P=0.006). Re-interventions were more frequent in the EBV versus LVRS group (52.3% vs. 20.5%, P=0.002) and so was the overall number of re-interventions (median 2 vs. 1, P<0.01). Breathing improved in more LVRS patients (86.4% vs. 70.5%, P<0.002). The decrease of the COPD Assessment Test (CAT) score was less significant in the EBV group (P=0.034). Survival was similar between 2 groups (P=0.350). Conclusions: EBV or LVRS as initial intervention are similar in terms of morbidity and mortality. EBV showed shorter LOS whilst LVRS necessitated less but more severe re-interventions and led to better overall quality of life.

[Lung Cancer Surgery for Severe COPD with Emphysema: Tumor Resection with Improvement of Lung Function]. / Lungenkrebschirurgie bei schwerer COPD mit Emphysem: Tumorresektion mit Verbesserung der Lungenfunktion.

Lung Cancer Surgery for Severe COPD with Emphysema: Tumor Resection with Improvement of Lung Function Abstract. The golden standard for the therapy of early stage non-small cell lung cancer consists of surgical resection, usually performed as lobectomy or segmentectomy. These procedures demand a certain operability, including certain lung functional reserves. Patients with COPD and emphysema usually have lung function values far below that. Nevertheless, these patients can be offered treatmentif at the same time they qualify for concomitant lung volume reduction surgery (LVRS). LVRS with simultaneous tumor resection can consolidate the diagnosis, provide definite histology, correct staging, and thorough tumor resection might even improve the postoperative lung function. As with all patients with a (possible) diagnosis of cancer, the indication must be discussed in an interdiscplinary tumor board.

Technical Aspects of Lung Volume Reduction Surgery Including Anesthetic Management and Surgical Approaches.

As palliative treatment, lung volume reduction surgery can be offered to a selected subset of chronic obstructive pulmonary disease patients. Careful adherence to established inclusion and exclusion criteria is critical to achieve good outcomes. The evolution of surgical techniques toward minimally invasive approaches has improved outcomes. The fully extrathoracic access combining a subxiphoid incision with subcostal port placement allowed a further decrease in perioperative pain, which favors spontaneous respiratory drive and early postoperative mobilization. Less aggressive resections and better match for size of the hemithorax have contributed to a short-term reduction in morbidity and continued improvements in cardiopulmonary function.

Lung Volume Reduction Surgery in Patients with Homogeneous Emphysema.

Randomized controlled trials have demonstrated that lung volume reduction surgery (LVRS) improves exercise capacity, lung function, and quality of life in patients with heterogenous emphysema on computed tomographic and perfusion scan. However, most patients have a nonheterogenous type of destruction. These patients, summarized under "homogeneous emphysema," may also benefit from LVRS as long they are severely hyperinflated, and adequate function is remaining with a diffusing capacity of the lungs for carbon monoxide greater than 20% and no pulmonary hypertension. Surgical mortality is low when patients are well selected.

Lung volume reduction surgery as salvage procedure after previous use of endobronchial valves.

OBJECTIVES: Lung volume reduction (LVR) is an efficient and approved treatment for selected emphysema patients. There is some evidence that repeated LVR surgery (LVRS) might be beneficial, but there are no current data on LVRS after unsuccessful bronchoscopic LVR (BLVR) with endobronchial valves (EBVs). We hypothesize good outcome of LVRS after BLVR with valves. METHODS: In this study, we retrospectively investigated all patients who underwent LVRS between 2015 and 2019 at 2 centres after previous unsuccessful EBV treatment. They were further divided into subgroups with patients who never achieved the intended improvement after BLVR (primary failure) and patients whose benefit was fading over time due to the natural development of emphysema (secondary failure). Patients with severe air leak after BLVR and immediate concomitant LVRS and fistula closure thereafter were analysed separately. RESULTS: A total of 38 patients were included. Of these, 19 patients had primary failure, 15 secondary failure and 4 were treated as an emergency due to severe air leak. At 3 months after LVRS, forced expiratory volume in 1 s had improved significantly by 12.5% (P = 0.011) and there was no 90-day mortality. Considering subgroups, patients with primary failure after BLVR seem to profit more than those with secondary failure. Patients with severe air leak after BLVR did not profit from fistula closure with concomitant LVRS. CONCLUSIONS: LVRS after previous BLVR with EBVs can provide significant clinical improvement with low morbidity, although results might not be as good as after primary LVRS.

Value of a Multidisciplinary Team Approach to Treatment of Emphysema.

Lung volume reduction surgery can significantly improve quality of life for properly selected patients who are symptomatic despite maximal medical management for emphysema. This requires a well-constructed multidisciplinary team (including transplant) to evaluate and treat these patients.

Endoscopic Lung Volume Reduction: Review of the EMPROVE and LIBERATE trials.

Endoscopic lung volume reduction is now included in the guidelines for treatment in severe chronic obstructive pulmonary disease. Since December 2018, 2 valve systems have been approved by the US Food and Drug Administration (FDA). To date, there is no head-to-head trial comparing both valve systems and no clear benefit of one over the other. This article provides an overview of the two largest prospective trials performed with the FDA-approved valve systems.

Lung volume reduction surgery: from National Emphysema Treatment Trial to non-intubated awake video-assisted thoracoscopic surgery.

Chronic obstructive pulmonary disease (COPD) is a major public health problem. Loss of elastic recoil, hyperinflation and obstruction of the expiratory airflow lead to an increased breathing work, which results in dyspnea during minimal physical activity of the patients. Reduction of the lung volume in these patients leads to improvement of dyspnea, physical activity and quality of life in these patients. Beside endoscopic lung volume reduction (ELVR), lung volume reduction surgery (LVRS) represents an important and valuable treatment option for patients with advanced lung emphysema. Since the National Emphysema Treatment Trial (NETT), thoracic surgery experienced a remarkable evolution of the surgical techniques enabling safe surgery and quick recovery in this critically ill patient cohort. A paradigm shift from open surgical approaches to most minimally invasive techniques accompanied by improvement of anesthesiologic management of these patients was evident. Moreover, indications for LVRS, which were originally described in the NETT, were extended to apply for further groups of patients with advanced lung emphysema, enabling significant clinical improvement in well-selected patients with a low perioperative morbidity and mortality. The current review will give an overview of the historical approaches for LVRS, highlight the indications for LVRS and discuss the development of the surgical approaches.

Bronchoscopic lung volume reduction: status quo.

Emphysema is associated with irreversible loss of lung compliance leading to gas trapping and hyperinflation. Surgical lung volume reduction has proven to improve lung function, exercise capacity, cardiac health and survival in patients with advanced emphysema; however, this procedure is associated with significant morbidity and mortality. Bronchoscopic lung volume reduction (BLVR) has emerged as an alternative approach for these patients. In this article, we review the different techniques used for the purpose of this procedure, its advantages and disadvantages. In addition, we discuss in length valve therapy and the studies that led to its recent FDA approval. Finally, we provide thought-provoking challenges that may be topics for further future investigation to enhance the efficacy and benefit of this technique.