Treatment Of Emphysema Research Articles

Negative pressure wound therapy for massive subcutaneous emphysema: a systematic review and case series.

BackgroundMassive subcutaneous emphysema can cause considerable morbidity with respiratory distress. To resolve this emphysema in short-term, negative pressure wound therapy could be applied as added treatment modality. However, its use is sparsely reported, and a variety of techniques are being described. This study provides a systematic review of the available literature on the effectiveness of negative pressure wound therapy as treatment for massive subcutaneous emphysema. In addition, our institutional experience is reported through a case-series.MethodsThe PubMed, Embase and Cochrane Library were systematically searched for publications on the use of negative pressure wound therapy for subcutaneous emphysema following thoracic surgery, trauma or spontaneous pneumothorax. Moreover, patients treated at our institution between 2019 and 2021 were retrospectively identified and analyzed.ResultsThe systematic review provided 10 articles presenting 23 cases. Studies demonstrated considerable heterogeneity regarding the location of incision, creation of prepectoral pocket, and surgical safety margin. Also closed incision negative pressure wound therapy and PICO© device were discussed. Despite the apparent heterogeneity, all techniques provided favorable outcomes. No complications, reinterventions or recurrences were documented. Furthermore, retrospective data of 11 patients treated at our clinic demonstrated an immediate response to negative pressure wound therapy and a full remission of the subcutaneous emphysema at the end of negative pressure wound therapy. No recurrence requiring intervention or complications were observed.ConclusionsThe findings of this study suggest that negative pressure wound therapy, despite the varying techniques employed, is associated with an immediate regression of subcutaneous emphysema and full remission at the end of therapy. Given the relatively low sample size, no technique of choice could be identified. However, in general, negative pressure wound therapy appears to provide fast regression of subcutaneous emphysema and release of symptoms in all cases.

Spiperone Stimulates Regeneration in Pulmonary Endothelium Damaged by Cigarette Smoke and Lipopolysaccharide.

BackgroundEndothelial dysfunction and destruction of the pulmonary microcirculation are important pathogenic factors in chronic obstructive pulmonary disease (COPD). In COPD, bronchial obstruction is associated with endothelial dysfunction. Thus, new pharmacological treatment options aimed at restoring the pulmonary endothelium represent a clinical need in COPD therapy. Notch1 has been shown to protect cells against apoptosis, inflammation, and oxidative stress caused by cigarette smoke extract (CSE). Therefore, drug which effect on Notch1 may be a potential therapeutic target for COPD in the future.MethodsIn this study, we assessed the potential of spiperone to mediate regeneration of pulmonary endothelium in model of pulmonary emphysema induced by a CSE and lipopolysaccharide (LPS) in female C57BL/6 mice.ResultsSpiperone increased the number of capillaries as well as the expression of the CD31 in the alveolar tissue compared to the controls. Moreover, application of spiperone prevented alveolar wall destruction (DI), and reduced the area of emphysema. Lastly, we demonstrated that spiperone positively influenced mobilization and migration of endothelial progenitor cells (EPC, CD45−CD34+CD31+), CD309+-endothelial cells, and angiogenesis precursors (CD45−CD117+CD309+) into the lung. Spiperone administration significantly reduced the number Notch1 positive CD309+-endothelial cells and Notch1+ EPCs.ConclusionOverall, our results suggest that spiperone mediates endothelial regeneration in an animal model of COPD. Thus, it could represent a novel therapeutic approach for treatment of emphysema associated with COPD.

Selective bronchial occlusion as treatment for pulmonary interstitial emphysema.

Selective bronchial occlusion as treatment for pulmonary interstitial emphysema.

Endobronchial treatment of severe asthma and severe emphysema with hyperinflation.

The field of interventional pulmonology has ushered in a wave of innovations for individuals with obstructive airways disease in whom established medical therapies have failed. Leading the charge are bronchial thermoplasty for severe refractory asthma and uni-directional valves for severe emphysema with hyperinflation: both have received regulatory approvals in the United Kingdom and United States. With the commissioning of these novel treatments comes new challenges relating to implementation, positioning within therapeutic algorithms, honing of patient selection, and establishing long-term safety and benefits beyond 5 years. This review summarises the evidence for their safety and efficacy, predictors of therapeutic response, mechanism(s) of action and emerging data supporting the durability of outcomes out to at least ten years. It is anticipated the experience of treating increasing numbers of patients, the adoption of international registries, and ongoing research evaluations will serve to optimise these therapies for future generations of patients.

ENDOBRONCHIAL VALVE EXCHANGE FOLLOWING BRONCHOSCOPIC LUNG VOLUME REDUCTION FOR MANAGEMENT OF COUGH

TOPIC: Procedures TYPE: Fellow Case Reports INTRODUCTION: Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality within the United States. Bronchoscopic lung volume reduction (BLVR) targets emphysematous lobes to reduce lung hyperinflation and improve patient symptoms. Both Zephyr Endobronchial Valves and the Spiration Valve System were evaluated and approved for single lobe, targeted BLVR in the treatment of emphysema [1-3]. To date, there are no clinical comparative trials between the two systems, and little is known regarding their interchangeability. We present a case of persistent cough following BLVR with resolution after exchange of endobronchial valves. CASE PRESENTATION: A 60 year old female, former smoker, with stage III, oxygen dependent COPD (FEV1 33%) underwent evaluation and placement of Zephyr valves for BLVR. Past medical history notable for stage I sarcoidosis. No known allergies to nickel, silicone, or plastic. A total of seven Zephyr valves were used for successful left lower lobe occlusion. At two months, she had stable PFTs (FEV1 39%) with subjective improvement in dyspnea. However, patient developed persistent dry, non-productive cough. She was treated with multiple courses of prednisone with improvement, and ultimately became steroid dependent. Bronchoscopy demonstrated well-seated valves with significant granulation tissue, and areas of partial obstruction. All seven valves were removed and steroids discontinued with subsequent improvement in cough, though return of dyspnea to baseline. After six months, patient again underwent BLVR with Spiration valve placement. A total of six Spiration valves were used for left lower lobe occlusion. She again reported subjective improvement in dyspnea with stable PFTs (FEV1 36%), though without return of cough at 6 month follow-up. DISCUSSION: Adverse events following BLVR are well-documented with both Zephyr and Spiration valves with pneumothorax being the most significant. However, patients do develop more subtle reactions including increased dyspnea, hypoxemia, and cough [1-3]. Results from the TRANSFORM trial document that 6.2% of patients develop cough following Zephyr endobronchial valve placement, and may contribute to patient morbidity as described above, though data regarding the management of valve intolerance is lacking [1]. In cases of symptomatic bronchial irritation secondary to valve placement as described above, patients may benefit from valve exchange. CONCLUSIONS: Here we illustrate a case of cough due to tissue granulation following endobronchial valve placement with resolution after valve exchange with an alternate manufacturer. Valve exchange may provide symptomatic relief while preserving BLVR benefits in select patients. REFERENCE #1: Kemp, S.V., et al., A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM). Am J Respir Crit Care Med, 2017. 196(12): p. 1535-1543. REFERENCE #2: Criner, G.J., 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): p. 1151-1164. REFERENCE #3: 3. Criner, G.J., et al., Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System (EMPROVE). A Multicenter, Open-Label Randomized Controlled Clinical Trial. Am J Respir Crit Care Med, 2019. 200(11): p. 1354-1362. DISCLOSURES: No relevant relationships by Raed Alalawi, source=Web Response No relevant relationships by Lisa Jarnagin, source=Web Response

CircRNA_0026344 via miR-21 is involved in cigarette smoke-induced autophagy and apoptosis of alveolar epithelial cells in emphysema.

Cigarette smoke (CS), a main source of indoor air pollution, is a primary risk factor for emphysema, and aberrant cellular autophagy is related to the pathogenesis of emphysema. Circular RNAs (circRNAs) affect the expression of mRNAs via acting as microRNA (miRNA) sponges, but their role in emphysema progression is not established. In the present investigation, CS, acting on alveolar epithelial cells, caused higher levels of miR-21, p-ERK, and cleaved-caspase 3 and led to lower levels of circRNA_0026344 and PTEN, which induced autophagy and apoptosis. miR-21 suppressed the expression of PTEN, which was involved in the regulation of autophagy and apoptosis. Further, in alveolar epithelial cells, overexpression of circRNA_0026344 blocked cigarette smoke extract (CSE)-induced autophagy and apoptosis, but this blockage was reversed by upregulation of miR-21 with a mimic. These results demonstrated that, in alveolar epithelial cells, CS decreases circRNA_0026344 levels, which sponge miR-21 to inhibit the miR-21 target, PTEN, which, in turn, activates ERK and thereby promotes autophagy and apoptosis, leading to emphysema. Thus, for emphysema, circRNA_0026344 regulates the PTEN/ERK axis by sponging miR-21, which is associated with the CS-induced autophagy and apoptosis of alveolar epithelial cells. In sum, the present investigation identifies a novel mechanism for CS-induced emphysema and provides information useful for the diagnosis and treatment of CS-induced emphysema.

Diallyl disulfide prevents cigarette smoke-induced emphysema in mice

IntroductionCigarette smoke (CS) is the main risk factor for the development of chronic obstructive pulmonary disease (COPD) and pulmonary emphysema. The use of antioxidants has emerged as a potential therapeutic strategy to treat airway inflammation and lung diseases. In the current study, we investigated the potential therapeutic impact of diallyl disulfide (Dads) treatment in a murine model of CS-induced emphysema. MethodsC57BL/6 mice were exposed to CS for 60 consecutive days and treated with vehicle or Dads (30, 60 or 90 mg/kg) by oral gavage for the last 30 days, three times/week. The control group was sham-smoked and received vehicle treatment. All mice were euthanized 24 h after day 60; bronchoalveolar lavage (BAL) was performed and lungs were processed for further experimentation. Histological (HE stained sections, assessment of mean linear intercept (Lm)), biochemical (nitrite, superoxide dismutase (SOD), glutathione transferase (GST), and malondialdehyde (MDA) equivalents), and molecular biology (metalloproteinase (MMP) 12, SOD2, carbonyl reductase 1 (CBR1), nitrotyrosine (PNK), 4-hydroxynonenal (4-HNE), and CYP2E1) analyses were performed. ResultsTreatment with Dads dose-dependently reduced CS-induced leukocyte infiltration into the airways (based on BAL fluid counts) and improved lung histology (indicated by a reduction of Lm). Furthermore, CS exposure dramatically reduced the activity of the antioxidant enzymes SOD and GST in lung tissue and increased nitrite and MDA levels in BAL; these effects were all effectively counteracted by Dads treatment. Western blot analysis further confirmed the antioxidant potential of Dads, showing that treatment prevented the CS-induced decrease in SOD2 expression and increase in lung damage markers, such as CBR1, PNK, and 4-HNE. Furthermore, increased MMP12 (an important hallmark of CS-induced emphysema) and CYP2E1 lung protein levels were significantly reduced in mice receiving Dads treatment. ConclusionOur findings demonstrate that treatment with Dads is effective in preventing multiple pathological features of CS-induced emphysema in an in vivo mouse model. In addition, we have identified several proteins/enzymes, including 4-HNE, CBR1, and CYP2E1, that are modifiable by Dads and could represent specific therapeutic targets for the treatment of COPD and emphysema.

Preliminary therapeutic and mechanistic evaluation of S-allylmercapto-N-acetylcysteine in the treatment of pulmonary emphysema

The objective of this work was to study the effects and mechanisms of S-allylmercapto-N-acetylcysteine (ASSNAC) in the treatment of pulmonary emphysema based on network pharmacology analysis and other techniques. Firstly, the potential targets associated with ASSNAC and COPD were integrated using public databases. Then, a protein–protein interaction network was constructed using String database and Cytoscape software. The Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on DAVID platform. The molecular docking of ASSNAC with some key disease targets was implemented on the SwissDock platform. To verify the results of the network pharmacology, a pulmonary emphysema mice model was established and treated with ASSNAC. Besides, the expressions of the predicted targets were detected by immunohistochemistry, Western blot analysis or enzyme-linked immunosorbent assay. Results showed that 33 overlapping targets are achieved, including CXCL8, ICAM1, MAP2K1, PTGS2, ACE and so on. The critical pathways of ASSNAC against COPD involved arachidonic acid metabolism, chemokine pathway, MAPK pathway, renin-angiotensin system, and others. Pharmacodynamic experiments demonstrated that ASSNAC decreased the pulmonary emphysema and inflammation in the pulmonary emphysema mice. Therefore, these results confirm the perspective of network pharmacology in the target verification, and indicate the treatment potential of ASSNAC against COPD.

Two-Stage Bronchoscopic Endobronchial Valve Treatment Can Lead to Progressive Lung Volume Reduction and May Decrease Pneumothorax Risk.

BackgroundSince successful development of endobronchial valves (EBV) as treatment for severe emphysema, its main complication, pneumothorax, remains an important concern.ObjectiveWe hypothesized that a two-step EBV implantation, during two distinct iterative procedures could lead to a more progressive target lobe volume reduction (TLVR) and thus ipsilateral lobe re-expansion, resulting in a significant decrease in the pneumothorax rate.MethodsThis retrospective bi-center study carried out by Limoges and Toulouse University Hospitals included patients following the inclusion criteria established by the BLVR expert panel. All patients were treated by two distinct procedures: first, EBVs were placed in all but the most proximal segment or sub-segment. The remaining segment was treated subsequently. All patients had a complete evaluation before treatment, and 3 months after the second procedure.ResultsOut of 58 patients included, only 4 pneumothoraxes (7%) occurred during the study. The other complications were pneumonia and severe COPD exacerbation (8.6% and 13.7% of patients, respectively). Significant improvement was found for FEV1 (+19.6 ± 25%), RV (−468 ± 960mL), 6MWD (30 ± 85m), BODE Index (−1.4 ± 1.8 point) and TLVR (50.6 ± 35.1%). Significant TLVR (MCID) was obtained in 74.1% of patients (43/58).ConclusionThis new approach using EBV could reduce the incidence of pneumothorax without increasing other complication rates. Clinical and physiological outcomes are similar to those reported in studies using the conventional single-step treatment.

Management of malignant pleural effusion. A retrospective study comparing efficiency and outcomes of VATS talcum pleurodesis, insertion of tunneled pleural catheter (PleurX®), and a combination of both

Abstract Objective The management of malignant pleural effusion is a common problem in thoracic surgery. Patients are often polymorbid and are usually referred at a terminal stage of their oncological disease. Our objective was to compare the efficiency and outcomes after different treatment strategies of malignant pleural effusion. Methods We retrospectively reviewed the charts of a total of 416 patients treated during the period of 2010 to 2020 who underwent thoracoscopic pleurodesis with or without implantation of tunneled pleural catheter (TPC) as well as patients who underwent the implantation of TPC alone. Primary outcome was postoperative survival and secondary outcome was length of stay (LOS). In addition, we documented the recurrence of ipsilateral pleural effusion and the need for reintervention as well as the pulmonary reexpansion of the lung on postoperative chest x-ray. Inclusion criteria were malignant pleural effusion and documented follow-up until time of death. Exclusion criteria were treatment for mesothelioma, pneumothorax and emphysema. Results A total of 199 patients were included for analysis. Median LOS of patients treated with implantation of TPC alone in analgosedation (n = 28) was 1 day (range:1-4 days). Median LOS of patients who received video-assisted talcum pleurodesis (n = 65) without implantation of a TPC was 6 days (range 1-38 days). Median LOS of patients who received VATS talcum pleurodesis and TPC (n = 106) was 3 days (range 1-34 day). The difference in LOS was statistically significant (p < 0.05). Median overall survival was 108 days (range 3-3001 days). There was no statistically significant difference in survival between the different treatment groups (p = 0.47). Conclusion The primary goal when treating patients with malignant pleural effusion is relief of dyspnea and/or pain and to keep the duration of the inpatient treatment to a minimum. In patients with a considerable surgical risk due to comorbidities and their underlying oncological disease and who don’t require the sampling of histological material, a conservative treatment option with implantation of a TPC can be sufficient. The additional insertion of a TPC not only reduces the length of stay, but also has a positive effect on the efficacy of the pleurodesis in terms of less recurrence. We therefore recommend the routine use of TPC when performing VATS talcum pleurodesis in patients with malignant pleural effusion.

Ethanolamine oleate as a sclerosant in bronchoscopic treatment of pulmonary emphysema

Introduction Loss of elastic recoil in pulmonary emphysema can be corrected by lung volume reduction through decreasing the volume of the most destroyed lung segments (dead space), which allow the remaining (less destroyed lung tissues) to regain its size. This article was planned to study the effectiveness and safety of ethanolamine oleate as a sclerosant in bronchoscopic lung volume reduction in patients with pulmonary emphysema. Patients and methods A total of 19 patients with pulmonary emphysema (age >40 years old) were included. Clinical evaluation, routine laboratory investigations, and bronchoscopic ethanolamine oleate instillation using fiberoptic video bronchoscopy were done. Outcome assessment measures were reviewed before bronchoscopic instillation of ethanolamine oleate and 4 weeks later using Modified Medical Research Council, 6-min walk distance, and pulmonary function tests such as a high-resolution computed tomography. Results Although there was a statistically significant improvement of Modified Medical Research Council scale after 1 month of bronchoscopic ethanolamine instillation, this value failed to meet the minimal clinically important difference (MCID) criteria. Moreover, forced expiratory volume in the 1 s improvement failed to meet the MCID criteria. Regarding 6-min walk distance, there was a statistically significant improvement that met the MCID criteria. There was a statistically significant and clinical improvement of high-resolution computed tomography volumetric quantification of emphysema. Approximately 31.5% of patients had no complications. Conclusion This study showed statistical improvement in exercise tolerance and pulmonary function tests in patients with pulmonary emphysema after bronchoscopic instillation of ethanolamine oleate. However, clinical improvement was detected only in exercise tolerance.

Revision Bronchoscopy After Endobronchial Valve Treatment for Emphysema: Indications, Findings and Outcomes.

BackgroundEndobronchial valve (EBV) treatment is an effective treatment for patients with severe emphysema. Revision bronchoscopies after endobronchial valve treatment can be essential to prolong the effect of treatment or address long-term complications.PurposeTo evaluate the indications, endoscopic findings and outcomes of revision bronchoscopies and investigate if any predictors for granulation tissue formation, after EBV treatment, can be identified.Patients and MethodsPatients who underwent EBV treatment between 2016 and 2019 in our hospital, as routine care, were included. If a patient underwent a revision bronchoscopy, data regarding revision bronchoscopies, including indication, finding, intervention and pulmonary function testing (PFT) after revision bronchoscopy were analysed.ResultsOne hundred seventy-nine patients were included of which 41% required at least one revision bronchoscopy. In 43% of the revision bronchoscopy patients, the indication was loss of initial treatment effect. In 53% of the revision bronchoscopy patients, granulation tissue was found to be the underlying cause. Valve replacement(s) were performed in 51% of the revision bronchoscopy cases. Permanent valve removal was required in 13% of all patients. Overall, revision bronchoscopies led to improvements in PFT outcomes for patients experiencing no or a loss of initial treatment effect. No clinically relevant predictors for granulation tissue formation were identified.ConclusionPerforming a revision bronchoscopy after EBV treatment is a useful procedure leading to an improved treatment effect in most patients. Granulation tissue formation, causing valve dysfunction, is the most common cause of longer term problems.

Identifying Responders and Exploring Mechanisms of Action of the Endobronchial Coil Treatment for Emphysema

Background: So far, 3 randomized controlled trials have shown that the endobronchial treatment using coils is safe and effective. However, the more exact underlying mechanism of the treatment and best predictors of response are unknown. Objectives: The aim of the study was to gain more knowledge about the underlying physiological mechanism of the lung volume reduction coil treatment and to identify potential predictors of response to this treatment. Methods: This was a prospective nonrandomized single-center study which included patients who were bilaterally treated with coils. Patients underwent an extensive number of physical tests at baseline and 3 months after treatment. Results: Twenty-four patients (29% male, mean age 62 years, forced expiratory volume in 1 s [FEV₁] 26% pred, residual volume (RV) 231% pred) were included. Three months after treatment, significant improvements were found in spirometry, static hyperinflation, air trapping, airway resistance, treated lobe RV and treated lobes air trapping measured on CT scan, exercise capacity, and quality of life. The change in RV and airway resistance was significantly associated with a change in FEV₁, forced vital capacity, air trapping, maximal expiratory pressure, dynamic compliance, and dynamic hyperinflation. Predictors of treatment response at baseline were a higher RV, larger air trapping, higher emphysema score in the treated lobes, and a lower physical activity level. Conclusions: Our results confirm that emphysema patients benefit from endobronchial coil treatment. The primary mechanism of action is decreasing static hyperinflation with improvement of airway resistance which consequently changes dynamic lung mechanics. However, the right patient population needs to be selected for the treatment to be beneficial which should include patients with severe lung hyperinflation, severe air trapping, and significant emphysema in target lobes.

α1-Antitrypsin deficiency and the risk of COVID-19: an urgent call to action

α1-Antitrypsin deficiency and the risk of COVID-19: an urgent call to action

Randomized trials and progress in surgery

It is very difficult to find certain surgical field in which surgeon's decision is absolutely evidence-based. The objective of evidence-based medicine (and surgery) is offering the best treatment for each patient that should encourage conducting the randomized trials (RT) as the highest level of evidence. The results of RTs often contradict the existing clinical experience, and experience per se does not always confirm the significance of the results obtained. One cannot make any conclusions based on RT data. Treatment strategy for a particular patient remains unclear. The authors have analyzed the results of large-scale RTs devoted to laparoscopic cholecystectomy, rectal surgery, lung cancer surgery, postoperative care, treatment of pulmonary emphysema. It was shown that RT data as the highest level of evidence are not always true for surgery. In most clinical situations, the decision is not based on RT results. The desire of surgeons to master a new technique is often more significant than patient care, while clinical experience and the laws of the market are more important than science. There is no doubt that knowledge of RT results are essential in training period, but this means quite a bit for a particular patient. The best decision can be made during discussion and conversation with colleagues, where an experience of each specialist will have the same value as the best evidence.

Nonoperative Treatment of Gastric Emphysema.

Nonoperative Treatment of Gastric Emphysema.

Integrative Analysis Reveals Common and Unique Roles of Tetraspanins in Fibrosis and Emphysema.

While both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are multifactorial disorders characterized by distinct clinical and pathological features, their commonalities and differences have not been fully elucidated. We sought to investigate the preventive roles of tetraspanins Cd151 and Cd9 -that are involved in diverse cellular processes in lung pathophysiology- in pulmonary fibrosis and emphysema, respectively, and to obtain a deeper understanding of their underlying molecular mechanisms toward facilitating improved therapeutic outcomes. Using an integrative approach, we examined the transcriptomic changes in the lungs of Cd151- and Cd9-deficient mice using functional-enrichment-analysis, pathway-perturbation-analysis and protein-protein-interaction (PPI) network analysis. Circadian-rhythm, extracellular-matrix (ECM), cell-adhesion and inflammatory responses and associated factors were prominently influenced by Cd151-deletion. Conversely, cellular-junctions, focal-adhesion, vascular-remodeling, and TNF-signaling were deeply impacted by Cd9-deletion. We also highlighted a “common core” of factors and signaling cascades that underlie the functions of both Cd151 and Cd9 in lung pathology. Circadian dysregulation following Cd151-deletion seemingly facilitated progressive fibrotic lung phenotype. Conversely, TGF-β signaling attenuation and TNF-signaling activation emerged as potentially novel functionaries of Cd9-deletion-induced emphysema. Our findings offer promising avenues for developing novel therapeutic treatments for pulmonary fibrosis and emphysema.

How to create negative pressure wound dressing with wall suction: novel treatment of subcutaneous emphysema with PICO dressing.

Significant subcutaneous emphysema can result in airway compromise. Infraclavicular blowhole incision with negative pressure wound therapy is an emerging therapy. Novel way of creating a functional negative pressure wound therapy using PICO dressing and wall suction for ongoing air leak is described.

PR1P Stabilizes VEGF and Upregulates Its Signaling to Reduce Elastase-induced Murine Emphysema.

Emphysema is a progressive and fatal lung disease with no cure that is characterized by thinning, enlargement, and destruction of alveoli, leading to impaired gas exchange. Disease progression is due in part to dysregulation of VEGF (vascular endothelial growth factor) signaling in the lungs and increased lung-cell apoptosis. Here we asked whether PR1P (Prominin-1-derived peptide), a novel short peptide we designed that increases VEGF binding to endothelial cells, could be used to improve outcome in in vitro and in vivo models of emphysema. We used computer simulation and in vitro and in vivo studies to show that PR1P upregulated endogenous VEGF receptor-2 signaling by binding VEGF and preventing its proteolytic degradation. In so doing, PR1P mitigated toxin-induced lung-cell apoptosis, including from cigarette-smoke extract in vitro and from LPS in vivo in mice. Remarkably, inhaled PR1P led to significantly increased VEGF concentrations in murine lungs within 30 minutes that remained greater than twofold above that of control animals 24 hours later. Finally, inhaled PR1P reduced acute lung injury in 4- and 21-day elastase-induced murine emphysema models. Taken together, these results highlight the potential of PR1P as a novel therapeutic agent for the treatment of emphysema or other lung diseases characterized by VEGF signaling dysregulation.

Vapor for lung volume reduction; pros and cons

ABSTRACT Introduction Bronchoscopic lung volume reduction (BLVR) is a novel approach for treatment of emphysema. Several techniques are available to accomplish BLVR including Bronchoscopic Vapor Thermal Ablation (BVTA). This technique is easy to perform and considered safe due to its gradual effect. We discuss BTVA in detail in this editorial. Areas covered We discuss our experience with BTVA in detail including patient selection, equipment, procedure, post-procedural care and complications. We also review the literature to determine the pros and cons for its use. Other modalities such as endobronchial valves, coils and lung sealants are also briefly discussed. Expert opinion Vapor ablation is a novel and safe approach in inducing lung volume reduction in emphysema patients. The effects are gradual, and therefore potentially making it safer than other minimally invasive modalities. Pneumonitis and infection are common side effects. Just as in other BLVR techniques, a case by case evaluation is needed to determine the right candidate for BTVA. Further larger studies are needed before BTVA becomes standard of care in treatment of patients with emphysema.