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Chronic Obstructive Pulmonary Disease (COPD) is a complex pulmonary condition characterized by chronic airflow limitation. Within the spectrum of COPD, distinct overlap conditions exist, including Asthma-COPD Overlap (ACO), COPD-Obstructive Sleep Apnea (COPD-OSA), Combined Pulmonary Fibrosis and Emphysema (CPFE), and Bronchiectasis-COPD Overlap (BCO). This review provides a comprehensive overview of the clinical and therapeutic implications of these conditions, highlighting the differences in complications compared with COPD alone in addition to the diagnostic challenges of identifying these conditions. Therapeutically tailored approaches are necessary for COPD overlap conditions considering the unique complications that may arise. Optimal pharmacological management, disease-specific interventions, and comprehensive patient-centered care are crucial components of treatment strategies. This review provides insights for healthcare professionals by enhancing their understanding and management of these conditions. This emphasizes the importance of accurate diagnosis and individualized treatment plans, considering the specific complications associated with each COPD overlap condition., Competing Interests: Declaration of competing interest No conflicts of interest or relationship with the industry to disclose by any of the authors. No funding or financial interests., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is an incurable, progressive respiratory disease that may have a significant negative impact on the morbidity and mortality of affected patients. A substantial portion of the world's population is affected by COPD, and despite optimal medical management with medications, supplemental oxygen, and pulmonary rehabilitation, many patients are left debilitated because of this disease. Bronchoscopic treatment modalities offer a less-invasive method for the treatment of refractory COPD compared to surgical interventions and have expanded the potential therapeutic options for these patients. Bronchoscopic lung volume reduction is aimed at decreasing the hyperinflation and air trapping that occur in emphysema, and the most studied and successful intervention is endobronchial valve placement. Endobronchial coils, polymeric sealants, and thermal ablation are other researched alternatives. Additional interventional procedures are being investigated for the treatment of the mucus hypersecretion and cough that are associated with the chronic bronchitis phenotype of COPD and include targeted lung denervation, metered dose spray cryotherapy, deobstruction balloon, and bronchial rheoplasty. This review summarizes the most recent evidence pertaining to available therapies for the management of COPD, including chronic bronchitis, with a particular focus on bronchoscopic interventions., Competing Interests: A.J.S. served as a consultant and advisory board member for Ambu., (Thieme. All rights reserved.)

Emphysema in patients with chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation. Preclinical studies suggest that lung volume reduction surgery (LVRS) and mesenchymal stromal cell (MSC) treatment dampen inflammation. We investigated the effects of bone marrow-derived MSC (BM-MSC) and LVRS on circulating and pulmonary immune cell profiles in emphysema patients using mass cytometry. Blood and resected lung tissue were collected at the first LVRS (L1). Following 6-10 weeks of recovery, patients received a placebo or intravenous administration of 2 × 10 6 cells/kg bodyweight BM-MSC (n = 5 and n = 9, resp.) in week 3 and 4 before the second LVRS (L2), where blood and lung tissue were collected. Irrespective of BM-MSC or placebo treatment, proportions of circulating lymphocytes including central memory CD4 regulatory, effector memory CD8 and γδ T cells were higher, whereas myeloid cell percentages were lower in L2 compared to L1. In resected lung tissue, proportions of Treg ( p = 0.0067) and anti-inflammatory CD163 - macrophages ( p = 0.0001) were increased in L2 compared to L1, while proportions of pro-inflammatory CD163 + macrophages were decreased ( p = 0.0004). There were no effects of BM-MSC treatment on immune profiles in emphysema patients. However, we observed alterations in the circulating and pulmonary immune cells upon LVRS, suggesting the induction of anti-inflammatory responses potentially needed for repair processes.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent and preventable condition. Mesenchymal stem cell (MSC) therapy is being explored to aid in the regeneration of lung cells and airway structure, aiming to restore lung function., Aim: To examine varied responses of MSCs when cultured with peripheral blood mononuclear cells (PBMCs) from different COPD phenotypes, patients were grouped into ACOS, emphysema, and chronic bronchitis categories., Methods: PBMCs from these groups and controls were co-cultured with MSCs derived from dental follicles, revealing differing rates of apoptosis among COPD phenotypes compared to controls., Results: While the chronic bronchitis group exhibited the least lymphocyte viability (p<0.01), introducing MSCs notably enhanced viability across all phenotypes except emphysema, with the chronic bronchitis group showing the most improvement (p<0.05)., Conclusion: Stem cell therapy might reduce peripheral lymphocyte apoptosis in COPD, with varying responses based on phenotype, necessitating further research to understand mechanisms and optimize tailored therapies for each COPD subtype., Competing Interests: Declaration of Competing Interest We declare that we have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Impaired and limited alveolar regeneration upon injury advances pulmonary disorders and irreversibly affects millions of people worldwide. Adult mammals do not have a strong potential to regenerate functional lung tissues, while neonatal lungs robustly proliferate and regenerate the functional tissue within a week of birth upon injury. The differential composition of the extracellular matrix (ECM) of neonatal tissues favors cellular proliferation and migration, fostering lung regeneration. Regardless, conventional ECM therapies employ adult-derived tissues. Therefore, the potential differences in regenerative properties of adult and neonatal lung ECM were investigated using in vitro and in vivo lung emphysema model. Decellularization of the neonatal and adult lungs was performed using freeze-thaw cycle method. Decellularization process was structurally characterized using SEM and immunostaining. In vitro treatment of neonatal lung-derived ECM (NECM) significantly enhanced the cellular migration and proliferation compared to adult-lung derived ECM (AECM) treated cigarette smoke-extract (CSE)-stimulated A549 cells. Following the administration of AECM and NECM, we observed a significant decline in emphysematous features and an improvement in lung functions in NECM group. NECM treatment increased the ratio of HOPX + /SpC + cells with an active proliferation in SpC + cells shown by colocalization of SpC + /Ki67 + and SpC + /Brdu + cells. Moreover, NECM treatment activated the Neureguline-1/Erbb2 signaling and fostered a regenerative environment by upregulating the expression of regenerative genes including FGF, WNTs and AXIN-2 as compared to AECM treatment. Our findings suggested the potential utilization of NECM as novel therapeutics in regenerative medicine, deviating from the conventional application of adult-derived ECM treatments in pre-clinical and clinical research., Competing Interests: Declaration of competing interest There are no known conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There has been an increased recognition of a subset of congenital lobar emphysema (CLE), termed congenital sublobar hyperinflation (CSLH), which may affect only a segment of lung as opposed to an entire lobe. This is an uncommon variant for which there is a paucity of information in published literature. The majority of CLE are managed surgically. Current literature suggests non-operative management for CSLH. However, there has been slow adoption of non-operative management and there is not a well-established observation pathway. A retrospective review of all pediatric patients diagnosed with CSLH at a single institution was performed from 2017 to 2023 to determine if this variant may be safely managed with observation. A total of 10 patients were identified. Of these, three patients had consolidation on cross-sectional imaging; therefore, operative intervention was undertaken given diagnostic uncertainty. All patients managed observationally remained asymptomatic. This case series validates non-operative management for patients with asymptomatic CSLH., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Severe alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of emphysema. However, the clinical manifestations are very heterogeneous, and an individual prognosis is very difficult to establish. Intravenous augmentation therapy with alpha-1 antitrypsin (AAT) from pooled blood donors is the only specific treatment available, but it requires weekly or biweekly administration for life. Several guidelines provide the indication criteria for the initiation of AAT augmentation therapy. However, in clinical practice, there are situations in which the decision as to when to start treatment becomes uncertain and some studies have shown great variability in the indication of this treatment even among specialists. The usual dilemma is between initiating augmentation therapy in individuals who may not develop significant lung disease or in whom disease will not progress or delaying it in patients who may otherwise rapidly and irreversibly progress. We illustrate this dilemma with five clinical cases: from the case of a patient with normal lung function who requests initiation of therapy to a moderately stable patient without augmentation or a mild patient who, after several years of remaining stable without treatment, deterioration in lung function initiated and, consequently, augmentation therapy was begun. All the nuances associated with the indication of augmentation justify a personalised approach and the decision about initiating augmentation therapy must be made after careful consideration of the pros and cons with the patient in reference centres with experience in treatment. These reference centres can work in collaboration with local hospitals where patients can be closely followed and augmentation therapy can be administered to avoid unnecessary travelling, making periodical administrations more comfortable for the patient.

Objectives: Pulmonary emphysema is characterized by the destruction of alveolar units and reduced gas exchange capacity. In the present study, we aimed to deliver induced pluripotent stem cell-derived endothelial cells and pneumocytes to repair and regenerate distal lung tissue in an elastase-induced emphysema model., Methods: We induced emphysema in athymic rats via intratracheal injection of elastase as previously reported. At 21 and 35 days after elastase treatment, we suspended 80 million induced pluripotent stem cell-derived endothelial cells and 20 million induced pluripotent stem cell-derived pneumocytes in hydrogel and injected the mixture intratracheally. On day 49 after elastase treatment, we performed imaging, functional analysis, and collected lungs for histology., Results: Using immunofluorescence detection of human-specific human leukocyte antigen 1, human-specific CD31, and anti--green fluorescent protein for the reporter labeled pneumocytes, we found that transplanted cells engrafted in 14.69% ± 0.95% of the host alveoli and fully integrated to form vascularized alveoli together with host cells. Transmission electron microscopy confirmed the incorporation of the transplanted human cells and the formation of a blood-air barrier. Human endothelial cells formed perfused vasculature. Computed tomography scans revealed improved vascular density and decelerated emphysema progression in cell-treated lungs. Proliferation of both human and rat cell was higher in cell-treated versus nontreated controls. Cell treatment reduced alveolar enlargement, improved dynamic compliance and residual volume, and improved diffusion capacity., Conclusions: Our findings suggest that human induced pluripotent stem cell-derived distal lung cells can engraft in emphysematous lungs and participate in the formation of functional distal lung units to ameliorate the progression of emphysema., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Since early in the HIV epidemic, emphysema has been identified among people with HIV (PWH) and has been associated with increased mortality. Smoking cessation is key to risk reduction. Health maintenance for PWH and emphysema should ensure appropriate vaccination and lung cancer screening. Treatment should adhere to inhaler guidelines for the general population, but inhaled corticosteroid (ICS) should be used with caution. Frontiers in treatment include targeted therapeutics. Major knowledge gaps exist in the epidemiology of and optimal care for PWH and emphysema, particularly in low and middle-income countries (LMIC)., Areas Covered: Topics addressed include risk factors, pathogenesis, current treatment and prevention strategies, and frontiers in research., Expert Opinion: There are limited data on the epidemiology of emphysema in LMIC, where more than 90% of deaths from COPD occur and where the morbidity of HIV is most heavily concentrated. The population of PWH is aging, and age-related co-morbidities such as emphysema will only increase in salience. Over the next 5 years, the authors anticipate novel trials of targeted therapy for emphysema specific to PWH, and we anticipate a growing body of evidence to inform optimal clinical care for lung health among PWH in LMIC.

COPD is a chronic lung disease that affects millions of people, declining their lung function and impairing their life quality. Despite years of research and drug approvals, we are still not capable of halting progression or restoring normal lung function. Mesenchymal stem cells (MSC) are cells with extraordinary repair capacity, and MSC-based therapy brings future hope for COPD treatment, although the best source and route of administration are unclear. MSC from adipose tissue (AD-MSC) represents an option for autologous treatment; however, they could be less effective than donor MSC. We compared in vitro behavior of AD-MSC from COPD and non-COPD individuals by migration/proliferation assay, and tested their therapeutic potential in an elastase mouse model. In addition, we tested intravenous versus intratracheal routes, inoculating umbilical cord (UC) MSC and analyzed molecular changes by protein array. Although COPD AD-MSC have impaired migratory response to VEGF and cigarette smoke, they were as efficient as non-COPD in reducing elastase-induced lung emphysema. UC-MSC reduced lung emphysema regardless of the administration route and modified the inflammatory profile in elastase-treated mice. Our data demonstrate equal therapeutic potential of AD-MSC from COPD and non-COPD subjects in the pre-clinical model, thus supporting their autologous use in disease.

We describe three patients with chronic obstructive pulmonary disease (COPD) and emphysema who developed a pneumothorax while receiving chronic home non-invasive ventilation (NIV). These cases raise the question whether the high alveolar pressures given by NIV may have contributed to the development of their pneumothorax by barotrauma. Pneumothorax in patients with COPD receiving NIV is uncommon, the pressures in our patients with COPD who developed pneumothorax were not extremely high and time to development of pneumothorax was relatively long after the initiation of NIV. Further, in our patients, the CT scan showed paraseptal emphysema, a known risk factor for pneumothorax. This suggests that COPD/emphysema phenotype is probably a more important factor for indicating pneumothorax risk than ventilator settings. Better phenotyping of patients with COPD in whom benefits of NIV can be expected at minimal risk of serious side-effects is needed to inform our patients properly and bring the field of chronic NIV in COPD forward., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Endoscopic lung volume reduction procedure with valves is a well-studied treatment option for advanced lung emphysema to target lung hyperinflation in carefully selected patients with COPD. Before valve implantation, collateral ventilation (CV) of the target lobe needs to be assessed to obtain an optimal treatment effect. The analysis of CV according to current standards occurs via an in vivo assessment with the Chartis®system (PulmonX Inc., Redwood City, CA, USA) and a computed tomography (CT) scan of the thorax with interlobar fissure analysis. The focus of this review is to provide detailed information about the Chartis®procedure and interpretation of Chartis® phenotypes. As a main tool in the assessment of CV and being a safe procedure, the Chartis® assessment should be performed by default to confirm interlobar fissure analysis in most emphysema patients. Based on the obtained results, lung volume reduction therapy options should be discussed in an interdisciplinary emphysema conference., (© 2023 S. Karger AG, Basel.)

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in chronic lung disease patients throughout the world. Mesenchymal stem cells (MSCs) have been shown to regulate immunomodulatory, anti-inflammatory, and regenerative responses. However, the effects of human-umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) on the lung pathophysiology of COPD remain unclear. We aimed to investigate the role of hUC-MSCs in emphysema severity and Yes-associated protein (Yap) phosphorylation (p-Yap) in a porcine-pancreatic-elastase (PPE)-induced emphysema model. We observed that the emphysema percentages (normalized to the total lung volume) measured by chest computed tomography (CT) and exercise oxygen desaturation were significantly reduced by hUC-MSCs at 107 cells/kg body weight (BW) via intravenous administration in emphysematous mice (p < 0.05). Consistently, the emphysema index, as assessed by the mean linear intercept (MLI), significantly decreased with hUC-MSC administration at 3 × 106 and 107 cells/kg BW (p < 0.05). Changes in the lymphocytes, monocytes, and splenic cluster of differentiation 4-positive (CD4+) lymphocytes by PPE were significantly reversed by hUC-MSC administration in emphysematous mice (p < 0.05). An increasing neutrophil/lymphocyte ratio was reduced by hUC-MSCs at 3 × 106 and 107 cells/kg BW (p < 0.05). The higher levels of tumor necrosis factor (TNF)-α, keratinocyte chemoattractant (KC), and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) were significantly decreased by hUC-MSC administration (p < 0.05). A decreasing p-Yap/Yap ratio in type II alveolar epithelial cells (AECII) of mice with PPE-induced emphysema was significantly increased by hUC-MSCs (p < 0.05). In conclusion, the administration of hUC-MSCs improved multiple pathophysiological features of mice with PPE-induced emphysema. The effectiveness of the treatment of pulmonary emphysema with hUC-MSCs provides an essential and significant foundation for future clinical studies of MSCs in COPD patients.

In addition to recommendations for pharmacological treatment stratified for risk and phenotype, the new 2021 edition of the Spanish COPD Guidelines (GesEPOC 2021) proposes a personalized approach to treatable traits, defined as a characteristic (clinical, physiological, or biological) that can be identified by diagnostic tests or biomarkers, for which a specific treatment is available. Some treatable traits, such as malnutrition, sedentarism, emphysema or respiratory failure, can be treated with non-pharmacological therapies, and this was not covered in detail in the guidelines. This section of GesEPOC 2021 includes a narrative update with recommendations on dietary treatment, physical activity, respiratory rehabilitation, oxygen therapy, non-invasive ventilation, volume reduction, and lung transplantation. A PICO question with recommendations on the use of supplemental oxygen during exercise in COPD patients without severe hypoxemia is also included., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Extensive inflammation and apoptosis in structural cells of the lung are responsible for the progression and pathogenesis of chronic obstructive pulmonary disease (COPD). Myotubularin-related protein 14 (MTMR14) has been shown to participate in various biological processes, including apoptosis, inflammation, and autophagy. Nonetheless, the role of MTMR14 in COPD remains elusive. In the present study, we explored the expression of MTMR14 in human lung tissues and investigated the effects of overexpressed MTMR14 on in vitro and in vivo COPD models. Moreover, one of the possible mechanisms of MTMR14 alleviating COPD was explored based on mitochondrial function and mitophagy homeostasis. The results showed that MTMR14 expression was reduced in COPD patients' lungs in comparison to control subjects. MTMR14 overexpression inhibited cigarette smoke extract-induced inflammation and apoptosis and improved mitochondrial function and mitophagy in vitro . Further verification was carried out in COPD model mice. MTMR14 overexpression inhibited lung inflammation and reduced levels of IL-6 and KC in bronchoalveolar lavage fluid, as well as prevented emphysema and a decline in lung function. Furthermore, MTMR14 overexpression improved mitochondrial function and mitophagy to a certain extent. Collectively, our data support the hypothesis that MTMR14 participates in the pathogenesis of COPD. Improving mitochondrial function and mitophagy homeostasis may be one of the mechanisms by which MTMR14 alleviates COPD and may potentially be a novel therapeutic target for COPD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yiya Gu et al.)

Background: Endobronchial valve therapy has proven to reduce lung hyperinflation and decrease disease burden in patients with severe lung emphysema. Exclusion of collateral ventilation (CV) of the targeted lobe by using an endobronchial assessment system (Chartis; PulmonX, Drive Redwood City, CA, USA) in combination with software-based fissure integrity analysis (FCS [fissure completeness score]) of computed tomography scans of the lung are established tools to select appropriate patients for endobronchial valve treatment. So far, there is no conclusive evidence if the ventilation mode during bronchoscopy impacts the outcome of Chartis assessments., Methods: Patients with Chartis assessments and software-based quantification of FCS (StratX; PulmonX, Drive Redwood City, CA, USA) were enrolled in this retrospective study. During bronchoscopy, pulmonary fissure integrity was evaluated with the Chartis assessment system in each patient first under spontaneous breathing and subsequently under high-frequency (HF) jet ventilation., Results: In total, 102 patients were analyzed. Four Chartis phenotypes CV positive (CV+), CV negative (CV-), low flow, and low plateau in spontaneous breathing and HF jet ventilation were identified. The frequency of each Chartis phenotype per lobe was similar in both settings. When comparing Chartis assessments in spontaneous breathing and HF jet ventilation, there was an overall good concordance rate for all analyzed fissures. In agreement, receiver operating characteristic analysis of the FCS showed an almost similar prediction for CV+ and CV- status independent of the ventilation modes., Conclusion: Chartis assessment in spontaneous breathing and HF jet ventilation had similar rates in detecting CV in lung emphysema. Our results suggest that both modes are equivalent for the assessment of CV., (© 2021 S. Karger AG, Basel.)

Background: Combined pulmonary fibrosis and emphysema (CPFE) is recognized as a characteristic syndrome of smoking-related interstitial lung disease that has a worse prognosis than idiopathic pulmonary fibrosis (IPF). However, outcomes after lung transplantation for CPFE have not been reported. The aim of this study is to describe the clinical features and outcomes of CPFE after lung transplantation., Research Question: What are the clinical features and outcomes of CPFE after lung transplantation?, Study Design and Methods: This is a single-center retrospective cohort study of patients with CPFE and IPF who underwent lung transplantation at our center between January 2011 and December 2016. We defined CPFE as ≥10% emphysema in the upper lung fields combined with fibrosis on high-resolution CT scan. We characterized the clinical features of patients with CPFE and compared their outcomes after lung transplantation with those with IPF., Results: Twenty-seven of 172 (16%) patients with IPF met criteria for CPFE. Severe pulmonary hypertension was present in 16 of 27 (59%) patients with CPFE. On logistic regression analysis, CPFE was significantly associated with primary graft dysfunction (PGD) grade 3 (OR, 3.14; 95% CI, 1.18-8.37; P = .02). On competing risk regression analysis, CPFE was associated with acute cellular rejection (ACR) grade ≥ A2, and chronic lung allograft dysfunction (CLAD) (hazard ratio [HR], 1.89; 95% CI, 1.10-3.25; P = .02; HR, 1.96; 95% CI, 1.02-3.77; P = .04, respectively). Five-year survival was 79.0% for the CPFE group and 75.4% for the IPF group (log-rank P = .684)., Interpretation: After transplantation, patients with CPFE were more likely to develop PGD, ACR, and CLAD compared with those with IPF. However, survival was not significantly different between the two groups., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Lung volume reduction with endobronchial coils treatment (ECT), for patients with severe emphysema, has shown modest improvement in exercise capacity and lung functions in clinical trials, yet the benefit of this procedure is still unclear., Methods: We conducted a multicenter retrospective cohort study including all patients who underwent ECT in Israel and a propensity score matched control group of patients with chronic obstructive pulmonary disease (COPD) that were treated with usual care. The primary outcome was six-minute walk test distance (6MWTD), secondary outcomes were lung function tests and patient survival., Results: Overall, 46 patients were included in the ECT group. Their mean 6MWTD at baseline and at 6 and at 24 months post procedure was 331.0±101.4, 372.9±76.8 and 338.8±104.8, respectively (overall P=0.04, pairwise comparison: baseline to 6 months (P=0.1), baseline to 24 months (P=1.0)). Mean FEV1 values at baseline and at 6 and at 24 months post procedure were 0.86±0.38, 0.92±0.37 and 0.82±0.36 liters, respectively (overall P=0.003, pairwise comparison: baseline to 6 months (P=0.04), baseline to 24 months (P=0.75)). The median 6MWTD for the ECT and control groups at 24 months were 333.0 (262.5-390) and 280 (210-405), respectively (P=0.16). There was no difference in overall survival (P=0.84). Heterogenous emphysema was a significant predictor of treatment success in univariate analysis (p=0.004)., Conclusion: Lung volume reduction with endobronchial coils may improve the exercise capacity and FEV1 of COPD patients. However, the majority of the effect was diminished after 24 months. The current state of evidence does not support regulatory approval of ECT and warrant its use only after consideration of the benefit-harm ratio in a highly selected patient population., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 Pertzov et al.)

Purpose: Chronic obstructive pulmonary disease (COPD) is a worldwide problem because of its high prevalence and mortality. However, there is no fundamental treatment to ameliorate their pathological change in COPD lung. Recently, adipose-derived mesenchymal stem cells (ADSCs) have attracted attention in the field of regenerative medicine to repair damaged organs. Moreover, their utility in treating respiratory diseases has been reported in some animal models. However, the detailed mechanism by which ADSCs improve chronic respiratory diseases, including COPD, remains to be elucidated. We examined whether human ADSCs (hADSCs) ameliorated elastase-induced emphysema and whether hADSCs differentiated into alveolar epithelial cells in a murine model of COPD., Methods: Female SCID-beige mice (6 weeks old) were divided into the following four groups according to whether they received an intratracheal injection of phosphate-buffered saline or porcine pancreatic elastase, and whether they received an intravenous injection of saline or hADSCs 3 days after intratracheal injection; Control group, hADSC group, Elastase group, and Elastase-hADSC group. We evaluated the lung function, assessed histological changes, and compared gene expression between hADSCs isolated from the lung of Elastase-hADSC group and naïve hADSCs 28 days after saline or elastase administration., Results: hADSCs improved the pathogenesis of COPD, including the mean linear intercept and forced expiratory volume, in an elastase-induced emphysema model in mice. Furthermore, hADSCs were observed in the lungs of elastase-treated mice at 25 days after administration. These cells expressed genes related to mesenchymal-epithelial transition and surface markers of alveolar epithelial cells, such as TTF-1, β-catenin, and E-cadherin., Conclusion: hADSCs have the potential to improve the pathogenesis of COPD by differentiating into alveolar epithelial cells by mesenchymal-epithelial transition., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Fujioka et al.)

Objectives: To identify, in fetuses with a congenital lung malformation (CLM), prenatal predictors of the need for postnatal respiratory support and the need for surgery by calculating the CLM volume ratio (CVR), and to evaluate the concordance between the prenatal appearance and the postnatal type of CLM., Methods: This was an analysis of prenatal, perinatal and postnatal data from fetuses diagnosed with a CLM at the Erasmus University Medical Center - Sophia Children's Hospital in Rotterdam, The Netherlands, between January 2007 and December 2016. For all included fetuses, CVR was measured retrospectively on stored ultrasound images obtained at 18 + 1 to 24 + 6 weeks (US1), 25 + 0 to 29 + 6 weeks (US2) and/or 30 + 0 to 35 + 6 weeks' gestation (US3). Postnatal diagnosis of CLM was based on computed tomography or histology. Primary outcomes were the need for respiratory support within 24 h and surgery within 2 years after birth., Results: Of the 80 fetuses with a CLM included in this study, 14 (18%) required respiratory support on the first postnatal day, and 17 (21%) required surgery within 2 years. Only the CVR at US2 was predictive of the need for respiratory support, with a cut-off value of 0.39. Four of 16 (25%) fetuses which showed full regression of the CLM prenatally required respiratory support within 24 h after birth. The CVR at US1, US2 and US3 was predictive of surgery within 2 years. Overall, the prenatal appearance of the CLM showed low concordance with the postnatal type. Prenatally suspected microcystic congenital pulmonary airway malformation (CPAM) was shown on computed tomography after birth to be congenital lobar overinflation in 15/35 (43%) cases. Respiratory support within 24 h after birth and surgical resection within 28 days after birth were needed in all cases of macrocystic CPAM., Conclusions: CVR can predict the need for respiratory support within 24 h after birth and for surgery within 2 years. Regression of a CLM prenatally does not rule out respiratory problems after birth. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., (© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.)

Introduction: Acquired pulmonary bullous emphysema is an infrequent complication of assisted ventilation in the premature infant that is difficult to manage., Objective: The goal of this report is to present the case of a premature infant who required selective bronchial intubation as well as to provide a review of the current literature on the subject., Clinical Case: The patient is a 27-week gestational age neonatal female patient whose clinical course was complicated by left unilateral bullous emphysema during assisted ventilation for respiratory distress syndrome. Lower peak inspiratory pressures, higher res piratory frequencies, patient positioning, and lower inspiration time failed to improve the patient's condition. The left lung became critically overinflated and compressed the right lung to the point of atelectasis. The patient was selectively mono intubated through the right main bronchus, which resulted in a collapse of the left emphysematous lung. Single right lung ventilation was continued for 48 hours before restarting conventional ventilation of both lungs. Our patient improved significantly, was extubated 6 days after the procedure and later discharged home with normal chest x-ray images., Conclusion: Selective bronchial intubation is a safe and effective procedure in cases of acquired bu llous emphysema when usual ventilatory management fails.

Purpose: For this study, we aimed to compare dynamic hyperinflation measured by cardiopulmonary exercise testing (CPET), a six-minute walking test (6-MWT), and a manually paced tachypnea test (MPT) in patients with severe emphysema who were treated with endobronchial coils. Additionally, we investigated whether dynamic hyperinflation changed after treatment with endobronchial coils., Methods: Dynamic hyperinflation was measured with CPET, 6-MWT, and an MPT in 29 patients before and after coil treatment., Results: There was no significant change in dynamic hyperinflation after treatment with coils. Comparison of CPET and MPT showed a strong association (rho 0.660, p < 0.001) and a moderate agreement (BA-plot, 202 ml difference in favor of MPT). There was only a moderate association of the 6-MWT with CPET (rho 0.361, p 0.024)., Conclusion: MPT can be a suitable alternative to CPET to measure dynamic hyperinflation in severe emphysema but may overestimate dynamic hyperinflation possibly due to a higher breathing frequency.

Competing Interests: Competing interests: None declared.

Background: Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47-90% of the patients and lung cancer in 46.8% of the patients., Objective: Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE., Methods: We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema]. Bibliographies of retrieved articles were searched as well. Further inclusion criteria were publications in English, French, German and Italian, with reference to humans. In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data., Results: Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies. A total of 890 patients are described in the literature. Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers., Conclusion: CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations. The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer. Smoking and male sex are important risk factors. There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options. Antifibrotic therapy might be an interesting treatment option for these patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Hage et al.)

Background: Pulmonary interstitial emphysema (PIE) is a pathological state when air escapes from ruptured alveoli and is trapped along the sheaths surrounding the bronchovascular bundle. PIE is not uncommon in infants who require mechanical ventilation and even less common in infants on noninvasive ventilatory support; however, it is extremely unusual in infants in room air., Case Presentation: A 2-week-old male infant developed worsening tachypnea in the special-care nursery. The patient was born at 33 weeks' gestation by induced vaginal delivery due to pre-eclampsia. He required positive pressure ventilation at birth and was admitted to the neonatal intensive care unit on nasal continuous positive airway pressure. On the second day of life, exogenous surfactant was administered via endotracheal tube due to increased oxygen requirement, and, soon after, he was weaned off all respiratory support. After 10 days of stability, he developed tachypnea with diminished air entry on the left side of the chest. Chest radiograph and chest computerized tomography confirmed left-sided unilateral PIE. The patient was treated conservatively with positional therapy alone. Significant clinical and radiographic improvement was noticed within 4 days; almost complete resolution by 10 days and the infant was discharged 23 days later. At follow-up at 7 months, the infant was found to be symptom-free with a normal chest radiograph., Conclusions: Traditional management of unilateral PIE generally involves a combination of invasive ventilatory support and positional therapy to break the vicious cycle pathophysiology of PIE. This report focuses on the insidious progression of PIE in nonventilated neonates and describes a nontraditional conservative management strategy for the management of unilateral PIE., (© 2020 Wiley Periodicals LLC.)

Interventional treatment of emphysema offers a wide range of surgical and endoscopic options for patients with advanced disease. Multidisciplinary collaboration of pulmonology, thoracic surgery, and imaging disciplines in patient selection, therapy, and follow-up ensures treatment quality. The present joint statement describes the required structural and quality prerequisites of treatment centres. This is a translation of the German article "Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Thoraxchirurgie in Kooperation mit der Deutschen Röntgengesellschaft: Strukturvoraussetzungen von Zentren für die interventionelle Emphysemtherapie" Pneumologie. 2020;74:17-23., (© 2021 S. Karger AG, Basel.)

We present a case of a 36-year old male who was a long-term smoker and was found to have giant bullous emphysema on chest imaging as an accidental finding. At the time, when his first chest CT was obtained, he was asymptomatic and was recommended to consult a pulmonologist but was lost to follow-up for a year until he presented to the emergency department with fever, dyspnea, and chest pain. He was admitted to a pulmonology department. Chest CT was performed and it revealed infected bullae containing air-fluid levels as a complication of community-acquired pneumonia. After successful antibacterial treatment, the patient was discharged and recommended to consult with a thoracic surgeon. A few months later, he had video-assisted thoracoscopic surgery and left upper lobectomy as part of definitive treatment.

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.

Pulmonary interstitial emphysema (PIE) is a severe complication of mechanical ventilation in preterm infants. Selective bronchial intubation is a rarely used treatment strategy, as it is challenging, especially left main stem bronchial intubation. We report our experience in an infant at 24 weeks gestation with bedside left main stem bronchial intubation using flexible fiberoptic bronchoscopy. We also describe in detail the procedural details involved in the selective left main stem bronchial intubation including the helpful technique of gently bending the tip of the endotracheal tube to create "memory" to better direct the tube into the left main-stem bronchus while using the flexible fiberoptic bronchoscope. A review of the literature regarding selective bronchial intubation in newborn infants is presented. This case report and literature review suggest that bedside left main stem bronchial intubation using a flexible fiberoptic bronchoscope is a viable option to successfully manage even the most unstable extreme premature infant with unilateral right lung cystic PIE. This may potentially prevent a rare but necessary invasive surgical procedure like lobectomy or even death.

Introduction: Bronchoscopic volume reduction treatments are among the important alternatives for selected emphysema patients with a dyspneic course despite optimal medical treatment. Our aim was to carry out a retrospective scan of the data for COPD patients subject to coil treatment at our center for assessing whether coil procedure has an impact on the respiratory symptom and pulmonary function tests in COPD patients., Materials and Methods: The data of 41 patients with severe emphysema and treated with coils between 2017-2020 were evaluated retrospectively. Cardiopulmonary rehabilitation programs were completed for all patients prior to the procedure and they were assessed with pulmonary function test (PFT), diffusing capacity for carbonmonoxide test (DLCO), body plethysmography, 6-minute walk test, ventilation/perfusion scintigraphy, St. George's Respiratory Questionnaire (SGRQ). Data acquired prior to the procedure and 3rd month control data after the procedure were recorded and SGRQ was applied via face-to-face interviews during the controls by doctors working on Pulmonary Diseases as was the case before the procedure., Result: SGRQ questionnaires of 32 patients were evaluated. Statistically significant changes were observed after the procedure in symptom, activity, impact score and total score which were calculated prior to the procedure. Pre and post procedure FEV1, FVC, FEV1/FVC, PEF, FEF25/75 parameters were used for the comparison made via SFT. Statistically significant changes were observed in FEV1, FVC, FEF25/75 when the pre and post-procedure SFT parameters of the 32 patients included in the study were compared., Conclusions: A statistically significant improvement was observed in the PFT parameters and quality of life questionnaires following the coil procedure which is a bronchoscopic volume reduction procedure.

Background: The Spanish chronic obstructive pulmonary disease (COPD) guideline phenotypes patients according to the exacerbation frequency and COPD subtypes. In this study, we compared the patients' health-related quality of life (HRQoL) according to their COPD phenotypes., Methods: This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23th January 2018 to 22th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c)., Results: Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the 185 COPD patients, 65.9% had exposure to biomass fuel and 69.1% were ex- or current smokers. The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p <  0.001). There were significantly more patients with mMRC 2-4 among AE (68.6%) (p <  0.001), compared to those with ACO (38.5%) and NON-AE (16.7%). AE patients had significantly higher total CAT (p = 0.003; p <  0.001) and SGRQ-c (both p <  0.001) scores than those with ACO and NON-AE. Patients with ACO had significantly higher total CAT and SGRQ-c (both p <  0.001) scores than those with NON-AE. AE patients had significantly higher score in each item of CAT and component of SGRQ-c compared to those with NON-AE (all p <  0.001), and ACO [(p = 0.003-0.016; p = < 0.001-0.005) except CAT 1, 2 and 7. ACO patients had significantly higher score in each item of CAT and component of SGRQ-c (p = < 0.001-0.040; p <  0.001) except CAT 2 and activity components of SGRQ-c., Conclusions: The HRQoL of COPD patients was significantly different across different COPD phenotypes. HRQoL was worst in AE, followed by ACO and NON-AE. This study supports phenotyping COPD patients based on their exacerbation frequency and COPD subtypes. The treatment of COPD should be personalised according to these two factors.

Objective: To report initial experience from the use of extracorporeal membrane oxygenation (ECMO) in patients who received lung transplantation., Methods: Retrospective study of a single tertiary center in the Brazilian state of São Paulo, a national reference in lung transplantation, based on the prospective collection of data from electronic medical records. The period analyzed extended from January 2009 (beginning of the program) until December 2018., Results: A total of 75 lung transplants were performed, with ECMO used in 8 (10.7%) cases. Of the patients, 4 (50%) were female. The mean age was 46.4±14.3 years. The causes of the end-stage lung disease that led to transplantation were pulmonary arterial hypertension in 3 (37.5%) patients, bronchiectasis in 2 (25%) patients, pulmonary fibrosis in 2 (25%) patients, and pulmonary emphysema in 1 (12.5%) patient. In our series, 7 (87.5%) cases were sequential bilateral transplantations. Prioritization was necessary in 4 (50%) patients, and in 1 patient, ECMO was used as a bridge to transplantation. The ECMO route was central in 4 (50%), peripheral venovenous in 2 (25%) and peripheral venoarterial in 2 (25%) patients. The mean length of the intensive care unit (ICU) stay was 14±7.5 days and of the hospital stay was 34.1±34.2 days. The mean ECMO duration was 9.3±6.6 days with a 50% decannulation rate. Three patients were discharged (37.5%)., Conclusion: Lung transplantation requires complex treatment, and ECMO has allowed extending the indications for transplantation and provided adjuvant support in the clinical management of these patients.

Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the combination of upper lobe emphysema and lower lobe fibrosis, the latter owing to various interstitial lung diseases. These patients have a characteristic lung function profile, with relatively preserved dynamic and static lung volumes, contrasting with a significant reduction of carbon monoxide transfer. The pathogenic mechanisms leading to the coexistence of emphysema with fibrosis remain unclear and different theories have been proposed. CPFE is frequently complicated by pulmonary hypertension, acute exacerbations, and lung cancer leading to poor natural history and prognosis. The syndrome of CPFE represents a distinct pulmonary manifestation in the spectrum of lung diseases associated with connective tissue diseases. Currently, there are no established recommendations regarding the management of patients with CPFE. We provide a review on the existing knowledge of CPFE regarding the epidemiology, pathogenesis, clinical manifestations, radiologic appearance, complications, prognosis, and possible treatment options., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: Emphysema is a progressive and irreversible disease, proceeding with the decrease in elastic recoil which is connected to tissue damage caused by chronic inflammation. Lung volume reduction coil (LVRC) method in patients with an advanced level of emphysema and irresponsive to medical treatment is shown to provide increase in lung volumes and exercise capacity, decrease in dyspnea, and increase in quality of life. The purpose of this study is to reveal that LVRC treatment is also efficient in severe COPD patients with hypercapnic respiratory failure., Patients and Methods: Eleven cases with severe COPD and emphysema were included in the study. LVRC treatment method was applied in upper lobes of both lungs in patients with severe COPD (FEV1 < %45) and Type-2 respiratory insufficiency (PCO 2 55-80 mmHg) who were having medical treatment and CPAP treatment. The patients were followed up for a period of twelve months using arterial blood gas analysis., Results: Beginning with the first month of the LVRC treatment, PCO 2 levels were found to be significantly decreased in all patients using arterial blood gas analysis., Conclusion: LVRC method can provide physiological and functional recovery and progress in quality of life in severe COPD cases. It is demonstrated that LVRC treatment caused significant decreases in carbon dioxide levels as well as causing improvement in life quality and respiratory function tests in the patients with hypercapnic respiratory failure., Competing Interests: The author reports no conflicts of interest in this work., (© 2020 Yildiz.)

AATD is a common inherited disorder associated with an increased risk of developing pulmonary emphysema and liver disease. Many people with AATD-associated pulmonary emphysema remain undiagnosed and therefore without access to care and counselling specific to the disease. AAT augmentation therapy is available and consists of i.v. infusions of exogenous AAT protein harvested from pooled blood products. Its clinical efficacy has been the subject of some debate and the use of AAT augmentation therapy was recently permitted by regulators in Australia and New Zealand, although treatment is not presently subsidized by the government in either country. The purpose of this position statement is to review the evidence for diagnosis and treatment of AATD-related lung disease with reference to the Australian and New Zealand population. The clinical efficacy and adverse events of AAT augmentation therapy were evaluated by a systematic review, and the GRADE process was employed to move from evidence to recommendation. Other sections address the wide range of issues to be considered in the care of the individual with AATD-related lung disease: when and how to test for AATD, changing diagnostic techniques, monitoring of progression, disease in heterozygous AATD and pharmacological and non-pharmacological therapy including surgical options for severe disease. Consideration is also given to broader issues in AATD that respiratory healthcare staff may encounter: genetic counselling, patient support groups, monitoring for liver disease and the need to establish national registries for people with AATD in Australia and New Zealand., (© 2020 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

α 1 -antitrypsin deficiency (AATD) is a hereditary disorder associated with a risk of developing liver disease and pulmonary emphysema, and other chronic respiratory disorders (mainly asthma and bronchiectasis); Z variant is the commonest deficient variant of AAT. Determining AAT concentration in serum or plasma and identifying allelic variants by phenotyping or genotyping are fundamental in the diagnosis of AATD. Initial evaluation and annual follow-up measurement of lung function, including post-bronchodilator forced expiratory volume in 1 s and gas transfer inform on disease progression. Lung densitometry is the most sensitive measure of emphysema progression, but must not be use in the follow-up of patients in routine clinical practice. The exogenous administration of purified human serum-derived AAT is the only approved specific treatment for AATD in PiZZ. AAT augmentation therapy is not recommended in PiSZ, PiMZ or current smokers of any protein phenotype, or in patients with hepatic disease. Lung volume reduction and endoscopic bronchial valve placement are useful in selected patients, whereas the survival benefit of lung transplant is unclear. There are several new lines of research in AATD to improve the diagnosis and evaluation of the response to therapy and to develop genetic and regenerative therapies and other treatments., Competing Interests: Conflict of interest: M. Cazzola has nothing to disclose. Conflict of interest: D. Stolz has nothing to disclose. Conflict of interest: P. Rogliani has nothing to disclose. Conflict of interest: M.G. Matera has nothing to disclose., (Copyright ©ERS 2020.)

Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed genetic predisposition for COPD and emphysema and other conditions, including liver disease. Although there have been improvements in terms of awareness of AATD and understanding of its treatment in recent years, current challenges center on optimizing detection and management of patients with AATD, and improving access to intravenous (IV) AAT therapy - the only available pharmacological intervention that can slow disease progression. However, as an orphan disease with geographically dispersed patients, international cooperation is essential to address these issues. To achieve this, new European initiatives in the form of the European Reference Network for Rare Lung Diseases (ERN-LUNG) and the European Alpha-1 Research Collaboration (EARCO) have been established. These organizations are striving to address the current challenges in AATD, and provide a new platform for future research efforts in AATD. The first objectives of ERN-LUNG are to establish a quality control program for European AATD laboratories and create a disease management program for AATD, following the success of such programs in the United States. The main purpose of EARCO is to create a pan-European registry, with the aim of understanding the natural history of the disease and supporting the development of new treatment modalities in AATD and access to AAT therapy. Going further, other patient-centric initiatives involve improving the convenience of intravenous AAT therapy infusions through extended-interval dosing and self-administration. The present review will discuss the implementation of these initiatives and their potential contribution to the optimization of patient care in AATD., Competing Interests: Professor Joanna Chorostowska-Wynimko reports grants, personal fees, non-financial support from Grifols, Boehringer Ingelheim, and CSL Behring, personal fees, non-financial support from Novartis, and personal fees from GSK, outside the submitted work. Dr Miriam Barrecheguren reports personal fees from Grifols, Menarini, CSL Behring, GSK, Novartis, and Gebro Pharma, outside the submitted work. Dr Ilaria Ferrarotti reports personal fees from Grifols and grants from CSL Behring, outside the submitted work. Dr Timm Greulich reports personal fees from AstraZeneca, Berlin-Chemie, Boehringer-Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, and Novartis, outside the submitted work. Professor Robert A Sandhaus reports participation in advisory boards for Grifols, CSL Behring, AstraZeneca, Mereo, and Inhibrx for which he receives reimbursement of travel expenses. Dr Michael Campos reports grants, non-financial support, and personal fees from CSL Behring, and grants and personal fees from Grifols, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Chorostowska-Wynimko et al.)

Introduction: The use of two quality-of-life questionnaires in a single clinical trial with an economic component can be challenging due to the associated workload in terms of data collection and an increased risk of missing data. The aim of our study was to determine whether the questionnaire chosen to measure health status, the St. George's Respiratory Questionnaire (SGRQ), could be administered on its own without adding the EuroQol five dimensions questionnaire (EQ-5D) for economic evaluation in emphysema studies., Materials and Methods: Data were prospectively collected during the REVOLENS trial assessing endobronchial coil treatment in severe emphysema. To quantify the association between the two questionnaires, correlations between the EQ-5D and the SGRQ were first tested and the concordance was then studied in order to know whether the two questionnaires were interchangeable. Finally, the Starkie et al algorithm predicting EQ-5D utility values from the SGRQ was used on REVOLENS's individual patient data. The Student's t -test, correlation and concordance between EQ-5D individual value (from the REVOLENS study) and predicted value (from the Starkie et al algorithm) were studied to test this algorithm., Results: Results showed a strong correlation but no concordance between the EQ-5D and the SGRQ, demonstrating that the two questionnaires are not interchangeable. Moreover, the algorithm predicting EQ-5D utilities from the SGRQ did not provide utility values comparable to those observed in the REVOLENS study. Indeed, our study demonstrated a strong correlation between predicted and individual EQ-5D values but no concordance., Conclusion: The use of both the EQ-5D and the SGRQ in a clinical study with an economic component is justified. Based on our results, the SGRQ should not be used to obtain a utility score to calculate the incremental cost-effectiveness ratio and conclude on the efficiency of an intervention in emphysema patients., Competing Interests: Charles Hugo Marquette and Gaëtan Deslée have been involved as investigators in previous studies sponsored by BTG/PneumRx and received travel reimbursements and speaker fees for educational sessions and consulting from BTG/PneumRx. Gaëtan Deslee also reports grants and personal fees from BTG/PneumRx during the conduct of the study, and personal fees from Boehringer, AstraZeneca, Chiesi, Novartis, and Nuvaira, outside the submitted work. Julie Bulsei, Jeanne Pfister, and Isabelle Durand-Zaleski report grants from French Ministry of Health, during the conduct of the study. Sylvie Leroy, Jeanne Marie Perotin, and Coralie Barbe indicated no conflicts of interest in this work., (© 2020 Bulsei et al.)

Bronchoscopic lung volume reduction (BLVR) offers alternative novel treatments for patients with emphysema. Comprehensive evidence for comparing different BLVR remains unclear. To estimate the effects of different BLVR on patients with emphysema. PubMed, EMBASE, Cochrane Library, and Web of Science databases from January 2001 to August 2017 were searched. Randomized clinical trials evaluated effects of BLVR on patients with emphysema. The relevant information was extracted from the published reports with a predefined data extraction sheet, and the risk of bias was assessed with the Cochrane risk of bias tools. Pair-wise metaanalyses were made using the random-effects model. A random-effects network meta-analysis was applied within a Bayesian framework. The quality of evidence contributing to primary outcomes was assessed using the GRADE framework. 13 trials were deemed eligible, including 1993 participants. The quality of evidence was rated as moderate in most comparisons. Medical care (MC)was associated with the lowest adverse events compared with intrabronchial valve (IBV)(-2.5,[-4.70 to -0.29]), endobronchial valve (EBV) (-1.73, [-2.37 to -1.09]), lung volume reduction coils (LVRC) (-0.76, [-1.24 to -0.28]), emphysematous lung sealant (ELS) (-1.53, [-2.66 to -0.39]), and airway bypass(-1.57, [-3.74 to 0.61]). Adverse events in LVRC were lower compared with ELS (-0.77,[-2.00 to 0.47]). Bronchoscopic thermal vapor ablation (BTVA) showed significant improvement in FEV1 compared with MC (0.99, [0.37 to 1.62]), IBV (1.25, [0.25 to 2.25]), and LVRC (0.72, [0.03 to 1.40] ). Six  minute walking distance (6 MWD) in ELS was significantly improved compared with other four BLVR, sham control, and MC (-1.96 to 1.99). Interestingly, MC showed less improvement in FEV1 and 6MWDcompared with EBV (-0.45, [-0.69 to -0.20] and -0.39, [-0.71 to -0.07], respectively). The mortality in MC and EBV was lower compared with LVRC alone (-0.38, [-1.16 to 0.41] and -0.50, [-1.68 to 0.68], respectively). BTVA and EBV led to significant changes in St George's respiratory questionnaire (SGRQ) compared with MC alone (-0.74, [-1.43 to -0.05] and 0.44, [0.11 to 0.78], respectively). BLVR offered a clear advantage for patients with emphysema. EBV had noticeable beneficial effects on the improvement of forced expiratory volume 1, 6MWD and SGRQ, and was associated with lower mortality compared with MC in different strategies of BLVR.

Nonsurgical approaches involving bronchoscopic lung volume reduction (BLVR) have been developed in the last decade. One of these, the BLVR coil procedure, is a treatment option for patients with homogeneous and heterogeneous end-stage emphysema and a forced expiratory volume in 1 second (FEV1) of 15-45%. This treatment decreases hyperinflation and improves lung function, the quality of life, and exercise capacity. It is very important to prepare patients for treatment, premedications, anesthesia applications, intubation, post-procedure follow-up and treatments. Further, it has been observed that various complications can develop during and after the procedure. Generally, the observed and reported complications are chronic obstructive pulmonary disease (COPD) exacerbation, chest pain, mild bleeding, pneumonia, pneumothorax, and respiratory failure. Rarely, aspergillus cavitation (coil-related aspergilloma), bronchopleural fistula and penetration into the pleural space, bronchiectasis, coil-associated inflammatory response and opacities, and hiccups are observed. Common complications are usually mild or moderate, while the rare ones can be life-threatening (except hiccup), so early diagnosis and treatment are necessary. However, patients treated with BLVR have lower mortality rates than untreated patients with similar morbidity. Based on the findings of this review, we can estimate that premedication one day before and just before the procedure may reduce potential complications. Some medical centers apply and recommend 30-day macrolide treatment after the procedure. New generation supraglottic devices may be preferred to avoid complications due to endotracheal intubation. Moreover, further research is needed to identify risk factors, prevent potential complications, and a common consensus is required for routine preventive treatment.

Patients with chronic obstructive pulmonary disease (COPD) usually develop skeletal muscle dysfunction, which represents a major comorbidity in these patients and is strongly associated with mortality and other poor outcomes. Although clinical data indicates that accelerated protein degradation and metabolic disruption are common associations of muscle dysfunction in COPD, there is very limited data on the mechanisms regulating the process, in part, due to the lack of research performed on a validated animal model of pulmonary emphysema. This model deficiency complicates the translational value of data generated with highly reductionist settings. Here, we use an established transgenic animal model of COPD based on inducible IL-13-driven pulmonary emphysema (IL-13 TG ) to interrogate the mechanisms of skeletal muscle dysfunction. Skeletal muscles from these emphysematous mice develop most features present in COPD patients, including atrophy, decreased oxygen consumption, and reduced force-generation capacity. Analysis of muscle proteome indicates downregulation of succinate dehydrogenase C (SDH-C), which correlates with reduced enzymatic activity, also consistent with previous clinical observations. Ontology terms identified with human data, such as ATP binding/bioenergetics are also downregulated in this animal's skeletal muscles. Moreover, chronic exercise can partially restore muscle mass, metabolic and force-generation capacity, and SDH activity in COPD mice. We conclude that this animal model of COPD/emphysema is an adequate platform to further investigate mechanisms of muscle dysfunction in this setting and demonstrates multiple approaches that can be used to address specific mechanisms regulating this process. NEW & NOTEWORTHY Skeletal muscle dysfunction is a relevant comorbidity in patients with chronic obstructive pulmonary disease (COPD). Mechanistic research in the area has so far been accomplished with models based on specific exposures to otherwise healthy animals, and no investigation using an established and validated animal model of COPD has been accomplished. We present an animal model of COPD that was previously shown to recapitulate pulmonary functional and histologic features present in patients with COPD, and demonstrates most of the features present in patients with pulmonary emphysema-associated muscle dysfunction, which we proposed as an adequate tool to develop mechanistic research in the area.

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema. Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management. Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control). Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV 1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV 1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment ( n  = 113) or control ( n  = 59). Mean FEV 1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax. Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

BACKGROUND: Preventive treatment for incidentally detected blebs or bullae is required for fast jet pilots, but their aeromedical risk is not clearly proven. METHODS: This is a retrospective study and includes 46 pilots 40 yr and older with incidentally detected emphysema-like changes (ELCs) comprising blebs or bullae in low-dose chest CT (LDCT) during health screening. Two radiologists retrospectively reviewed imaging features. Statistical analysis was done using independent t -tests and bivariate analysis. RESULTS: Among 46 pilots, 39 pilots flew fast jet aircraft and 7 pilots flew nonfast jet aircraft. The mean follow-up period was 1531 d and the LDCT follow-up interval mean period was 424.4 d. There was no evidence of rupture in incidentally detected ELCs during the follow-up period. The mean size of the ELCs was 19.15 mm. There were five cases showing changes in size. There was a statistically significant correlation between the size of ELCs and height. There were no statistically significant differences in the size or number of ELCs relating to smoking status or aircraft type, and there were no statistically significant correlations between the size or number of ELCs and multiple factors, including smoking quantity, flight time, age, BMI, and weight. CONCLUSION: This study demonstrates the aeromedical safety of incidentally detected ELCs in pilots 40 yr and older without underlying lung disease. The results indicate no need for recommending preventive treatment for ELCs in pilots 40 yr and older, even those flying fast jet aircraft, as a requisite to continue their flight duties. KEYWORDS: bleb, bulla, pilot, CT. Bang S, Yang S, Cho SW, Kim DH, Kang H. Follow-up of blebs and bullae in pilots 40 years and older using CT . Aerosp Med Hum Perform. 2019; 90(10):867-871.