Severe Emphysema Research Articles

Inhaled Steroids, Sex and Emphysema Index - Clinical Parameters with Impact on the Effectiveness of Valve Implantation in Patients with Severe Emphysema.

Aims and ObjectivesMany patients with chronic obstructive lung disease suffer from emphysema. Valve implantation may be a reasonable method in patients presenting advanced emphysema and absent interlobar collateral ventilation (CV). However, other clinical parameters influencing the effectiveness of endoscopic lung volume reduction (ELVR) are not well known.MethodsCOPD patients with advanced emphysema who received valve implantation in 2016 were retrospectively analyzed. The following characteristics were collected prior to valve implantation: age, sex, body mass index, presence of allergies, use of inhaled corticosteroids (ICS), lung function parameters, diffusion capacity, 6-minute walk distance (6-MWD), blood gases, COHb, smoking history, and emphysema index (quantitative multi-detector computed tomography). Three months following valve implantation, lung function parameters, diffusion capacity, 6-MWD and blood gases were measured. In this analysis, we evaluated the impact of these variables on an increase in FEV1 and 6-MWT as well as a decrease in RV three months after valve implantation.ResultsOverall, 77 COPD patients (57% male, mean age 66, mean FEV1 32%, mean RV 259%) who underwent valve therapy were enrolled. At 3-month follow-up, patients experienced a mean FEV1 increase of 0.09 ± 0.21 L, a mean RV decrease of 0.42 ± 1.80 L and a mean improvement of 8.3 ± 57 m in the 6-MWT. Overall, ICS, sex and emphysema index had an impact on the outcome following ELVR: ICS medication was associated with inferior FEV1 outcome. The higher the emphysema index, the less the RV reduction. Sex was a predictor for change of FEV1 (%), RV (L), and 6-MWT: male patients seem to benefit less than female patients from valve implantation.ConclusionThese findings suggest that ICS, emphysema index and sex are clinical parameters that may be associated with inferior outcome following ELVR. Further studies have to confirm these results to improve patient selection and clinical outcome of ELVR.

Surgical Plate Fixation of Simple Rib Fractures: A Case Report

Introduction: Rib fractures can cause patient morbidity that causes long hospitalization if conservative treatment is carried out. Current international guidelines recommend a minimally incisional surgical-based treatment approach to reduce pain and provide optimal clinical benefit. Numerous studies have demonstrated that surgical fixation in conjunction with multidisciplinary integrated care pathways offers the highest therapeutic benefit for developing countries, which are typically more accountable for a higher share of unfavorable global outcomes. This case report describes the selection of appropriate decision-making in the management of multiple rib fractures. Case description: We report that a 51-year-old, still actively working young female came to our emergency department after a motorcycle accident, left chest hitting the road boundary, 2 days earlier. He presented with severe upper chest pain, chest deformity, mild dyspnea, tachycardia, subcutaneous emphysema, and hematoma. The chest radiograph shows a hypo ventilated lung field and a minor pleural effusion. A computed tomography scan showed right lateral rib fractures 3–4 posterior and 5–6 posterolateral, with areas of hyperdensity of simple bone fragments, and pulmonary contusion. Treatment consists of minimal incision with surgical fixation of the 5th and 6th posterolateral ribs which causes pain. For rib fractures 3-4, because it is stable and protected by the scapula, we only perform conservative measures. Rib fixation uses titanium reconstruction plates and cortical fixing screws. The patient's clinical condition improved rapidly postoperatively with a length of stay of 2 days after surgery. Follow-up at 6 weeks, the patient confirmed a full return to preoperative daily activities with the return to normal work activities as well as high quality of life. Conclusion: In this case report, reported that in rib fractures in a developing country, thoracic trauma can be treated through medical treatment with minimal incisions which allows rapids recovery of the patient.

Meta-analysis and Systematic Review of Bronchoscopic Lung Volume Reduction Through Endobronchial Valves in Severe Emphysema.

Pharmacologic therapeutics for advanced emphysema have limited benefit. Bronchoscopic lung volume reduction with endobronchial valves (EBVs) have reported improvements in lung function, breathlessness, and quality of life through randomized clinical trials, with less morbidity as comparted to Surgical Lung volume Reduction. We here present a Meta-analysis and systematic review of bronchoscopic lung volume reduction in advanced chronic obstructive lung disease patients. PubMed (NLM), Embase (Elsevier), and Web of Science (Clarivate Analytics) search was conducted using a combination of keywords and subject headings. The search was confined to the last 15 years and was completed on October 23, 2020. Only placebo-controlled randomized control trials of emphysema patients with EBV were included. Quality assessment was done by 2 independent reviewers. Nine studies were included for the meta-analysis with a total number of 1383 patients of whom 888 received EBV and 495 standard of care (SOC) medications. Our Metanalysis show statistically significant improvement in forced expiratory volume in first second, percentage forced expiratory volume in first second, St. George's respiratory questionnaire, and 6-minute walk distance in EBV group compared with SOC. Residual volume had statistically significant reduction after EBV placement compared with SOC. These differences continued to be present during short-term (<=6 mo) and long-term follow-up (>=6 mo). These improvements were even higher when the EBV patients'. Collateral ventilation was negative/fissure was intact (CV-/FI >90%). The rate of hemoptysis and pneumothorax was higher in the EBV group compared with SOC, however, did not lead to increased fatal outcomes. In conclusion, EBV has favorable effects on patients' outcomes in patients who have heterogeneous emphysema particularly with no collateral ventilation.

The mutation PTPN6Ala455Thr causing pulmonary emphysema affects B lymphocyte populations and causes spontaneous pulmonary tertiary lymphoid tissue formation

Abstract Background A new mutation responsible for causing severe and early pulmonary emphysema was recently discovered in a French-Canadian family. The mutation is located in the PTPN6 gene (PTPN6Ala455Thr) leading to a reduction in the activity of SHP-1, a phosphatase that regulates numerous pathways including B cell differentiation and activation. Here, we aimed to characterize B cell abnormalities in both humans and mice carrying this mutation. Methods Circulating B cell populations in humans carrying the PTPN6Ala455Thr mutation were analyzed by flow cytometry and immunoglobulin levels were measured in serum. In mice carrying the same mutation (Ptpn6Ala457Thr) aged up to 12 months, B cell populations were analyzed by flow cytometry and lung tissue histology performed. Mice were immunized with the T cell-independent antigen NP-Ficoll and plasma was collected to assess NP-specific antibodies. Results Human carriers of the PTPN6Ala455Thr mutation had reduced IgG1 and IgG4, and increased IgG3 levels as well as high circulating immature/mature B cell ratio compared to controls. Aging Ptpn6Ala457Thr mice developed spontaneous pulmonary tertiary lymphoid tissues and exhibited higher B-1 cells and lower B-2 cells proportions in the lung and spleen. Ptpn6Ala457Thr mice had lower levels of NP-specific IgG1 antibodies compared to the wild-type group, but normal IgG3 in response to NP-Ficoll immunization. Conclusion SHP-1 appears to be important to B cell development and functions, as the PTPN6Ala455Thr mutation seems to cause a form of subclinical immunodeficiency that affects B cell populations and immunoglobulin levels. The link between B cell abnormalities and development of pulmonary emphysema requires further investigation. Supported by grants from Canadian Institutes of Health and Research and Fonds de Recherche du Québec- Santé

Lung Volume Reduction Surgery Reduces Pulmonary Arterial Hypertension Associated With Severe Lung Emphysema and Hypercapnia.

Lung volume reduction surgery (LVRS) represents a standard surgical approach for patients with severe pulmonary emphysema. One of the relevant risk factors for LVRS is the presence of pulmonary arterial hypertension (PAH). The aim of this study is to assess the postoperative changes in pulmonary arterial pressure (PAP) after LVRS for patients with severe pulmonary emphysema compared with preoperative measures. N = 61 consecutive patients with severe pulmonary emphysema and preoperative evidence for PAH (pulmonary arterial systolic pressure [PASP] ≥ 35 mmHg) were prospectively included into this study. In all patients, thoracoscopic LVRS was performed. PASP was assessed by echocardiography before surgery, early postoperatively, and 3 months after surgery. Data were prospectively recorded and analyzed retrospectively. Primary end points were the postoperative changes in PASP as well as the 90 day mortality rate. Secondary endpoints included: pulmonary function test, exercise capacity, quality of life, and dyspnea symptoms (Borg scale). Early after surgery, a significant reduction in PASP was observed at the day of discharge and at 3 month follow-up. In n = 34 patients, no tricuspid valve regurgitation was detectable anymore suggesting normal PAP. In n = 3 patients, venovenous extracorporeal lung support (VV ECLS) was already implemented preoperatively. In the remaining cases, VV ECLS was applied intraoperatively and continued postoperatively. Mean duration of postoperative ECLS support was 2 days. Four patients died due to acute right heart failure, two patients from sepsis with multiorgan failure, and one patient from acute pulmonary embolism. Ninety day mortality was 11.5 %. A significant improvement was postoperatively observed regarding the performance status, dyspnea scale, as well as quality of life. This study suggests a beneficial effect of LVRS on PAP, which may ultimately help to protect and stabilize right ventricular function. Further studies, implementing pre- and postoperative right heart catheterizations including invasive PAP evaluation, are necessary to support the findings in this study in greater detail.

Bronchoscopic Lung Volume Reduction Coil Treatment for Severe Emphysema: A Systematic Review and Meta-Analysis of Individual Participant Data

Background: Lung volume reduction coil (LVR-coil) treatment provides a minimally invasive treatment option for severe emphysema patients which has been studied in multiple clinical trials. Objectives: The aim of the study was to assess the effect of LVR-coil treatment on pulmonary function, quality of life, and exercise capacity using individual participant data. Method: PubMed, Web of Science, and EMBASE were searched until May 17, 2021. Prospective single-arm and randomized controlled trials that evaluated the effect of LVR-coil treatment on forced expiratory volume in 1 s (FEV₁), residual volume (RV), St. George Respiratory Questionnaire (SGRQ) total score, and/or 6-min walk distance (6MWD) and were registered in an official clinical trial database were eligible for inclusion. Individual patient data were requested, and a linear mixed effects model was used to calculate overall treatment effects. Results: Eight trials were included in the final analysis, representing 680 individual patients. LVR-coil treatment resulted in a significant improvement in FEV1 at 3- (0.09 L [95% confidence interval (95% CI): 0.06–0.12]) and 6-month follow-up (0.07 L [95% CI: 0.03–0.10]), a significant reduction in RV at 3- (−0.45L [95% CI: −0.62 to −0.28]), 6- (−0.33L [95% CI: −0.52 to −0.14]), and 12-month follow-up (−0.36L [95% CI: −0.64 to −0.08]), a significant reduction in SGRQ total score at 3- (−12.3 points [95% CI: −15.8 to −8.8]), 6- (−10.1 points [95% CI: −12.8 to −7.3]), and 12-month follow-up (−9.8 points [95% CI: −15.0 to −4.7]) and a significant increase in 6MWD at 3-month follow-up (38 m [95% CI: 18–58]). Conclusions: LVR-coil treatment in emphysema patients results in sustained improvements in pulmonary function and quality of life and shorter lived improvements in exercise capacity. Since the owner of this LVR-coil has decided to stop the production and newer generations LVR-coils are currently being developed, these results can act as a reference for future studies and clinical guidance.

The impact of endoscopic lung volume reduction on physical activity coaching in patients with severe emphysema.

IntroductionEndoscopic lung volume reduction (ELVR) aims to improve pulmonary function in severe emphysema. Physical activity (PA) coaching is expected to improve daily life PA. When improving ventilatory constrains in severe COPD, a better response to PA coaching is expected. The present study investigated the impact of PA coaching in addition to ELVR in severe emphysema.MethodsPatients allocated, based on fissure integrity, in the ELVR or no-ELVR cohort, received the PA coaching intervention with a step counter and smartphone application from 3 to 6 months follow-up. The primary end-point of this research question was the change in daily step count from baseline to 6 months follow-up compared between the ELVR and no-ELVR cohort. The secondary end-points were time spent in moderate to vigorous PA, movement intensity and patient-reported experience with PA between ELVR and no-ELVR.ResultsAt 6 months, PA in both ELVR+coaching (1479±460 steps·day−1; p=0.001) and no-ELVR+coaching (1910±663 steps·day−1; p=0.004) improved within group, without significant between-group differences (−405±781 steps·day−1; p=0.60). Patients in the ELVR group tended to experience less difficulty with PA compared to no-ELVR+coaching (7±4 points, p=0.08).ConclusionWe found that PA coaching is feasible and can help to enhance PA in patients with severe emphysema. Improving the ventilatory capacity through ELVR is not a prerequisite for a successful coaching intervention to increase objectively measured PA, although it alleviates patients’ experienced difficulty with PA in those with severe COPD.

Iatrogenic Tracheal Rupture After Successful LVAD-Explantation

<h3>Introduction</h3> Cardiac recovery followed by LVAD-explantation is rare and happens only in 1-2% of the cases. Tracheal rupture during tracheotomy is an even more rare but dreaded complication. <h3>Case Report</h3> We report the case of a 60 year old female patient who had received LVAD therapy (HeartWare) six years ago for DCM caused by myocarditis. She had an uncomplicated course for four years, had one medically treated episode of systemic infection after five years and recently sepsis together with minor cerebral bleeding. After recovery, a CT-scan showed infection of the LVAD including the outflow graft. As echocardiography and right heart catheterization revealed sufficiently recovered cardiac function, the decision for LVAD-explantation was made. The device was successfully explanted via a median re-sternotomy and the complete outflow graft was removed. The patient was stable and extubated on the 1. POD, but needed to be re-intubated on the 4. POD due to pneumonia. As prolonged weaning from the respirator was expected, the patient underwent a tracheotomy. Shortly after, she developed a severe emphysema, could not be sufficiently ventilated and received an emergency implantation of a VV-ECMO. Bronchoscopy showed a large laceration of the back wall of the trachea. This was repaired surgically by direct suture and two days later a re-operation to cover the tracheal laceration with an intercostal muscle flap was required. After this, the patient developed recurrent bleedings with hemothorax and the need for multiple re-thoracotomies. The patient was on VV-ECMO for two weeks without ventilation or blockage of the tube-cuff to allow the trachea to heal. After bronchoscopic confirmation of good tracheal healing, careful ventilation was initiated. The pulmonary function recovered and the ECMO could be explanted after 36 days. Further along the patient was discharged to a pulmonary weaning clinic. She further recovered and is currently in good shape with NYHA class I-II. Interestingly, during the course of this dramatic complication, the patient was always in good cardiac function without any need of inotropic support. <h3>Summary</h3> After complete cardiac recovery and successful LVAD-explantation even a close to fatal complication like a tracheal rupture can be survived with good clinical outcome. Avoiding mechanical stress to the lacerated trachea under VV-ECMO might be a promising strategy.

Association of air pollution exposure with exercise-induced oxygen desaturation in COPD

BackgroundThere is a link between exposure to air pollution and the increased prevalence of chronic obstructive pulmonary disease (COPD) and declining pulmonary function, but the association with O2 desaturation during exercise in COPD patients with emphysema is unclear. Our aims were to estimate the prevalence of O2 desaturation during exercise in patients with COPD, and determine the association of exposure to air pollution with exercise-induced desaturation (EID), the degree of emphysema, and dynamic hyperinflation (DH).MethodsWe assessed the effects of 10-year prior to the HRCT assessment and 7 days prior to the six-minute walking test exposure to particulate matter with an aerodynamic diameter of < 10 µm (PM10) or of < 2.5 µM (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in patients with emphysema in this retrospective cohort study. EID was defined as a nadir standard pulse oximetry (SpO2) level of < 90% or a delta (△)SpO2 level of ≥ 4%. Ambient air pollutant (PM2.5, PM10, O3, and NO2) data were obtained from Taiwan Environmental Protection Administration (EPA) air-monitoring stations, usually within 10 km to each participant’s home address.ResultsWe recruited 141 subjects with emphysema. 41.1% of patients with emphysema exhibited EID, and patients with EID had more dyspnea, worse lung function, more severe emphysema, more frequent acute exacerbations, managed a shorter walking distance, had DH, and greater long-term exposure to air pollution than those without EID. We observed that levels of 10-year concentrations of PM10, PM2.5, and NO2 were significantly associated with EID, PM10 and PM2.5 were associated with the severity of emphysema, and associated with DH in patients with emphysema. In contrast, short-term exposure did not have any effect on patients.ConclusionLong-term exposure to ambient PM10, PM2.5 and NO2, but not O3, was associated with EID.

Robotic Surgery and Adjunctive Technology: Stretching the Limits of What Is Possible

Chronic obstructive pulmonary disease is the fourth leading cause of death in the world and is a significant cause of mortality and morbidity. Although medical management is the standard of care, as the symptoms progress and lung function declines, nonmedical options become available to patients. Lung volume reduction surgery has been a well-established surgery for the treatment of severe emphysema since the National Emphysema Treatment Trial in 2003 showed a survival advantage for patients with upper lobe emphysema and low baseline exercise capacity. 1 Mannino D.M. Kiriz V.A. Changing the burden of COPD mortality. Int J Chron Obstruct Pulmon Dis. 2006; 1: 219-233 PubMed Google Scholar For patients without upper lobe emphysema, alternative modalities have been investigated to improve functional status. Endoscopic lung volume reduction is an emerging nonsurgical strategy to help bridge the gap between optimal medical management and surgery. In patients with severe emphysema, results from the Improving Patient Outcomes by Selective Implantation of the Zephyr EBV (IMPACT) trial and the Pulmonx Endobronchial Valves Used in Treatment of Emphysema (LIBERATE) study have shown excellent improvements in patient’s lung function, exercise capacity, and quality of life over medical therapy. 2 Fishman A. Martinez F. Naunheim K. et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003; 348: 2059-2073 Crossref PubMed Scopus (1656) Google Scholar ,3 Criner G.J. Sue R. Wright S. et al. A multicenter randomized controlled trial of Zephyr endobronchial valve treatment in heterogeneous emphysema (LIBERATE). Am J Respir Crit Care Med. 2018; 198: 1151-1164 Crossref PubMed Scopus (160) Google Scholar Robotic Lung Volume Reduction Surgery With Extracorporeal Membrane OxygenationThe Annals of Thoracic SurgeryVol. 114Issue 5PreviewLobectomy for consolidation of failed endoscopic lung volume reduction for emphysema has been reported in selected patients with favorable results but with considerable morbidity. The challenging issues in such patients are frailty caused by severe emphysema itself, poor tolerance to single-lung ventilation, target lobe hyperinflation, and inability to use gas inflation for the minimally invasive resection. Careful planning, including use of a robotic platform and extracorporeal membrane oxygenation support, can circumvent such difficulties and ensure a safe, minimally invasive resection in the high-risk emphysematous patient. Full-Text PDF

Bilateral endobronchial valves treatment for severe emphysema.

Bilateral endobronchial valves treatment can lead to additional significant benefits in patients who respond to the first procedure and have a clear target lobe on both lungs but increases the rate of complications https://bit.ly/3J0mZ8h

Short-term intermittent cigarette smoke exposure enhances alveolar type 2 cell stemness via fatty acid oxidation

BackgroundCigarette smoke (CS) is associated with chronic obstructive pulmonary disease (COPD) and cancer. However, the underlying pathological mechanisms are not well understood. We recently reported that mice exposed to long-term intermittent CS for 3 months developed more severe emphysema and higher incidence of adenocarcinoma than mice exposed to long-term continuous CS for 3 months and long-term continuous CS exposure activated alveolar stem cell proliferation. However, the influence of variations in the CS exposure pattern in alveolar stem cell in unknown. Here, we exposed mice to 3 weeks of continuous or intermittent CS to identify whether different CS exposure patterns would result in differential effects on stem cells and the mechanisms underlying these potential differences.MethodsFemale mice expressing GFP in alveolar type 2 (AT2) cells, which are stem cells of the alveolar compartment, were exposed to mainstream CS via nasal inhalation. AT2 cells were collected based on their GFP expression by flow cytometry and co-cultured with fibroblasts in stem cell 3D organoid/colony-forming assays. We compared gene expression profiles of continuous and intermittent CS-exposed AT2 cells using microarray analysis and performed a functional assessment of a differentially expressed gene to confirm its involvement in the process using activator and inhibitor studies.ResultsAT2 cells sorted from intermittent CS-exposed mice formed significantly more colonies compared to those from continuous CS-exposed mice, and both CS-exposed groups formed significantly more colonies when compared to air-exposed cells. Comparative microarray analysis revealed the upregulation of genes related to fatty acid oxidation (FAO) pathways in AT2 cells from intermittent CS-exposed mice. Treatment of intermittent CS-exposed mice with etomoxir, an inhibitor of the FAO regulator Cpt1a, for 5 weeks resulted in a significant suppression of the efficiency of AT2 cell colony formation. In vitro treatment of naïve AT2 cells with a FAO activator and inhibitor further confirmed the relationship between FAO and AT2 stem cell function.ConclusionsAlveolar stem cell function was more strongly activated by intermittent CS exposure than by continuous CS exposure. We provide evidence that AT2 stem cells respond to intermittent CS exposure by activating stem cell proliferation via the activation of FAO.

Different Smoking Statuses on Survival and Emphysema in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

ObjectiveTo investigate the association between different smoking statuses and survival and emphysema in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).MethodsThis retrospective study included patients admitted from October 2014 to September 2017. Demographic, clinical, laboratory, imaging, impulse oscillometry, and traditional pulmonary function data were collected. The relationship between smoking and EI was analyzed via binary logistic regression after adjusting for other factors. Survival was analyzed using the Kaplan–Meier method and the log rank test.ResultsThe patients with AECOPD (357 cases) were identified (and stratified into three groups: never smoked (NS; n=83), former smokers (FS, n=118), and current smokers (CS; n=156). Compared with CS, NS were older and predominantly female. No differences were observed in respiratory symptoms and acute exacerbation between CS and NS. NS had higher resistance and reaction in the central and peripheral airways, while CS exhibited more severe diffuse dysfunction. CS demonstrated more severe and extensive emphysema. Smoking was an independent risk factor for emphysema after adjusting for age, forced expiratory volume in the first second over predicted value, BMI, leukocyte count, and carbon monoxide transfer coefficient. No difference in 5-year survival rates between NS and CS was established.ConclusionCS has the worst pulmonary function, suggesting a more important destruction of the lung parenchyma, while AECOPD without smoking risk factors mostly affects the airways. Impulse oscillometry can be used for imaging airway-dominant AECOPD. There was no difference in the 5-year survival rate.

Fatal non-traumatic gas gangrene caused by Clostridium perfringens type A in a Siberian Husky dog.

An 8-y-old, castrated male Siberian Husky dog was admitted to an emergency clinic with acute collapse and severe swelling of both forelimbs, ventral thorax, and axillary region. The clinical assessment, with laboratory tests and radiologic investigation, confirmed severe subcutaneous emphysema and multi-organ failure. The animal died while receiving emergency treatment. On postmortem examination, Clostridium perfringens was isolated from the subcutaneous fluid and the effusion from the thoracic and abdominal cavities. Relevant histopathology findings included subcutaneous emphysema and multi-organ perivascular and intravascular, intralesional myriad 0.5-3-µm gram-positive rod bacteria, with no associated inflammation. Whole-genome sequencing and phylogenetic analysis identified C. perfringens type A. Virulence genes detected included cpa (alpha toxin), cadA (v-toxin), colA (collagenase A), nagH (hyaluronidase), nanH, nanI, nanJ (sialidases), and pfoa (perfringolysin). These virulence genes have previously been reported to act synergistically with alpha toxin in C. perfringens-mediated gas gangrene.

Quantitative assessment the longitudinal changes of pulmonary vascular counts in chronic obstructive pulmonary disease

BackgroundChest computed tomography (CT) is a widely used method to assess morphological and dynamic abnormalities in chronic obstructive pulmonary disease (COPD). The small pulmonary vascular cross-section (CSA), quantitatively extracted from volumetric CT, is a reliable indicator for predicting pulmonary vascular changes. CSA is associated with the severity of symptoms, pulmonary function tests (PFT) and emphysema and in COPD patients the severity increases over time. We analyzed the correlation longitudinal changes in pulmonary vascular parameters with clinical parameters in COPD patients.Materials and methodsA total of 288 subjects with COPD were investigated during follow up period up to 6 years. CT images were classified into five subtypes from normal to severe emphysema according to percentage of low-attenuation areas less than -950 and -856 Hounsfield units (HU) on inspiratory and expiratory CT (LAA-950, LAA-856exp). Total number of vessels (Ntotal) and total number of vessels with area less than 5 mm2 (N<5 mm) per 1 cm2 of lung surface area (LSA) were measured at 6 mm from the pleural surface.ResultsNtotal/LSA and N<5 mm/LSA changed from 1.16 ± 0.27 to 0.87 ± 0.2 and from 1.02 ± 0.22 to 0.78 ± 0.22, respectively, during Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage progression. Both parameters changed from normal to severe emphysema according to CT subtype from 1.39 ± 0.21 to 0.74 ± 0.17 and from 1.18 ± 0.19 to 0.67 ± 0.15, respectively. LAA-950 and LAA-856exp were negatively correlated with Ntotal/LSA (r = − 0.738, − 0.529) and N<5 mm /LSA (r = − 0.729, -− .497). On the other hand, pulmonary function test (PFT) results showed a weak correlation with Ntotal/LSA and N<5 mm/LSA (r = 0.205, 0.210). The depth in CT subtypes for longitudinal change both Ntotal/LSA and N<5 mm/LSA was (− 0.032, − 0.023) and (− 0.027) in normal and SAD, respectively.ConclusionsQuantitative computed tomography features faithfully reflected pulmonary vessel alterations, showing in particular that pulmonary vascular alteration started.

Association between plasma sRAGE and emphysema according to the genotypes of AGER gene

BackgroundHigher soluble receptor for advanced glycation end product (sRAGE) levels are considered to be associated with severe emphysema. However, the relationship remains uncertain when the advanced glycation end-product specific receptor (AGER) gene is involved. We aimed to analyse the association between sRAGE levels and emphysema according to the genotypes of rs2070600 in the AGER gene.MethodsWe genotyped rs2070600 and measured the plasma concentration of sRAGE in each participant. Emphysema was quantified based on the chest computed tomography findings. We compared sRAGE levels based on the presence or absence and severity of emphysema in each genotype. Multiple logistic and linear regression models were used for the analyses.ResultsA total of 436 participants were included in the study. Among them, 64.2% had chronic obstructive pulmonary disease and 34.2% had emphysema. Among the CC-genotyped participants, the sRAGE level was significantly higher in participants without emphysema than in those with emphysema (P < 0.001). In addition, sRAGE levels were negatively correlated with emphysema severity in CC-genotyped patients (r = − 0.268 P < 0.001). Multiple regression analysis revealed that sRAGE was an independent protective factor for the presence of emphysema (adjusted odds ratio, 0.24; 95% confidence interval (CI) 0.11–0.51) and severity of emphysema (β = − 3.28, 95% CI − 4.86 to − 1.70) in CC-genotyped participants.ConclusionPlasma sRAGE might be a biomarker with a protective effect on emphysema among CC-genotyped patients of rs2070600 on the AGER gene. This is important in determining the target group for the future prediction and treatment of emphysema.

Organoid-based expansion of patient-derived primary alveolar type 2 cells for establishment of alveolus epithelial Lung-Chip cultures.

Development of effective treatment strategies for lung tissue destruction as seen in emphysema would greatly benefit from representative human in vitro models of the alveolar compartment. Studying how cellular cross talk and/or (altered) biomechanical cues affect alveolar epithelial function could provide new insight for tissue repair strategies. Preclinical models of the alveolus ideally combine human primary patient-derived lung cells with advanced cell culture applications such as breathing-related stretch, to reliably represent the alveolar microenvironment. To test the feasibility of such a model, we isolated primary alveolar type 2 cells (AEC2s) from patient-derived lung tissues including those from patients with severe emphysema, using magnetic bead-based selection of cells expressing the AEC2 marker HTII-280. We obtained pure alveolar feeder-free organoid cultures using a minimally modified commercial medium. This was confirmed by known AEC2 markers as well as by detection of lamellar bodies using electron microscopy. Following (organoid-based) expansion, cells were seeded on both cell culture inserts and the Chip-S1 Organ-Chip that has a flexible polydimethylsiloxane (PDMS) membrane enabling the application of dynamic stretch. AEC2s cultured for 7 days on inserts or the chip maintained expression of HTII-280, prosurfactant protein C (SP-C), SP-A and SP-B, and zonula occludens-1 (ZO-1) also in the presence of stretch. AEC2s cultured on the chip showed lower expression levels of epithelial-mesenchymal transition-related vimentin expression compared with static cultures on inserts. The combination of a straightforward culture method of patient-derived AEC2s and their application in microfluidic chip cultures supports successful development of more representative human preclinical models of the (diseased) alveolar compartment.

Physical and mental health profile of patients with the early-onset severe COPD phenotype: A cross-sectional analysis

Patients with early-onset severe COPD are often female and characterized by severe emphysema. Extrapulmonary disease manifestations have not yet been investigated in this clinical phenotype. Therefore, this study aimed to study the physical and mental health profile of patients with early-onset severe COPD. This is a cross-sectional analysis including 1058 patients with COPD who were referred for pulmonary rehabilitation between July 2013 and August 2018. Based on a forced expiratory volume in 1s (FEV1) <50%predicted and age <55 years, 78 patients were identified having early-onset severe COPD. Using propensity score matching, these patients were matched to 54 early-onset mild-to-moderate, 158 older severe and 103 older mild-to-moderate COPD patients based on FEV1%predicted, age and gender. An extensive panel of pulmonary and extrapulmonary disease markers (i.e. body composition, physical performance and mental health) was compared between these groups. Pulmonary manifestations as well as physical and mental health were similar in patients with early-onset severe COPD compared to older severe patients, despite a mean age difference of 15.8 years. Remarkably, a high prevalence of depression was observed in early-onset severe COPD which was significantly higher compared to older severe patients (51.9 vs 32.7%, p=0.029). In line with a large difference in FEV1 (33.9 (25.1-41.5) vs 71.8 (61.3-85.4), p<0.001), patients with early-onset severe COPD had lower exercise performance, indicated by a lower 6-min walking distance and peak work rate (mean difference 71.1m, p=0.001, and 25.9%predicted, p<0.001, respectively), compared to patients with early-onset mild-to-moderate COPD. Interestingly, body composition and isokinetic muscle strength were not different between these comparable age groups. Pulmonary and physical health limitations are generally comparable between younger and older patients with severe airflow limitation, while more younger patients might have mental problems. These data suggest the need for early identification of subjects at risk for early-onset severe COPD.

Simple micro-drainage system for palliation of severe subcutaneous emphysema.

Subcutaneous emphysema (SE) occurs when air enters the tissues under the skin and passes into the soft tissues. We demonstrated a simple, minimally invasive technique for treating extensive SE, using a readily available infant nasogastric tube, in a mechanically ventilated patient.

Early Spirometry Following Bronchoscopic Lung Volume Reduction with Endobronchial Valves.

Bronchoscopic lung volume reduction (BLVR) by endobronchial valve (EBV) implantation has been shown to improve dyspnea, pulmonary function, exercise capacity, and quality of life in highly selected patients with severe emphysema and hyperinflation. The most frequent adverse event is a pneumothorax (PTX), occurring in approximately one-fifth of the cases due to intrathoracic volume shifts. The majority of these incidents are observed within 48 h post-procedure. However, the delayed occurrence of PTX after hospital discharge is a matter of concern. There is currently no approved concept for its prevention. Particularly, it is unknown whether and when respiratory manoeuvers such as spirometry post EBV treatment are feasible and safe. As per standard operating procedure at the University Hospital Zurich, early spirometry is scheduled after BLVR and prior to the discharge of the patient in order to monitor treatment success. The aim of our retrospective study was to investigate the feasibility and safety of early spirometry. In addition, we hypothesized that early spirometry could be useful to identify patients at risk for late PTX, which may occur after hospital discharge. All patients who underwent BLVR using EBVs between January 2018 and January 2020 at our hospital were enrolled in this study. After excluding 16 patients diagnosed post-procedure with PTX and four patients for other reasons, early spirometry was performed in 61 cases. There was neither a clinically relevant PTX during or after early spirometry nor a late PTX following hospital discharge. In conclusion, we found early spirometry, conducted not sooner than three days following EBV treatment, to be feasible and safe. Furthermore, early spirometry seems to be a useful predictor for successful BLVR, and it may help to decide whether a patient can be discharged. Given the small sample size and the retrospective design of our study, a prospective study that includes routine chest imaging after early spirometry to definitively exclude PTX is needed to recommend early spirometry as part of the standard protocol following EBV treatment.