Bronchoscopic Measurement of Collateral Ventilation: State of the Art

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 (R) 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 (R) procedure and interpretation of Chartis (R) phenotypes. As a main tool in the assessment of CV and being a safe procedure, the Chartis (R) 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

Impact of Ventilation Modes on Bronchoscopic Chartis Assessment Outcome in Candidates for Endobronchial Valve Treatment

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

Endoscopic Lung Volume Reduction with One-Way Valves in Patients with Severe Chronic Obstructive Pulmonary Disease with Hypercapnia

Background: Robust clinical evidence on the efficacy and safety of endoscopic lung volume reduction (ELVR) with one-way valves in patients with severe lung emphysema with chronic hypercapnic respiratory failure is lacking. Objective: The aim of this study was to compare patient characteristics, clinical outcome measures, and incidences of adverse events between patients with severe COPD undergoing ELVR with one-way valves and with either a partial pressure of carbon dioxide (pCO(2)) of 45 mm Hg. Methods: This was a multicentre prospective study of patients with severe lung disease who were evaluated based on lung function, exercise capacity (6-min walk test [6-MWT]), and quality-of-life tests. Results: Patients with pCO(2) 45 mm Hg (n = 40) showed similar baseline characteristics. Patients with pCO(2) 45 mm Hg had significant improvements in RV only (p < 0.05). There was a significant decrease in pCO(2) between baseline and follow-up in hypercapnic patients, relative to the decrease in patients with pCO(2) <= 45 mm Hg (p = 0.008). Patients who were more hypercapnic at baseline showed a greater reduction in pCO(2) after valve placement (r = -0.38, p < 0.001). Pneumothorax was the most common adverse event in both groups. Conclusions: ELVR with one-way valves seems clinically beneficial with a remarkably good safety profile for patients with chronic hypercapnic respiratory failure

Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe COPD (AIRFLOW):A Multicenter Randomized Controlled Trial

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Two-Year Outcomes for the Double-Blind, Randomized, Sham-Controlled Study of Targeted Lung Denervation in Patients with Moderate to Severe COPD:AIRFLOW-2

Purpose: COPD exacerbations are associated with worsening clinical outcomes and increased healthcare costs, despite use of optimal medical therapy. A novel bronchoscopic therapy, targeted lung denervation (TLD), which disrupts parasympathetic pulmonary innervation of the lung, has been developed to reduce clinical consequences of cholinergic hyperactivity and its impact on COPD exacerbations. The AIRFLOW-2 study assessed the durability of safety and efficacy of TLD additive to optimal drug therapy compared to sham bronchoscopy and optimal drug therapy alone in subjects with moderate-to-severe, symptomatic COPD two years post randomization. Patients and Methods: TLD was performed in COPD patients (FEV1 30-60% predicted, CAT≥10 or mMRC≥2) in a 1:1 randomized, sham-controlled, double-blinded multicenter study (AIRFLOW-2) using a novel lung denervation system (Nuvaira, Inc., USA). Subjects remained blinded until their 12.5-month follow-up visit when control subjects were offered the opportunity to undergo TLD. A time-to-first-event analysis on moderate and severe and severe exacerbations of COPD was performed. Results: Eighty-two subjects (FEV1 41.6±7.4% predicted, 50.0% male, age 63.7±6.8 yrs, 24% with prior year respiratory hospitalization) were randomized. Time-to-first severe COPD exacerbation was significantly lengthened in the TLD arm (p=0.04, HR=0.38) at 2 years post-TLD therapy and trended towards similar attenuation for moderate and severe COPD exacerbations (p=0.18, HR=0.71). No significant changes in lung function or SGRQ-C were found 2 years post randomization between groups. Conclusion: In a randomized trial, TLD demonstrated a durable effect of significantly lower risk of severe AECOPD over 2 years. Further, lung function and quality of life remained stable following TLD. Clinical Trial Registration: NCT02058459

CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding: Funded by Roche Sequencing Solutions, Inc

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Endobronchial valve treatment in patients with severe lung emphysema

Die chronisch obstruktive Lungenerkrankung (COPD) ist nach der Weltgesundheitsorganisation (WHO) der 4. häufigste Sterbegrund unter allen Erkrankungen weltweit. Hauptursache der COPD ist mit >90 % der Fälle der chronische Nikotinkonsum, so dass die wirkungsvollste Therapie ein dauerhafter und konsequenter Nikotinverzicht darstellt. Ein weiterer neuartiger Therapieansatz ist die endoskopische Lungenvolumenreduktion (ELVR), die sich aus der chirurgischen Lungenvolumenreduktion (LVRS) mit dem Ziel der Verkleinerung von stark überblähten Lungenlappen entwickelt hat, ohne dass Patienten dem hohen Risiko einer schweren perioperativen Komplikation ausgesetzt sind. Endobronchiale Ventile haben sich in den letzten Jahren aufgrund der Reversibilität und der besseren wissenschaftlichen Datenlage im klinischen Alltag vor den anderen Verfahren der ELVR durchgesetzt. Studien haben gezeigt, dass Patienten mit intakter Fissur im Behandlungslappen (CVneg) und einem heterogenen Lungenemphysem besonders gut von dem Eingriff profitieren, das Ansprechen jedoch sehr variabel ist. Daher wurde nach weiteren Kriterien gesucht, mit denen der Therapierfolg nach Ventilimplantation besser vorhergesagt werden kann. Außerdem stellt ein wesentlicher Nachteil der Ventiltherapie die hohe Rate an Pneumothoraxen dar, so dass untersucht wurde, ob mit einem modifizierten Management nach Ventileinlage die Pneumothoraxrate vermindert werden kann. 406 Chartis- Messungen wurden retrospektiv aufgearbeitet und in vier Phänotypen anhand neuer Chartis-Kriterien unterteilt. Patienten, dessen Ziellappen anhand dieser Kriterien als CVneg eingestuft wurde, zeigten nach Ventilimplantation eine signifikante Lungenvolumenreduktion und eine Verbesserung der Lungenfunktion, Lebensqualität und der Belastbarkeit. Der Vorhersagewert für eine erfolgreiche Behandlung ließ sich in einer anderen Studie zusätzlich verbessern, wenn eine Software gestützte Fissur-Analyse und eine Chartis-Messung kombiniert angewendet werden. Im weiteren ergaben Korrelationsanalysen, dass der Anstieg der forcierten expiratorischen Einsekundenkapazität (FEV1) nach Ventiltherapie mit der Heterogenität des Lungenemphysems zusammenhängt und die Verbesserung des 6-Minuten Gehtestes (6MGT) durch die Perfusion des ipsilateralen Nachbarlappens vom Ziellappen bestimmt wird. In einer prospektiven multizentrischen Studie konnte auch gezeigt werden, dass Patienten mit einem homogenen Lungenemphysem dennoch signifikant in der Lungenfunktion, Belastbarkeit und der Lebensqualität profitieren, so dass die endobronchiale Ventiltherapie Patienten mit einem homogenen Lungenemphysem nicht vorenthalten bleiben sollte. Die Pneumothoraxrate ließ sich durch strikte Bettruhe nach Ventilimplantation und bedarfsweiser Gabe von Hustenunterdrückern senken ohne dass dadurch das Outcome negativ beeinflusst wird. Zusammengefasst zeigt der in der vorliegenden Arbeit gegebene Überblick, dass Patienten mit einer fortgeschrittenen COPD von einer ELVR profitieren, indem Selektionskriterien optimiert und Komplikationen reduziert werden konnten. Einige Studien müssen in prospektiven Studien noch validiert werden.According to the World Health Organization (WHO) chronic obstructive pulmonary disease (COPD) became the 4th most leading cause of death among all diseases worldwide. Long-term cigarette smoking is the main cause of COPD responsible for over 90% of all cases, that permanent smoking cessation remains the most effective therapy. Another new treatment option includes endoscopic lung volume reduction (ELVR), which has developed from surgical lung volume reduction (LVRS) with the goal of reducing hyperinflated lobes without exposing patients to the high risk of severe perioperative complication. Endobronchial valves have been the preferred approach in the clinical setting among other options of ELVR technique because of its reversibility and better scientific evidence. Studies have shown that patients with complete fissures in the target lobe (CVneg) and heterogeneous lung emphysema respond particularly well from the procedure, although results are highly variable. Therefore, other criteria are needed to predict better treatment response after valve implantation. In addition, a major disadvantage of valve therapy is the high rate of pneumothoraces. It was evaluated whether pneumothorax rate may be reduced with modified post-operative medical management. 406 Chartis measurements were retrospectively analyzed and categorized into four phenotypes using new Chartis criteria. Patients whose target lobe was rated CVneg according to the Chartis criteria demonstrated significant lung volume reduction, improvement in pulmonary function test, quality of life, and exercise capacity after valve implantation. The predictive value for successful treatment could be further improved in another study when the combination of a semiautomated fissure analysis and Chartis assessment was used. Furthermore, correlation analyzes showed that the increase in forced expiratory capacity (FEV1) after valve treatment and the improvement in 6-minute walking test (6MWT) was correlated to perfusion of the ipsilateral adjacent lobe from the target lobe. In a prospective multicenter study, it was also shown that patients with homogeneous lung emphysema demonstrated an improvement in pulmonary function test, exercise capacity and quality of life, that valve therapy should not be withheld from patients with homogeneous lung emphysema. The incidence of pneumothorax was reduced by strict bed-rest after valve implantation and cough suppression if needed without affecting clinical outcome. In summary, this work shows that patients with severe COPD benefit from ELVR by optimizing selection criteria and reducing complications. Some studies have yet to be proven in prospective studies

NT-proBNP is not elevated in patients with obstructive sleep apnoea

SummaryBackgroundN-terminal pro-brain natriuretic peptide (NT-ProBNP) has emerged as an important marker of cardiac stress and may reflect the severity of underlying cardiac dysfunction, which is thought to be associated with obstructive sleep apnoea syndrome (OSAS).MethodsThis study evaluated the plasma concentration of NT-ProBNP in 60 consecutive patients (median age 55.7 years, median body mass index (BMI) 31.8) who were referred to a sleep laboratory with a suspicion of OSAS. Each subject underwent measurement of morning NT-ProBNP plasma levels, polysomnography and echocardiography. Patients were treated with nasal continuous or bilevel positive airway pressure ventilation (nCPAP/BIPAP) or without mechanical respiratory support, depending on clinical symptoms and results of polysomnography. Three months after treatment of OSAS 28 of the patients were reassessed for re-evaluation of NT-ProBNP and polysomnography.ResultsLow or high levels of NT-proBNP were not associated with AHI and other sleep related indices (p>0.3). There was no correlation between NT-proBNP and AHI or other sleep related indices. In multiple regression analysis, NT-proBNP was significantly correlated with left ventricular ejection fraction, creatinine clearance and the presence of systemic arterial hypertension but not with AHI.ConclusionsOur results show by a robust multiple regression analysis, that NT-pro BNP is not associated with OSAS and NT-pro BNP cannot be used as a sensitive marker for underlying cardiovascular abnormalities in patients with OSAS