Assessment of collateral ventilation with the Chartissystem before endoscopic lung volume reduction with endobronchial valves in advanced COPD with lung emphysema

Hintergrund Die endoskopische Lungenvolumenreduktion durch Ventiltherapie ist eine etablierte Behandlungsoption des fortgeschrittenen Lungenemphysems. Sie führt zu einer Verbesserung der Lungenfunktionsparameter, der Lebensqualität und der körperlichen Belastbarkeit. Entscheidend für ein Therapieansprechen ist der Ausschluss einer Kollateralventilation zwischen dem Ziellappen und dem benachbarten Lungenlappen. In der klinischen Praxis wird die Kollateralventilation (CV) durch eine Chartismessung (Pulmonx, USA) und eine Software gestützte Analyse der Fissurenintegrität (StratX, Pulmonx, USA) anhand von Computertomographien des Thorax analysiert. Die Auswirkungen der Beatmung auf das Chartismessergebnis sind ungeklärt. Methoden Es wurden Patient*innen mit einer Chartismessung in Spontanatmung und in Hochfrequenz Jet Ventilation sowie einer Analyse der Fissurenintegrität in die retrospektive, monozentrische Studie eingeschlossen. Die Chartismessungen zur Bestimmung einer Kollateralventilation erfolgten zuerst in Spontanatmung und anschließend in Hochfrequenz Jet Ventilation. Ergebnisse Insgesamt wurden 497 Chartismessungen in Spontanatmung und Hochfrequenz Jet Ventilation von 102 Patient*innen analysiert. Die Chartis Phänotypen (CV positiv, CV negativ, Low Plateau und Low Flow) waren in beiden Beatmungsmodi gleich. In beiden Beat- mungsmodi hatten die Chartismessergebnisse eine hohe Übereinstimmung bei allen untersuchten Fissuren. Auch die Verteilung der Chartis Phänotypen in Spontanatmung und Hochfrequenz Jet Ventilation war bei den untersuchten Fissuren ähnlich. Receiver Operating Curve (ROC) Analysen anhand der Fissurenintegrität konnten unter beiden Beatmungsmodi ähnlich präzise alle konklusiven Chartis Phänotypen (CV positiv und CV negativ) unabhängig vom Beatmungsmodus vorhersagen. Schlussfolgerung Die Chartismessung in Spontanatmung und Hochfrequenz Jet Ventilation hatte vergleichbare Ergebnisse in der Bewertung der Kollateralventilation beim fortgeschrittenen Lungenemphysem.Introduction Endoscopic lung volume reduction with valves is an accepted treatment option for advanced lung emphysema. It improves lung function, life quality and exercise capacity. The principal predictor for treatment response is the exclusion of collateral ventilation between the target lobe and its adjacent lobe. In clinical routine collateral ventilation is assessed using a combination of Chartis assessment system (Pulmonx, USA) and a soft ware-based fissure integrity analysis (StratX, Pulmonx, USA) of computed tomography scans of the lung. The impact of the ventilation mode on the Chartis assessment during bronchoscopy has never been investigated. Methods Patients with Chartis assessment in spontaneous breathing and high frequency jet ventilation and a fissure integrity analysis were included in this retrospective, monocentric study. To evaluate collateral ventilation (CV) status, a bronchoscopy with Chartis assessment was first performed in spontaneous breathing and subsequently in high frequency jet ventilation. Results In total, 497 Chartis assessments in spontaneous and high frequency jet ventilation of 102 patients were studied. Chartis phenotypes (CV positive, CV negative, Low Plateau and Low Flow) appeared in both ventilation modes. Chartis assessments in both ventilation modes had high concordance rates in the analysis of collateral ventilation status. The appearance of Chartis phenotypes was similar in spontaneous breathing and high frequency jet ventilation for all fissures. There was a similar distribution of Chartis pheno types in both ventilation modes among all analyzed fissures. Receiver Operating Curve (ROC) for fissure integrity were equally precise in predicting conclusive Chartis outcome (CV positive, CV negative) in both ventilation modes. Discussion Similar rates for detection of collateral ventilation during Chartis assessments in spontaneous breathing and high frequency jet ventilation were found

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

An Integrative Approach of the Fissure Completeness Score and Chartis Assessment in Endobronchial Valve Treatment for Emphysema

Purpose: Lung volume reduction using one-way endobronchial valves is a bronchoscopic treatment for patients with severe emphysema without collateral ventilation between the treatment target lobe and the ipsilateral lobe(s). CT-scan fissure analysis is often used as a surrogate to predict the absence of collateral ventilation. We aimed to evaluate the predictive value of the fissure completeness score (FCS) compared to the functional Chartis measurement of collateral ventilation and to provide cut-off values of the FCS in patient selection. Patients and Methods: Multicenter study in patients eligible for treatment with one-way valves. The FCS was calculated by quantitative CT analysis (Thirona, the Netherlands) and compared to status of interlobar collateral ventilation measured with Chartis system (PulmonX, USA). Thresholds were calculated for the predictive values of the presence of collateral ventilation. Results: An FCS >95% of the left major fissure had a positive predictive value (PPV) of 91%, with 1 in 11 fissures demonstrating collateral ventilation with Chartis measurement, whereas an FCS of ≤80% had a negative predictive value (NPV) of 100% for the presence of collateral ventilation. For the right major fissure, the NPV was 100% for an FCS ≤90%, but 69.7% for the right upper lobe fissure. Conclusion: Quantitative CT analysis is recommended in all patients evaluated for endo-bronchial valves. Patients with incomplete fissures (left major fissure: FCS 95%

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

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

Male carriers of HLA-C*04:01 have increased risk of cardiac injury in COVID-19

Identification of factors that lead to the severe clinical course of COVID-19 is crucial for timely allocation of resources. The purpose of this study was to evaluate possible sex differences in cardiac injury associated with HLA-C*04:01. High sensitivity troponin T on admission (hs-TnTa) and maximum high sensitivity troponin T (hs-TnTmax) were used to assess for cardiac injury in patients with COVID-19 (n = 435). We tested for the association of elevated hs-TnT with HLA-C* 04:01 and evaluated for potential sex-specific differences. An association between hs-TnTa and the severity of clinical course was identified. In addition, our study revealed that hs-TnTmax was higher in men who were carriers of HLA-C*04:01 compared to men without the risk allele. Male carriers of HLA-C*04:01 with COVID-19 developed higher hs-TnTmax, suggesting a larger extent of cardiac injury. This association suggests the presence of different pathomechanisms in COVID-19 based on sex

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

BackgroundSince 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.MethodsWe analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n&nbsp;=&nbsp;135), Spain (n&nbsp;=&nbsp;133), Switzerland (n&nbsp;=&nbsp;20) and the United States (n&nbsp;=&nbsp;147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS).FindingsWe 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&nbsp;=&nbsp;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.InterpretationHLA-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.FundingFunded 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 &amp;lt; 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p &amp;lt; 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 &amp;lt; 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