Reexpansion pulmonary edema after treatment of primary spontaneous pneumothorax.

A 24-year-old male patient, without further symptoms or comorbidities presented to the emergency room with acute dyspnea after heavy lifting two days before. On auscultation an attenuated vesicular breath was noticed on the right lung. In the initial chest radiograph a right-sided primary spontaneous pneumothorax with minor mediastinal shift was diagnosed. After insertion of a 12-French chest tube the patient's clinical condition deteriorated. The following chest radiograph and computed tomography of the thorax showed a reexpansion pulmonary edema in the right lung. The patient was admitted to the ICU and supportive treatment was initiated. Pulmonary reexpansion edema after drainage of a pneumothorax is a very rare complication with mortality rates reaching up to 20%. The exact pathophysiology remains unknown. Typical Symptoms include dyspnea, hypotension, and tachycardia. To minimize the risk of a pulmonary reexpansion edema, not more than 1200-1800 ml of air should be drained at once and the drainage should be stopped when the patient starts coughing.

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®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.

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 (pCO2) of ≤45 mm Hg or with pCO2 >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 pCO2 ≤45 mm Hg (n = 157) and pCO2 >45 mm Hg (n = 40) showed similar baseline characteristics. Patients with pCO2 ≤45 mm Hg demonstrated a significant increase in forced expiratory volume in 1 s (p < 0.001), a significant decrease in residual volume (RV) (p < 0.001), and significant improvements in the quality of life and 6-MWT at the 3-month follow-up. Patients with pCO2 >45 mm Hg had significant improvements in RV only (p < 0.05). There was a significant decrease in pCO2 between baseline and follow-up in hypercapnic patients, relative to the decrease in patients with pCO2 ≤45 mm Hg (p = 0.008). Patients who were more hypercapnic at baseline showed a greater reduction in pCO2 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.

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.

Uncapped Metered-Dose Inhalers: A Risk for Foreign Body Aspiration. A Case Report and Review of the Literature.

The risk of foreign body aspiration associated with uncapped handheld metered-dose inhalers (MDIs) is underestimated. We report a case in which a plastic cable clip accidentally lodged in the mouthpiece of an uncapped pressurized MDI was aspirated during its use. A literature search revealed 16 other cases of foreign body aspiration associated with uncapped handheld inhalers, all but one of which were pressurized inhalers. Patients should be informed of the risk of foreign body aspiration associated with uncapped pocket inhalers. The use of an uncuffed armoured tracheal tube with a separate oxygen tubing during flexible bronchoscopy for foreign body removal ensures a safe airway. Foreign bodies that exceed the lumen size of the tracheal tube can be pulled to the distal opening with forceps and removed when the tube is withdrawn.

Impact of Coronavirus Disease 2019 on Hospital Admissions, Health Status, and Behavioral Changes of Patients with COPD.

Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of acquiring severe coronavirus disease 2019 (COVID-19), which is why self-isolation was recommended. However, long periods of social isolation, accompanied by limited access to health care systems, might influence the outcome of patients with severe COPD negatively. Methods: Data from COPD and pneumonia patients at Charité-Universitätsmedizin Berlin and the volume of endoscopic lung volume reduction (ELVR) surgeries from the German Lung Emphysema Registry (Lungenemphysem Register e.V.) were analyzed from pre-pandemic (2012 to 2019) to the pandemic period (2020 and 2021). In addition, 52 patients with COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stage 4 status included in the lung emphysema registry received questionnaires during lockdowns from June 2020 to April 2021. Results: Admissions and ventilation therapies administered to COPD patients significantly decreased during the COVID-19 pandemic. Likewise, there was a reduction in ELVR treatments and follow-ups registered in German emphysema centers. Mortality was slightly higher among patients hospitalized with COPD during the pandemic. Increasing proportions of COPD patients with GOLD stage 3 and GOLD stage 4 status reported behavioral changes and subjective feelings of increasing COPD symptoms the longer the lockdown lasted. However, COPD symptom questionnaires revealed stable COPD symptoms over the pandemic time period. Summary: This study reveals reduced COPD admissions and elective treatment procedures of COPD patients during the pandemic, but a slight increase in mortality among patients hospitalized with COPD, irrespective of COVID-19. Correspondingly, patients with severe COPD reported subjective deterioration of their health status, probably caused by their very strict compliance with lockdown measures.

When Treatment of Pulmonary Emphysema with Endobronchial Valves Did Not Work: Evaluation of Quantitative CT Analysis and Pulmonary Function Tests Before and After Valve Explantation.

Purpose: To investigate changes in quantitative CT analysis (QCT) and pulmonary function tests (PFT) in pulmonary emphysema patients who required premature removal of endobronchial valves (EBV). Patients and Methods: Our hospital's medical records listed 274 patients with high-grade COPD (GOLD stages 3 and 4) and pulmonary emphysema who were treated with EBV to reduce lung volume. Prior to intervention, a complete evaluation was performed that included quantitative computed tomography analysis (QCT) of scans acquired at full inspiration and full expiration, pulmonary function tests (PFT), and paraclinical findings (6-minute walking distance test (6MWDT) and quality of life questionnaires). In 41 of these 274 patients, EBV treatment was unsuccessful and the valves had to be removed for various reasons. A total of 10 of these 41 patients ventured a second attempt at EBV therapy and underwent complete reevaluation. In our retrospective study, results from three time points were compared: Before EBV implantation (BL), after EBV implantation (TP2), and after EBV explantation (TP3). QCT parameters included lung volume, total emphysema score (TES, ie, the emphysema index) and the 15th percentile of lung attenuation (P15) for the whole lung and each lobe separately. Differences in these parameters between inspiration and expiration were calculated (Vol. Diff (%), TES Diff (%), P15 Diff (%)). The results of PFT and further clinical tests were taken from the patient's records. Results: We found persistent therapy effect in the target lobe even after valve explantation together with a compensatory hyperinflation of the rest of the lung. As a result of these two divergent effects, the volume of the total lung remained rather constant. Furthermore, there was a slight deterioration of the emphysema score for the whole lung, whereas the TES of the target lobe persistently improved. Conclusion: Interestingly, we found evidence that, contrary to our expectations, unsuccessful EBV therapy can have a persistent positive effect on target lobe QCT scores.

Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19.

Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to potentially improve future therapies. Disease dynamics can be characterized by deciphering the adaptive immune response. Methods: In this cross-sectional study we analyzed 117 peripheral blood immune repertoires from healthy controls and subjects with mild to severe COVID-19 disease to elucidate the interplay between B and T cells. We used an immune repertoire Primer Extension Target Enrichment method (immunoPETE) to sequence simultaneously human leukocyte antigen (HLA) restricted T cell receptor beta chain (TRB) and unrestricted T cell receptor delta chain (TRD) and immunoglobulin heavy chain (IgH) immune receptor repertoires. The distribution was analyzed of TRB, TRD and IgH clones between healthy and COVID-19 infected subjects. Using McFadden's Adjusted R2 variables were examined for a predictive model. The aim of this study is to analyze the influence of the adaptive immune repertoire on the severity of the disease (value on the World Health Organization Clinical Progression Scale) in COVID-19. Findings: Combining clinical metadata with clonotypes of three immune receptor heavy chains (TRB, TRD, and IgH), we found significant associations between COVID-19 disease severity groups and immune receptor sequences of B and T cell compartments. Logistic regression showed an increase in shared IgH clonal types and decrease of TRD in subjects with severe COVID-19. The probability of finding shared clones of TRD clonal types was highest in healthy subjects (controls). Some specific TRB clones seems to be present in severe COVID-19 (Figure S7b). The most informative models (McFadden´s Adjusted R2=0.141) linked disease severity with immune repertoire measures across all three cell types, as well as receptor-specific cell counts, highlighting the importance of multiple lymphocyte classes in disease progression. Interpretation: Adaptive immune receptor peripheral blood repertoire measures are associated with COVID-19 disease severity. Funding: The study was funded with grants from the Berlin Institute of Health (BIH).

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 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). 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.

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 endobronchial valves. Patients with incomplete fissures (left major fissure: FCS <80%; right major fissure: <90%) can be excluded from Chartis measurement and endobronchial valve treatment. In patients with more complete fissures, the FCS is not specific enough for endobronchial valve treatment decisions. In this case, additional Chartis measurements are always recommended in the right lung. For the left lung, Chartis assessments may be omitted if the FCS is >95%.

Sea buckthorn extract in the treatment of psoriasis.

Psoriasis is one of the most common chronic dermatological conditions, with a strong impact on patients' quality of life. Currently, psoriasis benefits from conventional therapy with a high rate of adverse effects and an increase in non-compliance and self-medication of patients. As such, there is a need to pinpoint low-adverse effects and accessible remedies for this condition. Our single-blind, placebo-controlled study assessed the effect of sea buckthorn extract on psoriasis lesions in previously untreated patients. Our results showed an improvement in Psoriasis Area Severity Index (PASI) scores and in Dermatology Life Quality Index (DLQI) scores when compared to the baseline values, as well as at the 4- and 8-week time marks for the lesions treated with sea buckthorn extract. By contrast, the measurements for the placebo treated lesions showed no alteration at the 4-week mark, and significant worsening at the end of the trial. These findings provide a solid, optimistic base for the in-depth research of sea buckthorn as an adjuvant or a component in psoriasis care protocols.