Cost-effectiveness analysis of surgical lung volume reduction compared with endobronchial valve treatment in patients with severe emphysema

BACKGROUND Lung volume reduction, either by surgery or bronchoscopically by endobronchial valve treatment have been shown to be a cost-effective alternative compared with conservative therapy. However, there is no comparative analysis of lung volume reduction by surgery and bronchoscopic lung volume reduction using endobronchial valves. OBJECTIVES The aim of this retrospective study was to provide a cost-effectiveness analysis of lung volume reduction by surgery compared with bronchoscopic lung volume reduction using endobronchial valves. METHODS The effectiveness of lung volume reduction was assessed using forced expiratory volume in the first second (FEV1), residual volume (RV) and 6-minute walking distance (6MWD), measured at baseline and at 4 to 12 weeks. Cost unit accounting derived from SwissDRG was used as a surrogate of the costs from the payer's perspective. RESULTS In total, 67 patients (37 men and 30 women) with a mean age of 68.3 ± 7.4 years were included. Both clinical effectiveness and costs were comparable between surgical and bronchoscopic lung reduction. The incremental cost-effectiveness ratios (ICERs) for bronchoscopic compared with lung volume reduction by surgery for FEV1, RV and 6MWD were -101, 4 and 58, respectively. For RV and 6MWD, it could be shown that endobronchial valve treatment is justified as a probably cost-effective alternative to lung volume reduction by surgery. Endobronchial valve treatment resulted in an improvement of 0.25 quality-adjusted life years (QALYs) and an ICER of € 7657 per QALY gained. CONCLUSION A robust statement on the superiority of one of the two procedures in terms of cost-effectiveness cannot be made from the present study. Therefore, the study is not suitable for resource allocation. Two upcoming trials comparing lung volume reduction surgery and endobronchial valve treatment may be able to answer this question

Influence of mycophenolate mofetil dosage and plasma levels on the occurrence of chronic lung allograft dysfunction in lung transplants: a retrospective cohort analysis

INTRODUCTION: Development of chronic lung allograft dysfunction is a limiting factor for post-lung transplant survival. We evaluated whether the dose of the immunosuppressant mycophenolate mofetil or plasma concentrations of the active metabolite mycophenolic acid affect the development of chronic lung allograft dysfunction. METHODS: In this retrospective cohort study we recruited 71 patients with a lung transplant between 2010 and 2014 which survived the first year after transplantation up to 1 July 2021. An event-time-analytical Cox proportional-hazards regression model with time-varying-covariates (18,431 measurements for MPA, mycophenolate mofetil dosage, lymphocytes) was used to predict chronic lung allograft dysfunction, with adjustment for sociodemographic factors and lung function at baseline. RESULTS: 37 patients did not develop chronic lung allograft dysfunction (age 41.3 ± 15.6 years, baseline FEV1 95.5 ± 19.1% predicted) and 34 patients developed chronic lung allograft dysfunction (age 50.9 ± 13.3 years, baseline FEV1 102.2 ± 25.4% predicted). Mean mycophenolic acid did not differ significantly between the groups (2.8 ± 1.7 and 3.0 ± 2.3 mg/l; p = 0.724). In the first 4 post-transplant years the death rate was 25%. A total of 50% of the patients died by the ninth post-transplant year. There was a dose-effect relationship between mycophenolate mofetil dosage, mycophenolic acid (r2 = 0.02, p <0.001), as well as lymphocyte levels (r2 = –0.007, p <0.001), but only the traditional risk factor age predicted chronic lung allograft dysfunction. Continuously measured mycophenolic acid did not predict chronic lung allograft dysfunction (hazard ratio 0.98, 95% confidence interval 0.90–1.06, p = 0.64 over a period of 382.97 patient-years). CONCLUSION: Mycophenolate mofetil dosage and mycophenolic acid were not associated with chronic lung allograft dysfunction development. Thus, the mycophenolate mofetil dose or mycophenolic acid plasma concentration are not a primary factor related to organ rejection, but chronic lung allograft dysfunction may be influenced by other components of immunosuppression or other factors

Lung Ultrasound for the Exclusion of Pneumothorax after Interventional Bronchoscopies—A Retrospective Study

A chest X-ray (CXR) is recommended after bronchoscopies with an increased risk of pneumothorax (PTX). However, concerns regarding radiation exposure, expenses and staff requirements exist. A lung ultrasound (LUS) is a promising alternative for the detection of PTX, though data are scarce. This study aims to investigate the diagnostic yield of LUS compared to CXR, to exclude PTX after bronchoscopies with increased risk. This retrospective single-centre study included transbronchial forceps biopsies, transbronchial lung cryobiopsies and endobronchial valve treatments. Post-interventional PTX screening consisted of immediate LUS and CXR within two hours. In total, 271 patients were included. Early PTX incidence was 3.3%. Sensitivity, specificity, and the positive and negative predictive values of LUS were 67.7% (95% CI 29.93–92.51%), 99.2% (95% CI 97.27–99.91%), 75.0% (95% CI 41.16–92.79%) and 98.9% (95% CI 97.18–99.54%), respectively. PTX detection by LUS enabled the immediate placement of two pleural drains along with the bronchoscopy. With CXR, three false-positives and one false-negative were observed; the latter evolved into a tension-PTX. LUS correctly diagnosed these cases. Despite low sensitivity, LUS enables early diagnosis of PTX, thus preventing treatment delays. We recommend immediate LUS, in addition to LUS or CXR after two to four hours and monitoring for signs and symptoms. Prospective studies with higher sample sizes are needed

The effect of longitudinal sleep monitoring on clinician agreement in obstructive sleep apnea diagnosis: The ELSA study

There is strong evidence for clinically relevant night‐to‐night variability of respiratory events in patients with suspected obstructive sleep apnea. Sleep experts retrospectively evaluated diagnostic data in 56 patients with suspected obstructive sleep apnea. Experts were blinded to the fact that they were diagnosing the same case twice, once based on a short report of a single in‐laboratory respiratory polygraphy and once with the additional information of 14 nights of pulse oximetry at home. All experts (n = 22) were highly qualified, 13 experts (59.1%) treated > 100 patients with suspected obstructive sleep apnea per year. In 12 patients, the apnea–hypopnea index in the respiratory polygraphy was  100 per year compared with 0–29 patients per year (Coef. [95% confidence interval] −0.63 [−1.22/−0.04] and −0.61 [−1.07/−0.15], respectively). Experts found already a high level of consensus regarding obstructive sleep apnea diagnosis, severity and continuous positive airway pressure recommendation after a single respiratory polygraphy. However, longitudinal sleep monitoring could help increase consensus in selected patients with diagnostic uncertainty

Transbronchial Cryobiopsy Compared to Forceps Biopsy for Diagnosis of Acute Cellular Rejection in Lung Transplants: Analysis of 63 Consecutive Procedures

BACKGROUND Acute cellular rejection (ACR) is a complication after lung transplantation (LTx). The diagnosis of ACR is based on histologic findings using transbronchial forceps biopsy (FB). However, its diagnostic accuracy is limited because of the small biopsy size and crush artifacts. Transbronchial cryobiopsy (CB) provides a larger tissue size compared with FB. METHODS FB and CB were obtained consecutively during the same bronchoscopy (February 2020-April 2021). All biopsies were scored according to the ISHLT criteria by three pathologists. Interobserver agreement was scored by the kappa index. We assessed the severity of bleeding and the presence of pneumothorax. RESULTS In total, 35 lung transplant recipients were included, and 126 CBs and 315 FBs were performed in 63 consecutive bronchoscopies. ACR (A1-A3, minimal-moderate) was detected in 18 cases (28.6%) by CB, whereas ACR was detected in 3 cases (4.8%) by FB. Moderate and severe bleeding complicated FB and CB procedures in 23 cases (36.5%) and 1 case (1.6%), respectively. Pneumothorax occurred in 6.3% of patients. The interobserver agreement was comparable for both CB and FB. CONCLUSIONS CB provided an improved diagnostic yield for ACR diagnosis, leading to reclassification and changes in treatment strategies in 28.6% of cases. Prospective studies should better define the role of CB after LTx

Investigation of in vitro modified human blood monocytes: Characterisation by immunohistochemistry and functional proof of their insulin

Monozyten lassen sich in vitro nicht nur zu Makrophagen und Dendritischen Zellen differenzieren, sondern auch in eine Vielzahl nicht-phagozytierender Zellen. Monozyten scheinen somit über pluripotente Eigenschaften zu verfügen. In dieser Arbeit wurde untersucht, ob sich kultivierte Monozyten tatsächlich in Insulin-exprimierende Zellen differenzieren lassen. Monozyten von gesunden Spendern im Alter zwischen 20 und 26 Jahren wurden untersucht. Die über eine Leukozytenapherese gewonnenen Mono- zyten wurden über Adhärenz angereichert und für sechs Tage in X-Medium mit den Cytokinen M-CSF und IL-3 und für weitere 15 Tage in Y-Medium mit den Cytokinen HGF und EGF inkubiert. Die Zellen wurden immunhistochemisch und funktionell untersucht. Frisch isolierte Blutmonozyten waren vor ihrer Kultivierung negativ für Insulin, C-Peptid und Glukagon. Am 4. Kulturtag wurden Insulin und C-Peptid in den kultivierten Monozyten nachgewiesen. Die Expression von Insulin war jedoch nicht stabil: während am Tag 11 der Anteil Insulin-positiver Zellen bei ca. 80% lag, waren am Tag 14 nur noch ca. 30% der kultivierten Zellen Insulin-positiv. Dies wurde ebenfalls für den Nachweis von C-Peptid beobachtet. Auch die Expression von Glukagon war nicht stabil. Diese Beobachtung wird darauf zurückgeführt, dass sich die Monozyten zu Makrophagen differenzierten und diese eindeutig kein Insulin produzieren. Da Zellen Insulin aufnehmen und speichern können, sollte in dieser Arbeit die Frage geklärt werden, ob immunhistochemisch zu unterscheiden ist, ob Zellen Insulin gebildet (de novo Insulin) oder unspezifisch aufgenommen haben. In dieser Arbeit wurde gezeigt, dass zum eindeutigen Nachweis von de novo Insulin der Nachweis von C-Peptid unbedingt zu fordern ist. Die in dieser Arbeit durchgeführten Experimente mit aufgereinigtem Insulin belegen, dass für aufgenommenes Insulin – im Gegensatz zu de novo Insulin – C-Peptid immun- histochemisch nicht nachzuweisen ist. Das aus in vitro kultivierten Monozyten isolierte Insulin war in diabetischen Mäusen biologisch aktiv, d.h. es senkte den Blutzuckerspiegel kurzfristig. Hierzu wurden geerntete Monozyten der Kulturtage 6-12 im Ultraschallbad aufgeschlossen und der zellfreie Überstand diabetischen Mäusen injiziert. Insgesamt senkten 11 der 31 (35,5%) in dieser Arbeit getesteten Überstände den Blutzuckerspiegel dieser Tiere um mehr als 15%. Bezogen auf die 18 Proben, die einen Effekt zeigten, sind dies sogar 61%. In dieser Arbeit wurde somit erfolgreich gezeigt, dass in vitro modifizierte Monozyten Insulin exprimieren, das den Blutzuckerspiegel diabetischer Mäuse senkt.Monocytes differentiate not only in macrophages and dendritic cells but also in a variety of non-phagocytic cells. Monocytes or a subpopulation of monocytes seem to exhibit pluripotent diversity. In the present study the potential of in vitro cultured monocytes to differentiate into insulin-expressing cells was analysed. Monocytes of healthy human donors between 20 and 26 years old were analysed. They were obtained by leukocyte aphaeresis, enriched by adherence and cultured six days in X-Medium containing MCS-F und IL-3 and a further 15 days in Y-Medium containing HGF and EGF. The cells were characterized by immunohistochemistry and functional assays. Freshly isolated blood monocytes were negative for insulin, C-peptide and glucagon. In contrast, cultured monocytes were positive for insulin and C-peptide, detectable after 4 days in culture. However, the insulin expression was unstable. On day 11 of culture the amount of insulin-positive cells reached a maximum of 80 percent positive, by day 14 of culture the amount of insulin-positive cells had decreased to 30 percent. Similar results were obtained for C-peptide and glucagon. It seems that monocytes lost the ability to express insulin during their differentiation into macrophages. It is well known, that cells are able to take up and accumulate exogenous insulin. One aim of this study was to differentiate by immunohistochemistry between de novo insulin and exogenous insulin taken up by the cells from the environment. We showed that the presence of C-peptide must be proven to clearly identify de novo insulin. Experiments with purified insulin demonstrated that cells that took up purified insulin were negative for C-peptide. Insulin isolated from in vitro cultured monocytes demonstrated biological activity and reduced blood glucose levels in diabetic mice. Eleven of 31 in vivo tested cell-free supernatants (35.5 percent) lowered blood glucose levels in diabetic mice by more than 15 percent. The results of the study show that in vitro modified monocytes are able to produce insulin that reduces blood glucose levels in diabetic mice

Bronchoscopic thermal vapor ablation after unsuccessful lung volume reduction surgery: A case report

Compared to surgery there is no evidence on bronchoscopic lung volume reduction (LVR) in patients with fading benefit after LVR surgery. CASE REPORT: We present a case of 64-year old female patient who was successfully treated with bronchial thermal vapor ablation (BTVA) after previous ineffective lung volume reduction (LVR) surgery several months earlier. CONCLUSIONS: Bronchoscopic LVR, in particular BTVA, might be considered in patients with fading or missing effects after previous LVRS. At least, the safety profile of BTVA seems not be adversely affected by previous LVRS, when proper patient selection and procedure planning are ensured

Calcineurin inhibitors revisited: A new paradigm for COVID-19?

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause mild, moderate or severe disease (COVID-19). In severe disease, there is hyperinflammation causing severe symptoms. Severe COVID-19 is an immunological phenomenon, rather than a direct viral damage disease. Therapies for COVID-19 are all investigational therapies. In case of severe disease, treatment with a calcineurin inhibitor could be promising. In this article we explain the mechanisms of calcineurin inhibitor treatment for COVID-19, based on experiences seen in solid organ transplant recipients who suffered from COVID-19

Clinical Aspects of COVID-19 in Patients with Solid Organ Transplantation: A Systematic Review

Background Coronavirus disease 19 (COVID-19), is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This virus is causing a pandemic with more than 40 million proven infections worldwide. Aim In order to summarize the clinical characteristics of coronavirus disease-19 (COVID-19) in solid organ transplant (SOT) recipients, we conducted a systematic review of studies on COVID-19 in these patients. Methods The literature search was conducted repeatedly between March 16th and May 1st, 2020. We searched original papers, observational studies, case reports, and meta-analyses published between December 2019 and May 1st 2020 using two databases (PubMed, Google Scholar) with the search terms: [transplant OR immune suppression] AND [COVID-19 OR SARS-CoV-2]. Further inclusion criteria were publications in English, French, German and Italian and reference to humans. We also searched the reference lists of the studies encountered. Studies on non-solid organ transplantation were excluded, as well as animal and in vitro studies. Results From an initial search 37 potential articles were retrieved, of which 15 were excluded after full-text screening (not being case reports or case series), leaving 22 studies for inclusion. No further studies were identified from the bibliographies of the retrieved articles. Conclusion Between March 16th and May 1st, 2020, only 49 SOT recipients have been described in literature. Most of these patients survived, and had a fairly mild disease course. Based on the limited research data, no firm conclusions can be made concerning specific treatment of SOT recipients, but the current evidence suggests that immunosuppression, especially the calcineurin inhibitors, decreases the incidence and improves the outcome of symptomatic COVID-19, by preventing hyperinflammation (cytokine storm). Evidence based guidelines are urgently needed for this particular group of patients

SARS-CoV-2 and Norovirus Co-Infection after Lung Transplantation

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spreading as a pandemic in 2020. Few reports on infections in thoracic transplantation have been published so far. We present a case of COVID-19 in a 55-year old female lung transplant recipient infected 5 months posttransplant, who additionally was co-infected with a Norovirus. Respiratory and gastrointestinal symptoms were observed without need of therapeutic escalation except for antibiotic therapy. We observed a moderate disease evolution likely due to triple immunosuppression