aLung Center, Cantonal Hospital St. Gallen, St. Gallen, Switzerland; bDepartment of Pulmonary Medicine, Inselspital, University Hospital of Berne, Berne, Switzerland; cClinics of Respiratory Medicine, University Hospital Basel, Basel, Switzerland; dDepartement of Pulmonary Medicine, University Hospital of Zurich, Zurich, Switzerland; eDepartement of Pulmonary Medicine, Réseau Hospitalier Neuchâtelois, Pourtalès Hospital, Neuchâtel, Switzerland; fDepartement of Pulmonary Medicine, Lucerne Cantonal Hospital, Lucerne, Switzerland; gDivision of Pneumology, Geneva University Hospitals, Geneva, Switzerland; hDepartement of Pulmonology, City Hospital Triemli, Zurich, Switzerland; iDepartement of Pneumology, Hospital of Bellinzona, Bellinzona, Switzerland

Daiana Stolz,1,2 Claudio Schuoler,3 Florian Charbonnier,4 Pierre-Olivier Bridevaux,4,5 Peter Jandus,6 Jörg D Leuppi,7 Nikolay Pavlov,8 Andreas Piecyk,9 Thomas Rothe10 1Pulmonology Clinic, University Hospital Basel, Basel, Switzerland; 2Clinic of Respiratory Medicine and Faculty of Medicine, University of Freiburg, Freiburg, Germany; 3Medical Department, AstraZeneca AG, Baar, Switzerland; 4Pulmonology Division, University Hospital Geneva, Geneva, Switzerland; 5Service de Pneumologie, Centre Hospitalier du Valais Romand, Sion, Switzerland; 6Immunology and Allergology Division, University Hospital Geneva, Geneva, Switzerland; 7University Centre of Internal Medicine, Cantonal Hospital Baselland, Liestal, Switzerland; 8Department for Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 9Pulmonary Center Hirslanden, Zurich, Switzerland; 10Pulmonology Clinic, Cantonal Hospital Graubünden, Chur, SwitzerlandCorrespondence: Claudio Schuoler, AstraZeneca AG, Medical Department, Baar, Switzerland, Email claudio.schuoler@astrazeneca.comPurpose: Although studies have evaluated benralizumab, a monoclonal IL-5 receptor α antibody in severe eosinophilic asthma (SEA), in real-world settings, additional evidence is needed to further characterize its effectiveness in specific patient populations. Our study aimed to evaluate asthma control over 56 weeks in patients treated with benralizumab in Swiss real-world settings.Patients and Methods: Conducted across 13 centres, this prospective, observational, non-interventional study involved 73 adults with physician confirmed SEA. Benralizumab 30 mg was administered according to the Swiss label at baseline and up to week 56. Primary outcome was the change in Asthma Control Questionnaire (ACQ-5) scores at week 8 compared to baseline. Exacerbations, use of oral corticosteroids (OCS), and lung function were assessed descriptively.Results: At baseline, the mean ACQ-5 score was 2.76 (SD 1.26), with 82.2% of patients showing not well-controlled asthma (ACQ-5 > 1.5). At week 8, the mean change in ACQ-5 compared to baseline was − 0.95 (95% CI: − 1.25, − 0.66; p < 0.001). More than half of patients (59.1%) reached a clinically relevant improvement (MCID ≥ 0.5) at week 8, with 40.9% of patients doing so at week 1 and 87.2% at week 56. The annualized exacerbation rate (AER) of 3.65 (95% CI: 3.18, 4.18) at baseline was reduced to 0.68 (95% CI: 0.39, 1.19) at week 56. The relative reduction in AER from baseline to week 56 was 81.3%. Maintenance usage of OCS at baseline (median 25.0 mg/day) decreased over the study leading to a median change of 17.50 mg/day (95% CI: 10.0; 40.0) from baseline compared to week 56. The mean pre-bronchodilator FEV1 change from baseline to week 56 was 0.23 L (95% CI: 0.08; 0.38, p = 0.003).Conclusion: Benralizumab demonstrated significant, rapid improvements in asthma control within one week of treatment initiation, with sustained benefits over 56 weeks.Keywords: severe eosinophilic asthma, asthma symptom control, patient reported outcomes, exacerbation reduction

Pulmonary hypertension (PH), especially pulmonary arterial and chronic thromboembolic pulmonary hypertension (PAH/CTEPH), are rare and progressive conditions. Despite recent advances in treatment and prognosis, PH is still associated with impaired quality of life and survival. Long-term PH-registry data provide information on the changing PH-epidemiology and may help to direct resources to patient's needs. This retrospective analysis of the Swiss Pulmonary Hypertension Registry includes patients newly diagnosed with PH (mainly PAH/CTEPH) registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient characteristics (age, body mass index, gender, diagnosis), hemodynamics at baseline, treatment, days of follow-up, and events (death, transplantation, pulmonary endarterectomy, or loss to follow-up) at last visit were analyzed. Patients were stratified into four time periods according to their date of diagnosis. Survival was analyzed overall and separately for PAH/CTEPH and time periods. 1427 PH patients were included (thereof 560 PAH, 383 CTEPH). Over the years, age at baseline (mean ± SD) significantly increased from 59 ± 14 years in 2001-2005 to 66 ± 14 years in 2016-2019 (p < 0.001) while the gender distribution tended toward equality. Mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased over time (from 46 ± 15 to 41 ± 11 mmHg, respectively, 9 ± 5 to 7 ± 4 WU, p < 0.001). Three-year survival substantially increased over consecutive periods from 69% to 91% (for PAH 63%-95%, for CTEPH 86%-93%) and was poorer in PAH than CTEPH independently of time period (p < 0.001). Most patients were treated with mono- or combination therapy and an increasing number of CTEPH underwent pulmonary endarterectomy (40% 2016-2019 vs. 15% 2001-2005). This long-term PH registry reveals that over two decades of observation, newly diagnosed patients are older, less predominantly female, have less impaired hemodynamics and a better survival.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program. FRAMEWORK: An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program. SCREENING APPROACH: General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a “lung health check”. Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules. CONCLUSION: Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make.

We describe a case of a SARS coronavirus 2 (SARS-CoV-2) infection in a Swiss 54-years-old immunocompromised patient (lymphoma, therapy with the anti-CD20 antibody Rituximab® ), with initial scarce respiratory symptoms but typical coronavirus disease 2019 (COVID-19) radiological presentation, and symptoms onset during a holiday trip to Texas (USA). Three nasopharyngeal swabs in the 96 hours following hospital admission were negative, despite a CT thorax suggestive for an early stage of infection. COVID-infection was finally confirmed in the bronchoalveolar lavage (BAL) fluid, performed for exclusion of an alternative diagnosis in immunocompromised. In the BAL an increased cellularity with marked lymphocytosis of 35%, a reduced CD4/CD8 ratio of 0.1 and borderline neutrophilia of 3% were found. This finding might be due to the concomitant therapy with anti-CD20 antibodies, but the presence of lymphocytosis in the BAL despite peripheral lymphopenia with decreased CD4/CD8 T-cells ratio are described here for the first time in a SARS-CoV-2 infection. Persistent gastrointestinal symptoms (diarrhea), fever and initially headache were the predominant symptoms. The respiratory symptoms were scarce (variable mild dyspnea mMRC1). The respiratory conditions worsened during the hospital stay, with tachypnea up to 35/min, increased need for supplemental oxygen up to 8 L/min and worsening lung infiltrates on CT thorax on day 5. A therapy with hydroxychloroquine (HCQ) and an immunoglobulin-supplementation were given, with clinical and respiratory improvement, without need for intensive care or any ventilator support, and hospital discharge on day 16. Our case highlights some diagnostic and therapeutical challenges occurring in patients with COVID-19 infection. As take-home message, in the presence of clinical and radiological findings compatible with SARS-CoV-2 infection we outline the importance of treating patients accordingly, also in presence of repeated negative nasopharyngeal swabs. In selected patients as in our case a bronchoscopic BAL should be considered to exclude other infections, but in our opinion not primarily to confirming COVID-19 infection. Our unique finding of a lymphocytosis in the BAL during a COVID-19 infection needs further investigations.

The SARS-CoV-2 virus (COVID-19) was initially observed in a group of Chinese patients with unclear pneumonia in Wuhan, Hubei [1] in late December 2019. The first positive case in Switzerland was confirmed on 25 February 2020 in a patient from canton Tessin, who most likely caught the virus during a visit to Milan, Italy [2]. The country has since been preparing for an imminent public health emergency caused by the pandemic. As of 14 May 2020, the Swiss healthcare system is facing a total of 30,463 corona virus-positive people [3]. With numbers of new infections decreasing after the first pandemic wave, the continuing endemic situation will continue to be a major challenge for the Swiss healthcare system. It remains crucial to separate the clinically low-symptomatic from the severely affected patients in order to offer a specific therapeutic strategy to every SARS-CoV-2 patient. Reports from Chinese cohorts describe an increasing role of imaging strategies in the detection and surveillance of COVID-19 patients because of insufficient testing sensitivity of real-time reverse transcription polymerase chain reaction (RT-PCR) tests [4]. Chest computed tomography (CT), with a reported sensitivity of up to 97% [5, 6], gained importance particularly in patients with false negative RT-PCR results. In this short communication, we describe our first clinical experiences with 55 COVID-19 patients in Central Switzerland, who were either imaged with a standard chest x-ray, chest CT, or both. We provide an illustrative and schematic description of typical COVID-19 imaging features and suggest that imaging plays an important role in the clinical work-up of suspected or confirmed COVID-19 patients. This study was approved by the national ethics review committee (EKNZ, Switzerland) and patients’ informed consent was waived.

BACKGROUND:Virtual reality (VR) simulation is an effective and safe method of teaching bronchoscopic skills. Few VR bronchoscopy simulators exist; all are expensive. The present study aimed to describe the design, development, and evaluation of a new, affordable, VR bronchoscopy simulator. METHODS:Anesthesiologists and engineers collaborated to design and develop the Computer Airway Simulation System (CASS), an iPad-based, high-fidelity, VR bronchoscopy simulator. We describe hardware and software development, as well as the technical and teaching features of the CASS. Twenty-two senior anesthesiologists evaluated various aspects of the simulator (using a 5-point Likert scale) to assess its face validity. RESULTS:Anesthesiologists performed a simulated bronchoscopy (mouth to carina) with a median (range) procedural time of 66 seconds (30-96). The simulator's ease of use was rated 4.3 ± 0.8 and the bronchoscope proxy's handling 4.0 ± 0.7. Criticisms included that excessive system reactivity created handling difficulties. Anatomical accuracy, 3-dimensional bronchial segmentation, and mucosal texture were judged to be very realistic. The simulator's usefulness for teaching and its educational value were highly rated (4.9 ± 0.3 and 4.8 ± 0.4, respectively). CONCLUSIONS:We describe the design, development, and initial evaluation of the CASS-a new, ultraportable, affordable, VR bronchoscopy simulator. The simulator's face validity was supported by excellent assessments from senior anesthesiologists with regard to anatomical realism, quality of graphics, and handling performance, even though some future refinements are required. All the practitioners agreed on the significant educational potential of the CASS.

BACKGROUND: The sit-to-stand (STS) test is a feasible tool for measuring peripheral muscle strength of the lower limbs. There is evidence of increasing use of STS tests in patients with COPD. We sought to evaluate in subjects with COPD the minimum clinically important difference in 30-s STS test after pulmonary rehabilitation. METHODS: Stable COPD subjects undergoing a 30-s STS test and a 6-min walk test (6MWT) before and after pulmonary rehabilitation were included. Responsiveness to pulmonary rehabilitation was determined by the change in 30-s STS test results (Delta 30-s STS) before and after pulmonary rehabilitation. The minimum clinically important difference was evaluated using an anchor-based method. RESULTS: 96 subjects with moderate-to-severe COPD were included. At baseline, 30-s STS test results were significantly related to distance covered in a 6MWT (6MWD) (r = 0.65, P < .001), FVC (r = 0.46, P <.001), P-aCO2 (r = -0.42, P < .001), FEV1 (r = 0.39, P <.001), and age (r = -0.31, P = .002). After pulmonary rehabilitation, a significant improvement in 30-s STS test results was observed (mean difference +2 repetitions, P < .001). The Delta 30-s STS was positively related to Delta 6MWD (r = 0.62, P < .001), transitional dyspnea index (r = 0.67, P <.001), and baseline residual volume (r = 0.27, P = .007). The receiver operating characteristic curves method identified a Delta 30-s STS cut-off of 2 repetitions as the best discriminating value (area under the curve: 0.892, P <.001) to identify the minimum clinically important difference for Delta 6MWD (30 m). In a multivariate logistic regression model, baseline 30-s STS (odds ratio 2.63; 95% CI 1.09-6.35, P = .031) and diffusing capacity of the lung for carbon monoxide (< 53% predicted) (odds ratio 2.49, 95% CI 1.04 -5.98, P = .041) predict the risk to have a Delta 30-s STS >= 2 repetitions. CONCLUSIONS: Our study indicates that in stable subjects with moderate-to-severe COPD, the 30-s STS test was a sensitive tool to assess the efficacy of pulmonary rehabilitation. A Delta 30-s STS of >= 2 repetitions represented the minimum clinically important difference, which may be predicted by the baseline ability in the 30-s STS test and lung function in terms of diffusing lung capacity.

Pulmonaire (SSHP) célèbre ses vingt ans.Nous souhaitons profiter de cet événement réjouissant pour susciter une réflexion sur son histoire et son évolution, sur les projets actuels et la maladie à laquelle nous consacrons tous nos efforts depuis deux décennies.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe complication of pulmonary embolism. Its incidence following pulmonary embolism is debated. Active screening for CTEPH in patients with acute pulmonary embolism is yet to be recommended.This prospective, multicentre, observational study (Multicentre Observational Screening Survey for the Detection of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Following Pulmonary Embolism (INPUT on PE); ISRCTN61417303) included patients with acute pulmonary embolism from 11 centres in Switzerland from March 2009 to November 2016. Screening for possible CTEPH was performed at 6, 12 and 24 months using a stepwise algorithm that included a dyspnoea phone-based survey, transthoracic echocardiography, right heart catheterisation and radiological confirmation of CTEPH.Out of 1699 patients with pulmonary embolism, 508 patients were assessed for CTEPH screening over 2 years. CTEPH incidence following pulmonary embolism was 3.7 per 1000 patient-years, with a 2-year cumulative incidence of 0.79%. The Swiss pulmonary hypertension registry consulted in December 2016 did not report additional CTEPH cases in these patients. The survey yielded 100% sensitivity and 81.6% specificity. The second step echocardiography in newly dyspnoeic patients showed a negative predictive value of 100%.CTEPH is a rare but treatable disease. A simple and sensitive way for CTEPH screening in patients with acute pulmonary embolism is recommended.

The sit-to-stand test (STST) is a feasible alternative for measuring peripheral muscle strength of the lower limbs. Our aim was to evaluate, in Chronic Obstructive Pulmonary Disease (COPD) patients, the minimal clinically important difference (MCID) of 30-second STST (30-STST) after pulmonary rehabilitation (PR). Stable COPD inpatients undergoing 30-STST and 6-minute walk test (6MWT) before and after PR were included. Responsiveness to PR was determined by pre-to-post PR (∆) evaluation of 30-STST. The MCID was evaluated using an anchor-based method. 96 moderate-to-severe COPD patients were included. At baseline, 30-STST was significantly related to distance at 6MWT (6MWD) (r=0.65; p<0.0001), FVC (r=0.46; p<0.0001), PaCO2 (r=-0.42; p<0.0001), FEV1 (r=0.39; p<0.0001) and age (r=-0.31; p<0.01). After PR a significant improvement in 30-STST was observed (mean difference +2 repetitions; p<0.0001). ∆30-STST was positively related to ∆6MWD (r=0.61, p<0.0001), TDI (r=0.61, p<0.0001) and baseline RV (r=0.27, p<0.01). Receiver operating characteristic curves identified a ∆30-STST cut-off of 2 repetitions as the best discriminating value (area under curve: 0.892; p<0.001) to identify the MCID for ∆6MWD (30 meters). In a multivariate logistic regression model, baseline MRC (Odds ratio 2.27; p=0.003) and RV/TLC (OR 1.05; p=0.040) predict the risk to have a value >2 repetitions ∆30-STST. In COPD patients 30-STST is a sensitive tool to assess PR efficacy. A ∆30-STST of at least 2 repetitions represents the MCID, that may be predicted by dyspnea and lung hyperinflation.

Since 1998 pulmonary hypertension has been clinically classified into five well-defined, distinct categories. A definitive diagnosis of pulmonary hypertension requires the invasive confirmation of an elevated mean pulmonary artery pressure of 25 mm Hg or above during a right heart catheterization. From a hemodynamic point of view, pulmonary hypertension is classified into precapillary and postcapillary pulmonary hypertension on the basis of a pulmonary artery wedge pressure threshold value of 15 mm Hg. Pulmonary vascular resistance is better characterized by multi-point pressure/flow measurements than by single-point determination. Multi-point pulmonary vascular resistance calculation could be useful for early disease identification as well as for treatment response assessment. Occlusion analysis of the pulmonary artery pressure decay curve after balloon inflation at the tip of the pulmonary artery catheter permits locating the site of predominantly increased resistance and could be useful in differentiating proximal from distal vasculopathy, especially in chronic thromboembolic pulmonary hypertension. The pulsatile hydraulic load of the pulmonary circulation can be better appreciated by pulmonary vascular impedance or via the resistance-compliance relationship than by means of pulmonary vascular resistance. Determination of right ventriculo-arterial coupling permits assessing the impact of an elevated afterload on right ventricular function, which ultimately determines the symptoms and prognosis of patients with pulmonary hypertension. The clinical utility of combining different invasive hemodynamic approaches is still uncertain and remains to be determined.

BACKGROUND:Violent behaviour (VB) occurs in first episode of schizophrenia and can have devastating impact both on victims and patients themselves. A better knowledge of the underlying mechanisms of VB may pave the way to preventive treatments.OBJECTIVES:1) To explore the nature of the link between impulsivity and VB in early psychosis (EP) patients; 2) To explore the interactions between impulsivity and substance abuse, insight, and positive symptoms, the main dynamic risk factors of VB described to date.DESIGN AND METHODS:Post hoc analysis of data acquired in the frame of a 36-months EP cohort study. A total of 265 EP patients, aged 18 to 35, treated at TIPP (Treatment and early Intervention in Psychosis Program), at the Department of Psychiatry in Lausanne, Switzerland, were included in the study. Logistic regression analyzes were performed as well as mediation analysis and interaction analysis RESULTS: Our data suggest that impulsivity is a predictor of VB when analyzed independently and as part of a multi-factorial model. Impulsivity continues to differentiate violent patients from non-violent ones at the end of the program. In addition, the relationship between impulsivity and VB is not mediated by substance abuse. Finally, the effect of impulsivity on the probability of VB is potentiated by the interaction of different levels of insight and positive symptoms.CONCLUSIONS:Early intervention strategies in psychotic disorders should include evaluation of impulsivity considering it is linked to increased risk of VB and may respond to treatment.

A 60-year-old woman under treatment with letrozole for metastatic breast cancer underwent 18F-FDG PET-CT for restaging. A new widespread intense splenic FDG uptake without nodular lesions and multiple FDG-avid mediastinal and abdominal nodes were observed. Based on these findings, a nodal and transbronchial lung biopsy was performed. Histological results were compatible with sarcoidosis. The patient began steroid treatment and 6 weeks after a PET-CT showed normalisation of both splenic and nodal uptake. In our case, 18F-FDG PET-CT has been useful in detecting a rare case of splenic sarcoidosis without typical nodular lesions on CT images, impacting the patient’s treatment and prognosis.

The term pulmonary hypertension refers to a serious condition characterised by high pulmonary vascular pressure, mainly as a consequence of various cardiac and respiratory diseases. Current clinical classification of pulmonary hypertension considers five distinct groups. Transthoracic echocardiography represents the first and most important noninvasive screening tool for estimating the probability of pulmonary hypertension. The diagnostic approach to pulmonary hypertension is supported by a proposed algorithm, which identifies the underlying cause. The definitive diagnosis and classification of pulmonary hypertension requires invasive confirmation of an elevated pulmonary artery mean pressure during a right heart catheterisation at rest. Pulmonary artery wedge pressure assessment has a pivotal role in differentiating precapillary from postcapillary pulmonary hypertension. The correct acquisition and interpretation of invasive pulmonary haemodynamic variables play a central role, not only in confirming the diagnosis but also in prognostication and treatment decision-making. During right heart catheterisation correct zero levelling of the external pressure transducer and pressure tracing readings at end-expiration should be assured. Obese patients and patients with obstructive lung diseases require special attention, given that spontaneous positive end-expiratory intrathoracic pressures are frequently observed. Because pressure and flow determinations with a fluid-filled flow-directed thermodilution catheter are potentially insufficiently precise, it is recommended to average at least three measurements. Acute vasoreactivity testing is indicated only in selected patients. Recent data suggest that invasive pulmonary haemodynamic measurement during exercise may be more sensitive than resting haemodynamics for early diagnosis, for treatment response assessment and for prognostic purposes.

Dual bronchodilator therapy is recommended for symptomatic patients with chronic obstructive pulmonary disease (COPD). There are limited data on effects of a combination of two long-acting bronchodilators on lung function including body plethysmography.