Pulmonary sarcoidosis is typically treated with prednisone, but its side effects are prompting the search for alternatives. The PREDMETH study compared methotrexate and prednisone, demonstrating similar efficacy on lung function at 24 weeks. Methotrexate causes fewer metabolic effects but more gastrointestinal and liver disturbances. These results support an alternative approach in sarcoidosis. Non-cystic fibrosis bronchiectasis (NCFBE) has long been limited to repeating what works in cystic fibrosis patients, such as supportive treatments, inhaled antibiotics and macrolides. The first phase 3 trial for a treatment targeting specifically neutrophil inflammation: brensocatib, is presented in this article.

Bronchiolitis Obliterans Syndrome (BOS), a fibrotic airway disease that may develop after lung transplantation, conventionally relies on pulmonary function tests (PFTs) for diagnosis due to limitations of CT imaging. Deep neural networks (DNNs) have not previously been used for BOS detection. This study aims to train a DNN to detect BOS in CT scans using an approach tailored for low-data scenarios. We trained a DNN to detect BOS in CT scans using a co-training method designed to enhance performance in low-data environments. Our method employs an auxiliary task that makes the DNN more sensitive to disease manifestations and less sensitive to the patient’s anatomical features. The DNN was tasked with predicting the sequence of two CT scans taken from the same BOS patient at least six months apart. We evaluated this approach on CT scans from 75 post-transplant patients, including 26 with BOS, and used a ROC-AUC metric to assess performance. We show that our DNN method achieves a ROC-AUC of 0.90 (95% CI: 0.840–0.953) in distinguishing BOS from non-BOS in CT scans. Performance correlates with BOS progression, with ROC-AUC values of 0.88 for stage I, 0.91 for stage II, and 0.94 for stage III BOS. Notably, the DNN shows comparable performance on standard- and high-resolution CT scans. It also demonstrates the ability to predict BOS in at-risk patients (FEV1 between 80% and 90% of best FEV1) with a ROC-AUC of 0.87 (95% CI: 0.735–0.974). Using visual interpretation techniques for DNNs, we reveal sensitivity to hyperlucent/hypoattenuated areas indicative of air-trapping or bronchiectasis. Our approach shows potential for improving BOS diagnosis by enabling early detection and management. The ability to detect BOS from standard-resolution scans at any stage of respiration makes this method more accessible than previous approaches. Additionally, our findings highlight that techniques to limit overfitting are crucial for unlocking the potential of DNNs in low-data settings, which could assist clinicians in BOS studies with limited patient data. Bronchiolitis Obliterans Syndrome (BOS) is a progressive disease that can occur after lung transplantation, leading to airway scarring. It is typically diagnosed through tests of lung function. In this study, we developed a computational approach to improve BOS detection from lung scans. We tested this approach on scans from 75 lung transplant patients, including 26 with BOS, and found that our approach could accurately distinguish BOS from non-BOS cases, even at early stages of disease. Our approach could improve early diagnosis and management of BOS, making detection more accessible using standard lung scans, and hence improving patient outcomes. Kozinski et al. develop a deep neural network-based model for detecting various stages of Bronchiolitis Obliterans Syndrome (BOS). This model addresses the current limitations of CT imaging in BOS diagnosis as it can use standard-resolution scans taken at any stage of respiration.

OBJECTIVES:Chronic thromboembolic pulmonary hypertension is a rare disease, characterized by delays in diagnosis and curative surgical treatment. After establishing a surgical pulmonary endarterectomy centre in Switzerland and due to a historically low resection rate of 14%, a national multidisciplinary evaluation board was established in January 2018. Herein, we summarize the impact of the board on our programme. METHODS:Patients discussed in the national chronic thromboembolic pulmonary hypertension board from January 2018 to December 2023 were included. Clinical characteristics, treatment allocation and survival were compared between patients undergoing surgery, patients refusing surgery and non-operable patients. Fisher's exact test or three-way ANOVA and Kaplan-Meier analyses were used. RESULTS:188 patients were discussed at our national chronic thromboembolic pulmonary hypertension board; 131 (70%) presented with operable disease, 77 (41%) were referred for pulmonary endarterectomy and 34 (18%) of operable patients declined surgery. There is a significant difference in survival between these groups (P = 0.048). One- and 2-year survival in the subgroup undergoing pulmonary endarterectomy was 97% and 79%, respectively, while 1- and 2-year survival in the subgroup refusing pulmonary endarterectomy was 91% and 76%, respectively. The pulmonary endarterectomy rate has increased from a historical low of 14-41% since establishing the board. CONCLUSIONS:Establishing an interdisciplinary board is essential to address diagnostic and management challenges in chronic thromboembolic pulmonary hypertension patients. The Swiss national chronic thromboembolic pulmonary hypertension board played an important role in substantially increasing the rate of curative surgery.

HomeCirculation: Heart FailureAhead of PrintAtrial Septal Defect, Pulmonary Arterial Hypertension, and Diastolic Left Heart Failure: When 3 Players Come into the Game No AccessCase ReportRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialNo AccessCase ReportRequest AccessAtrial Septal Defect, Pulmonary Arterial Hypertension, and Diastolic Left Heart Failure: When 3 Players Come into the Game Tobias Rutz, John-David Aubert, Maurice Beghetti, Eric Eeckhout, Olivier Muller, Judith Bouchardy and Patrick Yerly Tobias RutzTobias Rutz Correspondence to: Tobias Rutz, MD, Service of Cardiology, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Email E-mail Address: [email protected] https://orcid.org/0000-0001-5899-291X Service of Cardiology, Lausanne University Hospital and University of Lausanne, Switzerland. (T.R., E.E., O.M., J.B., P.Y.) , John-David AubertJohn-David Aubert https://orcid.org/0000-0001-8856-4000 Division of Pulmonology, Lausanne University Hospital and University of Lausanne, Switzerland. (J.-D.A.) , Maurice BeghettiMaurice Beghetti https://orcid.org/0000-0002-1841-0927 Pediatric Cardiology Unit and Centre Universitaire Romand de Cardiologie et Chirurgie Cardiaque Pédiatrique, Children's University Hospitals, Lausanne and Geneva, Switzerland (M.B.). , Eric EeckhoutEric Eeckhout Service of Cardiology, Lausanne University Hospital and University of Lausanne, Switzerland. (T.R., E.E., O.M., J.B., P.Y.) , Olivier MullerOlivier Muller https://orcid.org/0000-0003-2441-5799 Service of Cardiology, Lausanne University Hospital and University of Lausanne, Switzerland. (T.R., E.E., O.M., J.B., P.Y.) , Judith BouchardyJudith Bouchardy https://orcid.org/0000-0003-0149-288X Service of Cardiology, Lausanne University Hospital and University of Lausanne, Switzerland. (T.R., E.E., O.M., J.B., P.Y.) and Patrick YerlyPatrick Yerly https://orcid.org/0000-0001-8163-722X Service of Cardiology, Lausanne University Hospital and University of Lausanne, Switzerland. (T.R., E.E., O.M., J.B., P.Y.) Originally published21 Mar 2024https://doi.org/10.1161/CIRCHEARTFAILURE.123.010545Circulation: Heart Failure. 2024;0:e010545FootnotesFor Sources of Funding and Disclosures, see page xxx.Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCHEARTFAILURE.123.010545.Correspondence to: Tobias Rutz, MD, Service of Cardiology, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Email tobias.rutz@chuv.ch Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2024 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.123.010545PMID: 38511310 Originally publishedMarch 21, 2024 Keywordsatrial septal defectcongenital heart diseasediastolic heart failureheart failure with preserved ejection fractionpulmonary arterial hypertensionrenin-angiotensin-systemPDF download Advertisement SubjectsCongenital Heart DiseaseHeart Failure

Introduction Acute fibrinous and organizing pneumonia (AFOP) is a severe form of acute lung injury which can occur after lung transplantation. Treatment is empiric, based on immunosuppressive regimens and the mortality rate is very high. Case Presentation We report the case of a young lung transplant (LT) recipient who developed AFOP following a respiratory viral infection while on suboptimal maintenance immunosuppression due to adherence issues. Diagnosis was confirmed by cryobiopsies showing intra-alveolar fibrin balls. Despite high dose systemic corticosteroids, the patient developed severe respiratory failure requiring mechanical ventilation. IV infliximab and tocilizumab were administered. The patient was extubated 11 days later and discharged to home 42 days after intubation with 1L/min O2. She developed severe pleuritic pain needing opioid treatment and died 4 months later. Conclusion While high-dose systemic corticosteroids remain the first line of treatment, the use of anti TNF-α has shown promising results in case reports. Furthermore, we propose prompt realization of a cytokine panel analysis in both blood and bronchoalveolar lavage to better guide the adjuvant administration of a targeted anti-inflammatory therapy.

Abstract Background The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. Methods Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction–confirmed influenza and vaccine reactogenicity. Results A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12–1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16–1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08–1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. Conclusions In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. Clinical Trials Registration Clinicaltrials.gov NCT03699839.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus spp. ABPA diagnosis may be challenging due to its non-specific presentation. Standard ABPA treatment consists of systemic corticosteroids and antifungal agents. Mepolizumab, a monoclonal antibody against interleukin-5 seems to be a promising treatment for ABPA. Data about ABPA following lung transplantation (LuTx) are scarce. LuTx recipients are at higher risk for adverse effects of ABPA treatment compared to the general population.Here we present a case of a LuTx recipient who was successfully treated with mepolizumab for ABPA following LuTx. Prolonged administration of high dose prednisone was thus avoided. To our knowledge, this is the first case describing mepolizumab administration following LuTx. Mepolizumab seems particularly attractive as a corticosteroid-sparing agent or as an alternative option to antifungal treatments, because of its excellent safety profile and low risk of drug interactions.

In pulmonary arterial hypertension (PAH), 7% to 30% of patients experience chest pain during exercise1,2 and up to 40% of them may present left ventricular ischemia caused by extrinsic left main coronary artery (LMCA) compression by a dilated pulmonary artery (PA).2 Because LMCA stenting may provide a good outcome in this situation,2-4 percutaneous coronary intervention (PCI) is increasingly performed to alleviate symptoms, avoid arrythmias, and prevent left ventricular dysfunction and sudden cardiac death.

Abstract Aims Pulmonary hypertension (PH) is a complex clinical condition, and left heart disease is the leading cause. Little is known about the epidemiology and prognosis of combined post- and pre-capillary PH (CpcPH). Methods and results This retrospective analysis of the Swiss PH Registry included incident patients with CpcPH registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient baseline characteristics [age, sex, mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), and risk factors, including World Health Organization (WHO)-functional class (FC), 6 min walk distance (6MWD), and N-terminal pro-brain natriuretic peptide (NT-proBNP), treatment, days of follow-up, and events (death or loss to follow-up) at last visit] were analysed by Kaplan–Meier and Cox regression analyses. Two hundred and thirty-one patients (59.3% women, age 65 ± 12 years, mPAP 48 ± 11 mmHg, PAWP 21 ± 5 mmHg, PVR 7.2 ± 4.8 WU) were included. Survival analyses showed a significantly longer survival for women [hazard ratio (HR) 0.58 (0.38–0.89); P = 0.01] and a higher mortality risk for mPAP > 46 mmHg [HR 1.58 (1.03–2.43); P = 0.04] but no association with age or PVR. Patients stratified to high risk according to four-strata risk assessment had an increased mortality risk compared with patients stratified to low-intermediate risk [HR 2.44 (1.23–4.84); P = 0.01]. A total of 46.8% of CpcPH patients received PH-targeted pharmacotherapy; however, PH-targeted medication was not associated with longer survival. Conclusion Among patients with CpcPH, women and patients with an mPAP ≤46 mmHg survived longer. Furthermore, risk stratification by using non-invasively assessed risk factors, such as WHO-FC, 6MWD, and NT-proBNP, as proposed for pulmonary arterial hypertension, stratified survival in CpcPH, and might be helpful in the management of these patients.

Risk stratification in pulmonary arterial hypertension (PAH) is crucial in assessing patient prognosis. It serves a prominent role in everyday patient care and can be determined using several validated risk assessment scores worldwide. The recently published 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines underline the importance of risk stratification not only at baseline but also during follow-up. Achieving a low-risk status has now become the therapeutic goal, emphasising the importance of personalised therapy. The application of these guidelines is also important in determining the timing for lung transplantation referral. In this review, we summarise the most relevant prognostic factors of PAH as well as the parameters used in PAH risk scores and their evolution in the guidelines over the last decade. Finally, we describe the central role that risk stratification plays in the current guidelines not only in European countries but also in Asian countries.

Available data are limited concerning long-term lung function (LF) evolution after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in lung transplant (LT) recipients. The aim of this study is to determine the effect of first SARS-CoV-2 infection on long-term LF in LT recipients. We analyzed spirometry results of LT recipients followed at our institution (March 2020 to July 2022) at 3, 6, and 12 months after first SARS-CoV-2 infection. Overall, 42 LT patients of our cohort (70%) with COVID-19 were included for long-term LF analysis. Forced expiratory volume in 1 s (FEV 1 ) declined significantly at 3 months (−4.5%, −97 mL, 95% CI [−163; −31], p  < .01), but not at 6 and 12 months (−3.9%, −65 mL, 95% CI [−168; +39], p = .21). Results were quite similar for the forced vital capacity. Spirometry values declined significantly at 3 months after COVID-19 in LT recipients, presented a mixed decline at 6 months, and no significant decline at 12 months.

Background and Objectives: Community-acquired respiratory virus (CARV) infections pose a serious risk for lung transplant recipients (LTR) as they are prone to severe complications. When the COVID-19 pandemic hit Switzerland in 2020, the government implemented hygiene measures for the general population. We investigated the impact of these measures on the transmission of CARV in lung transplant recipients in Switzerland. Materials and Methods: In this multicenter, retrospective study of lung transplant recipients, we investigated two time periods: the year before the COVID-19 pandemic (1 March 2019-29 February 2020) and the first year of the pandemic (1 March 2020-28 February 2021). Data were mainly collected from the Swiss Transplant Cohort Study (STCS) database. Descriptive statistics were used to analyze the results. Results: Data from 221 Swiss lung transplant cohort patients were evaluated. In the year before the COVID-19 pandemic, 157 infections were diagnosed compared to 71 infections in the first year of the pandemic (decline of 54%, p < 0.001). Influenza virus infections alone showed a remarkable decrease from 17 infections before COVID-19 to 2 infections after the beginning of the pandemic. No significant difference was found in testing behavior; 803 vs. 925 tests were obtained by two of the three centers during the respective periods. Conclusions: We observed a significant decline in CARV infections in the Swiss lung transplant cohort during the first year of the COVID-19 pandemic. These results suggest a relevant impact of hygiene measures when implemented in the population due to the COVID-19 pandemic on the incidence of CARV infections.

BACKGROUND:Lung transplant recipients (LTRs) are at increased risk for coronavirus disease 2019 (COVID-19)-associated complications.METHODS:We aimed to describe the outcomes of polymerase chain reaction-documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LTRs followed at our institution from March 2020 to July 2022. The primary outcome investigated was hospitalization or death from COVID-19-related symptoms within 28 days from diagnosis.RESULTS:Overall, 60 cases were included, of which 18 (30%) reached the primary outcome. Only one patient (2%) died. Anti-spike monoclonal antibodies (mAbs) were administered as early treatment in 36 patients (casirivimab/imdevimab = 2, sotrovimab = 31, and tixagevimab/cilgavimab = 3). Multivariate analysis revealed that age >60 years (p = .003; odds ratio [OR] 9.41; confidence interval [CI] 2.52-41.05) was associated with a higher risk for the primary outcome, while administration of mAbs as early treatment (p = .030; OR 0.23; CI 0.06-0.87) was associated with a lower risk. No effect of vaccination and SARS-CoV-2 variant was observed. Forced expiratory volume in 1 s and forced vital capacity values did not decrease among 37 patients who had spirometry performed 1 month after COVID-19.CONCLUSIONS:We observed a relatively low morbidity and mortality of COVID-19 in LTR. mAb administration was associated with a better outcome.

EDITORIAL article Front. Med., 22 November 2023Sec. Pulmonary Medicine Volume 10 - 2023 | https://doi.org/10.3389/fmed.2023.1326429

Background and Aim: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. Approach and Results: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12–54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8–21.3, p < 0.001). Conclusions: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.

This selection of pneumological novelties of the year 2022 is not limited to pharmacological acquisitions but also includes progress in diagnostic strategies and the global management of respiratory diseases. We have chosen three pneumological issues. As cannabis is the most consumed illegal substance in Switzerland, it is important to know its impact on pulmonary physiology. An update of the international guidelines on pulmonary fibrosis as well as the European guidelines on pulmonary hypertension provides practical answers to the many clinical problems encountered in the management of these diseases. The key messages from these two consensus documents are reported here.

Right ventricular failure (RVF) is often caused by increased afterload and disrupted coupling between the right ventricle (RV) and the pulmonary arteries (PAs). After a phase of adaptive hypertrophy, pressure-overloaded RVs evolve towards maladaptive hypertrophy and finally ventricular dilatation, with reduced stroke volume and systemic congestion. In this article, we review the concept of RV-PA coupling, which depicts the interaction between RV contractility and afterload, as well as the invasive and non-invasive techniques for its assessment. The current principles of RVF management based on pathophysiology and underlying etiology are subsequently discussed. Treatment strategies remain a challenge and range from fluid management and afterload reduction in moderate RVF to vasopressor therapy, inotropic support and, occasionally, mechanical circulatory support in severe RVF.