Search

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired clot resolution and in sustained fibrothrombotic obstruction of the pulmonary arterial bed remain poorly understood. Since defective angiogenesis correlated to defective clot resolution based on observations in surgical material from patients with CTEPH, we aimed to validate its crucial pathogenic role by intrathrombus inhibition of angiogenesis in a novel CTEPH rabbit model. Methods: We aimed to compare whether intrathrombus administration of an antifibrinolytic agent, tranexamic acid, or an inhibitor of angiogenesis, SU5416, would contribute to CTEPH progression. Both products were administered on a weekly basis by autologous clot embolization in rabbits. Right ventricular pressure was monitored by telemetry, right ventricular function by transthoracic echocardiography, and a complete pulmonary hemodynamic evaluation was obtained through right heart catheterization. Markers of inflammation, endothelial dysfunction, heart failure, and fibrinolysis were measured in plasma. Pulmonary vessel remodeling was analyzed by immunohistochemistry. Results: Impairing intrathrombus angiogenesis by repeatedly embolizing autologous blood clots containing SU5416 resulted in elevated mean pulmonary arterial pressure (38 mm Hg), increased indexed pulmonary vascular resistance, and enhanced right ventricular hypertrophy (80%, 1.9-fold, 36%, respectively, compared with rabbits embolized with clots containing an antifibrinolytic agent). This was caused by both obstruction of large pulmonary arteries with fibrothrombotic material and muscularization of pulmonary microvessels, and accompanied by inflammatory cell infiltration and increased circulating endothelin-1. Conclusions: The key role of angiogenesis-driven clot resolution was validated in a reliable small-animal model reproducing the major pathophysiological hallmarks of CTEPH.

Fungal exposure and sensitization negatively affect outcomes in various respiratory diseases, however, the effect of fungal sensitization in lung transplant (LTx) recipients is still unknown. We performed a retrospective cohort study of prospectively collected data on circulating fungal specific IgG/IgE antibodies, and their correlation with fungal isolation, chronic lung allograft dysfunction (CLAD) and overall survival after LTx. 311 patients transplanted between 2014 and 2019 were included. Patients with elevated Aspergillus fumigatus or Aspergillus flavus IgG (10%) had more mold and Aspergillus species isolation (p = 0.0068 and p = 0.0047). Aspergillus fumigatus IgG was specifically associated with Aspergillus fumigatus isolation in the previous or consecutive year (AUC 0.60, p = 0.004 and AUC 0.63, p = 0.022, respectively). Elevated Aspergillus fumigatus or Aspergillus flavus IgG was associated with CLAD (p = 0.0355), but not with death. Aspergillus fumigatus, Aspergillus flavus or Aspergillus niger IgE was elevated in 19.3% of patients, but not associated with fungal isolation, CLAD or death. Mold isolation and Aspergillus species isolation from respiratory cultures were associated with CLAD occurrence (p = 0.0011 and p = 0.0005, respectively), and Aspergillus species isolation was also associated with impaired survival (p = 0.0424). Fungus-specific IgG could be useful in long-term follow-up post-LTx, as a non-invasive marker for fungal exposure, and thus a diagnostic tool for identifying patients at risk for fungal-related complications and CLAD.

OBJECTIVE: To describe our experience with lung transplantation (LTx) from donors ≥70 years and compare short- and long-term outcome to a propensity-matched cohort of donors

While chronic thromboembolic pulmonary hypertension (CTEPH) results from macroscopic and microscopic obstruction of the pulmonary vascular bed, the function of the right ventricle (RV) and increased RV afterload are the main determinants of its symptoms and prognosis. In this review, we assess RV function in patients diagnosed with CTEPH with a focus on the contributions of RV afterload and dysfunction to the pathogenesis of this disease. We will also discuss changes in RV function and geometry in response to treatment, including medical therapy, pulmonary endarterectomy, and balloon pulmonary angioplasty. ispartof: JOURNAL OF CLINICAL MEDICINE vol:12 issue:1 ispartof: location:Switzerland status: published

Pulmonary hypertension (PH) is a chronic disorder of the pulmonary circulation that often associates with other respiratory diseases (i.e., group III PH), leading to worsened symptoms and prognosis, notably when combined with interstitial lung diseases such as pulmonary fibrosis (PF). PH may lead to right ventricular (RV) failure, which accounts for a substantial part of the mortality in chronic lung disease patients. The disappointing results of pulmonary arterial hypertension (PAH)-related therapies in patients with PF emphasize the need to better understand the pathophysiologic mechanisms that drive PH development and progression in this specific setting. In this work, we validated an animal model of group III PH associated with PF (PH-PF), by using bleomycin (BM) intratracheal instillation and characterizing the nature of induced lung and vascular remodeling, including the influence on RV structure and function. To our knowledge, this is the first work describing this dose of BM in Sprague Dawley rats and the effects upon the heart and lungs, using different techniques such as echocardiography, heart catheterization, and histology. Our data shows the successful implementation of a rat model that mimics combined PF-PH, with most features seen in the equivalent human disease, such as lung and arterial remodeling, increased mPAP and RV dysfunction. ispartof: PULMONARY CIRCULATION vol:13 issue:1 ispartof: location:United States status: published

Video Abstract Download : Download video (50MB) Lung transplantation from a donor previously infected with SARS-CoV-2

Purpose of review New chronic lung allograft dysfunction (CLAD) consensus documents were published in 2019, defining four phenotypes; bronchiolitis obliterans syndrome, restrictive allograft syndrome, mixed and undefined. Clearly, validation of these guidelines in a real life cohort is critical. Recent findings Indeed, validation has been performed recently, both after bilateral lung transplantation (LTx) and after single LTx illustrating that precise phenotyping based on pulmonary function alone can be difficult. Undertaking regular chest computed tomography scanning does appear very helpful in establishing the prognosis of the patients with CLAD. Pulmonary function changes may not always identify the exact phenotype of CLAD and we provide further evidence for the important role of chest imaging at diagnosis and during the follow-up of patients with CLAD.

This report discusses 3 bilateral lung transplant recipients (2 female, 1 male) who presented with late hemoptysis (10 y, 18 y, and 19 y after transplantation). All patients had a history of pulmonary infections, bronchiectasis, and/or Aspergillus infection. Arteriography, through catherization of the common femoral artery, demonstrated spontaneous bronchial and systemic neovascularization arising from the thyrocervical trunk, internal thoracic artery, intercostal arteries, and dorsal scapular artery. Embolization was performed with microspheres, polyvinyl alcohol microparticles, and/or glue and effectively terminated hemoptysis. One patient died 10 d later as a result of fungal infection, and the 2 others remained in stable condition (18- and 26-mo postembolization follow-up available).

According to the US Centers for Disease Control and Prevention (CDC), patients with underlying health conditions, including all types of lung and cardiovascular diseases, have an increased risk of developing serious disease when infected by SARS-CoV-2 [1]. Based on prior publications on the effects of acute right heart failure superimposed on systemic infection [2–5], Ryan et al. [6] suggested that right heart failure and concomitant COVID-19 infection may result in increased mortality in pulmonary arterial hypertension (PAH) patients. Surprisingly, the number of hospitalised PAH-COVID-19 patients remained rather low in Italy and the USA so far [7]. In late March 2020, experts from over 32 US PH expert centres answered a query endorsed by the US Pulmonary Hypertension Association. COVID-19 infection was reported in 13 PAH patients, among whom three required intubation and one died. This is consequently raising the question whether and why PAH patients appear to be at lower risk of developing severe COVID-19 [7]., This international survey highlights that a limited number of PAH and CTEPH patients suffered from severe #COVID19 infection https://bit.ly/3jGuBQq

We conducted a prospective single-center observational study to determine lung ultrasound reliability in assessing global lung aeration in 38 hospitalized patients with non-critical COVID-19. On admission, fixed chest CT scans using visual (CTv) and software-based (CTs) analyses along with lung ultrasound imaging protocols and scoring systems were applied. The primary endpoint was the correlation between global chest CTs score and global lung ultrasound score. The secondary endpoint was the association between radiographic features and clinical disease classification or laboratory indices of inflammation. Bland−Altman analysis between chest CT scores obtained visually (CTv) or using software (CTs) indicated that only 1 of the 38 paired measures was outside the 95% limits of agreement (−4 to +4 score). Global lung ultrasound score was highly and positively correlated with global software-based CTs score (r = 0.74, CI = 0.55−0.86; p < 0.0001). Significantly higher median CTs score (p = 0.01) and lung ultrasound score (p = 0.02) were found in severe compared to moderate COVID-19. Furthermore, we identified significantly lower (p < 0.05) lung ultrasound and CTs scores in those patients with a more severe clinical condition manifested by SpO2 < 92% and C-reactive protein > 58 mg/L. We concluded that lung ultrasound is a reliable bedside clinical tool to assess global lung aeration in hospitalized non-critical care patients with COVID-19 pneumonia. ispartof: JOURNAL OF CLINICAL MEDICINE vol:11 issue:10 ispartof: location:Switzerland status: published

Primary graft dysfunction (PGD) is a major obstacle after lung transplantation (LTx), associated with increased early morbidity and mortality. Studies in liver and kidney transplantation revealed prolonged anastomosis time (AT) as an independent risk factor for impaired short- and long-term outcomes. We investigated if AT during LTx is a risk factor for PGD. In this retrospective single-center cohort study, we included all first double lung transplantations between 2008 and 2016. The association of AT with any PGD grade 3 (PGD3) within the first 72 h post-transplant was analyzed by univariable and multivariable logistic regression analysis. Data on AT and PGD was available for 427 patients of which 130 (30.2%) developed PGD3. AT was independently associated with the development of any PGD3 ≤72 h in uni- (odds ratio [OR] per 10 min 1.293, 95% confidence interval [CI 1.136-1.471], p

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) are chronic diseases of the pulmonary parenchyma and circulation, respectively, which may coexist, but underlying mechanisms remain elusive. Mutations in the GCN2 gene (EIF2AK4) were recently associated with pulmonary veno-occlusive disease. This study aims to explore the involvement of the GCN2/eIF2α pathway in the development of PH during PF, in both human disease and in an experimental animal model. Lung tissue from PF patients with or without PH were collected at the time of lung transplantation, and controls were obtained from tumor resection surgery. Experimental lung disease was induced in either male wild-type or EIF2AK4-mutated Sprague-Dawley rats, randomly receiving a single intratracheal instillation of bleomycin or saline. Hemodynamic studies, as well as organ collection were performed 3 weeks post-instillation. Only significant results (p

The MUC5B promoter polymorphism (rs35705950) has been associated with interstitial lung disease (ILD) and with prolonged pre-transplant survival in idiopathic pulmonary fibrosis (IPF), but no information is available regarding its prevalence in other respiratory diseases and its influence on post-transplant outcome. We included the Leuven lung transplantation cohort between 1991 and 2015 (n = 801). We assessed the minor allele frequency (MAF) of the MUC5B variant in the entire study cohort and investigated the influence of recipient MUC5B promoter polymorphism on post-transplant outcome in patients who were transplanted after 2004. MUC5B was successfully genotyped in 746 patients. The MAF was significantly higher in ILD (17.6%) compared to chronic obstructive pulmonary disease (COPD)/emphysema (9.3%), cystic fibrosis (CF)/bronchiectasis (BRECT) (7.5%) and pulmonary hypertension (PHT) (7.4%) (p < 0.001). No association was observed between rs35705950 and chronic lung allograft dysfunction (CLAD)/graft loss in the ILD population [CLAD: HR 1.37 95% CI (0.70-2.68); graft loss: HR 1.02 95% CI (0.55-1.89)], nor the entire study cohort [CLAD: HR 0.96 95% CI (0.69-1.34); graft loss: HR 0.97 95% CI (0.70-1.35)]. The MUC5B promoter polymorphism is a very specific predictive factor for the presence of pulmonary fibrosis as it is only associated with pulmonary fibrosis and not with other chronic respiratory diseases. While the MUC5B promoter variant is associated with better pre-transplant survival among IPF patients, recipient MUC5B promoter variant does not play a role in post-transplant outcome. ispartof: TRANSPLANT INTERNATIONAL vol:35 ispartof: location:Switzerland status: published

Organ transplantation is hampered by shortage of suitable organs. In countries with a legal framework, organ donation following euthanasia is an option labeled "donation after cardio-circulatory death category V" (DCD-V). We describe our experience with lung transplantation (LTx) after euthanasia and evaluate post-transplant outcome using a matched comparison to DCD-III (withdrawal from life-sustaining therapy) and donation after brain death (DBD).All bilateral LTx between 2007 and 2020 were retrospectively analyzed. Matching was performed for recipient age and gender, indication for LTx, mean pulmonary artery pressure, extracorporeal life support, and donor age, which resulted in 1:2 DCD-III and 1:3 DBD matching. Primary graft dysfunction (PGD), chronic lung allograft dysfunction (CLAD), and patient survival were analyzed.A total of 769 LTx were performed of which 22 from DCD-V donors (2.9%). Thirteen women and 9 men expressed their wish to become organ donor after euthanasia. Euthanasia request was granted for irremediable neuromuscular (N = 9) or psychiatric (N = 8) disorder or unbearable and unrecoverable pain (N = 5). PGD (grade 3, within 72 hours post-transplant) was 23.8% in the DCD-V cohort, which is comparable to DCD-III (27.9%; p = 1.00) and DBD (32.3%; p = .59). CLAD-free 3- and 5-year survival were 86.4% and 62.8%, respectively, and comparable to DCD-III (74.4% and 60.0%; p = .62) and DBD (72.6% and 55.5%; p = .32). Five-year patient survival was 90.9%, not significantly different from both DCD-III (86.0%; p = 1.00) and DBD (78.1%; p = .36).We observed that LTx with DCD-V allografts is feasible and safe, yielding no evidence for differences in short- and long-term outcome compared to matched cohorts of DCD-III and DBD.

Introduction: COVID-19 raises concerns for lung transplant recipients (LTX) due to the lung as a target organ in immunocompromised patients. Aims and objectives: Evaluating COVID-19 course, treatments received, radiological and functional evolution in LTX. Methods: We conducted a retrospective study of LTX with a PCR confirmed diagnosis of COVID-19. Results: 42 LTX were included from 18/03/2020 until 01/02/2021. Mean age was 54y (19-73), mean time after LTX 68mo (7-194). 30 (71%) LTX were hospitalised with a mean duration of 14d (1-41). Seven (17%) needed ICU, 5 (12%) endotracheal intubation and 1 (2%) VV ECMO. 4 (10%) died. From the 7 patients in ICU, 4 were aged>65y, 2 had diabetes, 2 hypertension, 2 BMI>30. In all hospitalised patients immunosuppression was adapted (mycophenolate mofetil withdrawn for at least 2 weeks, low level of calcineurin inhibitors, 5 day course of azithromycin 500mg). 8 (19%) received hydroxychloroquine, 8 (19%) remdesivir, 9 (21%) COVID-19 convalescent plasma and 9 (21%) higher corticosteroid dose. 4 (10%) LTX experienced recurrent COVID-19. 3 (7%) developed acute rejection shortly after COVID-19. In LTX with follow-up chest CT (n=15) minimal sequellae were described. Mean decrease in FEV1 compared to baseline at 1, 3 and 6 months was, respectively, -133mL (IQR -190 to 35, n=28), -176mL (IQR -330 to 75, n=16) and -48mL (IQR -140 to 90, n=11). No patient met criteria for onset of CLAD. Conclusions: We found a higher mortality and more severe disease course in LTX than in the healthy population. Recurrence of COVID-19 is a frequent event. At mid-term, we did not observe significant new incidence of CLAD onset. Treatment of COVID-19 and risk of CLAD after COVID-19 in LTX require further studies.

Healthcare providers outside pulmonary hypertension (PH) centers having misinformation or insufficient education, and a general lack of treatment awareness contribute to a massive underdiagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), diagnostic delay and refusal of surgery by patients. Together with the subjective operability assessment, this leads to too few patients undergoing pulmonary endarterectomy (PEA); even though this surgery results in improved survival and exercise capacity. Acute pulmonary embolism (PE) survivors should undergo a CTEPH screening strategy. Patients screened positive and those with CTEPH symptoms (with or without history of PE), should undergo transthoracic echocardiography (TTE) to determine the probability of PH. High PH probability patients should undergo a ventilation/perfusion (V/Q) scan. A negative scan rules out CTEPH. Patients with a positive V/Q scan, but also patients with findings suggestive for CTEPH on computed tomography pulmonary angiography (CTPA) to diagnose acute PE, should be referred to a CTEPH center. Further diagnostic work-up currently consists of catheter based pulmonary angiography, CTPA and right heart catheterization. However, new imaging technologies might replace them in the near future, with one single imaging tool to screen, diagnose and assess operability as the ultimate goal. Operability assessment should be performed by a multidisciplinary CTEPH team. PEA surgery should be organized in a single center per country or for each forty to fifty million inhabitants in order to offer the highest level of expertise. Informing patients about PEA should preferably be done by the treating surgeon. Based on the estimated incidence of CTEPH and with a better education of patients and healthcare providers, despite the advent of new interventional and medical therapies for CTEPH, the number of PEA surgeries performed should still have the potential to grow significantly. ispartof: ANNALS OF CARDIOTHORACIC SURGERY vol:11 issue:2 pages:82-97 ispartof: location:China status: published

ispartof: ANNALS OF CARDIOTHORACIC SURGERY vol:11 issue:2 pages:163-165 ispartof: location:China status: published

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:39 issue:11 pages:1171-1190 ispartof: location:United States status: published

Background Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the BMPR2 gene. Based on expert consensus, guidelines recommend annual screening echocardiography in asymptomatic BMPR2 mutation carriers. The main objectives of this study were to evaluate the characteristics of asymptomatic BMPR2 mutation carriers, assess their risk of occurrence of PAH and detect PAH at an early stage in this high-risk population. Methods Asymptomatic BMPR2 mutation carriers underwent screening at baseline and annually for a minimum of 2 years (DELPHI-2 study; ClinicalTrials.gov: NCT01600898). Annual screening included clinical assessment, ECG, pulmonary function tests, 6-min walk distance, cardiopulmonary exercise testing, chest radiography, echocardiography and brain natriuretic peptide (BNP) or N-terminal (NT)-proBNP level. Right heart catheterisation (RHC) was performed based on predefined criteria. An optional RHC at rest and exercise was proposed at baseline. Results 55 subjects (26 males; median age 37 years) were included. At baseline, no PAH was suspected based on echocardiography and NT-proBNP levels. All subjects accepted RHC at inclusion, which identified two mild PAH cases (3.6%) and 12 subjects with exercise pulmonary hypertension (21.8%). At long-term follow-up (118.8 patient-years of follow-up), three additional cases were diagnosed, yielding a PAH incidence of 2.3% per year (0.99% per year in males and 3.5% per year in females). All PAH cases remained at low-risk status on oral therapy at last follow-up. Conclusions Asymptomatic BMPR2 mutation carriers have a significant risk of developing incident PAH. International multicentre studies are needed to confirm that refined multimodal screening programmes with regular follow-up allow early detection of PAH., Asymptomatic BMPR2 mutation carriers have a 2.3% per year risk of developing PAH. DELPHI-2 provides the platform for future international multicentre studies to refine multimodal screening algorithms in BMPR2 mutation carriers. http://bit.ly/3oi2KJ1

Background:Exertional intolerance is a limiting and often crippling symptom in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally the pathogenesis has been attributed to central factors, including ventilation/perfusion mismatch, increased pulmonary vascular resistance, and right heart dysfunction and uncoupling. Pulmonary endarterectomy and balloon pulmonary angioplasty provide substantial improvement of functional status and hemodynamics. However, despite normalization of pulmonary hemodynamics, exercise capacity often does not return to age-predicted levels. By systematically evaluating the oxygen pathway, we aimed to elucidate the causes of functional limitations in patients with CTEPH before and after pulmonary vascular intervention.Methods:Using exercise cardiac magnetic resonance imaging with simultaneous invasive hemodynamic monitoring, we sought to quantify the steps of the O2transport cascade from the mouth to the mitochondria in patients with CTEPH (n=20) as compared with healthy participants (n=10). Furthermore, we evaluated the effect of pulmonary vascular intervention (pulmonary endarterectomy or balloon angioplasty) on the individual components of the cascade (n=10).Results:Peak Vo2(oxygen uptake) was significantly reduced in patients with CTEPH relative to controls (56±17 versus 112±20% of predicted;P2cascade, including O2delivery (product of cardiac output and arterial O2content), skeletal muscle diffusion capacity, and pulmonary diffusion. The total O2extracted in the periphery (ie, ΔAVo2[arteriovenous O2content difference]) was not different. After pulmonary vascular intervention, peak Vo2increased significantly (from 12.5±4.0 to 17.8±7.5 mL/[kg·min];P=0.036) but remained below age-predicted levels (70±11%). The O2delivery was improved owing to an increase in peak cardiac output and lung diffusion capacity. However, peak exercise ΔAVo2was unchanged, as was skeletal muscle diffusion capacity.Conclusions:We demonstrated that patients with CTEPH have significant impairment of all steps in the O2use cascade, resulting in markedly impaired exercise capacity. Pulmonary vascular intervention increased peak Vo2by partly correcting O2delivery but had no effect on abnormalities in peripheral O2extraction. This suggests that current interventions only partially address patients’ limitations and that additional therapies may improve functional capacity.

Background During the COVID-19 pandemic, most of the health care systems suspended their non-urgent activities. This included the cancellation of consultations for patients with rare diseases, such as severe pulmonary hypertension (PH), resulting in potential medication shortage and loss of follow-up. Thus, the aim of the study was to evaluate PH patient health status evolution, access to health care and mental health experience during the early phase of the pandemic. Methods We conducted an online patient survey, available in 16 languages, between 22/05/2020 and 28/06/2020. The survey included questions corresponding to demographic, COVID-19 and PH related information. Results 1073 patients (or relatives, 27%) from 52 countries all over the world participated in the survey. Seventy-seven percent (77%) of responders reported a diagnosis of pulmonary arterial hypertension and 15% of chronic thromboembolic PH. The COVID-19 related events were few: only 1% of all responders reported a diagnosis of COVID-19. However, 8% of patients reported health deterioration possibly related to PH, and 4% hospitalization for PH. Besides, 11% of the patients reported difficulties to access their PH expert centre, and 3% interruption of treatment due to shortage of medication. Anxiety or depression was reported by 67% of the participants. Conclusion Although COVID-19 incidence in PH patients was low, PH related problems occurred frequently as the pandemic progressed, including difficulties to have access to specialized care. The importance of primary health care was emphasized. Further studies are needed to evaluate the long-term consequences of COVID-related PH care disruption.

ispartof: BRITISH JOURNAL OF HAEMATOLOGY vol:192 issue:6 pages:1100-1105 ispartof: location:England status: published

Introduction: Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the BMPR2 gene (encoding Bone Morphogenetic Protein Receptor type II). Despite the lack of clear evidence, asymptomatic BMPR2 mutation carriers are recommended to undergo annual screening echocardiography for early detection of PAH. Objectives: To evaluate the utility of a comprehensive multimodal PAH screening program in asymptomatic adult BMPR2 mutation carriers. Methods: Asymptomatic BMPR2 mutation carriers underwent screening at baseline and annually for a minimum of two years (DELPHI-2 study, NCT01600898). Annual screening included clinical assessment, electrocardiogram, pulmonary function tests, 6-minute walk distance, cardiopulmonary exercise test (CPET), chest x-ray, echocardiography and N-terminal pro-brain natriuretic peptide level. Right heart catheterization (RHC) was performed based on predefined criteria. An optional RHC at rest and exercise was proposed at baseline. Results: Fifty-five subjects (26 males, median age 37 years) were included. At baseline, no PAH was suspected based on echocardiography and NT pro-BNP levels. All subjects accepted RHC at inclusion which identified two mild PAH cases (3.6%) and 12 subjects with exercise pulmonary hypertension of unknown significance (21.8%). At long term follow-up, three additional PAH cases were diagnosed, yielding a PAH incidence of 2.3%/year. All detected cases have remained at low risk status on oral PAH therapy at last follow-up. Conclusion: In adult BMPR2 mutation carriers, a multimodal screening program with regular follow-up allows early detection of PAH.

Introduction: Mammalian target of rapamycin-inhibitors (mTORi) are increasingly used after transplantation as part of a calcineurin-inhibitor (CNI) sparing regimen, aiming to preserve renal function. Aims: The aim of this study was to determine whether immunosuppressive therapy using mTORi in lung transplant recipients (LTR) is feasible in practice, or limited by intolerance and adverse events. Methods: Data were retrospectively assessed for all LTR transplanted between July 1991 and January 2020. Patients currently in follow-up ever receiving a mTOR inhibitor and reduced CNI as treatment of physicians9 choice were included for analysis. Data were obtained from the patients’ electronic medical records. Results: Of 676 LTR currently in follow-up, 111 (16.4%) received a mTORi (2 sirolimus, rest everolimus). In the majority (93.7%), mTORi was started from 2018 on, after a median of 989 (353-2457) days post-transplant. In 48 cases (43.2%) mTORi had to be stopped due to side effects or toxicity; median time to stop was 133.5 (42-229.5) days. Main reasons for discontinuation were lung toxicity (21.1%), edema (21.1%) and infection (19.3%). Early discontinuation ( Conclusion: mTORi had to be stopped due to adverse events or intolerance in 43.2% of LTR, suggesting that cautious consideration of advantages and disadvantages when starting mTORi is needed.

Study questionIn patients with sarcoidosis, past and ongoing immunosuppressive regimens, recurrent disease in the transplant and extrapulmonary involvement may affect outcomes of lung transplantation. We asked whether sarcoidosis lung phenotypes can be differentiated and, if so, how they relate to outcomes in patients with pulmonary sarcoidosis treated by lung transplantation.Patients and methodsWe retrospectively reviewed data from 112 patients who met international diagnostic criteria for sarcoidosis and underwent lung or heart–lung transplantation between 2006 and 2019 at 16 European centres.ResultsPatient survival was the main outcome measure. At transplantation, median (interaquartile range (IQR)) age was 52 (46–59) years; 71 (64%) were male. Lung phenotypes were individualised as follows: 1) extended fibrosis only; 2) airflow obstruction; 3) severe pulmonary hypertension (sPH) and airflow obstruction; 4) sPH, airflow obstruction and fibrosis; 5) sPH and fibrosis; 6) airflow obstruction and fibrosis; 7) sPH; and 8) none of these criteria, in 17%, 16%, 17%, 14%, 11%, 9%, 5% and 11% of patients, respectively. Post-transplant survival rates after 1, 3, and 5 years were 86%, 76% and 69%, respectively. During follow-up (median (IQR) 46 (16–89) months), 31% of patients developed chronic lung allograft dysfunction. Age and extended lung fibrosis were associated with increased mortality. Pulmonary fibrosis predominating peripherally was associated with short-term complications.Answer to the study questionPost-transplant survival in patients with pulmonary sarcoidosis was similar to that in patients with other indications for lung transplantation. The main factors associated with worse survival were older age and extensive pre-operative lung fibrosis.

BACKGROUND: Lung transplantation (LTx) requires a calcineurin inhibitor-based immunosuppressive regimen. A once daily (QD) tacrolimus regimen was developed to increase medication adherence. However, data concerning its safety and efficacy in LTx are lacking. METHODS: In this prospective study, stable LTx patients were consecutively converted from twice daily (BID) tacrolimus to QD tacrolimus on a 1 mg:1 mg basis. Trough level (Cmin), renal function, cholesterol, fasting glucose, potassium and lung function were monitored six months before and up to one year after conversion. Adherence and its barriers were assessed by self-reported questionnaires (Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and Identification of Medication Adherence Barriers questionnaire (IMAB)) and blood-based assays (mean Cmin and coefficient of variation (CV)). RESULTS: We included 372 patients, in whom we observed a decrease in tacrolimus Cmin of 18.5% (p < 0.0001) post-conversion, requiring subsequent daily dose adaptations in both cystic fibrosis (CF) (n = 72) and non-CF patients (n = 300). We observed a small decrease in eGFR one year post-conversion (p = 0.024). No significant changes in blood creatinine, potassium, fasting glucose, cholesterol or rate of lung function decline were observed. In a subgroup of 166 patients, significantly fewer patients missed doses (8.4% vs. 19.3%, p = 0.016) or had irregular intake post-conversion (19.3% vs. 32.5%, p = 0.019). Mean Cmin and CV, as well as the total number of barriers, also decreased significantly post-conversion. CONCLUSIONS: In LTx, conversion from BID to QD tacrolimus (1 mg:1 mg) requires close monitoring of tacrolimus Cmin. QD tacrolimus after transplantation is safe with respect to renal function, metabolic parameters and allograft function and improves LTx recipient adherence. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:40 issue:6 pages:467-477 ispartof: location:United States status: published

Several case reports and small case series have been published on coronavirus disease 2019 infection after solid organ transplantation; however, thus far there are limited data on coronavirus disease 2019 infections in lung transplant patients. In the present single-center case series we discuss 10 lung transplant patients with a documented severe acute respiratory syndrome coronavirus 2 infection, diagnosed with nasopharyngeal swab in 8 and bronchoalveolar lavage in 2. Eight of 10 patients needed hospital admission, of whom 1 was in the intensive care unit. He died after 2 weeks from multiple organ failure. The remaining nine patients recovered. Cell cycle inhibitors were withheld in all patients, whereas the calcineurin inhibitor and corticosteroids were continued at the same dose, with an acceptable outcome. ispartof: AMERICAN JOURNAL OF TRANSPLANTATION vol:20 issue:11 pages:3234-3238 ispartof: location:United States status: published

The 2019 European Respiratory Society (ERS) International Congress, held in Madrid, Spain, had exciting sessions regarding the field of pulmonary vascular disease. The symposia related to the new ERS/European Society of Cardiology (ESC) Guidelines for the diagnosis and management of acute pulmonary embolism were well received, as were sessions on pulmonary hypertension related to lung disease, demonstrating the concept of pulmonary hypertension not being the rarity that it was previously thought to be. The use of risk stratification in relation to pulmonary arterial hypertension (PAH) was heavily featured and the scientific sessions informing the respiratory community of potential biomarkers and targets for future therapies were thought-provoking. This article discusses highlights of the 2019 pulmonary vascular disease sessions as a summary of current knowledge and practice. We have summarised the key points from the sessions pertaining to the new ERS/ESC Guidelines for the management of acute pulmonary embolism. We have also focused on prognostic factors and potential therapies in pulmonary hypertension related to interstitial lung disease. Relating to PAH, we have reviewed the symposia on risk stratification, along with the use of noninvasive measures and the sessions relating to biomarkers in PAH., This article aims to summarise research presented at #ERSCongress 2019: the new @escardio/@EuroRespSoc guidance on acute PE diagnosis and management, PH in relation to chronic lung disease, and advances in pulmonary arterial hypertension https://bit.ly/3bAUG0o