Pulmonary vascular disease, environmental pollution, and climate change

Pollution and climate change constitute a combined, grave and pervasive threat to humans and to the life‐support systems on which they depend. Evidence shows a strong association between pollution and climate change on cardiovascular and respiratory diseases, and pulmonary vascular disease (PVD) is no exception. An increasing number of studies has documented the impact of environmental pollution and extreme temperatures on pulmonary circulation and the right heart, on the severity and outcomes of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (PH), on the incidence of pulmonary embolism, and the prevalence and severity of diseases associated with PH. Furthermore, the downstream consequences of climate change impair health care systems' accessibility, which could pose unique obstacles in the case of PVD patients, who require a complex and sophisticated network of health interventions. Patients, caretakers and health care professionals should thus be included in the design of policies aimed at adaptation to and mitigation of current challenges, and prevention of further climate change. The purpose of this review is to summarize the available evidence concerning the impact of environmental pollution and climate change on the pulmonary circulation, and to propose measures at the individual, healthcare and community levels directed at protecting patients with PVD

Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension

Pulmonary endarterectomy (PEA) resected material offers a unique opportunity to develop an in vitro endothelial cell model of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to comprehensively analyze the endothelial function, molecular signature, and mitochondrial profile of CTEPH-derived endothelial cells to better understand the pathophysiological mechanisms of endothelial dysfunction behind CTEPH, and to identify potential novel targets for the prevention and treatment of the disease. Isolated cells from specimens obtained at PEA (CTEPH-EC), were characterized based on morphology, phenotype, and functional analyses (in vitro and in vivo tubule formation, proliferation, apoptosis, and migration). Mitochondrial content, morphology, and dynamics, as well as high-resolution respirometry and oxidative stress, were also studied. CTEPH-EC displayed a hyperproliferative phenotype with an increase expression of adhesion molecules and a decreased apoptosis, eNOS activity, migration capacity and reduced angiogenic capacity in vitro and in vivo compared to healthy endothelial cells. CTEPH-EC presented altered mitochondrial dynamics, increased mitochondrial respiration and an unbalanced production of reactive oxygen species and antioxidants. Our study is the foremost comprehensive investigation of CTEPH-EC. Modulation of redox, mitochondrial homeostasis and adhesion molecule overexpression arise as novel targets and biomarkers in CTEPH.Peer ReviewedPostprint (published version

Association Between Systemic and Pulmonary Vascular Dysfunction in COPD

Introduction: In chronic obstructive pulmonary disease (COPD), endothelial dysfunction and stiffness of systemic arteries may contribute to increased cardiovascular risk. Pulmonary vascular disease (PVD) is frequent in COPD. The association between PVD and systemic vascular dysfunction has not been thoroughly evaluated in COPD. Methods: A total of 108 subjects were allocated into four groups (non-smoking controls, smoking controls, COPD without PVD and COPD with PVD). In systemic arteries, endothelial dysfunction was assessed by flow-mediated dilation (FMD) and arterial stiffness by pulse wave analysis (PWA) and pulse wave velocity (PWV). PVD was defined by a mean pulmonary artery pressure (PAP) ≥ 25 mmHg at right heart catheterization or by a tricuspid regurgitation velocity > 2.8 m/s at doppler echocardiography. Biomarkers of inflammation and endothelial damage were assessed in peripheral blood. Results: FMD was lower in COPD patients, with or without PVD, compared to non-smoking controls; and in patients with COPD and PVD compared to smoking controls. PWV was higher in COPD with PVD patients compared to both non-smoking and smoking controls in a model adjusted by age and the Framingham score; PWV was also higher in patients with COPD and PVD compared to COPD without PVD patients in the non-adjusted analysis. FMD and PWV correlated significantly with forced expiratory volume in the first second (FEV1), diffusing capacity for carbon monoxide (DLCO) and systolic PAP. FMD and PWV were correlated in all subjects. Discussion: We conclude that endothelial dysfunction of systemic arteries is common in COPD, irrespective if they have PVD or not. COPD patients with PVD show increased stiffness and greater impairment of endothelial function in systemic arteries. These findings suggest the association of vascular impairment in both pulmonary and systemic territories in a subset of COPD patients

ERS International Congress 2023: highlights from the Pulmonary Vascular Diseases Assembly

Pulmonary vascular diseases such as pulmonary embolism and pulmonary hypertension are important and frequently under-recognised conditions. This article provides an overview of key highlights in pulmonary vascular diseases from the European Respiratory Society International Congress 2023. This includes insights into disease modification in pulmonary arterial hypertension and novel therapies such as sotatercept and seralutinib. Exciting developments in our understanding of the mechanisms underpinning pulmonary hypertension associated with interstitial lung disease are also explored. A comprehensive overview of the complex relationship between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) is provided along with our current understanding of the molecular determinants of CTEPH. The importance of multidisciplinary and holistic care cannot be understated, and this article also addresses advances beyond medication, with a special focus on exercise training and rehabilitation

ERS International Congress 2021: highlights from the Pulmonary Vascular Diseases Assembly

This article aims to summarise the latest research presented at the virtual 2021 European Respiratory Society (ERS) International Congress in the field of pulmonary vascular disease. In light of the current guidelines and proceedings, knowledge gaps are addressed and the newest findings of the various forms of pulmonary hypertension as well as key points on pulmonary embolism are discussed.Despite the comprehensive coverage of the guidelines for pulmonary embolism at previous conferences, discussions about controversies in the diagnosis and treatment of this condition in specific cases were debated and are addressed in the first section of this article.We then report on an interesting pro–con debate about the current classification of pulmonary hypertension.We further report on presentations on Group 3 pulmonary hypertension, with research exploring pathogenesis, phenotyping, diagnosis and treatment; important contributions on the diagnosis of post-capillary pulmonary hypertension are also included.Finally, we summarise the latest evidence presented on pulmonary vascular disease and COVID-19 and a statement on the new imaging guidelines for pulmonary vascular disease from the Fleischner Society

Clinical significance of pulmonary hypertension in interstitial lung disease. a consensus statement from the pulmonary vascular research Institute's innovative drug development initiative—Group 3 pulmonary hypertension

Pulmonary hypertension (PH) has been linked to worse outcomes in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, an increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is the first step in trying to define a roadmap to facilitate and encourage future research in this area. The aim of our working group is to strengthen the communities understanding of PH due to lung diseases and to improve the care and quality of life of affected patients. This introductory statement provides a broad overview and lays the foundation for further in‐depth papers on specific topics pertaining to PH‐ILD

Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension

Pulmonary endarterectomy (PEA) resected material offers a unique opportunity to develop an in vitro endothelial cell model of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to comprehensively analyze the endothelial function, molecular signature, and mitochondrial profile of CTEPH-derived endothelial cells to better understand the pathophysiological mechanisms of endothelial dysfunction behind CTEPH, and to identify potential novel targets for the prevention and treatment of the disease. Isolated cells from specimens obtained at PEA (CTEPH-EC), were characterized based on morphology, phenotype, and functional analyses (in vitro and in vivo tubule formation, proliferation, apoptosis, and migration). Mitochondrial content, morphology, and dynamics, as well as high-resolution respirometry and oxidative stress, were also studied. CTEPH-EC displayed a hyperproliferative phenotype with an increase expression of adhesion molecules and a decreased apoptosis, eNOS activity, migration capacity and reduced angiogenic capacity in vitro and in vivo compared to healthy endothelial cells. CTEPH-EC presented altered mitochondrial dynamics, increased mitochondrial respiration and an unbalanced production of reactive oxygen species and antioxidants. Our study is the foremost comprehensive investigation of CTEPH-EC. Modulation of redox, mitochondrial homeostasis and adhesion molecule overexpression arise as novel targets and biomarkers in CTEPH

ERS International Congress 2023: highlights from the Pulmonary Vascular Diseases Assembly.

peer reviewedPulmonary vascular diseases such as pulmonary embolism and pulmonary hypertension are important and frequently under-recognised conditions. This article provides an overview of key highlights in pulmonary vascular diseases from the European Respiratory Society International Congress 2023. This includes insights into disease modification in pulmonary arterial hypertension and novel therapies such as sotatercept and seralutinib. Exciting developments in our understanding of the mechanisms underpinning pulmonary hypertension associated with interstitial lung disease are also explored. A comprehensive overview of the complex relationship between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) is provided along with our current understanding of the molecular determinants of CTEPH. The importance of multidisciplinary and holistic care cannot be understated, and this article also addresses advances beyond medication, with a special focus on exercise training and rehabilitation

Effects of Exercise Training on Circulating Biomarkers of Endothelial Function in Pulmonary Arterial Hypertension

In stable patients with pulmonary arterial hypertension (PAH), pulmonary rehabilitation (PR) is an effective, safe and cost-effective non-pharmacological treatment. However, the effects of PR on vascular function have been poorly explored. This study aimed to compare the amounts of circulating progenitor cells (PCs) and endothelial microvesicles (EMVs) in patients with PAH before and after 8 weeks of endurance exercise training as markers of vascular competence.This study has been funded by grants CP17/00114, CPII22/00006, PI12/00510, PI15/00582, PI21/01212, PI21/00215, PI18/00960, FI19/00001, INT19/00002 from the Institute of Health Carlos III (ISCiii), Spain, co-funded by the European Union (ERDF/ESF); the Catalan Society of Respiratory Medicine (SOCAP); the Spanish Society of Respiratory Medicine (SEPAR) and the Fundación Contra la Hipertensión Pulmonar (FCHP). Marie Curie Post-Doctoral Fellowship. Award BIOTRACK-IDIBAPS.Peer reviewe

Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases

BACKGROUND Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD). METHODS Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure. RESULTS The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results. CONCLUSION By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD