An unprecedented pathology in a 20-year-old with progressive dyspnoea and parenchymal infiltrates.

https://bit.ly/42kscnz.

Recent Advances in the Diagnosis and Management of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a rare, progressive, debilitating and life shortening condition characterized by raised pulmonary arterial pressures. PAH includes a group of conditions sharing similar pathophysiology, clinical features and response to therapy. The commonest sub-groups of PAH include idiopathic pulmonary arterial hypertension (IPAH), and PAH associated with connective tissue disease.

Pulmonary vascular manifestations of hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant, multisystem disorder that manifests with a spectrum of disease including cardiopulmonary complications. HHT is characterised by aberrant signalling via the transforming growth factor β (TGFβ) pathway, with loss of vascular integrity, angiogenesis and vascular dysplasia. The disease has an estimated prevalence of 1 in 5000 persons and the penetrance increases with increasing age.

The impact of gas transfer on responses to exercise training in patients with pulmonary hypertension.

Exercise training is recommended for pulmonary hypertension (PH). Post hoc analysis of the PH and Home-Based (PHAHB) trial stratified patients into two groups based on median diffusing capacity of the lungs for carbon monoxide (DLCO). Patients with higher DLCO had a greater improvement in physical activity performance in response to exercise training, compared to those with lower DLCO.

Safety, feasibility and effectiveness of the remotely delivered Pulmonary Hypertension and Home-Based (PHAHB) physical activity intervention.

Background: Pulmonary hypertension (PH) is a heterogeneous condition, associated with a high symptom burden and a substantial loss of exercise capacity. Despite prior safety concerns regarding physical exertion, exercise training as a supportive therapy is now recommended for PH patients. Currently, most programmes are hospital-based, which limits accessibility.

Exploration of physical activity knowledge, preferences and support needs among pulmonary hypertension patients.

Objective: Physical activity (PA) is an established adjunct therapy for pulmonary hypertension (PH) patients to mitigate PH symptoms and improve quality of life. However, PA engagement within this population remains low. This study investigated PH patients' knowledge of PA, recalled advice, exercise preferences and PA support needs.

Incidence and outcomes of pulmonary hypertension in the Ireland.

Introduction: Pulmonary hypertension (PH) is a progressive disease of the pulmonary vasculature, which is characterised by premature morbidity and mortality. The aim of this study is to define the characteristics of PH in the national PH unit (NPHU) in Ireland between 2010 and 2020.

Methods: Cases of PH which were referred to the NPHU between 2010 and 2020 were included.

Real-world experience of selexipag titration in pulmonary arterial hypertension.

Selexipag is an oral selective prostacyclin-receptor agonist that was approved for use in patients with World Health Organisation (WHO) functional class II-III pulmonary arterial hypertension (PAH). Treatment with individualised doses of selexipag resulted in significant reductions in the composite end point of death or a complication related to PAH in the phase III GRIPHON (Prostacyclin [PGI2] Receptor Agonist In Pulmonary Arterial Hypertension) study. In order to better understand the real-world approach to selexipag titration and to establish the individualised maintenance regimens used in our centre, we performed this retrospective study of the first 20 patients prescribed selexipag.

Progressive dyspnoea in a patient with idiopathic non-cirrhotic portal hypertension.

https://bit.ly/3rwEkhP.

Non-severe COVID-19 is associated with endothelial damage and hypercoagulability despite pharmacological thromboprophylaxis.

Background: Hypercoagulability and endothelial dysfunction are hallmarks of coronavirus disease 2019 (COVID-19) and appear to predict disease severity. A high incidence of thrombosis despite thromboprophylaxis is reported in patients with moderate to severe COVID-19. Recent randomized clinical trials suggest that therapeutic-intensity heparin confers a survival benefit in moderate-severity COVID-19 compared to standard-intensity heparin, potentially by harnessing heparin-mediated endothelial-stabilizing and anti-inflammatory effects.

"It is the fear of exercise that stops me" - attitudes and dimensions influencing physical activity in pulmonary hypertension patients.

Pulmonary hypertension is a progressive cardiorespiratory disease that is characterized by considerable morbidity and mortality. While physical activity can improve symptoms and quality of life, engagement in this population is suboptimal. The aim of this study was to explore attitudes towards exercise and the dimensions that influence physical activity participation in individuals with pulmonary hypertension.

Characteristics of chronic thromboembolic pulmonary hypertension in Ireland.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and under-recognised complication of acute pulmonary embolism. Information regarding the characteristics of CTEPH in Ireland is limited, and the aim of this retrospective cohort study was to address this knowledge gap. Seventy-two cases of CTEPH were diagnosed in the National Pulmonary Hypertension Unit (NPHU) in Ireland between 2010 and 2020.

Routine Hematological Parameters May Be Predictors of COVID-19 Severity.

To date, coronavirus disease 2019 (COVID-19) has affected over 100 million people globally. COVID-19 can present with a variety of different symptoms leading to manifestation of disease ranging from mild cases to a life-threatening condition requiring critical care-level support. At present, a rapid prediction of disease severity and critical care requirement in COVID-19 patients, in early stages of disease, remains an unmet challenge.

An interesting case of progressive dyspnoea and diffuse mediastinal adenopathy in a 25-year-old man.

https://bit.ly/3cfe9pX.

Genomic Evolution of SARS-CoV-2 Virus in Immunocompromised Patient, Ireland.

We examined virus genomic evolution in an immunocompromised patient with prolonged severe acute respiratory syndrome coronavirus 2 infection. Genomic sequencing revealed genetic variation during infection: 3 intrahost mutations and possible superinfection with a second strain of the virus. Prolonged infection in immunocompromised patients may lead to emergence of new virus variants.

Platelets, extracellular vesicles and coagulation in pulmonary arterial hypertension.

Pulmonary arterial hypertension is a rare disease of the pulmonary vasculature, characterised pathologically by proliferation, remodelling and thrombosis . Unfortunately, existing therapeutic interventions do not reverse these findings and the disease continues to result in significant morbidity and premature mortality. A number of haematological derangements have been described in pulmonary arterial hypertension which may provide insights into the pathobiology of the disease and opportunities to explore new therapeutic pathways.

Pulmonary hypertension and home-based (PHAHB) exercise intervention: protocol for a feasibility study.

Introduction: Novel therapies for pulmonary hypertension (PH) have improved survival and slowed disease progression. However, patients still present with symptoms of exertional dyspnoea and fatigue, which impacts their ability to perform activities of daily living, reduces exercise tolerance and impairs their quality of life (QoL). Exercise training has shown to be safe and effective at enhancing QoL and physical function in PH patients, yet it remains an underused adjunct therapy.

Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis.

Background: Cystic fibrosis (CF) lung disease is defined by large numbers of neutrophils and associated damaging products in the airway. Delayed neutrophil apoptosis is described in CF although it is unclear whether this is a primary neutrophil defect or a response to chronic inflammation. Increased levels of neutrophil extracellular traps (NETs) have been measured in CF and we aimed to investigate the causal relationship between these phenomena and their potential to serve as a driver of inflammation.

Monocyte derived macrophages from CF pigs exhibit increased inflammatory responses at birth.

Background: We sought to address whether CF macrophages have a primary functional defect as a consequence of CFTR loss and thus contribute to the onset of infection and inflammation observed in CF lung disease.

Methods: Monocyte derived macrophages (MDMs) were prepared from newborn CF and non-CF pigs. CFTR mRNA expression was quantified by rtPCR and anion channel function was determined using whole cell patch clamp analysis.

Elevated plasma CXCL12α is associated with a poorer prognosis in pulmonary arterial hypertension.

Rationale: Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortality.

Methods: Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44).

NETs and CF Lung Disease: Current Status and Future Prospects.

Cystic Fibrosis (CF) is the most common fatal monogenic disease among Caucasians. While CF affects multiple organ systems, the principle morbidity arises from progressive destruction of lung architecture due to chronic bacterial infection and inflammation. It is characterized by an innate immune defect that results in colonization of the airways with bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa from an early age.

Detection of high-sensitivity troponin in outpatients with stable pulmonary hypertension identifies a subgroup at higher risk of adverse outcomes.

Background: The detection of elevations in cardiorenal biomarkers, such as troponins, B-type natriuretic peptides (BNPs), and neutrophil gelatinase-associated lipocalins, are associated with poor outcomes in patients hospitalized with acute heart failure. Less is known about the association of these markers with adverse events in chronic right ventricular dysfunction due to pulmonary hypertension, or whether their measurement may improve risk assessment in the outpatient setting.

Methods And Results: We performed a cohort study of 108 patients attending the National Pulmonary Hypertension Unit in Dublin, Ireland, from 2007 to 2009.

A role for the CXCL12 receptor, CXCR7, in the pathogenesis of human pulmonary vascular disease.

Given the critical role that endothelial cell dysfunction plays in the pathogenesis of pulmonary hypertensive diseases, we set out to establish if CXCR7, a receptor for the pro-angiogenic ligand CXCL12, is expressed in the vasculature of human lung diseases and examine its role in mediating CXCL12-induced responses in primary pulmonary human microvascular endothelial cells. Receptor and ligand expression was examined in control and explanted human hypertensive lungs, in human plasma and in hypoxic rodent lungs, by ELISA and immunohistochemical studies. Functional in vitro experiments examined the role of CXCR7 in CXCL12-induced lung microvascular endothelial cell proliferation, migration, and wound regeneration and repair.