264 research outputs found
The impact of hypoxia on B cells in COVID-19
No full textBackground: Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This presentation resembles the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19. Methods: Detailed B cell phenotyping was undertaken by flow-cytometry on longitudinal samples from patients with COVID-19 across a range of severities (NIHR Cambridge BioResource). The impact of hypoxia on the transcriptome was assessed by single-cell and whole blood RNA sequencing analysis. The direct effect of hypoxia on B cells was determined through immunisation studies in genetically modified and hypoxia-exposed mice. Findings: We demonstrate the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes also observed in B cell VHL-deficient mice. These findings were associated with hypoxia-related transcriptional changes in COVID-19 patient B cells, and similar B cell abnormalities were seen in mice kept in hypoxic conditions. Interpretation: Hypoxia may contribute to the pronounced and persistent B cell pathology observed in acute COVID-19 pneumonia. Assessment of the impact of early oxygen therapy on these immune defects should be considered, as their correction could contribute to improved outcomes. Funding: Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trus
Drug Development for Pulmonary Arterial Hypertension: Unleashing the Potential of Single-Patient Studies Using Continuous Monitoring
No full textDrug development for pulmonary arterial hypertension: unleashing the potential of single‐patient studies using continuous monitoring
No full textThe Relationship between Mean and Systolic Pulmonary Artery Pressure in Idiopathic (IPAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH).
No full textAuthor Correction: Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood (Nature Communications, (2021), 12, 1, (7104), 10.1038/s41467-021-27326-0)
No full text\ua9 2022, The Author(s).The original version of this Article omitted Richard C Trembath from the UK National PAH Cohort Study consortium from Health and Life Sciences, King’s College London. This has been corrected in both the PDF and HTML versions of the Article
Whole-lake Herbicide Treatments for Eurasian Watermilfoil in Four Wisconsin Lakes: Effects on Vegetation and Water Clarity
No full textAcute haemodynamic responses to inhaled nitric oxide and intravenous sildenafil in distal chronic thromboembolic pulmonary hypertension
No full textArrhythmic burden and outcomes in pulmonary arterial hypertension
No full textPulmonary arterial hypertension (PAH) is a devastating, life-limiting disease driven by small vessel vascular remodeling leading to a rise in pulmonary vascular resistance (PVR). Patients present with a range of symptoms including shortness of breath, exercise intolerance, palpitations or syncope. Symptoms may be related to vascular disease progression or arrhythmia secondary to the adaptation of the right heart to pressure overload. Arrhythmic burden is high in patients with left heart disease and guideline-based treatment of arrhythmias improves quality of life and prognosis. In PAH the incidence and prevalence of arrhythmias is less well-defined and there are no PAH-specific guidelines for arrhythmia management. We undertook a literature search identifying 13 relevant papers; detection of arrhythmias was acquired from 12-lead electrocardiogram (ECG) or Holter monitors. In all forms of pulmonary hypertension (PH) the prevalence of supraventricular arrhythmias (SVA) was 26–31%, ventricular arrhythmias (VA) 24% and a 5-year incidence of SVA ~13.2–25.1%. Prevalence and incidence of arrhythmias in PAH is less clear due to limited study numbers and the heterogenous nature of the patient population studied. For arrhythmia treatment, only single-arm studies of therapeutic strategies were reported using antiarrhythmic drugs (AAD), direct current cardioversion (DCCV) and ablation. Periods between ECG or Holter have not been investigated, highlighting the possibility that significant arrhythmias may be undetected. Advances in monitoring allow long-term surveillance via implanted/non-invasive monitors. Use of such technologies may provide an accurate estimate of incidence and prevalence of arrhythmias in patients with PAH, further defining relationships to adverse outcomes, and therapeutic options
Increased Antielastase Activity in Idiopathic Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.
No full textPulmonary arterial hypertension (PAH) is characterized by abnormal remodeling and occlusion of pre-capillary arterioles in the lung with a subsequent increase in pulmonary vascular resistance. This can lead to right ventricular hypertrophy and ultimately right heart failure. Elastase is implicated in the pathobiology of PAH with evidence including: ultra-structural studies showing increased elastase activity in pulmonary arteries from children with congenital heart disease-associated PAH (1), increased elastase release from peripheral blood neutrophils isolated from patients with pulmonary hypertension compared with healthy controls (2) and elevated plasma concentrations of elastase in patients with idiopathic PAH (IPAH) (3)
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