Circulating Factors in Pulmonary Hypertension
Research type
Research Study
Full title
Transpulmonary Gradients- Assessment of circulating factors in pulmonary hypertension
IRAS ID
168813
Contact name
Joanna Pepke-Zaba
Contact email
Sponsor organisation
Papworth Hospital NHS Foundation Trust
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Research Summary
Pulmonary hypertension is a disease where there is high pressure in the blood vessels in the lungs.
It is a serious disease which can cause patients to die early.
As the condition gets worse, the high pressure in the lung blood vessels puts strain on the heart and the heart is not able to work properly.
Previous research (including research done in our unit) has shown that the levels of several substances we can measure in blood samples are abnormal in patients with pulmonary hypertension. However, we do not know if the levels are directly related to blood vessel disease in the lungs.
To find out more about this, we will take samples of blood before and after blood has passed through the lungs and identify the substances in the blood. We will measure the amounts of the substances to see how the amounts increase, decrease or change by passing through the lungs in patients with pulmonary hypertension. We will also study a 'control' group of patients who do not have pulmonary hypertension, for comparison.
By doing this, we will be able to identify substances specifically involved in lung blood vessel disease. This will give us important information about the ways in which the function of the lung circulation is disturbed in pulmonary hypertension and identify biomarkers which may improve diagnosis, monitoring and treatment of patients with the disease in the future.
(A biomarker is a measurable indicator of the severity or presence of a disease state).
Summary of Results
Pulmonary hypertension (PH, elevated blood pressure in pulmonary arteries) is a condition with limited effective treatment options. A subtype of PH, chronic thromboembolic pulmonary hypertension (CTEPH) is a notable exception, with pulmonary endarterectomy (PEA), a surgical procedure aiming at removing scar tissue from pulmonary arteries, often proving curative. This study investigated a collection of small plasma molecules (metabolome) of CTEPH patients, estimated reversibility to effective treatment (surgical intervention) and explored the source of metabolic perturbations (by sampling patients at three anatomical locations). We performed an untargeted analysis of plasma metabolites in CTEPH patients compared to healthy controls and disease comparators. Changes in metabolite levels were evaluated in response to surgical intervention (PEA). A subset of patients was sampled at three anatomical locations and plasma metabolite gradients were calculated. We defined and validated altered plasma metabolite profiles in patients with CTEPH. 12 metabolites were confirmed to distinguish CTEPH and both healthy and disease controls. Many of the metabolic changes were notably similar to those observed in another type of pulmonary hypertension called idiopathic pulmonary arterial hypertension (IPAH) - reported previously. Only five metabolites distinguished CTEPH from chronic thromboembolic disease or IPAH. Significant corrections (15-100% of perturbation) in response to the surgical intervention (PEA) were observed in some, but not all metabolites. Anatomical sampling identified 188 plasma metabolites, with significant gradients in tryptophan, sphingomyelin, methionine and Krebs cycle metabolites. In addition, metabolites associated with CTEPH and gradients showed a correlation with disease severity. We identified a specific subset of metabolites that distinguished CTEPH from controls and disease comparators, despite the observation that most metabolic changes were common to both CTEPH and IPAH patients. Plasma metabolite gradients implicated heart and lung tissue metabolism of metabolites associated with pulmonary hypertension and metabolites that respond to PEA surgery. These metabolites could serve as a noninvasive marker for evaluating future targeted therapeutic interventions.
.REC name
East of England - Cambridge South Research Ethics Committee
REC reference
15/EE/0201
Date of REC Opinion
19 Jun 2015
REC opinion
Further Information Favourable Opinion