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Translational cardiorespiratory physiology, with a focus on hypoxia and iron.

Measurement of cardiorespiratory responses to hypoxia using dynamic end-tidal forcing and echocardiography

My research focuses on integrative cardiorespiratory physiology. My particular interest is in translational physiology, and several of my current projects span from basic science to interventional clinical research studies.

Interaction of iron and oxygen homeostasis

Many systemic physiological responses to hypoxia are regulated by cellular hypoxia inducible factor (HIF) pathways, which are themselves sensitive to cellular iron availability. In collaboration with Professor Peter Robbins and Professor Sir Peter Ratcliffe, we have demonstrated that cardiorespiratory responses to hypoxia, including at high altitude, can be influenced by systemic iron availability. This has implications for patients with chronic respiratory disease. We have recently shown that intravenous iron improves exercise capacity in non-anaemic patients with chronic obstructive pulmonary disease (COPD), and I am currently leading an NIHR-funded clinical trial exploring the effects of iron supplementation in patients with cystic fibrosis.

Pathophysiology of coronavirus disease 2019 (COVID-19)

There is evidence to suggest that SARS-CoV-2 infection may inhibit the pulmonary vascular response to hypoxia, contributing to the severe hypoxia seen in COVID-19 pneumonia. I am Chief Investigator for the ABC-19 study, a multicentre randomised controlled trial of almitrine bismesylate, a compound known to enhance the effects of hypoxia in the pulmonary circulation (https://www.lifearc.org/funding/covid-19-funding/almitrine/). In collaboration with Dr Nayia Petousi, I am also studying the long term effects of COVID-19 on the respiratory system, including responses to hypoxia, and I am a local investigator in the national NIHR/UKRI post hospitalisation COVID-19 study (PHOSP-C).

Non-invasive assessment of lung inhomogeneity

Currently, we rely upon a small number of relatively insensitive and imprecise measures of lung function to characterise respiratory pathophysiology. As part of a collaboration between the groups of Peter Robbins and Professor Grant Ritchie (Chemistry), a novel gas analyser based on laser absorption spectroscopy has been developed, which measures the composition of respiratory gases with significantly greater accuracy and time-resolution than has previously been possible. In combination with a mathematical model of the lung, this device can be used to estimate the inhomogeneity of gas exchange, and to provide a range of novel indices of lung function. We are assessing the utility of this approach in the clinical setting.

Funders

NIHR RfPB scheme

BRC respiratory theme

Our team

Selected publications