Other Research Interests

Further research interests in the department include altitude medicine, chronic obstructive pulmonary disease (COPD), pneumonia and dyspnoea. We are setting up a COPD Cohort with careful phenotyping and genotyping of over 1000 patients, some of whom (around 400), will be followed-up long-term in a longitudinal cohort. This will provide a powerful resource for future studies, including an attempt to identify genetic differences between ‘pink puffers' and ‘blue bloaters' who have strong and blunted responses to hypoxia respectively. We will compare detailed genetic analysis (genotyping) with detailed assessment of symptoms, lung function, exercise ability and lung imaging (phenotyping). This will help us understand origins of patient differences.

There is a need for a long term study of the effects of home mechanical ventilation (HMV) in patients with hypercapnic COPD, as there is a considerable morbidity and mortality with frequent hospital admissions associated with this condition. There are also an increasing number of referrals of patients with hypercapnic COPD to units specialising in ventilatory support for consideration of HMV, yet there is no good evidence for the long term effectiveness of this therapy. Information is required on any predictive factors for improvement with HMV and on the relation between hours of use of HMV and outcome. There are currently over 86,630 patients on long term oxygen therapy (LTOT) in England and Wales, of which 61.8%% (53,537) have COPD.

Previous uncontrolled or short-term studies of HMV in COPD have shown encouraging results, with improvements in gas exchange, sleep quality, exercise capacity and quality of life, which do not improve with LTOT alone, or reductions in hospital admissions, intensive care admissions and general practitioner consultations, particularly in patients who are hypercapnic. A larger international study has attempted to compare longer term HMV with LTOT in patients with hypercapnic COPD. Reports suggested no benefit after three years of therapy, however the study was inadequately powered for mortality as an endpoint, and levels of pressured delivered by the ventilators would be deemed low compared to current practice. Furthermore, more recent advances in portable lightweight ventilators, with improved triggering system, pressure delivery and advances in interfaces have led to improved compliance with HMV.

A multicentre study to investigate the effect of HMV in patients with severe COPD is therefore being undertaken. The purpose of the trial is to test the hypothesis that HMV and LTOT increases admission free survival compared with LTOT alone in COPD patients who remain persistently hypercapnic following an acute exacerbation requiring non-invasive ventilation (NIV). Patients who tolerate NIV during an acute hypercapnic exacerbation, and remain hypercapnic afterwards, will be randomised to either HMV plus LTOT, or LTOT alone. The effect on admission-free survival, exacerbation frequency, disease progression, health-related quality of life, exercise capacity and healthcare utilisation over a 12 month follow-up period will be examined. This would be a pivotal study in the management of COPD and this proposal has been developed with and has the full support of the Global Medical Excellence Cluster (GMEC) for COPD.

Another interest is how iron supplementation in iron deficient patients changes responses to hypoxia, and in particular pulmonary vascular responses. The rationale behind this work is that iron is an essential co-factor for the breakdown of hypoxia inducible factor, and therefore affects how the body responds to hypoxia. In iron deficiency, supplementing iron anecdotally relieves fatigue and improves well being and exercise capacity remarkably quickly, long before anaemia has resolved. This is particularly true if is given intravenously resulting in rapid iron repletion, rather than in tablet form. The mechanism by which these improvements occur quickly in people who are iron deficient is not understood, since it takes many weeks for anaemia to resolve. We speculate one of the ways in which iron improves well being is to reduce high blood pressure through the lungs when oxygen levels are low.

In our study of lung infection (PIPAP), we are developing novel techniques for the rapid microbiological diagnosis of pneumonia with the aim of improving diagnosis and treatment and reducing antibiotic associated complications. Our research using functional imaging to understand brain mechanisms that modulate the sensation of dyspnoea will help develop new treatments for this common and disabling sensation.

We welcome contact from centres that would like to recruit to these trials or scientists who would like to collaborate with us in the set up and running of respiratory clinical trials.