Investigating brain mechanisms of dyspnoea in humans with functional and structural MRI

Lead Research Organisation: University of Oxford
Department Name: Clinical Neurosciences

Abstract

Dyspnoea is the uncomfortable shortness of breath that debilitates millions of patients with lung disease, heart failure and cancer. It is often very difficult to treat. The sensations of dyspnoea are processed in the brain, and we believe that psychological factors modify and amplify these sensations, frequently exacerbating symptoms.

In patients with chronic pain, neuroimaging has revealed a brain network that is responsible for processing pain and is strongly influenced by psychological factors. Preliminary studies suggest that there may be similarities in the way the brain processes the unpleasant aspects of dyspnoea.

This research will focus upon identifying brain mechanisms that process dyspnoea in healthy humans and in patients undergoing pulmonary rehabilitation therapy for chronic lung disease. We shall apply novel functional and structural magnetic resonance imaging techniques to assess how psychological factors influence the perception of dyspnoea.

The Oxford Centre for Functional MRI of the Brain (FMRIB) has developed highly sensitive MRI techniques combined with novel analysis tools to enable the success of these challenging studies. This research will provide new insights into the mechanisms of dyspnoea that may provide new therapies to relieve suffering in millions of patients.

Technical Summary

Background: Dyspnoea, the sensation of uncomfortable shortness of breath, is the primary symptom of chronic obstructive pulmonary disease (COPD), cardiac failure and some types of terminal cancer and is a major cause of disability and poor quality of life. COPD costs the NHS >£4 billion p.a., occupies >1 million inpatient UK bed days and generates ~40 million drug prescriptions each year. Dyspnoea due to COPD leads to ~25 million certified sickness days p.a. Pulmonary rehabilitation (PR), that includes exercise and education, is the most effective treatment for chronic dyspnoea of COPD. As subjective measures of dyspnoea correlate poorly with respiratory function and improvements due to PR therapy strongly suggest that mechanisms related to cognition and emotion contribute to its positive effects, we hypothesise that brain mechanisms cause amplification of respiratory sensations, exacerbating dyspnoea.

Aims: To understand how central nervous system (CNS) mechanisms contribute to dyspnoea.

Objectives: The identification of CNS biomarkers through integration of clinical, physiological and psychological measures with functional and structural magnetic resonance imaging (MRI) in healthy human volunteers and patients with chronic dyspnoea.

Design: Healthy volunteer studies: Three separate conventional BOLD functional MRI experiments exploring specific aspects of laboratory dyspnoea. Patient study: Longitudinal randomised parallel group study of structural and functional MRI measures in COPD patients before and after PR.

Methodology: In healthy volunteers I wish to separate the brain processing of unpleasantness of dyspnoea from its intensity and to determine how anticipation to dyspnoea is processed. These tightly controlled laboratory experiments will develop a platform for further investigating psychological and pharmacological manipulations of dyspnoea, and will inform design and analysis of the patient studies.

In patients with COPD pulmonary rehablitation improves dyspnoea but not lung function. We hypothesise that PR will induce neural plasticity in brain regions related to improvement in dyspnoea symptoms, and that we will observe changes in functional activation due to altered cognitive and emotional processing.

Scientific and medical opportunities: The identification of dyspnoea-related biomarkers in the human brain will contribute to individualised and targeted treatments for dyspnoea which will result in improvement of an individual‘s quality of life and economic productivity. The extent of disease attributable to dyspnoea is sufficient for this to be a credible target to improve the burden of disease at a societal, as well as at the individual level.

Publications

10 25 50
 
Description BJA small research grant
Amount £14,000 (GBP)
Organisation National Institute of Academic Anaesthesia 
Sector Learned Society
Country United Kingdom
Start  
 
Description Clinical Research Training Fellowship
Amount £175,400 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description Flexibility Sustainability Funding
Amount £15,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start  
 
Description Flexibility Sustainability Funding
Amount £39,700 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start  
 
Description MRC Centenary Award
Amount £99,517 (GBP)
Funding ID HARQLX0 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start  
 
Description NIHR Biomedical Research Centre, Oxford
Amount £42,000 (GBP)
Organisation Oxford University Hospitals NHS Foundation Trust 
Department NIHR Oxford Biomedical Research Centre
Sector Public
Country United Kingdom
Start  
 
Description NIHR Biomedical Research Centre, Oxford
Amount £119,000 (GBP)
Organisation Oxford University Hospitals NHS Foundation Trust 
Department NIHR Oxford Biomedical Research Centre
Sector Public
Country United Kingdom
Start  
 
Description NIHR Biomedical Research Centre, Oxford
Amount £232,673 (GBP)
Funding ID RWAA0 
Organisation Oxford University Hospitals NHS Foundation Trust 
Department NIHR Oxford Biomedical Research Centre
Sector Public
Country United Kingdom
Start  
 
Description National Institute of Academic Anaesthesia Project Grant/National Institute for Academic Anaesthesia
Amount £7,800 (GBP)
Organisation National Institute of Academic Anaesthesia 
Sector Learned Society
Country United Kingdom
Start  
 
Description Oxford Health Services Research Committee Research Training Fellowship
Amount £52,230 (GBP)
Organisation University of Oxford 
Sector Academic/University
Country United Kingdom
Start  
 
Description Oxford NIHR Biomedical Research Centre Research Training Fellowship
Amount £38,511 (GBP)
Organisation Oxford University Hospitals NHS Foundation Trust 
Department NIHR Oxford Biomedical Research Centre
Sector Public
Country United Kingdom
Start  
 
Description Small research grant
Amount £14,940 (GBP)
Funding ID WKR0-2012-0070 
Organisation National Institute of Academic Anaesthesia 
Sector Learned Society
Country United Kingdom
Start 01/2013 
End 01/2015
 
Description Translational Physiology Theme, NIHR Biomedical Research Centre, Oxford
Amount £32,435 (GBP)
Funding ID HMRWAM9 
Organisation Oxford University Hospitals NHS Foundation Trust 
Department NIHR Oxford Biomedical Research Centre
Sector Public
Country United Kingdom
Start 04/2013 
End 03/2014
 
Description Translational Physiology Theme, NIHR Biomedical Research Centre, Oxford
Amount £65,606 (GBP)
Funding ID HMRWAM9 
Organisation Oxford University Hospitals NHS Foundation Trust 
Department NIHR Oxford Biomedical Research Centre
Sector Public
Country United Kingdom
Start 04/2013 
End 03/2014
 
Description CUBRIC 
Organisation Cardiff University
Department School of Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborations with Professor Richard Wise and Kevin Murphy
Collaborator Contribution Collaborations with Professor Richard Wise and Dr Kevin Murphy regarding methodological aspects of my work
Impact 9 peer reviewed papers since 2005
 
Description Breathe Easy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact Meeting with patients at "Breathe Easy" groups across the Oxfordshire/ Buckinghamshire / Berkshire region....these meetings are organised for the early part of 2013 -- presentation and discussions with patients so that they may help design future studies.


Patients have helped shape the research in grant applications currently under review
Year(s) Of Engagement Activity 2012,2013
 
Description Charity Concert (Oxford) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We held a charity concert to raise awareness and money for the British Lung Foundation & for the local head injury charity, Headway Oxfordshire.

Increased public awareness
Year(s) Of Engagement Activity 2013
 
Description Curiosity Carnival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Friday 29th September saw Oxford's City Centre transformed by the Curiosity Carnival. This University-organised event sought to bring together researchers across fields of study to share knowledge, answer questions, and interact in creative ways with the public in order to stimulate curiosity and dialogue (which is of course where all research journeys begin)

The Breathe Oxford team braved the moody weather and set up stall in a gazebo on Broad Street to share their research on the brain, anxiety and breathlessness. (picture of gazebo on street). Neuroscientist and Life of Breath collaborator Professor Kyle Pattinson brought his portable step, a nose clip, some drinking straws, a couple of camping chairs and his team of researchers who were on hand to talk about their research throughout the day. The idea was to convince people of all ages to take a 30 second step test, first without accessories but the second time with their breathing restricted with the nose clip breathing only through the straw. Participants were offered a delicious slice of brain cake as a reward for taking part. The team wanted to show people what it might be like to live with breathlessness, and informally gather data about their impressions of exercising with impaired ability to breathe.Restricting, Frightening, panicky, clumsy, had to stop, horrible were some of the comments from those who took part. After this, they were offered the chance to come with me into a corner of the tent for a short breath re-training. We demonstrated how the mindful breath-regulation techniques that I use clinically with patients with severe breathlessness could change the way breathing felt: Peaceful, calming, relaxing, in a bubble, safe, in control were some of people's thoughts. Interestingly, each practice was typically only 3 minutes long, and took place in the hubbub of the carnival and next to the competitive pounding of the step-test participants, revealing that even in such a stimulating environment it's possible to focus the mind, regulate the breath and shift affective responses.It was fascinating to talk to people about their relationship with their breath, whether living with asthma or COPD or prone to anxiety or panic attacks. It seemed from my interactions (with young girls of 18 to older men in their 70s) that in opening up this conversation about breathing, anxiety, the brain and breathlessness, we were scratching the surface of a need for information about this most primal and central experience of being alive. When breath is compromised, so is life. And this can be due to an underlying pathology like asthma and/or the body's response to anxiety, especially when the brain is wired to "trip" from past traumatic experiences thus setting up a cycle of negative expectations and body-mind interactions. Unlike other vital functions of the body - e.g. our heartbeat or the flow of hormones regulating digestion, sleep and mood - we can consciously tune into and regulate our breathing, manipulating the rest of the nervous system and the way we feel. What I found inspiring was the way in which people seemed so hungry to understand and discuss this process, sharing their often very personal experiences, fears and vulnerabilities around the topic.

It was a huge pleasure and privilege to share some of the ancient techniques from the traditions of yoga and mindfulness with curious people off the street. I certainly learned a lot and am delighted if any of them came away with a mini-tool for self-regulation or an interest in finding out more about their breathing and their brain.
Year(s) Of Engagement Activity 2017
URL https://lifeofbreath.org/2017/10/curious-about-breath-at-the-oxford-curiosity-carnival/
 
Description Engagement with schools 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact The morning of Tuesday January 30th saw members of the Breathe Oxford team pack up their trusty aerobic steps and drive the short distance to the little village of Radley, home to the world famous Radley College School.

The team had been invited to take part in the schools very first STEMfest! This Science Technology, Engineering and Mathematics initiative brought researchers from across the University of Oxford's faculties to join the school and host a series of workshops, to which students aged 14-15 from not only Radley College School, but also their neighbouring schools were invited to attend.

In a fascinating day of talks, Breathe Oxford presented cutting-edge research looking at the relationship between brain networks and breathing before asking the students to conduct an experiment. "How many steps on the aerobic step could they do in 30 seconds, and, how many could they do if only breathing through a straw?" Armed with their predictions the room was soon filled with the sound of loud counting and competitive running. As expected, breathing through a straw made the exercise much harder, although the effect on each individual was markedly different. The team pointed out that such variability is also seen in people with chronic lung disease and for some, every day can feel like breathing through a straw. Next the team asked students to consider questions such as "how could you improve this experiment?" and "is this a fair test?" Looking for ways to improve your experiment is a key part of being a scientist and the students had some excellent suggestions, including: "more trials", "manipulating expectations" and "a longer break between the two tests".

After a tour of the school's science department (everyone was a little jealous of the terrapin tank) the Breathe Oxford team returned to their Oxford office, delighted with the enthusiasm of all attendees and the hard work that Radley College staff had put into the day to make it a success. STEM days are a great opportunity to reach out, and hopefully not only inspire young minds to keep asking questions, but also to feel empowered to find out the answers.

Thank you Radley College School! We hope to see you next year!
Year(s) Of Engagement Activity 2018
URL https://www.ndcn.ox.ac.uk/research/breathe-oxford/news-and-events/breathe-oxford-heads-to-stemfest-a...
 
Description Interview on BBC Radio Oxford 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact https://podcasts.ox.ac.uk/saturday-scientist-bbc-radio-oxford
Year(s) Of Engagement Activity 2017
URL https://podcasts.ox.ac.uk/saturday-scientist-bbc-radio-oxford
 
Description Interview with The Independent newspaper 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview with the Independent Newspaper & associated article.
Year(s) Of Engagement Activity 2017
URL http://www.independent.co.uk/news/health/brain-scanning-could-hold-the-key-to-helping-treat-breathin...
 
Description Open day held at the John Radcliffe Hospital 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Stall at the open day organised by the NIHR Biomedical Research Centre, Oxford. Attended by public and by other healthcare workers.

Improved public awareness.
Year(s) Of Engagement Activity 2013
 
Description Poetry Evening - exploring breathing and breathlessness 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact A cappella singing, a lone rower in the Pacific Ocean, fungal spores, clairvoyance and a baby's crieswhat could possibly tie these things together? The surprising answer is breath and poetry.

It was standing room only in the Oxford Retreat pub for an evening exploring breathing and breathlessness through poetry and song. Entitled 'To breathe ourselves into some other lungs', the purpose of the evening was to provoke deeper thought and discussion around the lived experience of breathing.

The session started with a choral ensemble led by writer and music therapist Kate Binnie. 'Breaths', originally recorded by the a cappella group Sweet Honey on the Rocks, is based on a poem about ancestors by Senegalese poet Birago Diop.

Then award-winning travel writer Elsa Hammond drew everyone into her experiences of her solo rowing trip across the Pacific Ocean, describing how often she only had her breath to accompany her.

Poet Gregory Leadbetter read from his new book 'The Fetch', in which breath is a recurring motif. In 'Dendrites and Axons', a poem about his father's death, he poignantly realises 'I will not breathe with you again when I leave'.

Scientist turned poet Sarah Watkinson shared her experiences of living with asthma. 'Rescue Medication' was a humorous hymn to the tetrad of drugs that help to keep her asthma at bay.

The floor was opened up and audience members shared their choice of poems including 'Oxygen' by Mary Oliver, 'Vanishing Lung Syndrome' by Miroslav Holub and the lyrics to 'Breathing' by Kate Bush.

To finish the evening Kate Binnie played her moving soundscape 'First and Last Breath' which is a compilation of breath sounds recorded at various life stages from a baby to her own father's final days.

The event was organised by Breathe Oxford, a research group led by Kyle Pattinson within the Nuffield Department of Clinical Neurosciences. The group teamed up with Life of Breath, based at the Universities of Bristol and Durham. Listen Here to a recording of the evening!

The inspiring and thought-provoking evening began a conversation about breathing and breathlessness that both Breathe Oxford and Life of Breath are keen to continue.
Year(s) Of Engagement Activity 2017
URL https://www.ndcn.ox.ac.uk/research/breathe-oxford
 
Description Radio Interview (BBC Radio Oxford 2012) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Short interview on BBC Radio Oxford regarding breathlessness and the research I'm doing

difficult to define, certainly helped with recruitment of participants.
Year(s) Of Engagement Activity 2012
 
Description Royal Society Summer Science Exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact My research group will run an exhibition titled "Breathing with your Brain" at the Royal Society's Summer Festival of Science" that will be held in London in July 2019. This event is the largest public engagement with science exhibitions in the UK, and in 2018 attracted over 14,000 visitors
Year(s) Of Engagement Activity 2019
URL https://royalsociety.org/science-events-and-lectures/2017/summer-science-exhibition
 
Description Web Blog 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Oxford University Science Blog. Has helped with setting up further engagement activitites.
Year(s) Of Engagement Activity 2016
URL https://www.ndcn.ox.ac.uk/research/breathe-oxford