An integrated epidemiological approach to understanding the relationship between lung health and multi-morbidity

Lead Research Organisation: University of Bristol
Department Name: Faculty of Health Sciences

Abstract

The UK spends 70% of its healthcare budget caring for patients with multiple long-term health conditions such as dementia and chronic obstructive pulmonary disease (COPD); driven by aging populations and lifestyle factors, this figure is expected to rise. Chronic lung disease and dementia are therefore key global health challenges.

Cognition describes mental abilities, such as thinking, problem solving and remembering. Problems with cognition (cognitive dysfunction) can lead to dementia and appear very common in people with chronic lung disease. Although cognitive dysfunction may be mild and unnoticed at first, it may gradually make it more difficult for patients to perform their daily activities including taking medicines correctly. Cognitive dysfunction in chronic lung disease eventually leads to worse health, more time in hospital and shorter survival.

Individuals with chronic lung disease may be at increased risk of mild cognitive impairment (MCI) and dementia due to a combination of factors, which are both more frequent among those with lung disease and known to negatively impact on cognition (e.g., smoking and high blood pressure) or as a direct result of lung disease (e.g., low oxygen levels). However, there does seem to be a consistent link between cognitive impairment and lung disease independent of these shared factors, suggesting mechanisms specific to respiratory limitation.

The aim of this project is to determine whether chronic lung disease and cognitive impairment share a common causal pathway. It will do this by bringing together interdisciplinary expertise in epidemiology and statistics, to understand the complex interaction between genetic, developmental and early life events which determine lung health and cognition (MRC strategic aim 4).

It will also explore the relationship between early life cognition, co-morbidity and lung function trajectories using a population-based life course perspective applied to the Avon Longitudinal Study of Parents And Children (ALSPAC) cohort. (MRC strategic aim 1).

The objectives are:
a) Apply integrated genetic epidemiological methods developed by our team (2 sample Mendelian Randomisation) from large European populations to determine the causal association between lung function, cognitive impairment and risk of dementia
b) Determine if early life changes in lung function are associated with cognitive dysfunction and multi-morbidity using existing data from the ALSPAC cohort.

Benefits and applications are:
1) Help to identify modifiable risk factors and potential therapeutic targets to reduce the risk of developing dementia.

2) Advance our understanding behind the mechanisms of cognitive dysfunction in chronic lung disease.

3) Initiate the development of new ways to detect, prevent or delay progression of cognitive dysfunction in at risk populations. This will help patients to manage their treatment, maintain their health and keep out of hospital. It could also prolong survival.

4) Increase our understanding about early life risk factors for chronic lung disease and multi-morbidity

5) Inform public health policy through engagement with organisations responsible for health services delivery and management of two major long-term conditions, Chronic Obstructive Pulmonary Disease (COPD) and Dementia.
a. Awareness of cognitive dysfunction & multi-morbidity
b. Inform self-management and education
c. Keeping people with COPD and Dementia healthy at home

6) Inform and open new research questions about the interaction between long-term conditions and lung health such as cardiovascular disease, depression and diabetes.

Technical Summary

The WHO estimates that dementia will affect 80 million people in 20 years, so there is an urgent need to identify modifiable risk factors. Mild cognitive impairment is associated with a 5-10% annual conversion rate to dementia but is considered a potentially reversible state.
3 million people live with COPD in the UK, the majority have two or more long-term health conditions, it is therefore a disease of 'multi-morbidity'. (MRC strategic theme 'living a long and healthy life')
The majority of observational studies provide evidence for an independent association between lung function and cognitive impairment. However a number of unmeasured or unaccounted confounders are likely to bias this relationship.
Objectives & Methods
Part 1: Two-sample Mendelian Randomisation using existing Genome Wide Association Studies to determine the causal association between lung function, cognitive impairment and risk of dementia
Mendelian Randomization (MR) is a form of analysis that uses genetic variants as instrumental variables. Using summary data from GWAS consortia in two-sample MR increases statistical power, particularly in relation to testing effects on binary disease outcomes, such as Alzheimer's Disease (AD) or Cognitive Impairment (CI).
Part 2: Determine if early life course lung function trajectories are associated with cognitive dysfunction and multi-morbidity using existing longitudinal data from the ALSPAC cohort.
Several measures of functional cognition and comorbidity are available from the ALSPAC clinic at 24 years. Four FEV1 trajectories from childhood to early adulthood were identified in using latent profile modelling: persistently high (4%), normal (45%), below average (44%), and persistently low (7%).
Setting the normal FEV1 trajectory as the baseline group, we will use multinomial logistic regression model to investigate the risk (betas & 95%CIs) of the membership of other trajectories per unit increase of a continuous measure of functional cognition.

Planned Impact

This research project has the potential for far reaching impact. It aims to help identify modifiable risk factors and potential treatments to reduce the risk of developing dementia and advance our understanding of the mechanisms that cause cognitive dysfunction and multi-morbidity in chronic lung disease.
Ultimately this should allow development of new ways to detect, prevent or delay progression of cognitive dysfunction in chronic lung disease, thereby helping patients to manage their treatment, maintain their health and keep out of hospital. It could also prolong survival.

National & International policy makers:
There will be policy implications relating to findings that may lead to improved recognition or enhanced screening for dementia and multi-morbidity in high-risk populations (such as those with chronic lung disease). In addition this could lead to improved healthcare advice and public health interventions to lessen the risk of adverse outcomes. Although these are likely to include tobacco control and cardiovascular risk reduction there are other modifiable factors of potential importance, including diet, obesity and physical activity that are not currently recognised as adverse factors for future lung health.

Health Professionals & Commissioners:
Clinicians including GPs, specialists in respiratory & elderly medicine, and memory clinics will benefit from an increased awareness and understanding about early life risk factors for chronic lung disease and multi-morbidity and dementia.
It also has implications for the organisation of health services delivery. Specifically, these include regional clinical commissioning groups (CCG) and NHS England who are working on sustainability and transformations plans (STPs) in key themes of respiratory, dementia and long-term conditions such as COPD and Dementia.
This work on cognition and co-morbidity in chronic lung disease will also benefit front line clinical staff to develop new ways of supporting people with COPD to self-manage and deliver effective education.

Charities and research funding bodies:
This project addresses the key global health challenges highlighted by the NIHR, MRC and British Lung Foundation. It will allow these funding bodies to prioritise and allocate resources appropriately for future research and improve communications and support for patients and carers who may be affected by chronic lung disease and dementia.

The general public:
3 million people live with COPD in the UK but only 1 million have been diagnosed, meaning many miss out on the opportunity for the help and support of healthcare professionals. The wider public will benefit from a raised awareness of the increasing health challenge and implications of living longer with multiple health conditions. It will allow people to consider the lifestyle changes that they may be able to take in order to protect themselves. The findings could also be used to help people with COPD and Dementia and their carers better understand what is needed to stay healthy and manage their long terms conditions to stay in their own home

We will use 'PolicyBristol', a dedicated policy unit working with researchers to enhance the influence and impact of research from across the University of Bristol on policy and practice at the local, national and international level. On a practical level this is achieved through Policy Briefings and Reports, Events such as a policy workshop or seminar and Communications: including via social media platforms such as blogs and Twitter

Publications

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Arnold DT (2021) Standard pleural interventions are not high-risk aerosol generating procedures. in The European respiratory journal

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Hamilton F (2021) Aerosol generating procedures: are they of relevance for transmission of SARS-CoV-2? in The Lancet. Respiratory medicine

 
Description AERosolisation And Transmission Of SARS-CoV-2 in Healthcare Settings (AERATOR)
Amount £432,785 (GBP)
Funding ID COV0333 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 07/2020 
End 08/2021
 
Description Bristol Evaluation of novel Airways diagnostics, Therapeutics & healthcare OutcomEs (BREATHE study)
Amount £20,000 (GBP)
Organisation Southmead Hospital Charity 
Sector Public
Country United Kingdom
Start 01/2022 
End 01/2023
 
Description DISCOVER DIagnostic and Severity markers of COVID-19 to Enable Rapid triage study
Amount £152,000 (GBP)
Organisation Southmead Hospital Charity 
Sector Public
Country United Kingdom
Start  
 
Description Digital health champions and uptake of myCOPD apps
Amount £194,000 (GBP)
Organisation NHS Digital 
Sector Public
Country United Kingdom
Start 11/2021 
End 09/2022
 
Description Digital spirometry in patients with respiratory symptoms - RCT. Springboard grant
Amount £20,000 (GBP)
Organisation Southmead Hospital Charity 
Sector Public
Country United Kingdom
Start 06/2021 
End 10/2022
 
Description Religious belief, health and disease: II. The follow-up and data analysis,
Amount £8,000,000 (GBP)
Organisation The John Templeton Foundation 
Sector Academic/University
Country United States
Start  
 
Description Understanding the origins of chronic lung disease
Amount £30,000 (GGP)
Organisation Chiesi 
Sector Private
Country Italy
Start 11/2021 
End 11/2024
 
Description Understanding the origins of chronic lung disease & the impact of COVID-19
Amount £191,000 (GBP)
Organisation Southmead Hospital Charity 
Sector Public
Country United Kingdom
Start 11/2021 
End 11/2024
 
Description ALSPAC Respiratory theme lead 
Organisation University of Bristol
Department Avon Longitudinal Study of Parents and Children (ALSPAC)
Country United Kingdom 
Sector Academic/University 
PI Contribution I am clinical advisory board chair for ALSPAC study, this body advises the study PI Nic Timpson on clinical measures undertaken in ALSPAC. With Raquel Granell (respiratory statistician) we lead the respiratory theme within ALSPAC. I supervise a PhD student using integrative epidemiology methods to explore the causal relationship between lung function, COPD and comorbid cognitive and vascular disease. We are also looking at the psychological aspect of Asthma in ALSPAC
Collaborator Contribution George Davey Smith is Co app on MRC CARP award with Raquel Granell, they are also co supervisors of my PhD student. I work with Nic Timpson on grant submission for respiratory measures in ALSPAC
Impact MRC CARP award PhD studentship MRC PSMB bid 2 papers in write up
Start Year 2019
 
Description MRC integrative epidemiology unit. University of Bristol 
Organisation University of Bristol
Department MRC Integrative Epidemiology Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution Clinical academic partner. Research theme on lung function and causal associations with cognition and multi morbidity
Collaborator Contribution Expertise, methodology, access to people and training
Impact Application to MRC CARP -successful Clinical research fellow PhD project with peer review publications in high impact journals (see linked publications) Conference abstracts of findings New collaborations and research grants in progress replication GWAS of preserved ratio impaired impaired spirometry (CHARGE consortium) Submission to MRC PSMB research grant for collection and completion of lung health measures at age 30 in Avon Longitudinal Study of Parents and Children (ALSPAC)
Start Year 2020
 
Description Public appeal for engagement with COVID-19 study for participants of ASLPAC cohort 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact In support of COVID-19 questionnaire to be emailed to over 10,000 participants I was asked to record a short video to share on social media/our website .

"As a respiratory/chest consultant at Southmead I know how important the Children of the 90s health study is - right now - in the fight against the Coronavirus. If you are a participant in the study please find 10 minutes to fill in this new Coronavirus questionnaire. Its findings will tell the government how many participants have already had the virus, even with very mild symptoms. And this will help us to stop this deadly infection more quickly. Thanks for doing your bit to help the NHS! "

"If you were born in Bristol between April 1991-December 1992 you could be part of the study. Please text 07772 909090 or visit childrenofthe90s.ac.uk for more information. Your help will make a real difference, thank you"

Feedback on impact from ALSPAC comms team
Hi James
I just wanted to thank you for making the film clips. You might not be aware but we have had a big response to the films on social media. The second video reached 13,700+ people and was shared 102 times, while the first video was shared 113 times, these are much bigger than the normal reach for our posts. What's more, I'm sure that the films directly lead to participants re-engaging in the study as we've had a big spike in numbers getting back in touch in April. Some haven't been involved since they were children and certainly fall into our 'disengaged' category. At last count we are at over 5,000 responses to the questionnaire, which is great news.

On the back of this, we would ideally like to use a quote from you in our local media outreach - would you be happy for this to be included in a press release - going out to local Bristol media this week?
Article here: https://www.bristolpost.co.uk/news/bristol-news/6000-people-take-part-groundbreaking-4107341
Year(s) Of Engagement Activity 2020
URL https://www.facebook.com/login/?next=https%3A%2F%2Fwww.facebook.com%2Fchildrenofthe90s%2Fposts%2F101...