MR1006 - Gedling Lung Health Study

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling The University of Nottingham to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance).

Background to the Gedling cohort

In 1991, a large cross-sectional study of 2,628 participants randomly selected from the electoral roll of Gedling Borough was conducted to investigate the association between diet and respiratory disease and specifically chronic obstructive airways disease (COPD) and asthma and was led by John Britton, Professor of Epidemiology at University of Nottingham. This study population has been followed up with a written questionnaire (1999) and interview/examination (2000). This was followed by additional questionnaires – with the help of ONS at the time – in 2007. To date University of Nottingham researchers have used the Gedling cohort to investigate the relationship between diet and various markers of these obstructive airways diseases and a variety of other research questions. This cohort has produced at least 30 peer-reviewed publications.

Strengths of the cohort

The strengths of this study population are that it is a randomly selected population which is representative of the general Nottingham population and has excellent baseline data on diet and other disease risk factors collected in 1991 with follow-up data in 1999, 2000, 2007, with GP records for various members of the cohort. Therefore the cohort can deliver a wide range of incidence of common diseases, which can then be studied. Combining the baseline data with the incidence of common diseases (obtained from GP notes) was a cost-effective method of establishing a cohort population with the ability to investigate the role of diet and other risk factors on the incidence of common doctor-diagnosed diseases such as hypertension, cancers (lung, breast, prostate, and bowel), rheumatoid arthritis, type 2 diabetes, and respiratory infections. Continuing to add the cancer incidence and death certificate will continue to enrich this dataset.

Data Request and GDPR

This data is processed under Article 6(1)(e) of the General Data Protection Regulation, on the basis of the research being a task performed in the public interest . This cohort was established in 1991 with clinical measurement and provides a unique opportunity in terms of understanding the epidemiology of disease progression through to the development of cancer and instances of mortality. The University wishes to process the data for the purpose of expanding knowledge into the effects of diet as a potential risk factor for disease. Diet is a factor openly modifiable by and to the public, therefore an increased understanding of the how diet is associated with development of diseases would benefit public knowledge into improving health outcomes. This can done for minimal cost to the research community as establishing cohorts is normally extremely expensive; in this case there is a cohort already established with a rich dataset which can be further enhanced with the data from the NHS Digital. Processing of special category data is supported by Article 9(2)(j) in that the data will be used for scientific research purposes with a public interest, the public interest being a better understanding of the progression of disease and how individual fatty acid intake impact on health. This research has been approved by an ethics committee and no identifiable data will be released into the public domain.

Funding

The Gedling cohort study has been made possible thanks to several funding initiatives throughout the term of the study. The timeline for funding grants is outlined below:

Beginning of Study to 1997 - National Asthma Campaign (Asthma UK) & British Lung Foundation. The University of Nottingham is unable to provide written evidence of this grant being issued 22 years ago as University records are maintained for the recommended period of 20 years. However reference to the funding provided by these organisations can be found in published papers such as "Factors influencing the occurrence of airway hyperreactivity in the general population: the importance of atopy and airway calibre" - J Britton, I Pavord, K Richards, A Knox, A Wisniewski, I Wahedna, W Kinnear, A Tattersfield, S Weiss - European Respiratory Journal 1994 7: 881-887;

1997 to 2002 - National Asthma Campaign (as above)

2002 to 2006 - Wellcome Trust Fellowship for Tricia McKeever (Associate Professor of Epidemiology) - Evidenced in the supporting documents.

2006 to Current Funding - the funding for the current period, which backdates to the conclusion of the above Wellcome Trust grant, consists of contributions made by researchers who recognise the long-term value of collecting the data, permanently employed by the University of Nottingham. The applicant, Tricia McKeever, entered full-time employment with the University following the Wellcome Trust grant which included devoting resource to the progression of the study.

Aims

To investigate the relation between diet, and in particular individual fatty acids, with the incidence of other common diseases.

Rationale for proposed study

Diet is an important potential risk factor for disease; as it is open to modification, it is important that the effect of many of the major nutrients (antioxidants, fibre, total fat intake) and their association with disease is thoroughly studied. One particular aspect of the diet which needs further clarification is the effect of dietary fatty acids on disease, as to date there is limited research on the relation between individual fatty acids and medical conditions, mainly due to the technical difficulties associated with accurately estimating intakes of individual fatty acids. The study team have recently developed and validated a food frequency questionnaire which allows researchers to estimate the dietary intake of a number of individual fatty acids and therefore to investigate the effect of dietary fatty acids on the incidence disease in the Gedling cohort. Particular diseases of interest are:

Cardiovascular disease

There is some evidence that a diet rich in polyunsaturated fatty acids reduces hypertension in men, coronary heart disease, mortality after a myocardial infarction and sudden death possibly due to a protective effect against cardiac arrhythmias. Further investigation is required however to clarify the active agents responsible for these effects.

Cancer

While there have been a variety of large prospective studies on the effect of diet on the risk of cancer, focusing particularly on common cancers such as breast, lung, prostate and bowel cancers. There is only very limited evidence

on the relation between individual fatty acids and cancer and one study found that increase intake of linoleic acid and total polyunsaturated fatty acids also appear to reduce the incidence any cancer and also specifically prostrate cancer, therefore more research is needed to understand these associations.

Other common medical diseases

The prevalence of other relatively common conditions including rheumatoid arthritis, type 2 diabetes and respiratory tract infections may also be modified by the immunomodulatory effects of fatty acids. This is thus another area of research potential, that has not to date been explored extensively.

Current research plan

In 2007, with the help of the ONS, University of Nottingham tracked as many of the original cohort as possible and provided them the questionnaire on respiratory health, diet intake (in particular fatty acid intake), and gained permission at the time for participants to be tracked by the ONS for cancer and death certificates notifications. Researchers aim to continue tracking individuals for the cancers and death notifications.

This project aims to follow-up as many individuals as possible from the original study population, and as a novel development, to link the study's current dietary data on these individuals with data contained in their GP record, establishing a database that will help to address a variety of research questions relating to the effect of diet on the incident disease. In addition, University of Nottingham researchers will use MRIS output from NHS Digital to be notified of fact, date and cause of death.

Summary

This project now aims to collect further data available on deaths and cancer registry available for an established cohort that has a wealth of information already available with the cohort. This is expected to take another 5 to 15 years to occur, as the youngest in the cohort are now around 67 years old.

Under this Agreement, the data may be securely stored but not otherwise processed. No new data will be provided by NHS Digital under this Agreement.

Mortality and cancer registry data are being requested. University of Nottingham have previously supplied the names, dates of birth, and most recent known address of the cohort of people that were originally studies in 1991 to NHS Digital. The NHS Digital data is received and linked to the Gedling cohort dataset. The University of Nottingham are the sole data controller/processor and no other organisations are involved in processing the data.

Data analysis

As describe in this application, data can be analysed using a detailed fatty acid database to produce estimates of individual saturated, omega-3 and omega-6 fatty acid intakes in relation to the prevalence and incidence of common medical diseases linked to diet and obesity including acute respiratory infections, cardiovascular disease (blood pressure, angina, and myocardial infarction), cancers, diabetes, rheumatoid arthritis and liver disease. In addition, the effects of other factors in diet will also be investigated in relation to common medical outcomes. The analyses will be conducted using linear or logistic regression as appropriate and all relations will be explored for the possibility of confounding factors.

NHS Digital linkage

To maximise the number of people from the original cohort identified and followed-up, University of Nottingham used the NHS Digital Medical Research Service (MRIS) to trace all survivors from the original 2,633 cohort members, which was completed in 2007. Where the current address held on University of Nottingham’s systems is correct, as verified by the NHS Digital data, questionnaires (respiratory health and dietary) will be posted directly to the individual. When the current address is incorrect, then the questionnaire will be sent out with a covering letter to the individual via their General Practitioner.

In addition the MRIS service will also identify all deaths in the original cohort and provide information on the cause of death. All living study participants will be flagged for notification of cause of death in the future. Mortality data will be used to investigate the relation between diet and all-cause mortality and between diet and specific causes of death.

NHS Digital already have the cohort population identified and data on deaths and cancer registrations will be sent to University of Nottingham which will then be linked to datasets held at the University of Nottingham on an encrypted hard drive. No data will be shared with individuals/organisations outside the University of Nottingham. All data will be held on an encrypted hard drive.

This Agreement permits the secure retention of the data only and no other processing.

No new outputs will be produced under this Data Sharing Agreement.

University of Nottingham have published over 25 research papers using data from this cohort, a list of the publications made since the use of ONS data in 2007 are detailed in the Yielded Benefits. University of Nottingham researchers have been able to combine the dietary details on half of the cohort linked with data from cohort members' GP electronic record and created a database that can be used for research. Together with the data collected in 1991 and 2000 in the face-to-face research visits within the cohort, a rich dataset with which to investigate a wide range of research questions has been obtained, as set out in the University of Nottingham's previous application. The aim is to continue to publish using the GP data on a wide variety of research questions, in particularly on respiratory health effects on long-term survival. The yearly updates on mortality are increasing the ability to examine outcomes of mortality and cancer. Currently the youngest members of the cohort are around 67 years old, meaning an increased likelihood of certain health outcomes for researchers to examine.

This Agreement permits the secure retention of the data only and no other processing.

Respiratory disease kills more people in the UK than ischaemic heart disease and costs the NHS nearly £6.6 billion a year; however ,unlike heart disease there is a lack of longitudinal data on the long-term impact of respiratory health within a general population. The Gedling cohort is rich in data, with face-to-face research visits in 1991 and 2000, questionnaire data in 1999 and 2007, GP electronic notes, and with the MRIS data on cancer and mortality. There have already been over 25 published papers which help to understand the wide range of aetiology of disease with the main focus of the research on how diet effects respiratory health. With the continued longitudinal data University of Nottingham researchers further investigated how respiratory health, in particular lung function affects long term mortality.

Since the University put in the application, at least 10 peer-reviewed publications have been published using data from this cohort. In addition, 2 PhD students, 1 MPhil student and at least 5 Masters in Public Health (MPH) students have used the data for their dissertations. The research itself has help to progress the understanding of the relationship between diet and respiratory disease, has been hugely beneficial in understanding the relationship between genetics and lung disease, and has added to the understanding of how a variety of exposures are associated with the decline of lung function. Although much of the work is in understanding of the aetiology of disease and disease progression, these fundamentals have to be understood before clinicians are able to successfully intervene. From work in this cohort, 3 intervention trials locally have been conducted to examine whether different dietary interventions can affect the progress of respiratory disease.

Publications from this cohort since 2007 ONS application.

1. Patterns of dietary intake and relation to respiratory disease, forced expiratory volume in 1 s, and decline in 5-y forced expiratory volume. McKeever TM, Lewis SA, Cassano PA, Ocké M, Burney P, Britton J, Smit HA. Am J Clin Nutr. 2010 Aug;92(2):408-15. doi: 10.3945/ajcn.2009.29021. Epub 2010 Jun 16.

2. The association between blood coagulation activity and lung function: a population-based study. Fogarty AW, Lewis SA, McKeever TM, Lowe GD, Clark L, Britton J. PLoS One. 2010 Nov 16;5(11):e15014. doi: 10.1371/journal.pone.0015014.

3. A population-based epidemiologic study of Helicobacter pylori infection and its association with systemic inflammation.

4. A population-based epidemiologic study of Helicobacter pylori infection and its association with systemic inflammation. Jackson L, Britton J, Lewis SA, McKeever TM, Atherton J, Fullerton D, Fogarty AW. Helicobacter. 2009 Oct;14(5):108-13. doi: 10.1111/j.1523-5378.2009.00711.x

5. Effect of traffic pollution on respiratory and allergic disease in adults: cross-sectional and longitudinal analyses. Pujades-Rodríguez M, McKeever T, Lewis S, Whyatt D, Britton J, Venn A. BMC Pulm Med. 2009 Aug 24;9:42. doi: 10.1186/1471-2466-9-42.

6. McKeever TM, Britton JR. Am J Clin Nutr. 2009 Jun;89(6):1901-4. doi: 10.3945/ajcn.2008.27006. Epub 2009 Apr 22

7. Systemic inflammation and decline in lung function in a general population: a prospective study. Fogarty AW, Jones S, Britton JR, Lewis SA, McKeever TM. Thorax. 2007 Jun;62(6):515-20. Epub 2007 Jan 24.

8. Is higher sodium intake associated with elevated systemic inflammation? A population-based study. Fogarty AW, Lewis SA, McKeever TM, Britton JR. Am J Clin Nutr. 2009 Jun;89(6):1901-4. doi: 10.3945/ajcn.2008.27006. Epub 2009 Apr 22.

9. Helicobacter pylori and lung function, asthma, atopy and allergic disease--a population-based cross-sectional study in adults. Fullerton D, Britton JR, Lewis SA, Pavord ID, McKeever TM, Fogarty AW. Int J Epidemiol. 2009 Apr;38(2):419-26. doi: 10.1093/ije/dyn348. Epub 2008 Dec 23.

10. A prospective study of weight change and systemic inflammation over 9 y. Fogarty AW, Glancy C, Jones S, Lewis SA, McKeever TM, Britton JR. Am J Clin Nutr. 2008 Jan;87(1):30-5.