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Current projects

Introduction

We have particular expertise in design and analysis of occupational and environmental epidemiological surveys

In addition to our specific research projects, we provide assistance with:

  • statistical design
  • data management
  • analysis
  • presentation of results
  • dissemination of findings

We also have a well-established, highly thought of teaching programme.


Current Projects

Asthma in Ashford

Now part of STELAR (Study Team for Early Life Asthma Research)

The Ashford study is a longitudinal study and aims at investigating asthma and other allergic disorders, their development during children’s lives and the effect of risk factors on these conditions. The study recruited pregnant women who gave birth to 642 infants born in Ashford, Kent between 1992 and 1993. Environmental measurements were collected from the babies' homes soon after birth. Additional data were collected at each annual visit along with health information, such as wheezing and other respiratory symptoms, other allergies and family history (including skin prick tests for the parents).

In 2013, the Ashford cohort joined the Study Team for Early Life Asthma Research (STELAR) consortium, a collaborative network of all asthma UK birth cohorts (ALSPAC, MAAS, SEATON and IoW), the North West Institute for Bio-Health Informatics and Microsoft Research Cambridge.

In March 2015, a new Ashford follow-up began to collect information from the cohort children, now aged 20 years, through the use of a short, self-completed, paper or web questionnaire. The questionnaires were first dispatched in late February 2015 and reminders were sent in May and July respectively in order to engage more participants in completing the survey. The response rate since then has been about 60%.


The Cystic Fibrosis Epidemiological Network (CF-EpiNet)

  • Olga Archangelidi, Siobhan Carr (Royal Brompton Hospital), Diana Bilton, Debbie Jarvis, David Taylor Robinson (Liverpool University), Jenny Whitty (University of East Anglia), Ruth Keogh (LSHTM), Sanja Stanojevic (University of Toronto), Paul Cullinan

CF-EpiNet: Harnessing Data to Improve Lives project has 4 main objectives:

1) To develop appropriate methods to link, securely store and analyse information held within the UK CF Registry with other UK data administrative sources.

2) To apply advanced statistical techniques appropriate for analysis of longitudinal outcome data in CF to assess causal pathways and therapeutic impacts.

3) To identify social and other risk factors at critical time points that are associated with and predict the impact of disease on patients’ lives, disease progression and survival.

4) To improve the evidence available to inform economic models and decisions about appropriate CF care.

The project uses data of cystic fibrosis patients that has been collected through:1) The UK CF Registry that records CF patients’ clinical, demographic and treatment data on the day of their annual reviews at CF clinics in UK, 2) an online survey on Quality of Life of CF patients (Living with Cystic Fibrosis study) that started in November 2016. The project started in 2015 and is due to finish in 2019. The Quality of Life stream is currently at a pilot stage and will move to a national rollout in March 2017.


Developing laboratory methods to identify airborne allergens present in ambient air pollution

Our project is focused on attempting to identify unknown allergens present in air pollution, which may contribute to life-threatening asthma exacerbations. Using recent advances in biomedical laboratory science, allergens are detected by immunological techniques, and protein sequences identified with mass spectrometry at King’s College London. This project forms the basis of a PhD in public health research but also contributes towards increasing understanding of allergens in occupational and environmental allergic disease mechanisms.


Fire Service audit

Jo and Bernadette are currently undertaking a pre-employment assessment of fire service applicants with a history of asthma. Such individuals are referred to our specialist clinic for assessment of their asthma status and suitability for work as a firefighter. Follow-up questionnaires determine the outcome of their application, current asthma control and treatment.

 

Follow–up study on patients diagnosed with occupational asthma or rhinitis

All patients diagnosed with occupational asthma or rhinitis are contacted 12 months later to find out how their condition has affected their life. Key points of enquiry are symptom improvement, changes to workplace exposures, effect on career, income and quality of life, satisfaction with their care, and how fairly they were treated by their employer. The study is on-going.

 

Idiopathic Pulmonary Fibrosis Job Exposure Study (IPF JES)

IPF JES is a UK based multi-center case-control study that aims to find out if job exposures are an under-recognized cause of idiopathic pulmonary fibrosis (IPF). 

Men with IPF and hospital controls will be interviewed to collect information about previous job exposures. Blood will be drawn to investigate genetic susceptibility.

The study is supervised by Prof Paul Cullinan and funded by a Wellcome Trust Clinical Research Training Fellowship awarded to Dr Carl Reynolds.  See www.ipfjes.org for further information. 

 

Occupational lung and heart disease in welders

The research comprises:

  • A cross-sectional and panel study looking at the effects of welding fume exposure on welders’ lungs and heart who are working in a repair shipyard in the Middle East; specifically looking at lung disease and arterial stiffness.
  • Analysis of historical longitudinal data of welders from the same shipyard.
  • Systematic review and meta-analysis of cross-sectional studies on arc welding fume effects and obstructive lung disease.

Patient Reported Outcome Measure in Interstitial Lung Disease

  • Anne Marie Russell, Lesley Anne Saketkoo, Georgina Jones, Zoe Borrill, Melissa Wickremasinghe, Huzaifa Adamali, Athol Wells, Elizabeth Renzoni, Toby Maher, Sharon Fleming, Paul Cullinan

This is an NIHR-funded study. We are developing a new concise Patient Reported Outcome Measure (PRoM) in patients diagnosed with Idiopathic Pulmonary Fibrosis (IPF) employing patient centered mixed methodology. This is an iterative process.  Qualitative approaches and consensus methods ensure a rigorous approach to item generation thereby enhancing construct validity. This study commenced in 2013.

Phase one is complete – Focus Groups held at the Royal Brompton Hospital London, Pennine Acute Hospitals Trust and North Bristol NHS Trust.

Phase two is complete. An electronic Delphi survey completed by Patients, relatives and specialist ILD physicians and clinical nurse specialists. Supported by UK and Ireland IPF charities.

Phase three: item reduction, psychometric testing is complete.

Active January 2017: recruiting to test re-test and validation phase.

http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=15468


Exploring the gender gap in CF

  • Sabine Hippolyte (Royal Brompton and Harefield NHS Trust), Uta Griesenbach (National Heart and Lung Institute, Imperial College), Stephanie MacNeill, Nick Simmonds (Royal Brompton and Harefield NHS Trust) and Diana Bilton (Royal Brompton and Harefield NHS Trust)

Epidemiological studies have identified a number of predictors of survival in CF including FEV1 and BMI. There exists some evidence that females have worse lung function and nutritional status than males, but these results are not conclusive. In this study – forming  Sabine Hippolyte’s MD project – we will be using both cross-sectional and longitudinal data from the UK CF Registry patient database to assess whether there exists differences between men and women in terms of FEV1 and BMI then explore potential causes of such differences. Analyses will be confirmed using longitudinal data from the US CF Foundation Registry database. Sabine is supported by a fellowship from the Robert Luff Foundation.


Traffic air pollution and transplant failure

A fairly small study in Belgium suggests that about 30% of mortality following lung transplantation can be attributed to traffic-related air pollution.  We will test this through another, much larger study which will include patients who have undergone other solid organ transplants.  If our findings confirm those from Belgium. this research could lead to important advances in the understanding of transplant survival, and in the monitoring and treatment of patients. 


A pilot study comparing non-invasive and invasive tests of nasal and airway responses to inhalation challenges in patients with suspected occupational asthma and rhinitis

Sindhu Sivagnanasithiyar, Jo Szram, Paul Cullinan

This study aims to compare non-invasive tests with nasal cytokine responses and airway responses measured during standard specific inhalation occupational challenges, in order to improve diagnosis, and as a result, patient experience and care. 

Non-invasive methods have the potential to measure nasal reactions in patients who are unable to tolerate or otherwise undergo nasal secretion sampling; they could also be used as a method of diagnosis and monitoring in the workplace. 

It is possible that in the future, rather than a resource-intensive specific inhalation challenge, non-invasive methods could be used to support the diagnosis of occupational rhinitis. Refined diagnosis and subsequent management of occupational rhinitis may help reduce the clinical and socioeconomic impact of assessment and diagnosis and lead to improved quality of life.


Individually Ventilated Cages in laboratory animal facilities and the prevention of laboratory animal allergy: a proof of concept study

The SPIRAL (Safe Practice in Reducing Allergy in Laboratories) study is funded by an NIHR post-doctoral fellowship for Dr Johanna Feary.  The project is designed to determine if the introduction of individual ventilated cages has resulted in a significant reduction in the risk of laboratory animal allergy. We have recruited some of the largest and most prestigious research institutions in and around London with whom we have a close clinical and /or academic relationship. The study started in 2014 and recruitment will take place over four years.


Lungs At Work in Kent

A study, funded by the Colt Foundation, is examining the impact of respiratory symptoms, COPD and airflow obstruction (FEV1) on present and future employment in 51-60 year olds in Kent. 

Phase 1: initial postal cross-sectional survey of over 20,000 people completed in 2007, demonstrating the significant impact of breathlessness on work performance in this age group. 

Phase 2: Just under 2000 volunteers in full time work completed a detailed clinical assessment, involving spirometry, exercise and muscle strength testing and measurement of fat free mass as well as blood sampling. 

Spirometry results demonstrated that airflow obstruction was significantly associated with impairment in work performance in this general population, particularly in individuals reporting breathlessness.

Phase 3: follow up postal questionnaire survey focusing on job changes in the intervening 18 months, repeat clinical assessment to compare participants experiencing job loss or change in circumstances with individuals from the same population who reported no difference in their employment situation.


The causes of occupational chronic obstructive pulmonary disease (COPD) in the UK

  • Paul Cullinan, Lesley Rushton (School of Public Health, Imperial College), Debbie Jarvis (National Heart and Lung Institute, Imperial College), Sara De Matteis, Jon Ayres (University of Birmingham), David Fishwick (Health and Safety Laboratory, Buxton, Derbyshire/Northern General Hospital, Sheffield), Steven Sadhra (University of Birmingham),

Occupational hazards are important and preventable causes of COPD worldwide. However the list of occupations and underlying specific exposures responsible for the increased risk is still unknown. The overarching goal of the HSE-COPD study is to identify the occupational causes of COPD and related burden in the UK general population in order to implement focused preventive strategies at workplace.

To achieve this goal the UK Biobank study, a UK population-based cohort including half a million subjects, was established.

The specific goals achieved so far are:

  1. Identification of occupations associated with COPD risk using a cross-sectional analysis (see this paper)
  2. Development of a new efficient web-based tool (OSCAR) to collect and code lifetime job-histories (see this paper)
  3. Development of a new job-exposure-matrix (ACE-JEM) to estimate the exposure to specific agents associated with increased COPD risk (see this paper)
  4. Estimation of the work-related COPD burden in the UK general population (publications pending)

Future steps are:

  1. Analysis of the longitudinal lifetime job-histories collected and coded using OSCAR to identify the occupations at increased COPD risk
  2. Application of the new ACE-JEM to both the cross-sectional and longitudinal data in order to identify the specific agents responsible of the increased COPD risk

The effects of real-world exposures to diesel traffic emissions on cardio-respiratory outcomes in patients with COPD and IHD: ‘Oxford Street 2’ - a BHF funded study

  • Paul Cullinan, Fan Chung, Rudy Sinharay; Ben Barratt and Frank Kelly (Environmental Research Group, KCL); Jim Zhang (Dukes University USA)

The objectives of this study are to compare the clinical, physiological and inflammatory responses in patients with COPD and IHD after exposure to ambient levels of diesel emission particles in Oxford Street (high levels) and in Hyde Park (low levels).

Physiological outcomes measured included lung function, impulse oscillometry and arterial stiffness.

We would like determine the mechanistic explanations for any physiological findings. In particular we have taken serum samples to look at:

  • Markers that relate to endothelial dysfunction including P-selectin (sCD62P) & sCD40L
  • Markers of oxidative stress including 8-isoprostane and malondialdehyde (oxidative stress)