Characterise the natural history of IPF vs non-IPF ILD in terms of FVC lung function decline

To utilize historical patient records to identify “non strictly IPF” patients with progressive lung fibrosis who may benefit from pharmacological management with approved IPF therapies by characterizing and comparing (i) clinical presentation (over time); (ii) characteristics (clinical and demographic) at time of diagnosis and (iii) clinical progression of patients diagnosed with IPF and those with “non strictly IPF” progressive fibrotic lung conditions.

Lead Investigators:
Luca Richeldi
Mark Jones
David Price

Research Team:
Alison Chisholm, UK
Anjan Nibber, UK
Status: Proposed Study, Seeking Funding
Support:
Registration:

Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
Additional Material

Characterise the natural history of patients with alpha-1 antitrypsin deficiency in routine care patients with/without COPD

 

COPD is a major cause of death worldwide and few treatments improve survival. Recent research suggests that, in patients with COPD ischaemic heart disease treatments — statins and beta blockers – can improve overall survival. COPD and ischaemic heart disease commonly co-exist and it may be that the beneficial effect of statins and beta blockers is due to improvements in heart disease rather than effects on the COPD disease course. At this time, it is not known if the apparent effects of statins and beta blockers on COPD exacerbation frequency and overall survival are independent of COPD severity.

The study aims to investigate the effect of statins and beta blockers on COPD exacerbation frequency and survival in an observational primary care population stratified by COPD severity (i.e. by lung function and DOSE Index Score).

There will be five core study objectives evaluated for the following patient groups, those treated with:

  • Statins
  • Beta blockers
  • Statins and beta blockers
  • Neither statins nor beta blockers (“control patients”)

Objective 1: Determine the difference in COPD exacerbation frequency in COPD patients
Objective 2: Determine the difference in COPD exacerbation frequency in COPD patients with an apparent “frequent exacerbation phenotype” (defined as ≥2 COPD exacerbations in the prior 12 months)
Objective 3: Determine the difference in all-cause mortality rate (if there are sufficient data available)
Objective 4: Stratify patients according to GOLD classifications and DOSE Index and explore potential differential prescribing levels for statins and beta blockers for different COPD severities.
Objective 5: Evaluate whether lone or combination use of beta blockers and statins results in a greater benefit, in terms of exacerbation frequency or survival.

Dataset: The study will be a retrospective observational study using data from the Optimum Patient Care Research Database (OPCRD). The OPCRD is a UK respiratory dataset containing anonymized, longitudinal, research-quality clinical records and patient-reported outcome data from practices that subscribe to OPC for respiratory review services; the database includes in excess of 341,000 patients at 176 practices. It has Multicentre Research Ethics Committee (MREC) approval for medical research.
Population: All the patients aged ≥18years with a COPD diagnosis.
Index date: the date for a patient’s first prescription for a statins and/or beta blocker (following the date of their first COPD diagnosis).
Duration: 3 year study periodcomprising 1 baseline year for patient characterisation prior to the index date and a 2-year period immediately following the index date.
Primary Outcomes: COPD Exacerbations, defined as: hospitalisation, out of hours medical attendance or accident and emergency attendance for COPD, or treatment with oral corticosteroids and/or antibiotics in patients diagnosed with COPD, or primary care consultation for lower respiratory tract infection/exacerbation.
Secondary Outcomes: All-cause mortality

Recommended Reading
Blamoun AI, Batty GN, DeBari VA, Rashid AO, Sheikh M, Khan MA. Statins may reduce episodes of exacerbation and the requirement for intubation in patients with COPD: evidence from a retrospective cohort study. Int. J. Clin. Pract. 2008 Sep;62(9):1373–8.
Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N. Engl. J. Med. 2010 Sep 16;363(12):1128–38.
Salpeter SR, Ormiston TM, Salpeter EE. Cardioselective beta-blockers in patients with reactive airway disease: a meta-analysis. Ann. Intern. Med. 2002 Nov 5;137(9):715–25.
Short PM, Lipworth SIW, Elder DHJ, Schembri S, Lipworth BJ. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ. 2011;342:d2549.
Rutten FH, Zuithoff NPA, Hak E, Grobbee DE, Hoes AW. Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch. Intern. Med. 2010 May 24;170(10):880–7.

Lead Investigator:
Andrew Wilson, Clinical Senior Lecturer in Respiratory Health, University of East Anglia, Norwich and Honorary Consultant Physician in Respiratory Medicine, Norfolk and Norwich University Hospital, Colney Lane, Norwich, UK
Research Team:
The research team is made up of researchers working at the University of East Anglia, Norwich, UK:
Katie Hawkins, UK
Phyo Myint, UK
Erika Sims, UK

Status: Completed Study
Support: Respiratory Effectiveness Group
Registration:
Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
Additional Material

Characterise the natural history of patients with alpha-1 antitrypsin deficiency in routine care patients with/without COPD

This study aims to determine trends in AATD prevalence, incidence and mortality in the UK population using large databases from primary care records, in all and by subgroups of major determinants (gender, age, calendar year, geography, smoking status, with/without COPD, other comorbidities, …), and to characterize the UK AATD population natural history versus a reference population with/without COPD.

The primary objective of the study will be to establish the extent of the AATD burden in the UK, and to benchmark it with other respiratory and non-respiratory conditions.

Lead Investigator:
Dr Joan B Soriano
Research Team:
Dr Ravi Mahadeva
Dr Rupert Jones
Dr Marc Miravitlles

Status: Active Study
Support:
Registration:
Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
Additional Material

Item reduce the EXACT (Exacerbations of Chronic Pulmonary Disease Tool) Questionnaire for improved exacerbation risk prediction (clinical use and self-(tele) monitoring)

Through analysis of existing datasets utilising the EXerbAtions of Chronic Pulmonary Disease Tool (EXACT), to develop a reduced questionnaire that is sufficiently sensitive and specific to be a practical clinical tool for identifying the onset of exacerbations of chronic obstructive pulmonary disease (COPD). The aim is to use the existing EXACT database to develop a reduced (approximately five-item) questionnaire that is sufficiently sensitive and specific to be a practical clinical tool, and to validate the instrument in a second database.

Lead Investigator:
Paul Jones: Professor of Respiratory Medicine, Consultant chest physician, St George’s Healthcare NHS Trust
Research Team:
Dermot Ryan: Honorary clinical Research Fellow, Centre for Population Health Sciences, University of Edinburgh
Hilary Pinnock: Reader, Allergy & Respiratory Research Group, Centre for Population Health Sciences, University of Edinburgh

Status: Proposed Study, Seeking Funding
Support:
Registration:
Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
Additional Material

Utilise routine care data to develop a risk prediction model patients with COPD

Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited. The goal of the study was to develop a robust, clinically based model to predict frequent exacerbation risk

Lead Investigator:
Marjan Kerkhof
Research Team:
Daryl Freeman
Rupert Jones
Alison Chisholm
David B Price

Status: Completed Study
Support: Respiratory Effectiveness Group
Registration:
Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
International Journal of COPD
Additional Material

Evaluate the potential role of blood eosinophils as a biomarker—predictor of future risk and / or treatment response—in COPD

The primary aim of the proposed study is to explore the relationship between blood eosinophil count and future exacerbation risk in COPD and effect of preventative COPD therapy on eosinophil level. Additional analysis will also aim to investigate the stability of the phenotype, defined by change in eosinophils over time and in response to treatment.

Exploratory investigations will also seek to characterise features of COPD patients with eosinophilia in terms of their COPD stage and categorisation, comorbid conditions and other clinical characteristics (respiratory symptoms, past history of exacerbations, risk factors).
This study will be the first in a series of REG-funded studies designed to explore the relationship between blood eosinophil count, COPD disease status, COPD exacerbations and to explore its value and utility as a measureable marker of future risk in COPD.

In particular, this study aims to:

  • Establish the relationship between blood eosinophil count and:
    o Future COPD exacerbations.
    o Response to preventative COPD therapy; and
  • Investigate the stability of the phenotype, defined by change in eosinophils over time and in response to treatment.

Lead Investigator:
David Price
Research Team:
Antonio Anzueto
Alvar Augusti
Mona Bafadhel
Guy Brusselle
Alison Chisholm
Daryl Freeman
Rupert Jones
Nicolas Roche
Ian Pavord
Todor Popov
Alberto Papi
Dirkje S. Postma
Emilio Pizzichini
Dermot Ryan
Mike Thomas
Claus Vogelmeier

Status: Active Study
Support: Respiratory Effectiveness Group
Registration: ENCEPP/SDPP/492
Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
Additional Material

Role of Exhaled Breath Temperature (EBT) in the monitoring of asthma and COPD

EBT decreases over the Asthma – COPD spectrum in stable disease proportional to the reduction of the airways vascular bed; however, fluctuations in diseases activity over time will be different between the two extremes (Asthma & COPD) in terms of variability of the daily measurements (similar to peak expiratory flow (PEF)-metry) and during exacerbations; intermediate group(s) of patients may shape up corresponding to intermediate (ACOS) phenotype(s).
This project examines whether daily measurement of exhaled breath temperature (EBT) under standardized ICS-LABA treatment will identify intermediate phenotypes along the asthma – COPD spectrum?
Lead Investigator:
Todor Popov
Research Team:
Status: Proposed Study, Seeking Funding
Support:
Registration:
Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
Additional Material

Investigate bronchiolitis in early childhood as a predictor of future and asthma

The aim of the proposed study is to evaluate the risk of asthma at different ages (3-4yrs, 6-7 yrs, 9-10yrs, 13-14yrs) that can be attributed to RSV bronchiolitis, in a UK primary care population.
Secondary objectives are to evaluate the overall risk of bronchiolitis on asthma diagnosis and activity (medication prescription, healthcare utilisation), effect on overall health, interaction with other risk factors (gender, age, prematurity, tobacco exposure, allergic diseases) and long-term bronchioltis burden.
The date/season of the bronchiolitis incident will be used as a surrogate marker for disease aetiology.
Asthma diagnosis will be the primary outcome measure. Asthma activity will also be evaluated.

Lead Investigator:
Nikos Papadopoulos
Research Team:
Status: Proposed Study, Seeking Funding
Support:
Registration:
Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
Additional Material

Development of a Longitudinal Asthma Treatment Step Algorithm and Association with Asthma Outcomes

Objective 1.a Based on asthma management guidelines (British Thoracic Society and Global Initiative for Asthma), we will develop pharmacy utilization treatment step algorithms using a quality controlled, primary care research database from the United Kingdom.
Objective 1.b We will examine longitudinal pharmacy utilization treatment step patterns and associate them with patient characteristics.
From Objective 1, we will be able to characterize patients within a large-scale primary care research database in terms of their asthma management guideline-based treatment step, track how patients’ treatment steps change over time, and relate treatment steps and changes to various patient characteristics.
Objective 2. Within age categories, we will compare asthma outcomes by treatment step utilization patterns.
From Objective 2, we will be able to test for differences in the likelihood of achieving asthma control and the risk of exacerbation by commonly observed treatment step patterns, adjusting for differences in patient characteristics across patterns. For example, is the likelihood of control higher for those who have a longer history of a stable treatment step as compared to those who are consistently stepping up or down? Is the likelihood of control or exacerbation modified by treatment step?

Lead Investigators:
Jon Campbell
Alexandra Dima
Research Team:
Status: Proposed Study, Seeking Funding
Support:
Registration:
Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
Additional Material

Utilise routine care data to develop a risk prediction model patients with asthma

This study aims to identify patient characteristics recorded within routine primary care datasets that are associated with increased risk of frequent asthma exacerbations, with the ultimate goal of:

1. Characterising the frequent exacerbator subgroup of asthma patients
2. Identifying individual risk factors associated with increased future exacerbation risk
3. Exploring clusters of risk factors associated with increased risk of future exacerbation risk.
Lead Investigator:
Mike Thomas, Professor of Primary Care Research at the University of Southampton.
Research Team:
David Price: Primary Care Respiratory Society UK, Professor of Primary Care Respiratory Medicine, University of Aberdeen, UK; Director Optimum Patient Care Ltd and Research in Real Life Ltd
John Blakey: Liverpool School of Tropical Medicine, Aintree University Hospital, North Mersey HIS, UK
Vibeke Backer: Dept of Respiratory Medicine L, Respiratory Research Unit, Bispebjerg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark
Lynn Josephs: Primary Care research, University of Aberdeen
Ian Pavord: Institute for Lung Health, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK
Borislav Dimitrov: Senior Lecturer in Medical Statistics at the University of Southampton
Dirkje Postma: Professor of Pulmonary Medicine at the University of Groningen and the University Medical Center of Groningen
Alberto Papi: Professor of Respiratory Medicine and Director of the Section of Respiratory Diseases of the Department of Clinical And Experimental Medicine of the University of Ferrara at S.Anna University Hospital, Ferrara
Alexandra Dima: Researcher in Health Psychology, Department of Communication Science, University of Amsterdam, The Netherlands
Todor Popov: Professor at Clinical Centre of Allergology in Sofia
Hilary Pinnock: Principal in General Practice, Whitstable Medical Practice, UK; Reader, Allergy and Respiratory Research Group, Centre for Population Health Sciences: GP Section, University of Edinburgh, UK
Iain Small: General Practitioner from Peterhead, Aberdeenshire, UK Chair of the Primary Care Respiratory Society in the UK; Trustee of Asthma UK
Alan Kaplan: Family physician, Ontario, Canada and Chair of the Respiratory Medicine Special Interest Focus Group of the College of Family Physicians of Canada
Cindy Rand: Professor of Medicine, John Hopkins University, USA
Janet Holbrook: Associate Professor of Epidemiology, Johns Hopkins Center for Clinical Trials, USA
Emilio Pizzichini: Head of the Pulmonology Department of the Universidade Federal de Santa Catarina – UFSC, Federal University of Santa Catarina – School of Medicine, Florianópolis, Brazil
Gene Colice: Chest Physician, Pulmonary, Critical Care and Respiratory Services, Washington Hospital Center, and The George Washington University School of Medicine
Samantha Walker: Executive Director, Research & Policy and Deputy Chief Executive, Asthma UK
Alison Chisholm: Respiratory Effectiveness Group Implementation Manager
Status: Active Study
Support: Respiratory Effectiveness Group
Registration: ENCEPP EUPAS4869
Documents and Publications:
Protocol
Abstracts
Presentations
Final Publications
Additional Material