Title: What happens between first symptoms and first acute exacerbation of COPD? Mapping and prediction study
Funder: Department of Health and Social Care

Abstract: Background and why this research matters:_x000D_ _x000D_ Chronic obstructive pulmonary disease (COPD) is the name used to describe a number of conditions including emphysema and chronic bronchitis. It affects over a million people in the UK alone. It is a serious condition, reduces quality of life and costs the NHS a lot to treat. It can be hard to diagnose, but not much is known about how patients get their diagnosis, for instance whether when seeing their GP, following various tests or during an emergency admission to hospital. We need to understand how long it takes to get diagnosed and what can cause delays._x000D_ A common consequence of COPD is that breathing can quickly get much harder (known as an acute exacerbation, AECOPD), causing lung damage. If we can predict which patients are the most likely to go on and have an AECOPD, then treatment and monitoring can be adjusted. Previous attempts to do this prediction have failed for various reasons, but with our data and statistical approach we can overcome those problems._x000D_ _x000D_ _x000D_ Our aims are:_x000D_ _x000D_ 1. To map out patients’ “routes to diagnosis”: whether in hospital during their first AECOPD or by their GP, and whether their other medical conditions affect how and how quickly they get their diagnosis_x000D_ 2. To see how all this differs depending on where people live in England and whether things have changed since ten years ago_x000D_ 3. To see who is most at risk of an AECOPD and how the risk changes with time since diagnosis, paying particular attention to patients who also have conditions such as asthma and heart failure that have similar symptoms_x000D_ _x000D_ How we will do this:_x000D_ _x000D_ We will use a UK database of existing electronic health records for patients at GP practices who have consented to provide their records for research. These records have no names, addresses or other information that can reveal the identities of patients to the researchers. We will look separately at people who also have other specific conditions, particularly heart failure and asthma, which can make the COPD diagnosis more difficult for GPs. We will look at regional variations to see if some areas of England get faster diagnosis and lower AECOPD rates than others. We will look at patterns now and ten years ago to see if there have been any changes for the better or for the worse._x000D_ All this will use various statistical modelling methods. For example, to find out which patients are at higher risk of an AECOPD, we will include factors such as their age, gender, medications, test results and other medical conditions; we will need to model the fact that some of these factors change over time as patients’ health changes over time. We will also look at the effect of the weather (particularly the cold) on risk. The project team have a lot of experience with applying these methods to these databases._x000D_ _x000D_ Benefits of this research:_x000D_ _x000D_ We will describe for the first time in detail how NHS patients across England get their COPD diagnosed and how long this takes. If some parts of the country do this better than others it will suggest opportunities for improvement._x000D_ Comparing now with ten years ago will tell us if the NHS is going in the right direction regarding helping patients with COPD._x000D_ To help general practices monitor their COPD patients better, alerting them to who is at greater risk of an AECOPD will help staff and patients have better discussions together on managing this common and serious condition.

Lay abstract: Background:_x000D_ Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death and affects nearly 400 million worldwide. In the UK over a million people live with it, but, despite the National Audit and local prevalence estimates, we have limited understanding of how people are diagnosed, how long this takes, and the different approaches to clinical management taken in primary care. In addition, management should be tailored to each patient to improve outcomes, for instance by stratifying patients according to the risk of acute exacerbations of COPD (AECOPD). A recent systematic review of risk prediction models for AECOPD stated that “exacerbations are an ideal target for risk-stratified treatment, but…none of the existing models fulfilled the requirements for risk-stratified treatment to personalise COPD care”. We plan to overcome the statistical shortcomings of these models to produce a risk prediction model for the first AECOPD, which is a better point at which to intervene than afterwards due to the cumulative lung damage caused by repeat exacerbations._x000D_ _x000D_ Aims and objectives:_x000D_ To describe and model the patient journey from symptom presentation to diagnosis and first acute exacerbation for COPD patients in England. This will include examining variations by Clinical Commissioning Group (CCG), GP practice and time period, followed by the construction and validation of a risk prediction or risk trajectory model for the first AECOPD._x000D_ _x000D_ Methods:_x000D_ Using CPRD and two cohorts ten years apart, we will describe the management of the patient following initial presentation with symptoms through to their diagnosis of COPD and their first AECOPD, which for some patients will be the same event. Given that COPD can present differently depending on comorbidity, the mapping will be described separately for people with asthma and heart failure in particular. This quantitative analysis will be informed and supplemented by directly asking patients for their experiences in different ways, including attending Breathe Easy meetings, two focus groups, and an online survey._x000D_ The second part will model the risk of the first AECOPD using factors such as airways obstruction, age, smoking, BMI, gender, comorbidities and public data on temperature and pollution. This will use logistic regression, random forests and cause-specific hazards modelling. Predictors will be ranked in importance from GP, patient and system perspectives. Models will be externally validated using CPRD “Aurum” practices._x000D_ _x000D_ Timelines for delivery:_x000D_ Months -3 to 0: study set up; months 1-12: data extraction, patient experience activities and objectives 1 and 2; months 13-24: objectives 3 and 4; months 25-27: report writing_x000D_ _x000D_ Anticipated impact and dissemination:_x000D_ This study will fill key gaps in our understanding of how patients obtain their COPD diagnosis (their “route to diagnosis”), how they are managed in primary care, and how they get their first AECOPD. Comparisons between the two time periods will highlight what has changed and inform NHS preparation for future needs regarding COPD. A risk prediction model for first acute exacerbation will aid shared decision-making between GPs and patients and facilitate early intervention; ranking the predictors will suggest priorities for action. Dissemination will be to clinicians, patients and policy-makers, through academic outputs, local clinical leadership fora such as CLAHRC/ARC, the RCGP and Primary Care Respiratory Society, and relevant charities such as our local Breathe Easy patient group and the British Lung Foundation. Our approach and results will inform the National Audit and also NICE guidelines on diagnosis and management.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: RESPIRATORY