Severe Asthma Research Programme

A person-centred approach to evaluating the impact of severe asthma

The team

This project is a collaborative effort between the University of Plymouth’s Faculty of Health: Medicine, Dentistry and Human Sciences, the School of Psychology, and University Hospitals Plymouth NHS Trust. The team consists of Professor Michael Hyland, Professor Rupert Jones, Joseph Lanario, Lucy Cartwright, Dr Yinghui Wei and Dr Matthew Masoli, who is the clinical lead for asthma at the Royal Devon and Exeter Hospital and has established a regional severe/difficult asthma service.

Background

Severe asthma is a disease of the airways characterised by high symptom burden and resistance to treatment. Approximately 5 – 10% of asthma patients have severe asthma but this small patient group experience disproportionate disease burden.
In recent years, the National Institute for Clinical Healthcare Excellence (NICE) has approved new treatments for severe asthma. Many of these new treatments are drugs known collectively as ‘biologics’. These biologics target specific and different pro-inflammatory mechanisms, depending on which one you are prescribed. The approval of these new drugs has changed the way we treat patients with severe asthma, but also the way we think about the disease.
The programme of research below focuses on understanding what it is like to have severe asthma from a patient perspective and aims to give patients a voice in the clinical literature.

Our Projects

Derivation and validation of a severe asthma-specific quality of life questionnaire

Why is a new questionnaire needed?

Existing questionnaires are not valid for assessing quality of life in severe asthma, according to the 2009 guidelines on questionnaire construction provided by the Federal Drug and Food Administration (FDA). This is because these questionnaires fail to address some of the quality of life deficits experienced by this group of patients.

How did we develop the Severe Asthma Questionnaire (SAQ)?

Three studies were carried out to create a valid health-related quality of life (HRQoL) measure in accordance with FDA guidelines. First, we conducted a series of qualitative interviews with patients diagnosed with severe asthma. These interviews concerned factors affecting a patient’s HRQoL, including asthma symptoms and medication side effects. The qualitative data from this study showed that many of the burdens experienced by this patient group were not assessed by the asthma-specific HRQoL questionnaires available at the time.

A draft SAQ was then made using the information gained from the interviews. Relevant questions for a severe asthma-specific questionnaire were chosen for this draft. This draft SAQ was evaluated in four focus groups by patients diagnosed with severe asthma, and iterative changes were made after each group. Participants were encouraged to suggest changes to the questionnaires in order to improve its comprehensibility and relevance to the experience of severe asthma.

The final step was a quantitative assessment of the SAQ, using data from 160 patients diagnosed with severe asthma. This was the final step in the FDA’s stepwise process of validation of a severe asthma quality of life questionnaire.

One of our published papers provides data that validates the use of the SAQ in clinical practice and in clinical trials of severe asthma.

A multi-centre study collecting data on the SAQ is currently underway. This data will be used to further assess the psychometric properties of the questionnaire, assess sensitivity to change, and determine its minimum clinically important difference (MCID).

The group developing the questionnaire have also investigated the similarities between severe asthma and functional disorders such as fibromyalgia and have published theoretical work on the reasons for individual differences in response to biologic treatments for severe asthma.

National validation of the SAQ

National validation of a scale to measure the quality of life in patients with severe asthma

Further data collection was needed to further assess the statistical properties of the SAQ. Data were collected from an additional 300 patients attending 5 specialist severe asthma centres in the UK. Analysis is ongoing.

With this data it will be possible:

to reassess the construct validity of the SAQ, e.g. 'does the questionnaire score worsen as the patient’s severity increases as indicated by clinical measures?'
to show that the SAQ correlates with accepted measures of asthma control
to provide a description of the factor structure of the SAQ and to demonstrate equivalence across populations.

This research is in collaboration with healthcare professionals and researchers from:

University of Plymouth, Faculty of Health, Plymouth UK
Royal Brompton and Harefield NHS Foundation Trust, London, UK
University Hospital of South Manchester, Manchester University NHS Foundation Trust, UK
Heartlands Hospital of the University Hospitals Birmingham NHS Foundation Trust, UK
Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK
Southmead Hospital, North Bristol NHS Trust, Bristol UK

Sensitivity to change of the SAQ

Assessment of the sensitivity to change and minimum clinically important difference (MCID) of a scale to measure the quality of life in patients with severe asthma

When designing a new questionnaire, it is important to (a) determine if the questionnaire measures what it supposed to measure and (b) assess if the questionnaire is sensitive to changes in what it is measuring. This first objective was the focus of our two previous SAQ studies. This study addresses the second objective by:

assessing the sensitivity to change of the SAQ, for patients who initiate a new biologic treatment for their asthma
determining the SAQ’s MCID.

For questionnaires, an MCID is the smallest change in the questionnaire’s score that can be considered clinically meaningful. Without this value, it is not possible to demonstrate if a patient’s quality of life has improvement up to or beyond a meaningful level according to a quality of life questionnaire.

Data were collected from patients who had commenced a biologic treatment for their severe asthma. Analysis is ongoing. This data will be used to determine if the SAQ is sensitive to improvements in quality of life following this treatment change. The MCID of the SAQ will be calculated using an anchor method. The “anchor” used in this study is an 11-point Global Rating of Change Questionnaire which includes descriptors alongside 5 levels of improvement, 5 levels of deterioration and for no change.

This research project is in collaboration with healthcare professionals and researchers from:

University of Plymouth, Faculty of Health, Plymouth UK
University Hospitals Plymouth NHS Trust, Plymouth, UK
Royal Brompton and Harefield NHS Foundation Trust, London, UK
University Hospital of South Manchester, Manchester University NHS Foundation Trust, UK
Heartlands Hospital of the University Hospitals Birmingham NHS Foundation Trust, UK
Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK
Southmead Hospital, North Bristol NHS Trust, Bristol UK

Super-responders in severe asthma

Qualitative study of super-responders in severe asthma with biologics

Biologics are a new and expensive type of treatment that is offered to some patients who have severe asthma which is uncontrolled by other treatments. The extent to which patients experience benefit varies widely, but there is a group of patients, called ‘super-responders’, who experience substantial benefit. This benefit is seemingly more than can be explained only by a reduction in asthma symptoms and asthma attacks.

We wish to find out more about these patients and as a first step intend to interview patients so they can describe in their own words what happened when they started taking biologic treatment. There is currently no consensus on the definition of a ‘super-responder’ and the judgement of the patent’s asthma Consultant is usually used to identify these patients. This the method we will be used for this study.

Work is underway by different research groups to define what a super-responder is, using clinical markers such as improvement in lung function or reduction in eosinophils (a type of white blood cell) following treatment.

For our study, we will interview patients thought of as super-responders by the Consultant responsible for their asthma care. By doing this we aim to:

explore what it is to be a super-responder from a patient’s perspective
identify what improvements in symptoms patients experienced after starting their biologic treatment, and whether this improvement included non-respiratory as well as respiratory symptoms
begin formulating a patient-centred definition of what it is to be a super-responder to biologic treatment for severe asthma.

This research project is in collaboration with healthcare professionals and researchers from:

University of Plymouth, Faculty of Health
University Hospitals Plymouth NHS Trust, Plymouth, UK
Royal Brompton and Harefield NHS Foundation Trust, London, UK

Body reprogramming for severe asthma

Body reprogramming as an adjunct to biologic administration in patients with severe asthma: a pilot study

Our research demonstrates that the HRQoL deficit in patients with severe asthma is affected by both pulmonary (associated with asthma) and extra-pulmonary (e.g. mental fog, fatigue, unexplained pain) symptoms that contribute equally to the total HRQoL deficit.

Body reprogramming (BR) is a non-drug, multi-component intervention originally developed in Plymouth for patients with fibromyalgia. The intervention focuses on optimising patient knowledge of disease management, physical activity, relaxation and other psychological and biological lifestyle changes that increase wellbeing and mood. We hypothesise that patients with severe asthma who experience similar symptoms to patients with fibromyalgia will find this intervention beneficial.

This is a two-part study:

Part 1 – Four-week trial of body reprogramming and post-trial focus groups

Aims:

To assess the feasibility and acceptability of BR to people with severe asthma in a pilot study
To adapt and optimise the intervention for people with severe asthma following focus group feedback.

Part 2 – Biologic priming study

Aims:

To assess the feasibility of running a remote BR course before patients commence a biologic treatment for their severe asthma
To assess the acceptability of BR, testing a modified intervention having learned lessons from the pilot study, testing the performance of outcome measures to inform a potential randomised controlled trial of the intervention.

SHARP - Burden of severe asthma on HRQoL in a European population

To assess the burden of severe asthma on health-related quality of life in a European population

This is a multi-centre longitudinal study including limited clinical data collected in 11 European countries. Royal Devon and Exeter Hospital will be the UK site.

Research into severe asthma has been limited by the lack of a health-related quality of life questionnaire (HRQoL) suited to this population. Greater knowledge is also needed on how the quality of life of these patients may change throughout the year, e.g. when experiencing summer allergies or winter viruses. The Severe Asthma Questionnaire (SAQ) is a HRQoL questionnaire developed specifically for patients with severe asthma.

In this study participants will be asked to complete the SAQ once a month for 12 months to assess change in their asthma specific quality of life over time using the SAQ.

Other questionnaires will assess general quality of life (EQ-5D-5L), Asthma Control (ACQ), ability to work (ICECAP-A and WPAI) and depression/anxiety (PHQ-2/GAD-2). Questionnaires will be completed using a smartphone app, PatientCoach.

The main aims of this study are to:

assess the burden of living with severe asthma on HRQoL in a European population
further validate the SAQ within a European population
assess the feasibility of the PatientCoach app to collect data from patients.