Development of two disease specific scales to assess the impact of severe asthma on patients' lives

Abstract

Joseph W Lanario

Title: Development of two disease specific scales to assess the impact of severe asthma on patients’ lives

Asthma is a disease of the airways, characterised by airway obstruction, inflammation, and hyper-responsiveness resulting in symptoms of breathlessness, wheeze, shortness of breath and chest tightness. Severe asthma is distinct from mild/moderate asthma in terms of symptom severity, frequency of exacerbations, medication side effects and disruption to life.

The increasing availability of biologic treatments have revolutionised the treatment of severe asthma. Randomised Controlled Trials (RCTs) provide evidence of their efficacy at improving objective outcomes, e.g., lung function. However, scores of Health-Related Quality of Life (HRQoL) do not consistently increase beyond the level considered to signify minimum clinically important difference (MCID). While this may be a true failure of treatment to improve HRQoL, assessing the reasons for this observation is made difficult by limitations in the available asthma HRQoL questionnaires.

To construct a HRQoL questionnaire “fit for purpose” in severe asthma, I followed the Food and Drug Administration’s (FDA) 2009 guidelines for the development of Patient Reported Outcome Measures (PROMS). The guidelines specify that the content of a questionnaire must be consistent with the target concept (e.g., HRQoL) and population (e.g., severe asthma).

Information from an earlier qualitative study on the concerns of severe asthma patients was used to construct a draft Severe Asthma Questionnaire (SAQ). This draft SAQ was iteratively modified following feedback collected over four patient focus groups (N=16). Three quantitative papers were published. The first was a single centre study that provided preliminary quantitative validation including test re-test reliability (N=160). Next two multisite studies were conducted to identify the subscales of the SAQ (N=460) and a longitudinal study concerning the sensitivity to change and MCID of the SAQ (N=110). In addition, I conducted a systematic review to explore the use of HRQoL as an outcome in RCTs for severe asthma, where 52 studies were identified for inclusion. I discuss factors that may have influenced the selection of one HRQoL questionnaire over another.

The original validation of a 65-item General symptom Questionnaire (GSQ-65) in a population of patients with one or more functional disorder (fibromyalgia, chronic fatigue syndrome and/or irritable bowel syndrome) is reported here (N=1751). I discuss the usefulness of this questionnaire in severe asthma.

Two studies using the GSQ-65 in severe asthma are included in this thesis: first concerning the frequency of non-asthma (extra-pulmonary) symptoms and their impact on HRQoL, second on the overlap between fibromyalgia symptoms and these extra-pulmonary symptoms (both N=100). The GSQ-65 was subsequently shortened using a statistical method (LASSO regression) that identified items relevant to the aetiology of severe asthma (N=100). This resulted in the GSQ-A.

The SAQ and GSQ-A are valid measures of HRQoL and extra-pulmonary symptom burden respectively. Both burdens are often under-estimated in clinical practice and research in severe asthma. The validation of these two measures provides a means of accurately measuring these burdens and will reduce the chance they are missed. Next steps in the validation of these new questionnaires are discussed.