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Lissa, Sutherland (2019) THE IDENTIFICATION OF BIOMARKERS TO PREDICT RESPONSE TO TREATMENTS IN ASTHMA. PhD thesis, University of Nottingham.

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Abstract

Background: Asthma is a complex heterogeneous disease of the airways characterized by non-specific symptoms such as cough, wheeze and shortness of breath. Despite this known heterogeneity asthma patients are generally treated the same way. As such, patients are at risk of taking medications they either do not require or will not benefit from. The identification of biomarkers capable of aiding in disease phenotyping is essential to ensure patients receive treatments that will be of the most benefit to them.

Aim: To personalize asthma treatments by identifying clinical and physiological characteristics that can reliably identify the patients who will and will not benefit from traditional corticosteroid and novel biologic treatments.

Method: Three clinical studies were conducted to describe and characterize individual responses. Two studies evaluated responses to corticosteroids, while the third study investigated responses to treatment with mepolizumab, an anti-IL-5 monoclonal antibody. Clinical features as well as systemic cytokine levels were documented for each study.

Results: The first study determined that a low level of fractional exhaled nitric oxide (≤27 ppb) excluded a clinical benefit from initiating treatment with an inhaled corticosteroid in steroid-naïve patients with suspected asthma in the short-term. The second study identified that patients with poorly controlled asthma have varying responses to increased doses of corticosteroid. This study failed to identify specific markers that were predictive of response with the exception that those on a low level of maintenance inhaled corticosteroid were most likely to benefit from an increased dose. The third study found that 61.5 % of patients responded to treatment with mepolizumab. The responders were significantly older at diagnosis, experienced fewer exacerbations in the previous year, were on a slightly higher daily maintenance dose of systemic corticosteroids and reported better controlled asthma than the non-responders.

Conclusions: The work performed in this thesis demonstrated a high level of heterogeneity in response to asthma treatments which supports the need to personalize treatments in asthma by identifying biomarkers predictive of response so that the right treatments can be given to the right patients maximizing benefit and minimizing unnecessary treatment effects.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Lucy, Fairclough Tim, Harrison
Keywords:	Asthma, Biomarkers
Subjects:	R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID:	57156
Depositing User:	Sutherland, Lissa
Date Deposited:	26 Jul 2019 09:14
Last Modified:	16 Aug 2023 08:47
URI:	https://eprints.nottingham.ac.uk/id/eprint/57156

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