The emerging role of the eosinophil and its measurement in chronic cough : airway inflammation in chronic cough

Haji Sadeghi, Mahboobeh

Medicine
October 2017

Thesis or dissertation


Rights
© 2017 Mahboobeh Haji Sadeghi. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

Although the aetiology of chronic cough in guidelines is clearly stated as asthma and related syndromes, gastro-oesophageal reflux disease, and upper airways disease, the inflammatory mechanisms underlying these conditions differ. Recent studies on asthma have increasingly focused on its molecular phenotypes instead of clinical characteristics. Predominantly in this thesis I hypothesize that by dividing cough patients into the clinical characteristics of eosinophilic and neutrophilic groups will enhance our ability to recognise the type of airway inflammation, and consequently will lead us to more targeted treatment approaches.

To investigate this hypothesis I conducted a randomized, single centre, open label, controlled, clinical trial to examine the outcome of anti-inflammatory therapy with either montelukast or prednisolone in 50 patients with chronic cough. Furthermore, I studied the epidemiology of 137 chronic cough patients attending the Hull cough clinic.

Results from the clinical study demonstrated that patients with FeNO≤20ppb had twice the number of coughs compared with patients with FeNO≥30ppb. This was reflected on quality of life as assessed by the LCQ and HARQ. Confirming this finding I found in the epidemiological study, that patients attending the hull cough clinic with FeNO≤25ppb scored significantly higher in HARQ compared with FeNO≥25ppb.

In the clinical trial study I have shown that FeNO was a good marker for eosinophilic inflammation. There was a high degree of correlation with FeNO, blood and sputum eosinophilia thus confirming phenotypic identity. Whether the FeNO can be used to identify the different characteristics between eosinophilic and non-eosinophilic coughs needs further investigation. Cough patients in both low and high FeNO groups have shown a similar response to montelukast despite anticipating little or no effect in those without eosinophilic inflammation. These results suggest that response to montelukast may not be predicted by presence of eosinophilic biomarkers alone but may be act by effecting localised leukotriene mediated inflammation.

Publisher
Hull York Medical School, The University of Hull and The University of York
Supervisor
Wright, Caroline (Caroline E.); Morice, Alyn H.
Qualification level
Doctoral
Qualification name
PhD
Language
English
Extent
2 MB
Identifier
hull:16543
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