Molecular characterisation of human atopic asthma and house dust mite induced pulmonary inflammation in a murine experimental model

Whittle, Emma Louise

Abstract

Asthma is one of the most common chronic diseases of the 21st century, affecting over 300 million people worldwide 1. It is an inflammatory disorder of the airways that is a major public concern globally due to increasing prevalence and rates of mortality 2–5, and each year the disease is estimated to cause 250,000 premature deaths 1.
There is an unmet need for the identification of phenotype-specific markers and accompanying molecular tools that facilitate the classification of asthma phenotypes/ endotypes. This study utilised a range of molecular techniques to characterise a well-defined group of female adults with poorly controlled atopic asthma associated with a house dust mite (HDM) sensitivity and non-asthmatic subjects.
Quantification and differential expression analysis of circulating messenger RNA (mRNA) and microRNA (miRNA) revealed significant alterations to circulating RNA expression in the asthmatic subjects compared to the control subjects that may influence systemic immune activity. Quantification of circulatory inflammatory proteins (IL-4, 5, 10, 13, 17A, eotaxin, GM-CSF, IFNy, MCP-1, RANTES, TARC, TNFa, total IgE) found an overall trend of increased inflammatory protein in the asthmatic subjects, although no individual protein was identified as being significantly increased in the asthmatic subjects. Quantification of the bacterial protein, endotoxin, was observed to be decreased in the asthmatic subjects.
Comparison of the circulatory microbiome in atopic and non-atopic subjects revealed that atopic disease was associated with significant changes to the circulatory microbiome composition and function potential. Moreover, characterisation of the murine gut and airway microbiome in an experimental model of atopic asthma found that HDM-induced pulmonary inflammation significantly altered the composition and function potential of the airway and gut microbiomes, thus demonstrating that atopic disease can actively induce changes to the microbiome.
In conclusion, this study provides a valuable insight into the systemic changes that occur in HDM-associated asthma. A number of circulatory molecules were identified that were condition-specific and have biomarker potential, and clear changes in the atopic microbiome were detected.

Citation

Whittle, E. L. (2020). Molecular characterisation of human atopic asthma and house dust mite induced pulmonary inflammation in a murine experimental model. (Thesis). Keele University

• Thesis Type: Thesis
• Publicly Available Date: May 26, 2023
• Award Date: 2020-03