Shining the transcriptomic microscope on asthma pathogenesis

Abstract

Asthma is a chronic inflammatory disorder associated with airway hyperresponsiveness and airway remodeling. The complex pathophysiology of asthma results from the interaction of multiple cells and inflammatory mediators. Standard therapy includes glucocorticosteroids and β2 agonists that are aimed at managing symptoms. These are usually effective in controlling mild and moderate asthma, however, severe asthma remains difficult to control. The majority of studies in asthma have focused assessments in central airways and have largely ignored the utility of transcriptomics. The small peripheral airways, which comprise the majority of the lung volume, remain an unexplored area in severe asthma and were targeted for global gene expression profiling in this thesis. The work presented here also focuses on identifying novel endotypes in severe asthma using an unsupervised transcriptomics approach, as the current phenotypes of asthma have been established primarily using clinical features and inflammatory mediators while ignoring the underlying biology. Moreover, multiple tissues were profiled for gene expression analysis across a spectrum of asthma severities to understand the interactions between these tissues and their contribution to disease pathogenesis. The studies in this thesis have identified a need for better therapies to target the peripheral airway and sputum compartments as well as to target distinct endotypes of asthma. The results presented here underscore the need for the utilization of transcriptomics approaches in order to advance our understanding of the global gene expression signatures driving asthma pathogenesis.

More information

Identifiers

Catalogue record

Export record