Phenotyping Asthma Attacks: Clinical, Physiological and Inflammatory Characteristics of Acute Asthma

Abstract

Asthma is increasingly recognised as a heterogeneous disease, encompassing a range of phenotypes and endotypes. This evolving understanding of the pathophysiology of stable asthma has enabled the development of targeted anti-inflammatory treatments that have significantly improved clinical outcomes. Unfortunately, this is not the case with asthma attacks (AA), as they remain poorly understood and largely treated the same way since the 1950s. This is mainly owed to the lack of longitudinal investigations of asthma at the time of acute symptoms worsening and during periods of recovery, and the subsequent poor understanding of the pathophysiology of AAs. This is further confounded by the absence of a clear definition of these episodes, and the lack of easily performed lung function assessments and reliable attack-specific inflammatory biomarkers, which, collectively, has fostered a one-size-fits-all approach to managing these episodes irrespective of the underlying pathophysiological mechanism. This thesis aims to investigate asthma attacks, with a specific focus on objectively assessed airflow obstruction and the underlying inflammatory phenotypes that characterise these events. Additionally, it will explore the utility of point-of-care biomarkers in phenotyping inflammation during AAs and their potential role in guiding and predicting treatment responses.