Melbourne School of Population and Global Health - Theses
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ItemLifetime asthma and the development of fixed airflow obstruction( 2023-05)Asthma is a major public health problem worldwide and its prevalence has risen considerably over recent decades. Asthma prevalence in Australia is among the highest in the world and thus has been recognised as an Australian National Health Priority Area since 1999. There is now established evidence that asthma has adverse effects on lung health over the life course and strategies aimed at improving long-term outcomes are urgently needed. The natural history of asthma is influenced by complex interactions between genetic and environmental factors. Despite extensive research in this area over recent decades, many uncertainties remain. An important limiting factor has been the lack of suitable prospective studies with follow-up from childhood (when asthma is most prevalent) into middle-age (when respiratory complications manifest clinically). To address these knowledge gaps, my doctoral work utilises data from the Tasmanian Longitudinal Health Study (TAHS), the world’s largest and longest-running population-based study of respiratory disease. The primary aim within my thesis is to characterise the natural history of asthma and its cumulative effects on lung health over the life course, focusing on a complication known as fixed airflow obstruction. I also aim to evaluate strategies which might improve these outcomes in asthma, and to validate novel methods of detecting these complications earlier in the disease process. The findings of this work will have important clinical and public health implications, with the overall objective of improving asthma outcomes in Australia and worldwide. In chapter 4, I present a study on the diagnostic utility of bronchodilator responsiveness (BDR) as a test for adult asthma, both with and without fixed airflow obstruction (FAO). I provide specific data on the sensitivity and specificity of commonly-used BDR cut-offs, and additional normative data on BDR ranges in a general population cohort. In chapter 5, I present my findings that asthma follows five longitudinal pathways (phenotypes) from childhood to middle-age, each associated with different risks of developing FAO. Importantly, I found that even apparently remitted asthma was associated with FAO in middle-age, despite an absence of symptoms. In chapter 6, I present my findings of several biomarkers which hold prognostic value in adults in spontaneous asthma remission. I showed that abnormal serum cytokine profiles (Th2-high and Th2-low) were associated with accelerated lung function decline in these individuals. In chapter 7, I present the findings of a systematic review and meta-analysis showing that long-term use of inhaled corticosteroids (ICS) are associated with modest, age-dependent improvements in lung function children and adults with asthma. In chapter 8, I present my findings that lung function thresholds can accurately identify individuals at high-risk of developing FAO in the future. I describe a particular threshold of pre-BD FEV1/FVC < 10th percentile as accurately identifying 88% of individuals who developed COPD over an 8-year follow-up period, while excluding 87% of individuals who did not. Collectively these findings provide new insight into the complex relationship between asthma and lung function over the life-course, with a particular focus on the development of FAO. My work highlights lifetime asthma as a potentially-modifiable risk factor for FAO, and describes the high-risk subgroups in whom early detection and prevention strategies might be beneficial.