Melbourne School of Population and Global Health - Theses
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ItemA longitudinal study of atopy, asthma and lung function from birth to 18 years in a high risk birth cohort( 2012)Background: The global burden of allergic disease, including asthma, eczema and allergic rhinoconjunctivitis is still increasing. Of these, asthma is the most important in terms of morbidity, mortality and financial cost. Asthma is a global problem, estimated to affect 300 million people worldwide. Childhood asthma is the most common chronic disease of children in many westernized countries including Australia. We currently have no effective strategies to prevent development or persistence of asthma. A range of strategies have been trialled, including avoiding environmental triggers (dust mites, animal dander), modification of mothers’ and infants’ diets and randomized controlled trials of anti-inflammatory medications in children at high risk. To date, the results have been disappointing with very modest, if any, impact found. The lack of preventive strategies appears to be related to a poor understanding of asthma aetiology. There are many areas of controversy regarding the early life risk factors for the development of childhood asthma. Asthma is believed to result from a complex interaction between genetic, environmental and biological factors. Of these, the only consistent major risk factors to emerge to date are a family history of atopy or asthma, an individual history of atopy, early childhood eczema, environmental tobacco smoke and viral infections in early childhood. Asthma is known to be a heterogeneous disease in childhood, so that poor classification of asthma groups, or phenotypes, may be part of the reason for the lack of results within and inconsistent findings between studies. There is a critical need for studies which can provide a solid basis for accurate classification of asthma phenotypes as well as investigating plausible risk factors for the development and persistence of asthma. To address questions concerning the classification of asthma phenotypes and the natural history of asthma and allergic disease, along with genetic and environmental factors which may influence aetiology and progression, it is important to use the evidence provided by longitudinal studies. In longitudinal studies, especially birth cohorts with frequent ascertainment of potential aetiological exposures and allergic disease outcomes, it is possible to determine the temporal relationship between exposures and outcomes. This thesis addressed some of the issues in asthma and allergic disease research using data from a longitudinal birth cohort study. The Melbourne Atopy Cohort Study comprises 620 children who were selected before birth for familial allergic disease. These children were very closely followed in the first 2 years of life with 18 telephone interviews. They had yearly follow-ups between ages 3 and 7 and again at ages 12 and 18. Additionally they had clinic testing including cord blood, skin prick testing, and respiratory function testing. The three main objectives which I researched within the MACS were: Objective 1: To document the natural history of wheeze in early childhood (from birth to 7 years) and to use this information to identify longitudinal wheeze phenotypes and to identify potential risk factors for these phenotypes Objective 2: To determine the impact of longitudinal wheeze phenotypes on subsequent respiratory function, respiratory symptoms and allergen sensitization Objective 3: To identify early life risk factors for childhood and adolescent asthma and allergic disease Conclusions: I addressed three broad research areas and 9 specific research questions and to contribute to the existing literature concerning allergic disease in childhood. Firstly through defining childhood wheeze phenotypes using latent class analysis, I defined 5 wheeze classes and confirmed the presence of the newly discovered intermediate onset wheeze phenotype. Additionally, I found distinct patterns of associations with specific early-life factors for each wheeze phenotype. Furthermore, I investigated the respiratory and allergic outcomes of these phenotypes up to 18 years of age. An important finding of this analysis was that children who wheeze transiently in early life do not have an increased risk of allergic disease or sensitization, or any deficit in respiratory function by age 18 when compared to never/infrequent wheezers. Conversely, persistent wheezing phenotypes in childhood (including early persistent, intermediate and late onset) were associated with reduced growth in FEV1 over adolescence and persistent lung function deficits. These findings highlight the importance of categorizing early childhood wheeze in asthma research and the detrimental effects of persistent wheeze on adolescent respiratory health. Furthermore, investigating two specific early life factors: sensitization and pet keeping, I have shown that sensitization to dust mite at ages 1 or 2 years is a good predictor for long-term wheeze and that the presence of a cat or dog at birth in high risk families is not a risk factor for allergic disease in the child, and in fact may reduce the risk of asthma or hay fever by 12 years.