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    The independent and combined effects of host and environmental factors on lung function in mid-adult life

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    Author
    Perret, Jennifer Louise
    Date
    2015
    Affiliation
    Melbourne School of Population and Global Health
    Metadata
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    Document Type
    PhD thesis
    Access Status
    This item is currently not available from this repository
    URI
    http://hdl.handle.net/11343/56251
    Description

    © 2015 Dr. Jennifer Louise Perret

    Abstract
    This doctoral work has investigated the independent and combined effects of potential risk factors on lung function phenotypes in middle age, principally ‘spirometrically-defined COPD’, which is a likely antecedent to Chronic Obstructive Pulmonary Disease (COPD). Worldwide, COPD is leading cause of morbidity and mortality. While personal smoking is the main risk factor for COPD in Westernized countries, only a fraction of active smokers appear to be susceptible. Genetic-environmental interactions are likely to be involved in increasing the likelihood of developing COPD, however environmental-environmental interactions between personal smoking, lifetime asthma, second hand smoke exposure and/or lung infections might also play a role. From the population-based Tasmanian Longitudinal Health Study (TAHS) cohort which was initially surveyed in 1968 when participants were seven-years old (n=8,583), an invited sub-sample underwent complex lung function testing as middle-aged adults between 2006 and 2008 (n=1,389). Using these data, this thesis has contributed knowledge to address the following issues: The Asthma/COPD overlap: There are few population-based cohort studies that have been of sufficient size to look at the interactions between asthma and smoking with regard to COPD. Using the TAHS data, current clinical asthma was found to be associated with spirometrically-defined COPD in middle-age, particularly for those with early-onset wheezing and/or asthma, independent of personal smoking. A significant interaction between the effects of asthma and personal smoking on post-bronchodilator airflow obstruction was observed, particularly for those who were atopic. A similar asthma-smoking interaction was seen for those unimmunized with a history of childhood measles infection. Both these findings in part explain the heterogeneity of lung function for individuals of the same sex, age and pack-year history of smoking. Maternal smoking and the growing lung: Exposure to heavy maternal smoking (more than 20 cigarettes daily) in childhood was associated with post-BD airflow obstruction for middle-aged offspring. Maternal smoking additionally augmented the adverse effect of personal smoking on gas transfer factor. Paradoxically, maternal smoking was associated with a degree of relative lung restriction. As maternal smoking was only documented when participants were seven-years old, it is unclear whether the findings occurred in utero, in childhood, or both. In contrast to the above findings, paternal smoking was associated with pulmonary hyperinflation, but not airflow obstruction or reduced gas transfer factor. Adult second-hand smoke exposure and complex lung function: Second-hand smoke (SHS) exposure in middle-age was associated with gas trapping and reductions in gas transfer factor, even after the maternal-personal smoking interaction was taken into account. Childhood pneumonia and lung restriction: An association between childhood pneumonia by before the age-of-school entry and reductions in total lung capacity was noted, with lung restriction seen particularly for females. Conclusions: Collectively these findings highlight a role for these less traditional risk factors in the development of spirometrically-defined COPD and/or ‘unusually low’ lung function. A greater awareness of such factors might result from the knowledge transfer between investigators and clinicians, with the potential to target public health recommendations such as smoking abstinence and childhood immunization to those most at-risk.
    Keywords
    respiratory epidemiology; adult lung function; active smoking; passive smoking; childhood asthma; childhood infections

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