Melbourne School of Population and Global Health - Theses
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ItemEpidemiology of adult chronic cough( 2023-10)Background: Cough is common in adults and has major impacts on individuals’ physical and mental health, and a high economic burden. Cough is a heterogenous condition and clinical guidelines recommend classifying or phenotyping cough by its duration (i.e., acute, subacute, and chronic cough) and the underlying conditions causing the cough (e.g., asthmatic cough, reflux cough, etc.). Diagnosing and treating the underlying conditions responsible for cough is often challenging, as sometimes no underlying conditions can be identified and treating the conditions may not fully resolve the cough. Therefore, using cough-related symptoms to explore heterogeneity can be simpler and more practical. Research Gaps: The heterogeneity of cough in the general adult population is poorly understood as most studies have recruited patients from cough clinics, reducing the generalisability of the findings. Furthermore, several studies have been published to investigate the longitudinal risk factors of cough in adults, but the evidence has not been systematically synthesised. There is also inadequate and inconsistent evidence on some risk factors of cough such as occupational exposures and ambient air pollution. This inconsistency may stem from the use of standard definitions of cough (i.e., chronic cough, chronic phlegm, and chronic bronchitis) which may not fully capture the heterogeneity of cough. Aim: My overall aim was to investigate the risk factors for and heterogeneity of cough in the general adult population. My specific objectives are: i) to systematically synthesise the evidence on longitudinal risk factors for adult cough; ii) to investigate the heterogeneity of cough based on cough-related symptoms (i.e., denoted as cough subclasses in my thesis) among a middle-aged population; and iii) to investigate the associations between potential risk factors and the novel cough subclasses identified in the previous objectives. Methods: My doctoral research utilised systematic review methodology and original data from the population-based Tasmanian Longitudinal Health Study (TAHS) that followed participants from age 7 to 53 years. Latent class analysis was used to identify cough subclasses in middle age based on cough-related symptoms. Clinical features of different cough subclasses were described using prevalence with logit-transformed 95% confidence intervals (CIs) and were compared using t-tests or chi2 tests. Occupational exposures were coded into a Job-Exposure Matrix (JEM) using data from participant work history calendars. Markers of ambient air pollution were derived from the residential addresses of participants using satellite-based land-use regression models. Multinomial logistic regression models were performed to assess associations between exposures and the cough subclasses, after adjusting for confounders. Logistical regression models were used for the standard cough definitions (chronic cough, chronic phlegm, and chronic bronchitis) to enable comparisons with the results from my newly identified cough subclasses. Results: In Chapter 3, I present my findings from the systematic review and meta-analysis. It found heterogeneous definitions of chronic cough used in the literature. Asthma, persistent smoking, and lower education were consistently associated with an increased risk of chronic cough in adults with little to moderate heterogeneity. There was inconsistent evidence for risk factors such as occupational exposures and ambient air pollution and substantial heterogeneity was observed across primary studies precluding any meta-analysis for these factors. In Chapter 5, I present my novel classification of six cough subclasses in a middle-aged general population using latent class analysis. Each of the cough subclasses had distinct clinical features cross-sectionally and longitudinally from childhood to middle age. The subclasses were labelled as “minimal cough”, “cough with colds only”, “cough with allergies”, “intermittent productive cough”, “chronic dry cough”, and “chronic productive cough”. In Chapter 6, I report my findings on the associations between occupational exposures and my novel cough subclasses. Specific occupational risks were identified for different cough subclasses, which were not fully captured when using standard cough definitions as outcomes. These included associations between aromatic solvents and chronic dry cough; biological dust and allergic cough; and herbicides, other solvents, and productive cough. In Chapter 7, I report my results of associations between ambient air pollution and my novel cough subclasses. There was a linear, dose-response relationship between ambient nitrogen dioxide (NO2) and productive cough (intermittent and chronic), as well as fine particulate matter with an aerodynamic diameter <= 2.5um (PM2.5) and chronic dry cough. These associations were present even in a low polluted setting as the pollution levels in this study were lower than the Australian National Environment Protection Measure. Conclusions: The identified novel cough subclasses have largely addressed the heterogeneity of cough in the community as shown by their distinct clinical characteristics cross-sectionally and longitudinally. Distinct associations between occupational exposures, ambient air pollution, and cough subclasses were uncovered, which were not detected by the standard cough definitions. Future studies should consider adopting a similar framework to address the heterogeneity of cough in general populations. This will help generate better quality evidence to inform individualised clinical management of cough.