Melbourne School of Health Sciences Collected Works - Research Publications

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    Association of novel adult cough subclasses with clinical characteristics and lung function across six decades of life in a prospective, community-based cohort in Australia: an analysis of the Tasmanian Longitudinal Health Study (TAHS).
    Zhang, J ; Lodge, CJ ; Walters, EH ; Chang, AB ; Bui, DS ; Lowe, AJ ; Hamilton, GS ; Thomas, PS ; Senaratna, CV ; James, AL ; Thompson, BR ; Erbas, B ; Abramson, MJ ; Perret, JL ; Dharmage, SC (Elsevier, 2024-02)
    BACKGROUND: Cough is a common yet heterogeneous condition. Little is known about the characteristics and course of cough in general populations. We aimed to investigate cough subclasses, their characteristics from childhood across six decades of life, and potential treatable traits in a community-based cohort. METHODS: For our analysis of the Tasmanian Longitudinal Health Study (TAHS), a prospective, community-based cohort study that began on Feb 23, 1968, and has so far followed up participants in Tasmania, Australia, at intervals of 10 years from a mean age of 7 years to a mean age of 53 years, we used data collected as part of the TAHS to distinguish cough subclasses among current coughers at age 53 years. For this analysis, participants who answered Yes to at least one cough-related question via self-report questionnaire were defined as current coughers and included in a latent class analysis of cough symptoms; participants who answered No to all nine cough-related questions were defined as non-coughers and excluded from this analysis. Two groups of longitudinal features were assessed from age 7 years to age 53 years: previously established longitudinal trajectories of FEV1, forced vital capacity [FVC], FEV1/FVC ratio, asthma, and allergies-identified via group-based trajectory analysis or latent class analysis-and symptoms at different timepoints, including asthma, current productive cough, ever chronic productive cough, current smoking, and second-hand smoking. FINDINGS: Of 8583 participants included at baseline in the TAHS, 6128 (71·4%) were traced and invited to participate in a follow-up between Sept 3, 2012, and Nov 8, 2016; 3609 (58·9%) of these 6128 returned the cough questionnaire. The mean age of participants in this analysis was 53 years (SD 1·0). 2213 (61·3%) of 3609 participants were defined as current coughers and 1396 (38·7%) were categorised as non-coughers and excluded from the latent class analysis. 1148 (51·9%) of 2213 participants in this analysis were female and 1065 (48·1%) were male. Six distinct cough subclasses were identified: 206 (9·3%) of 2213 participants had minimal cough, 1189 (53·7%) had cough with colds only, 305 (13·8%) had cough with allergies, 213 (9·6%) had intermittent productive cough, 147 (6·6%) had chronic dry cough, and 153 (6·9%) had chronic productive cough. Compared with people with minimal cough, and in contrast to other cough subclasses, people in the chronic productive cough and intermittent productive cough subclasses had worse lung function trajectories (FEV1 persistent low trajectory 2·9%, 6·4%, and 16·1%; p=0·0011, p<0·0001; FEV1/FVC early low-rapid decline trajectory 2·9%, 12·1%, and 13·0%; p=0·012, p=0·0007) and a higher prevalence of cough (age 53 years 0·0%, 32·4% [26·1-38·7], and 50·3% [42·5-58·2]) and asthma (age 53 years 6·3% [3·7-10·6], 26·9% [21·3-33·3], and 41·7% [24·1-49·7]) from age 7 years to age 53 years. INTERPRETATION: We identified potential treatable traits for six cough subclasses (eg, asthma, allergies, and active and passive smoking for productive cough). The required management of productive cough in primary care (eg, routine spirometry) might differ from that of dry cough if our findings are supported by other studies. Future population-based studies could apply our framework to address the heterogeneity and complexity of cough in the community. FUNDING: The National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, Victorian Asthma Foundation, Queensland Asthma Foundation, Tasmanian Asthma Foundation, The Royal Hobart Hospital Research Foundation, the Helen MacPherson Smith Trust, GlaxoSmithKline, and the China Scholarship Council.
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    Preclinical investigations on broccoli- derived sulforaphane for the treatment of ophthalmic disease
    Kwa, FAA ; Bui, BV ; Thompson, BR ; Ayton, LN (ELSEVIER SCI LTD, 2023-09)
    Vision loss causes a significant burden on individuals and communities on a financial, emotional and social level. Common causes include age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and retinitis pigmentosa (RP; also known as 'rod-cone dystrophy'). As the population continues to grow and age globally, an increasing number of people will experience vision loss. Hence, there is an urgent need to develop therapies that can curb early pathological events. The broccoli-derived compound, sulforaphane (SFN), is reported to have multiple health benefits and modes of action. In this review, we outline the preclinical findings on SFN in ocular diseases and discuss the future clinical testing of this compound.
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    Race/Ethnicity and Reference Equations for Spirometry
    Miller, MR ; Graham, BL ; Thompson, BR (AMER THORACIC SOC, 2022-09-15)
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    Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort study
    Dharmage, SC ; Bui, DS ; Walters, EH ; Lowe, AJ ; Thompson, B ; Bowatte, G ; Thomas, P ; Garcia-Aymerich, J ; Jarvis, D ; Hamilton, GS ; Johns, DP ; Frith, P ; Senaratna, C ; Idrose, NS ; -Baker, RRW ; Hopper, J ; Gurrin, L ; Erbas, B ; Washko, GR ; Faner, R ; Agusti, A ; Abramson, MJ ; Lodge, CJ ; Perret, JL (ELSEVIER SCI LTD, 2023-03)
    BACKGROUND: Interest in lifetime lung function trajectories has increased in the context of emerging evidence that chronic obstructive pulmonary disease (COPD) can arise from multiple disadvantaged lung function pathways, including those that stem from poor lung function in childhood. To our knowledge, no previous study has investigated both obstructive and restrictive lifetime patterns concurrently, while accounting for potential overlaps between them. We aimed to investigate lifetime trajectories of the FEV1/forced vital capacity (FVC) ratio, FVC, and their combinations, relate these combined trajectory groups to static lung volume and gas transfer measurements, and investigate both risk factors for and consequences of these combined trajectory groups. METHODS: Using z scores from spirometry measured at ages 7, 13, 18, 45, 50, and 53 years in the Tasmanian Longitudinal Health Study (n=2422), we identified six FEV1/FVC ratio trajectories and five FVC trajectories via group-based trajectory modelling. Based on whether trajectories of the FEV1/FVC ratio and FVC were low (ie, low from childhood or adulthood) or normal, four patterns of lifetime spirometry obstruction or restriction were identified and compared against static lung volumes and gas transfer. Childhood and adulthood characteristics and morbidities of these patterns were investigated. FINDINGS: The prevalence of the four lifetime spirometry patterns was as follows: low FEV1/FVC ratio only, labelled as obstructive-only, 25·8%; low FVC only, labelled as restrictive-only, 10·5%; both low FEV1/FVC ratio and low FVC, labelled as mixed, 3·5%; and neither low FEV1/FVC ratio nor low FVC, labelled as reference, 60·2%. The prevalence of COPD at age 53 years was highest in the mixed pattern (31 [37%] of 84 individuals) followed by the obstructive-only pattern (135 [22%] of 626 individuals). Individuals with the mixed pattern also had the highest prevalence of parental asthma, childhood respiratory illnesses, adult asthma, and depression. Individuals with the restrictive-only pattern had lower total lung capacity and residual volume, and had the highest prevalence of childhood underweight, adult obesity, diabetes, cardiovascular conditions, hypertension, and obstructive sleep apnoea. INTERPRETATION: To our knowledge, this is the first study to characterise lifetime phenotypes of obstruction and restriction simultaneously using objective data-driven techniques and unique life course spirometry measures of FEV1/FVC ratio and FVC from childhood to middle age. Mixed and obstructive-only patterns indicate those who might benefit from early COPD interventions. Those with the restrictive-only pattern had evidence of true lung restriction and were at increased risk of multimorbidity by middle age. FUNDING: National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline.
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    Parental preconception BMI trajectories from childhood to adolescence and asthma in the future offspring
    Bowatte, G ; Bui, DS ; Priyankara, S ; Lowe, AJ ; Perret, JL ; Lodge, CJ ; Hamilton, GS ; Erbas, B ; Thomas, P ; Thompson, B ; Schlunssen, V ; Martino, D ; Holloway, JW ; Svanes, C ; Abramson, MJ ; Walters, EH ; Dharmage, SC (MOSBY-ELSEVIER, 2022-07)
    BACKGROUND: Recent evidence suggests that parental exposures before conception can increase the risk of asthma in offspring. OBJECTIVE: We investigated the association between parents' preconception body mass index (BMI) trajectories from childhood to adolescence and subsequent risk of asthma in their offspring. METHODS: Using group-based trajectory modeling from the Tasmanian Longitudinal Health Study, we identified BMI trajectories for index participants (parents) when aged 4 years to 15 years. Multinomial regression models adjusted for potential confounders were utilized to estimate the association between these early-life parents' BMI trajectories and asthma phenotypes in their subsequent offspring. RESULTS: The main analysis included 1822 parents and 4208 offspring. Four BMI trajectories from age 4 years to 15 years were identified as the best-fitting model: low (8.8%), normal (44.1%), above normal (40.2%), and high (7.0%). Associations were observed between father's high BMI trajectory and risk of asthma in offspring before the age of 10 years (relative risk ratio [RRR] =1.70 [95% CI = 0.98-2.93]) and also asthma ever (RRR = 1.72 [95% CI = 1.00-2.97]), especially allergic asthma ever (RRR = 2.05 [95% CI = 1.12-3.72]). These associations were not mediated by offspring birth weight. No associations were observed for maternal BMI trajectories and offspring asthma phenotypes. CONCLUSION: This cohort study over 6 decades of life and across 2 generations suggests that the high BMI trajectory in fathers, well before conception, increased the risk of asthma in their offspring.
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    The Opportunities and Challenges of Digital Anatomy for Medical Sciences: Narrative Review
    Wickramasinghe, N ; Thompson, BR ; Xiao, J (JMIR PUBLICATIONS, INC, 2022-05-20)
    BACKGROUND: Anatomy has been the cornerstone of medical education for centuries. However, given the advances in the Internet of Things, this landscape has been augmented in the past decade, shifting toward a greater focus on adopting digital technologies. Digital anatomy is emerging as a new discipline that represents an opportunity to embrace advances in digital health technologies and apply them to the domain of modern medical sciences. Notably, the use of augmented or mixed and virtual reality as well as mobile and platforms and 3D printing in modern anatomy has dramatically increased in the last 5 years. OBJECTIVE: This review aims to outline the emerging area of digital anatomy and summarize opportunities and challenges for incorporating digital anatomy in medical science education and practices. METHODS: Literature searches were performed using the PubMed, Embase, and MEDLINE bibliographic databases for research articles published between January 2005 and June 2021 (inclusive). Out of the 4650 articles, 651 (14%) were advanced to full-text screening and 77 (1.7%) were eligible for inclusion in the narrative review. We performed a Strength, Weakness, Opportunity, and Threat (SWOT) analysis to evaluate the role that digital anatomy plays in both the learning and teaching of medicine and health sciences as well as its practice. RESULTS: Digital anatomy has not only revolutionized undergraduate anatomy education via 3D reconstruction of the human body but is shifting the paradigm of pre- and vocational training for medical professionals via digital simulation, advancing health care. Importantly, it was noted that digital anatomy not only benefits in situ real time clinical practice but also has many advantages for learning and teaching clinicians at multiple levels. Using the SWOT analysis, we described strengths and opportunities that together serve to underscore the benefits of embracing digital anatomy, in particular the areas for collaboration and medical advances. The SWOT analysis also identified a few weaknesses associated with digital anatomy, which are primarily related to the fact that the current reach and range of applications for digital anatomy are very limited owing to its nascent nature. Furthermore, threats are limited to technical aspects such as hardware and software issues. CONCLUSIONS: This review highlights the advances in digital health and Health 4.0 in key areas of digital anatomy analytics. The continuous evolution of digital technologies will increase their ability to reinforce anatomy knowledge and advance clinical practice. However, digital anatomy education should not be viewed as a simple technical conversion and needs an explicit pedagogical framework. This review will be a valuable asset for educators and researchers to incorporate digital anatomy into the learning and teaching of medical sciences and their practice.
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    Childhood 'bronchitis' and respiratory outcomes in middle-age: a prospective cohort study from age 7 to 53 years
    Perret, JL ; Wurzel, D ; Walters, EH ; Lowe, AJ ; Lodge, CJ ; Bui, DS ; Erbas, B ; Bowatte, G ; Russell, MA ; Thompson, BR ; Gurrin, L ; Thomas, PS ; Hamilton, G ; Hopper, JL ; Abramson, MJ ; Chang, AB ; Dharmage, SC (BMJ PUBLISHING GROUP, 2022-06)
    BACKGROUND: Chronic bronchitis in childhood is associated with a diagnosis of asthma and/or bronchiectasis a few years later, however, consequences into middle-age are unknown. OBJECTIVE: To investigate the relationship between childhood bronchitis and respiratory-related health outcomes in middle-age. DESIGN: Cohort study from age 7 to 53 years. SETTING: General population of European descent from Tasmania, Australia. PARTICIPANTS: 3202 participants of the age 53-year follow-up (mean age 53, range 51-55) of the Tasmanian Longitudinal Health Study cohort who were born in 1961 and first investigated at age 7 were included in our analysis. STATISTICAL METHODS: Multivariable linear and logistic regression. The association between parent reported childhood bronchitis up to age 7 and age 53-year lung conditions (n=3202) and lung function (n=2379) were investigated. RESULTS: Among 3202 participants, 47.5% had one or more episodes of childhood bronchitis, classified according to severity based on the number of episodes and duration as: 'non-recurrent bronchitis' (28.1%); 'recurrent non-protracted bronchitis' (18.1%) and 'recurrent-protracted bronchitis' (1.3%). Age 53 prevalence of doctor-diagnosed asthma and pneumonia (p-trend <0.001) and chronic bronchitis (p-trend=0.07) increased in accordance with childhood bronchitis severities. At age 53, 'recurrent-protracted bronchitis' (the most severe subgroup in childhood) was associated with doctor-diagnosed current asthma (OR 4.54, 95% CI 2.31 to 8.91) doctor-diagnosed pneumonia (OR=2.18 (95% CI 1.00 to 4.74)) and, paradoxically, increased transfer factor for carbon monoxide (z-score +0.51 SD (0.15-0.88)), when compared with no childhood bronchitis. CONCLUSION: In this cohort born in 1961, one or more episodes of childhood bronchitis was a frequent occurrence. 'Recurrent-protracted bronchitis', while uncommon, was especially linked to multiple respiratory outcomes almost five decades later, including asthma, pneumonia and raised lung gas transfer. These findings provide insights into the natural history of childhood 'bronchitis' into middle-age.
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    Interrelationships Among Small Airways Dysfunction, Neutrophilic Inflammation, and Exacerbation Frequency in COPD
    Day, K ; Ostridge, K ; Conway, J ; Cellura, D ; Watson, A ; Spalluto, CM ; Staples, KJ ; Thompson, B ; Wilkinson, T (ELSEVIER, 2021-04)
    BACKGROUND: Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline. RESEARCH QUESTION: Is SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation? STUDY DESIGN AND METHODS: Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n = 17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n = 22) underwent the forced oscillation technique (resistance at 5 Hz minus 19 Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions. RESULTS: Sacin was significantly higher in the COPD FE group compared with the IFE group (P = .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, ρ = 0.560), residual volume to total lung capacity ratio (P = .004, r = 0.730), and the mean lung density of the paired CT scans (P = .018, r = 0.639). INTERPRETATION: Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.
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    Putting lung function reference equations into context
    Borg, BM ; Thompson, BR (EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2021-09-01)
    Knowing the limitations of reference equations is essential to minimising errors in diagnosis and clinical management. Choice of reference sets may impact access to treatment options where lung function based eligibility criteria exist. https://bit.ly/2WdOFDj.