Melbourne School of Population and Global Health - Research Publications

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    Early life exposures contributing to accelerated lung function decline in adulthood - a follow-up study of 11,000 adults from the general population
    Kirkeleit, J ; Riise, T ; Wielscher, M ; Accordini, S ; Carsin, A-E ; Dratva, J ; Franklin, KA ; Garcia-Aymerich, J ; Jarvis, D ; Leynaert, B ; Lodge, CJ ; Real, FG ; Schlunssen, V ; Corsico, AG ; Heinrich, J ; Holm, M ; Janson, C ; Benediktsdottir, B ; Jogi, R ; Dharmage, SC ; Jarvelin, M-R ; Svanes, C (ELSEVIER, 2023-12)
    BACKGROUND: We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements. METHODS: Participants (20-68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991-2013 and 1997-2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV1) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV1, FVC and height at baseline, accounting for personal smoking. FINDINGS: Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV1 2.6 ml/year; 0.9, 4.4) (FEV1/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found. INTERPRETATION: Mothers' smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV1 and FVC later in life comparable to smoking 10 pack-years. FUNDING: European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya.
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    Genetic and Epigenetic Associations with Pre-Chronic Obstructive Pulmonary Disease Lung Function Trajectories
    Martino, DJ ; Bui, DS ; Li, S ; Idrose, S ; Perret, J ; Lowe, AJ ; Lodge, CJ ; Bowatte, G ; Moodley, Y ; Thomas, PS ; Zosky, G ; Hansbro, PM ; Holloway, JW ; Svanes, C ; Faner, R ; Walters, EH ; Dharmage, SC (AMER THORACIC SOC, 2023-11-15)
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    Efficacy and safety of oral immunotherapy for peanut, cow's milk, and hen's egg allergy: A systematic review of randomized controlled trials
    Lodge, CJ ; Waidyatillake, N ; Peters, RL ; Netting, M ; Dai, X ; Burgess, J ; Hornung, CJ ; Perrett, KP ; Tang, MLK ; Koplin, JJ ; Dharmage, SC (WILEY, 2023-07)
    BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for food allergies; however, safety is a concern. We synthesized evidence from the best randomized controlled trials (RCTs) on efficacy/safety of OIT for desensitization (DS) and remission (sustained unresponsiveness (SU)) in IgE mediated allergy to peanut, hen's eggs, and cow's milk. BODY: We searched Pubmed, EMBASE, and Cochrane databases (Until Oct 22) identifying 16 eligible RCTs published in English measuring food allergy by food challenge at the beginning and at the end of the study. The Cochrane Risk of Bias tool was used to assess study quality. We found 18 eligible studies. There was evidence of efficacy for DS for all allergens: peanut (RR 11.32; 95% CI 5.93, 21.60, I2 49%, 8 studies); hen's egg (RR 4.67; 2.66, 8.21, I2 0%, 5 studies); cow's milk (RR 13.98; 3.51, 55.65, I2 0%, 4 studies) and evidence for SU for peanut (RR 7.74; 2.90, 20.69, I2 0%, 3 studies) and hen's egg (RR 6.91; 1.67, 28.57, I2 0%, 2 studies). Allergic events were increased with intervention, and risk of adrenaline use increased for peanut RR 2.96; 1.63, 5.35, I2 0%, 8 studies; egg RR 1.71; 0.42, 6.92, I2 0%, 6 studies; and milk RR 8.45; 2.02, 35.27, I2 0%, 4 studies. CONCLUSION: We found strong evidence that peanut, hen's egg, and cow's milk OIT can induce DS and some evidence for remission. There was a high risk of allergic reactions. Generalizability to the entire food allergic population is not known.
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    Bidirectional Associations Between Asthma and Types of Mental Disorders.
    Liu, X ; Plana-Ripoll, O ; McGrath, JJ ; Petersen, LV ; Dharmage, SC ; Momen, NC (Elsevier BV, 2023-03)
    BACKGROUND: Asthma and mental disorders frequently co-occur. Studies of their comorbidity have generally focused on associations related to a subset of mental disorders. OBJECTIVE: To estimate bidirectional associations between asthma and 10 broad types of mental disorders. METHODS: In a population-based cohort study, including all individuals born in Denmark between 1955 and 2011 (N = 5,053,471), we considered diagnoses of comorbid mental disorders among those with asthma, and vice versa, between 2000 and 2016. We used Cox regression models to calculate overall and time-dependent hazard ratios for mental disorder-asthma pairs and competing-risks survival analyses to estimate absolute risks. RESULTS: Altogether, 376,756 individuals were identified as having an incident mental disorder and 364,063 incident asthma during follow-up. An increased risk was seen for all bidirectional mental disorder-asthma pairs. Following an asthma diagnosis, adjusted hazard ratios for different subsequent mental disorders ranged from 1.75 (95% CI, 1.64-1.87) for organic disorders to 2.75 (95% CI, 2.69-2.81) for personality disorders. Following a prior mental disorder diagnosis, hazard ratios for asthma ranged from 1.06 (95% CI, 1.00-1.12) for developmental disorders to 2.33 (95% CI, 2.28-2.39) for substance use disorders. Risks varied with time since prior disorder diagnosis but remained elevated. Cumulative incidence of (1) asthma after a mental disorder and (2) a mental disorder after asthma was higher in those with prior disorders than in matched reference groups. CONCLUSIONS: Our findings provide evidence of bidirectional associations between asthma and each of the mental disorder types, suggesting possible shared etiological factors or pathophysiologic processes.
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    The longitudinal association between physical activity, strength and fitness, and lung function: A UK Biobank cohort study
    Li, LSK ; Cassim, R ; Perret, JL ; Dharmage, SC ; Lowe, AJ ; Lodge, CJ ; Russell, MA (W B SAUNDERS CO LTD, 2023-12)
    BACKGROUND: While physical activity is hypothesized to slow lung-function decline, the evidence is limited at a population level. This study investigated the longitudinal association between physical activity and related measures (grip strength, cardiovascular fitness) and lung function decline. METHODS: 20,111 UK Biobank cohort participants with lung function measures at baseline (2006-2010) and follow-up (2012-2014) were included. Physical activity (International Physical Activity Questionnaire: low, moderate, high categories), grip strength (dynamometer) and cardiovascular fitness (subsample, submaximal stationary bicycle) data were collected. Linear regression was utilized to assess the effect on follow-up FEV1, FVC, FEV1/FVC ratio (as decline in ml/yr and as z-scores) adjusting for baseline lung function and confounders. RESULTS: After 6.3 years mean follow-up, the decline in mean FEV1 and FVC was 30 ml/year and 38 ml/year respectively (n = 20,111). Consistent low physical activity (across baseline and follow-up) was associated with accelerated decline in FEV1 z-score (-0.119, 95 % Confidence Interval (CI) -0.168, -0.071, n = 16,900) and FVC z-score (-0.133, 95%CI -0.178, -0.088, n = 16,832). Accelerated decline in FEV1 z-scores was observed with decreasing baseline grip strength (-0.029, -95%CI -0.034, -0.024, n = 19,903), and with less strong evidence, decreasing fitness (-0.024, 95%CI -0.070, 0.022, n = 3048). CONCLUSION: This is the largest ever study to date to identify that lower physical activity, grip strength, and potentially cardiovascular fitness over time is associated with accelerated lung function decline. Although the effect sizes appear modest, such changes at population levels can have a substantial overall impact. This study provides evidence for adding 'lung health benefits' to the current physical activity guidelines.
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    Fathers' preconception smoking and offspring DNA methylation
    Kitaba, NT ; Knudsen, GTM ; Johannessen, A ; Rezwan, FI ; Malinovschi, A ; Oudin, A ; Benediktsdottir, B ; Martino, D ; González, FJC ; Gómez, LP ; Holm, M ; Jõgi, NO ; Dharmage, SC ; Skulstad, SM ; Watkins, SH ; Suderman, M ; Gómez-Real, F ; Schlünssen, V ; Svanes, C ; Holloway, JW (BMC, 2023-08-31)
    BACKGROUND: Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are, however, limited. We aim to identify epigenetic marks in offspring associated with father's preconception smoking. METHODS: We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort (7-50 years) on father's any preconception smoking (n = 875 offspring) and father's pubertal onset smoking < 15 years (n = 304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, own smoking and maternal smoking. EWAS of maternal and offspring personal smoking were performed for comparison. Father's smoking-associated dmCpGs were checked in subpopulations of offspring who reported no personal smoking and no maternal smoking exposure. RESULTS: Father's smoking commencing preconception was associated with methylation of blood DNA in offspring at two cytosine-phosphate-guanine sites (CpGs) (false discovery rate (FDR) < 0.05) in PRR5 and CENPP. Father's pubertal onset smoking was associated with 19 CpGs (FDR < 0.05) mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (p < 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. Father's smoking-associated sites did not overlap with dmCpGs identified in EWAS of personal and maternal smoking (FDR < 0.05), and all sites remained significant (p < 0.05) in analyses of offspring with no personal smoking and no maternal smoking exposure. CONCLUSION: Father's preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underlie epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity.
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    Longitudinal Asthma Phenotypes from Childhood to Middle-Age A Population-based Cohort Study
    Tan, DJ ; Lodge, CJ ; Walters, EH ; Lowe, AJ ; Bui, DS ; Bowatte, G ; Pham, J ; Erbas, B ; Hui, J ; Hamilton, GS ; Thomas, PS ; Hew, M ; Washko, G ; Wood-Baker, R ; Abramson, MJ ; Perret, JL ; Dharmage, SC (AMER THORACIC SOC, 2023-07-15)
    Rationale: Asthma is a heterogeneous condition, and longitudinal phenotyping may provide new insights into the origins and outcomes of the disease. Objectives: We aimed to characterize the longitudinal phenotypes of asthma between the first and sixth decades of life in a population-based cohort study. Methods: Respiratory questionnaires were collected at seven time points in the TAHS (Tasmanian Longitudinal Health Study) when participants were aged 7, 13, 18, 32, 43, 50, and 53 years. Current-asthma and ever-asthma status was determined at each time point, and group-based trajectory modeling was used to characterize distinct longitudinal phenotypes. Linear and logistic regression models were fitted to investigate associations of the longitudinal phenotypes with childhood factors and adult outcomes. Measurements and Main Results: Of 8,583 original participants, 1,506 had reported ever asthma. Five longitudinal asthma phenotypes were identified: early-onset adolescent-remitting (40%), early-onset adult-remitting (11%), early-onset persistent (9%), late-onset remitting (13%), and late-onset persistent (27%). All phenotypes were associated with chronic obstructive pulmonary disease at age 53 years, except for late-onset remitting asthma (odds ratios: early-onset adolescent-remitting, 2.00 [95% confidence interval (CI), 1.13-3.56]; early-onset adult-remitting, 3.61 [95% CI, 1.30-10.02]; early-onset persistent, 8.73 [95% CI, 4.10-18.55]; and late-onset persistent, 6.69 [95% CI, 3.81-11.73]). Late-onset persistent asthma was associated with the greatest comorbidity at age 53 years, with increased risk of mental health disorders and cardiovascular risk factors. Conclusions: Five longitudinal asthma phenotypes were identified between the first and sixth decades of life, including two novel remitting phenotypes. We found differential effects of these phenotypes on risk of chronic obstructive pulmonary disease and nonrespiratory comorbidities in middle age.
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    Exploration of associations between occupational exposures and current adult eczema
    Lopez, DJ ; Alif, S ; Dharmage, S ; Lodge, CJ ; Bui, DS ; Le Moual, N ; Waidyatillake, NT ; Su, JC ; Abramson, M ; Walters, EH ; Hamilton, GS ; Bowatte, G ; Erbas, B ; Benke, G ; Perret, J ; Lowe, AJ (BMJ PUBLISHING GROUP, 2023-10)
    OBJECTIVES: There is a scarcity of evidence on occupational exposures that may increase eczema in adults. We aimed to investigate potential associations between occupational exposures and eczema in middle-aged adults. METHODS: A lifetime work history calendar was collected from the Tasmanian Longitudinal Health Study participants when they were at age 53. Their work history was collated with the occupational asthma-specific job exposure matrix to define ever-exposure and cumulative exposure unit-years since no eczema job exposure matrix is available. Eczema was determined using the report of flexural rash that was coming and going for at least 6 months in the last 12 months. Skin prick tests were used to further subgroup eczema and atopic eczema (AE) or non-AE (NAE). Logistic and multinomial regression models were used to investigate the associations. RESULTS: Eczema prevalence was 9.1%. Current occupational exposure to animals (adjusted OR, aOR=3.06 (95% CI 1.43 to 6.58)), storage mites (aOR=2.96 (95% CI 1.38 to 6.34)) and endotoxin (aOR=1.95 (95% CI 1.04 to 3.64)) were associated with increased risk of current eczema. Furthermore, increased odds of NAE were associated with current exposure to animals (aOR=5.60 (95% CI 1.45 to 21.7)) and storage mites (aOR=5.63 (95% CI 1.45 to 21.9)). Current exposures to isocyanates (aOR=5.27 (95% CI 1.17 to 23.7)) and acrylates (aOR=8.41 (95% CI 1.60 to 44.3)) were associated with AE. There was no evidence of associations between cumulative exposures and eczema prevalence. Cumulative exposure to metalworking fluids (aOR=1.10 (95% CI 1.01 to 1.22)) was associated with NAE and acrylates (aOR=1.24 (95% CI 1.04 to 1.46)) with AE. CONCLUSIONS: In this exploratory assessment, multiple occupational exposures were associated with current eczema in middle-aged adults. Raising awareness and limiting these exposures during an individual's productive working life will likely have various health benefits, including reducing eczema prevalence.
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    Disease burden, comorbidities and antecedents of chronic cough phenotypes in Australian adults.
    Suresh, S ; Perret, JL ; Walters, EH ; Abramson, MJ ; Bowatte, G ; Lodge, C ; Lowe, A ; Erbas, B ; Thomas, P ; Hamilton, GS ; Chang, AB ; Dharmage, SC ; Bui, DS (Elsevier BV, 2023-09-22)
    BACKGROUND AND OBJECTIVES: While adult chronic cough has high burden, its phenotypes, particularly those without aetiologically related underlying conditions, are understudied. We investigated the prevalence, lung function and comorbidities of adult chronic cough phenotypes. METHODS: Data from 3608 participants aged 53 years from the Tasmanian Longitudinal Health Study (TAHS) were included. Chronic cough was defined as cough on most days for >3 months in a year. Chronic cough was classified into "explained cough" if there were any one of four major cough-associated conditions (asthma, COPD, gastroesophageal reflux disease or rhinosinusitis) or "unexplained cough" if none were present. Adjusted regression analyses investigated associations between these chronic cough phenotypes, lung function and non-respiratory comorbidities at 53 years. RESULTS: The prevalence of chronic cough was 10% (95%CI 9.1,11.0%) with 46.4% being "unexplained". Participants with unexplained chronic cough had lower FEV1/FVC (coefficient: -1.2% [95%CI:-2,3, -0.1]) and increased odds of comorbidities including obesity (OR=1.6 [95%CI: 1.2, 2.3]), depression (OR=1.4 [95%CI: 1.0, 2.1]), hypertension (OR=1.7 [95%CI: 1.2, 2.4]) and angina, heart attack or myocardial infarction to a lesser extent, compared to those without chronic cough. Participants with explained chronic cough also had lower lung function than both those with unexplained chronic cough and those without chronic cough. CONCLUSIONS: Chronic cough is prevalent in middle-age and a high proportion is unexplained. Unexplained cough contributes to poor lung function and increased comorbidities. Given unexplained chronic cough is not a symptom of major underlying respiratory conditions it should be targeted for better understanding in both clinical settings and research.
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    Cashew Allergy Prevalence and Sensitization in 1-Year-Old Infants
    Brettig, T ; Soriano, VX ; Dharmage, SC ; Mcwilliam, V ; Peters, RL ; Perrett, K ; Koplin, JJ (ELSEVIER, 2023-11)
    BACKGROUND: Cashew allergy is the most common tree nut allergy in Australia, but there are limited data on the population-level prevalence and risk factors. OBJECTIVE: Describe the prevalence of cashew sensitization and allergy in 12-month-old infants and identify risk factors. METHODS: Data were from the EarlyNuts cohort, a population-based sample of infants recruited in Melbourne, Australia. Families completed a questionnaire and infants underwent a skin prick test (SPT) to cashew. Infants with positive SPTs were offered food challenges. Questionnaires collected demographic data and allergy risk factors. Allergy outcomes were determined by challenge outcomes or a convincing history of an allergic reaction. We used weights to adjust estimated prevalence to reflect the distribution of risk factors among the combined sample of participants and nonparticipants. RESULTS: We recruited 1,933 participants and identified 1,414 cashew allergy outcomes. Of these, 1.96% (95% CI, 1.28-2.99) had an SPT result of 3 mm or greater and 1.49% (95% CI, 0.91-2.44) were allergic to cashew. Infants with eczema or peanut allergy in the first year of life were more likely to be allergic to cashew (adjusted odds ratio = 5.75; 95% CI, 2.08-15.88; P = .001; and adjusted odds ratio = 19.30; 95% CI, 5.44-68.43; P < .001, respectively). Twenty-five percent of participants had cashew introduced before 12 months (95% CI, 22.7-27.8). There was no association between the timing of cashew introduction and cashew allergy. CONCLUSIONS: To our knowledge, this is the first study describing the prevalence of and risk factors for cashew allergy in a population-based infant cohort. Eczema and peanut allergy were associated with an increased risk of cashew allergy. Few infants were introduced to cashew before age 12 months, which suggests that infant feeding guidelines have not yet translated to the earlier introduction of all allergens.