Paediatrics (RCH) - Research Publications
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ItemThe Exposome Approach in Allergies and Lung Diseases: Is It Time to Define a Preconception Exposome?(MDPI, 2021-12)Emerging research suggests environmental exposures before conception may adversely affect allergies and lung diseases in future generations. Most studies are limited as they have focused on single exposures, not considering that these diseases have a multifactorial origin in which environmental and lifestyle factors are likely to interact. Traditional exposure assessment methods fail to capture the interactions among environmental exposures and their impact on fundamental biological processes, as well as individual and temporal factors. A valid estimation of exposure preconception is difficult since the human reproductive cycle spans decades and the access to germ cells is limited. The exposome is defined as the cumulative measure of external exposures on an organism (external exposome), and the associated biological responses (endogenous exposome) throughout the lifespan, from conception and onwards. An exposome approach implies a targeted or agnostic analysis of the concurrent and temporal multiple exposures, and may, together with recent technological advances, improve the assessment of the environmental contributors to health and disease. This review describes the current knowledge on preconception environmental exposures as related to respiratory health outcomes in offspring. We discuss the usefulness and feasibility of using an exposome approach in this research, advocating for the preconception exposure window to become included in the exposome concept.
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ItemEpigenetic programming underpins B-cell dysfunction in peanut and multi-food allergy(WILEY, 2021)OBJECTIVE: Rates of IgE-mediated food allergy (FA) have increased over the last few decades, and mounting evidence implicates disruption of epigenetic profiles in various immune cell types in FA development. Recent data implicate B-cell dysfunction in FA; however, few studies have examined epigenetic changes within these cells. METHODS: We assessed epigenetic and transcriptomic profiles in purified B cells from adolescents with FA, comparing single-food-allergic (peanut only), multi-food-allergic (peanut and ≥1 other food) and non-allergic (control) individuals. Adolescents represent a phenotype of persistent and severe FA indicative of a common immune deviation. RESULTS: We identified 144 differentially methylated probes (DMPs) and 116 differentially expressed genes (DEGs) that distinguish B cells of individuals with FA from controls, including differential methylation of the PM20D1 promoter previously associated with allergic disorders. Subgroup comparisons found 729 DMPs specific to either single-food- or multi-food-allergic individuals, suggesting epigenetic distinctions between allergy groups. This included two regions with increased methylation near three S100 genes in multi-food-allergic individuals. Ontology results of DEGs specific to multi-food-allergic individuals revealed enrichment of terms associated with myeloid cell activation. Motif enrichment analysis of promoters associated with DMPs and DEGs showed differential enrichment for motifs recognised by transcription factors regulating B- and T-cell development, B-cell lineage determination and TGF-β signalling pathway between the multi-food-allergic and single-food-allergic groups. CONCLUSION: Our data highlight epigenetic changes in B cells associated with peanut allergy, distinguishing features of the epigenome between single-food- and multi-food-allergic individuals and revealing differential developmental pathways potentially underpinning these distinct phenotypes.
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ItemNo obvious impact of caesarean delivery on childhood allergic outcomes: findings from Australian cohorts(BMJ PUBLISHING GROUP, 2020-07)BACKGROUND AND OBJECTIVE: As caesarean delivery and childhood allergy continue to rise, their inter-relationships may change. We examined whether caesarean delivery predicts allergic disease and impaired lung function in two contemporary harmonised population-based cohorts. METHODS: Parent-reported asthma and eczema data were drawn from two prospective Australian infant cohorts, HealthNuts (n=5276, born 2006-2010) and the Longitudinal Study of Australian Children (LSAC, n=5107, born 2003-2004) at age 6-7 years, and spirometric lung function from LSAC's Child Health CheckPoint (n=1756) at age 11-12 years. Logistic regression estimated associations between delivery mode and current asthma and eczema at 6-7 years, and linear regression examined lung function at 11-12 years. Models were adjusted for potential confounding factors. RESULTS: Complete case analysis included 3135 HealthNuts and 3654 LSAC children (32.2% and 30.9% born by caesarean, respectively). An association was evident between caesarean delivery and asthma at age 6-7 years in HealthNuts (adjusted OR (aOR) 1.25, 95% CI 1.00 to 1.57) but not in LSAC (aOR 1.05, 95% CI 0.86 to 1.28), while neither study showed clear associations with eczema (HealthNuts: aOR 1.09, 95% CI 0.88 to 1.35; LSAC: aOR 0.89, 95% CI 0.69 to 1.15). Spirometric lung function parameters at age 11-12 years were similar by delivery mode. Associations were not modified by duration of breast feeding, maternal history of asthma/eczema, childcare attendance, number of older siblings or pet exposure. CONCLUSIONS: In two unselected populations using harmonised protocols, the likely association of caesarean delivery with developing childhood allergy was small.
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ItemAre Young Children With Asthma More Likely to Be Less Physically Active?(AMER ACAD PEDIATRICS, 2021-12)BACKGROUND: Previous research suggests that children who experience asthma may be less physically active; however, results have been inconclusive. This study aimed to investigate whether the presence of asthma or wheeze is associated with lower physical activity levels in children, and whether sex, body mass index or earlier asthma or wheeze status modifies the association. METHODS: This study was conducted in 391 HealthNuts participants in Melbourne, Australia. Asthma and wheeze data were collected via questionnaire at age 4 and 6, and physical activity was measured through accelerometry. Using adjusted linear regression models, the cross-sectional and longitudinal associations were investigated. RESULTS: There was no evidence of a difference in time spent in moderate-to-vigorous physical activity (MVPA) at age 6 years between children with and without asthma at age 4; children with asthma spent 8.3 minutes more time physically active per day (95% CI: -5.6, 22.1, P = .24) than children without asthma. Similar results were seen for children with current wheeze (5.8 minutes per day more, 95% CI: -5.9, 17.5, P = .33) or ever wheeze or asthma (7.7 minutes per day more, 95% CI: -4.8, 20.2, P = .23) at age 4 years. Comparable null results were observed in the cross-sectional analyses. Interaction with BMI could not be assessed; however, previous asthma or wheeze status and sex were not found to modify these associations. CONCLUSION: This analysis found no evidence of asthma hindering physical activity in these young children. These results are encouraging, as they indicate that the Australian asthma and physical activity public health campaigns are being effectively communicated and adopted by the public.
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ItemSerum cytokine concentrations and asthma persistence to middle age(WILEY, 2020-11)
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ItemChildren of Asian ethnicity in Australia have higher risk of food allergy and early-onset eczema than those in Singapore(WILEY, 2021-10)BACKGROUND: In Western countries, Asian children have higher food allergy risk than Caucasian children. The early-life environmental exposures for this discrepancy are unclear. We aimed to compare prevalence of food allergy and associated risk factors between Asian children in Singapore and Australia. METHODS: We studied children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort (n = 878) and children of Asian ancestry in the HealthNuts cohort (n = 314). Food allergy was defined as a positive SPT ≥3 mm to egg or peanut AND either a convincing history of IgE-mediated reaction at 18 months (GUSTO) or a positive oral food challenge at 14-18 months (HealthNuts). Eczema was defined as parent-reported doctor diagnosis. RESULTS: Food allergy prevalence was 1.1% in Singapore and 15.0% in Australia (P<0.001). Egg introduction was more often delayed (>10 months) in Singapore (63.5%) than Australia (16.3%; P<0.001). Prevalence of early-onset eczema (<6 months) was lower in Singapore (8.4%) than Australia (30.5%) (P<0.001). Children with early-onset eczema were more likely to have food allergy than those without eczema in Australia [aOR 5.11 (2.34-11.14); P<0.001] and Singapore [aOR4.00 (0.62-25.8); P = 0.145]. CONCLUSIONS: Among Asian children, prevalence of early-onset eczema and food allergy was higher in Australia than Singapore. Further research with larger sample sizes and harmonized definitions of food allergy between cohorts is required to confirm and extend these findings. Research on environmental factors influencing eczema onset in Australia and Singapore may aid understanding of food allergy pathogenesis in different parts of the world.
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ItemChildhood vaccination and allergy: A systematic review and meta-analysis(WILEY, 2021-07)BACKGROUND AND OBJECTIVE: As the rise in prevalence of allergic diseases worldwide corresponds in time with increasing infant vaccination, it has been hypothesized that childhood vaccination may increase the risk of allergic disease. We aimed to synthesize the literature on the association between childhood vaccination and allergy. DESIGN: We searched the electronic databases PubMed and EMBASE (January 1946-January 2018) using vaccination and allergy terms. METHODS: Two authors selected papers according to the inclusion criteria. Pooled effects across studies were estimated using random-effects meta-analysis. Due to inadequate number of homogeneous publications on newer and underused vaccines, meta-analysis was limited to allergic outcomes following administration of (Bacillus Calmette-Guérin) BCG, measles or pertussis vaccination. The review was prospectively registered in the PROSPERO systematic review registry (NO: CRD42017071009). RESULTS: A total of 35 publications based on cohort studies and 7 publications based on randomized controlled trials (RCTs) met the inclusion criteria. RCTs: From 2 studies, early vaccination with BCG vaccine was associated with a reduced risk of eczema (RR = 0.83; 95% CI = 0.73-0.93; I2 = 0%) but not food allergy or asthma. No association was found between pertussis vaccine and any allergic outcome based on a single RCT. COHORT STUDIES: Childhood measles vaccination was associated with a reduced risk of eczema (RR = 0.65; 95% CI = 0.47-0.90, I2 = 0.0%), asthma (RR = 0.78; 95% CI = 0.62-0.98, I2 = 93.9%) and, with a similar, statistically non-significant reduction in sensitization (RR = 0.78; 95% CI = 0.61-1.01, I2 = 19.4%). CONCLUSIONS: We found no evidence that childhood vaccination with commonly administered vaccines was associated with increased risk of later allergic disease. Our results from pooled analysis of both RCTs and cohort studies suggest that vaccination with BCG and measles vaccines were associated with a reduced risk of eczema.