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Background: Food allergy is considered a precursor to asthma in the context of the atopic march, but the relationship between infant food allergy phenotypes and lung function and asthma in childhood is unclear. We aimed to examine the association between food sensitisation and challenge-confirmed food allergy in infancy, as well as persistent and resolved food allergy up to age 6 years, and the risk of lung function deficits and asthma at age 6 years., Methods: The longitudinal, population-based HealthNuts cohort study in Melbourne, VIC, Australia, recruited 5276 infants children aged 1 year who attended council-run immunisation sessions between Sept 28, 2007, and Aug 5, 2011. At age 1 year, all children completed skin prick testing to four food allergens (egg, peanut, sesame, and either shrimp or cow's milk) and an oral food challenge (egg, peanut, and sesame) at the Royal Children's Hospital in Melbourne. Parents completed questionnaires about their infant's allergy history, demographic characteristics, and environmental exposures. At age 6 years, children were invited for a health assessment that included skin prick testing for ten foods (milk, egg, peanut, wheat, sesame, soy, shrimp, cashew, almond, and hazelnut) and eight aeroallergens (alternaria, cladasporum, house dust mite, cat hair, dog hair, bermuda grass, rye grass, and birch mix), oral food challenges, and lung function testing by spirometry. Questionnaires completed by parents (different to those completed at age 1 year) captured the child's allergy and respiratory history and demographics. We investigated associations between food allergy phenotypes (food-sensitised tolerance or food allergy; and ever, transient, persistent, or late-onset food allergy), lung function spirometry measures (forced expiratory volume in 1 sec [FEV 1 ] and forced vital capacity [FVC] z-scores, FEV 1 /FVC ratio, forced expiratory flow at 25% and 75% of the pulmonary volume [FEF 25-75% ], and bronchodilator responsiveness), and asthma using regression methods. Only children with complete data on the exposure, outcome, and confounders were included in models. Infants without food sensitisation or food allergy at age 1 year and 6 years served as the reference group., Findings: Of 5276 participants, 3233 completed the health assessment at age 6 years and were included in this analysis. Food allergy, but not food-sensitised tolerance, at age 1 year was associated with reduced FEV 1 and FVC (aβ -0·19 [95% CI -0·32 to -0·06] and -0·17 [-0·31 to -0·04], respectively) at age 6 years. Transient egg allergy was associated with reduced FEV 1 and FVC compared with never having egg allergy (-0·18 [95% CI -0·33 to -0·03] and -0·15 [-0·31 to 0·00], respectively), whereas persistent egg allergy was not (FEV 1 -0·09 [-0·48 to 0·31]; FVC -0·20 [-0·62 to 0·21]). Transient peanut allergy was associated with reduced FEV 1 and FVC (FEV 1 aβ -0·37 [-0·79 to 0·04] and FVC aβ -0·55 [-0·98 to -0·12]), in addition to persistent peanut allergy (FEV 1 aβ -0·30 [-0·54 to -0·06] and FVC aβ-0·30 [-0·55 to -0·05]), and late-onset peanut allergy (FEV 1 aβ -0·62 [-1·06 to -0·18] and FVC aβ-0·49 [-0·96 to -0·03]). Estimates suggested that food-sensitised tolerance and food allergy were associated with reduced FEF 25-75% , although some estimates were imprecise. Food allergy phenotypes were not associated with an FEV 1 /FVC ratio. Late-onset peanut allergy was the only allergy phenotype that was possibly associated with increased risk of bronchodilator responsiveness (2·95 [95% CI 0·77 to 11·38]). 430 (13·7%) of 3135 children were diagnosed with asthma before age 6 years (95% CI 12·5-15·0). Both food-sensitised tolerance and food allergy at age 1 year were associated with increased asthma risk at age 6 years (adjusted odds ratio 1·97 [95% CI 1·23 to 3·15] and 3·69 [2·81 to 4·85], respectively). Persistent and late-onset peanut allergy were associated with higher asthma risk (3·87 [2·39 to 6·26] and 5·06 [2·15 to 11·90], respectively)., Interpretation: Food allergy in infancy, whether it resolves or not, is associated with lung function deficits and asthma at age 6 years. Follow-up studies of interventions to prevent food allergy present an opportunity to examine whether preventing these food allergies improves respiratory health., Funding: National Health & Medical Research Council of Australia, Ilhan Food Allergy Foundation, AnaphylaxiStop, the Charles and Sylvia Viertel Medical Research Foundation, the Victorian Government's Operational Infrastructure Support Program., Competing Interests: Declaration of interests MLKT has received research funding from Prota Therapeutics, is an employee of Prota Therapeutics, has received consultancy fees from Pfizer, and is an inventor on patents owned by MCRI “A method for of inducing tolerance to an allergen” and “Allergy Treatment”. KPP is Chair of the scientific advisory board for AllergyPal; has received research grants from DBV Technologies, Novartis, Aravax, and Siolta; and consultant fees from Aravax, outside of the submitted work, paid to their institution. SCD, CJL, and AJL received investigator-initiated grants from GSK for unrelated work. AJL, SCD, and JJK have received grant funding from Sanofi Regeneron for unrelated research. AJL has received in kind contributions of study intervention (EpiCeram) from Primus Pharmaceuticals for unrelated research. RLP receives honoraria for editorial involvement with the journal Paediatric Allergy and Immunology. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Grass pollen exposure is a risk factor for childhood asthma hospital attendances. However, its short-term influence on lung function, especially among those with other allergic conditions, has been less well-studied., Objective: To investigate this association in a population-based sample of children., Methods: Within the HealthNuts cohort, 641 children performed spirometry during the grass pollen season. Grass pollen concentration was considered on the day of testing (lag 0), up to 3 days before (lag 1-lag 3), and cumulatively (lag 0-3). We used linear regression to assess the relevant associations and examined potential interactions with current asthma, hay fever or eczema, and food allergy., Results: Associations were observed only in children with allergic disease (P value for interaction ≤ 0.1). In children with food allergy, grass pollen concentration was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV 1 /FVC) and lower mid-forced expiratory flows (FEF 25%-75% ) at all lags (eg, at lag 2, FEV 1 /FVC z-score = -0.50 [95% CI -0.80 to -0.20] and FEF 25%--75% z-score = -0.40 [-0.60 to -0.04] per 20 grains/m 3 pollen increase), and increased bronchodilator responsiveness (BDR) at lag 2 and lag 3 (eg, at lag 2, BDR = (31 [95% CI -0.005 to 62] mL). In children with current asthma, increasing grass pollen concentration was associated with lower FEF 25%-75% and increased BDR, whereas children with current hay fever or eczema had increased BDR only., Conclusions: A proactive approach needs to be enforced to manage susceptible children, especially those with food allergy, before high-grass pollen days., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Longer duration of breastfeeding may be protective against asthma. However, early manifestations of allergic disease, such as eczema, are risk factors for asthma and can influence the duration of breastfeeding, and hence, may bias observable associations., Objective: To examine the relationship between breastfeeding ever and duration and the development of asthma and allergic asthma phenotypes, stratified by a diagnosis of eczema during or after the breastfeeding period., Methods: A total of 3663 children participated in the 6-year-old follow-up of the HealthNuts study, a population-based, longitudinal study of allergic diseases in Australia. At age 1 year, breastfeeding and eczema data were collected and at age 6 years, information on wheeze, medication use, and parental report of doctor-diagnosed asthma were obtained, both via questionnaire. Skin prick test responses to food and aeroallergens at age 6 years further distinguished asthmatic children into allergic and nonallergic phenotypes., Results: Breastfeeding initiation was not associated with current asthma at age 6 years (adjusted odds ratio, 0.76; 95% CI, 0.45-1.29) when compared with never breastfeeding. Results were similar for length of exclusiveness and overall duration of breastfeeding, and allergic and nonallergic asthma phenotypes. However, increased duration of breastfeeding among children without eczema in infancy was associated with reduced odds of asthma (per month increase, adjusted odds ratio, 0.98; 95% CI, 0.95-1.0; P = .05), which equates to 0.86 (95% CI, 0.74-1.0) reduced odds of asthma for a 6-month increase in breastfeeding. This association was not apparent in children who were diagnosed with eczema during breastfeeding (adjusted odds ratio, 1.03; 95% CI, 0.98-1.08; P = .3)., Conclusions: Longer duration of breastfeeding was associated with a reduced odds of asthma among children without eczema in the first year of life; this association was masked before stratification by eczema in infancy. Future studies examining breastfeeding practices and the risk of allergic outcomes in later childhood need to consider the presence of early-life allergic manifestations impacting on breastfeeding behavior., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We previously reported that infants with Asian-born parents are 3 times more likely to have IgE-mediated food allergy than those with Australian-born parents. It is unknown whether this translates to the increased risk of other allergic diseases later in childhood and whether ancestry interacts with other risk factors for allergic disease development., Objective: To compare prevalence and risk factors for allergic rhinitis, asthma, and aeroallergen sensitization at age 6 between children with East Asian-born and Caucasian-born parents., Methods: A total of 5276 1-year-old infants were recruited into a population-based longitudinal study of allergy. A total of 4455 children participated in age 6 follow-up (84.4%), including 3015 with Caucasian-born parents and 415 with East Asian-born parents. Children underwent skin prick tests to aeroallergens and questionnaires captured data on asthma, eczema, and allergic rhinitis., Results: Compared with children with Caucasian-born parents, children of East Asian-born parents had more allergic rhinitis (19.9% [95% confidence interval (CI) 14.9-26] vs 9.3% [95% CI 8-10.8], P < .001) and aeroallergen sensitization (64.3% [95% CI 57.5-70.5] vs 34.4% [95% CI 32.2-36.7], P < .001) at age 6. Asthma was similar in both groups (9.1% [95% CI 6.2-13.2] vs 11.7% [95% CI 10.4-13.1]), P = .21. Children with IgE-mediated food allergy and eczema in infancy were 3 times more likely to have asthma and 2 times more likely to have allergic rhinitis at age 6, irrespective of ancestry., Conclusions: Children of East Asian ancestry born in Australia have a higher burden of most allergic diseases in the first 6 years of life, whereas asthma may follow a different pattern. IgE-mediated food allergy and eczema at age 1 increase the risk of asthma and allergic rhinitis irrespective of ancestry., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The risk of developing asthma in those with early food allergy is unknown, particularly when early life food allergy has resolved., Objective: To understand whether challenge-proven food allergy in infancy increases the risk of asthma at age 4 years, using data from a population-based cohort., Methods: A total of 5,276 12-month-old infants were recruited using a population-based sampling frame. Infants underwent skin prick test to egg, peanut, and sesame and those with a detectable skin prick test result had oral food challenges. At age 4 years, food challenges were repeated to determine persistence or resolution of food allergy. The association between food allergy and doctor-diagnosed asthma was examined using binomial regression in 2,789 participants., Results: Children with food allergy at age 1 year had an increased risk of asthma (1 food allergy: relative risk [RR], 1.69; 95% CI, 1.29-2.21; 2 or more food allergies: RR, 2.76; 95% CI, 1.94-3.92). The risk of asthma was highest in children with food allergy and coexistent eczema in infancy (RR, 2.87; 95% CI, 2.22-3.70). Transient food allergy and persistent food allergy were both associated with an increased risk of asthma (transient egg allergy: RR, 1.92; 95% CI, 1.46-2.51; persistent egg allergy: RR, 2.60; 95% CI, 1.76-3.85)., Conclusions: Asthma at age 4 years is twice as common in those with challenge-proven food allergy at age 1 year, irrespective of whether the food allergy subsequently resolves. Children with 2 or more food allergies and those with coexistent eczema were almost 3 times as likely to develop asthma compared with those with no food allergies., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Adolescents are at the highest risk of death from anaphylaxis, yet few population-based studies have described the frequencies and risk factors for allergic reactions caused by accidental allergen ingestion in this group., Methods: We describe the prevalence, frequency, and associated risk factors for recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia, recruited from a stratified, random, population-based sample of schools (SchoolNuts, n = 9663; 48% response rate). Self-reported food allergy and adverse reaction details, including anaphylaxis, were identified by using a student questionnaire over the past year., Results: Of 547 students with possible IgE-mediated food allergy, 243 (44.4%; 95% CI, 40.3% to 48.7%) reported a reaction to a food. Fifty-three (9.7%; 95% CI, 7.2% to 12.2%) students reported 93 anaphylaxis episodes. Peanut and tree nuts were the most common food triggers. Among students with current IgE-mediated food allergy, those with resolved or current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI, 1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1]) were at greatest risk of any adverse food reaction, and those with nut allergy were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or current asthma was not associated with increased risk of severe reactions (aOR, 0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7])., Conclusions: Adolescents with food allergy are frequently exposed to food allergens. Those with asthma and more than 2 food allergies were at the greatest risk for adverse food reactions. Those with nut allergies were most at risk of severe reactions., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: The HealthNuts study previously reported interim prevalence data showing the highest prevalence of challenge-confirmed food allergy in infants internationally. However, population-derived prevalence data on challenge-confirmed food allergy and other allergic diseases in preschool-aged children remain sparse., Objective: This study aimed to report the updated prevalence of food allergy at age 1 year from the whole cohort, and to report the prevalence of food allergy, asthma, eczema, and allergic rhinitis at age 4 years., Methods: HealthNuts is a population-based cohort study with baseline recruitment of 5276 one-year-old children who underwent skin prick test (SPT) to 4 food allergens and those with detectable SPT results had formal food challenges. At age 4 years, parents completed a questionnaire (81.3% completed) and those who previously attended the HealthNuts clinic at age 1 year or reported symptoms of a new food allergy were invited for an assessment that included SPT and oral food challenges. Data on asthma, eczema, and allergic rhinitis were captured by validated International Study of Asthma and Allergies in Childhood questionnaires., Results: The prevalence of challenge-confirmed food allergy at age 1 and 4 years was 11.0% and 3.8%, respectively. At age 4 years, peanut allergy prevalence was 1.9% (95% CI, 1.6% to 2.3%), egg allergy was 1.2% (95% CI, 0.9% to 1.6%), and sesame allergy was 0.4% (95% CI, 0.3% to 0.6%). Late-onset peanut allergy at age 4 years was rare (0.2%). The prevalence of current asthma was 10.8% (95% CI, 9.7% to 12.1%), current eczema was 16.0% (95% CI, 14.7% to 17.4%), and current allergic rhinitis was 8.3% (95% CI, 7.2% to 9.4%). Forty percent to 50% of this population-based cohort experienced symptoms of an allergic disease in the first 4 years of their life., Conclusions: Although the prevalence of food allergy decreased between age 1 year and age 4 years in this population-based cohort, the prevalence of any allergic disease among 4-year-old children in Melbourne, Australia, is remarkably high., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

HealthNuts is a single-centre, multi-wave, population-based longitudinal study designed to assess prevalence, determinants, natural history and burden of allergy (particularly food allergy) in the early years of life. It is novel in the use of serial food challenge measures within its population frame to confirm food allergy. The cohort comprises 5276 children initially recruited at age 12 months from council-run immunization sessions across Melbourne, Australia. As well as parent-completed questionnaires and researcher-observed eczema status, all infants underwent skin-prick testing to egg, peanut, sesame and either cow's milk or shellfish, and those with detectable wheals underwent food challenges to determine clinical allergy. In wave 2, conducted at age 4 years, validated questionnaires collected data on asthma, allergic rhinitis (hay fever), eczema and food allergies. Food challenges were repeated in children previously identified as food allergic to determine resolution. In wave 3, all children (irrespective of food allergy status) were invited for clinical assessment at age 6 years, including lung function, physical measurements, skin-prick testing to foods and aeroallergens and food challenges if food sensitized. Biological specimens (blood, cheek swabs) were collected at each wave for ancillary immunological, genetic and epigenetic studies. Applications to access data and/or samples can be submitted to [katrina.allen@mcri.edu.au]., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)