Infant food allergy phenotypes and association with lung function deficits and asthma at age 6 years: a population-based, prospective cohort study in Australia

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 (a ss -0 center dot 19 [95% CI -0 center dot 32 to -0 center dot 06] and -0 center dot 17 [-0 center dot 31 to -0 center dot 04], respectively) at age 6 years. Transient egg allergy was associated with reduced FEV 1 and FVC compared with never having egg allergy (-0 center dot 18 [95% CI -0 center dot 33 to -0 center dot 03] and -0 center dot 15 [-0 center dot 31 to 0 center dot 00], respectively), whereas persistent egg allergy was not (FEV 1 -0 center dot 09 [-0 center dot 48 to 0 center dot 31]; FVC -0 center dot 20 [-0 center dot 62 to 0 center dot 21]). Transient peanut allergy was associated with reduced FEV 1 and FVC (FEV 1 a ss -0 center dot 37 [-0 center dot 79 to 0 center dot 04] and FVC a ss -0 center dot 55 [-0 center dot 98 to -0 center dot 12]), in addition to persistent peanut allergy (FEV 1 a ss -0 center dot 30 [-0 center dot 54 to -0 center dot 06] and FVC a ss-0 center dot 30 [-0 center dot 55 to -0 center dot 05]), and lateonset peanut allergy (FEV 1 a ss -0 center dot 62 [-1 center dot 06 to -0 center dot 18] and FVC a ss-0 center dot 49 [-0 center dot 96 to -0 center dot 03]). Estimates suggested that foodsensitised 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 center dot 95 [95% CI 0 center dot 77 to 11 center dot 38]). 430 (13 center dot 7%) of 3135 children were diagnosed with asthma before age 6 years (95% CI 12 center dot 5-15 center dot 0). Both foodsensitised tolerance and food allergy at age 1 year were associated with increased asthma risk at age 6 years (adjusted odds ratio 1 center dot 97 [95% CI 1 center dot 23 to 3 center dot 15] and 3 center dot 69 [2 center dot 81 to 4 center dot 85], respectively). Persistent and late-onset peanut allergy were associated with higher asthma risk (3 center dot 87 [2 center dot 39 to 6 center dot 26] and 5 center dot 06 [2 center dot 15 to 11 center dot 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.