The Atopic March: The Pattern of Allergic Disease Development in Childhood

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.

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 [FEV₁] and forced vital capacity [FVC] z-scores, FEV₁/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.

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 FEV₁ 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 FEV₁ 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 (FEV₁ –0·09 [–0·48 to 0·31]; FVC –0·20 [–0·62 to 0·21]). Transient peanut allergy was associated with reduced FEV₁ and FVC (FEV₁ aβ –0·37 [–0·79 to 0·04] and FVC aβ –0·55 [–0·98 to –0·12]), in addition to persistent peanut allergy (FEV₁ aβ –0·30 [–0·54 to –0·06] and FVC aβ–0·30 [–0·55 to –0·05]), and late-onset peanut allergy (FEV₁ 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 FEV₁/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).

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.

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.

Very few studies have examined lung function parameters using tidal breath analysis (TBA) in atopic dermatitis (AD) with its high potential for progression to asthma.

To measure lung functions using TBA in infants with AD and in healthy controls (HCs), and to investigate the effects of disease severity, food sensitivity, and history of recurrent wheezing on TBA parameters in infants with AD.

Two hundred thirty infants were included in this prospective cross-sectional study, including an AD group (n = 150) and an HC group (n = 80). Food sensitivity was assessed by means of food-specific IgE or the skin prick test. The severity of the disease was evaluated using the SCORing Atopic Dermatitis. Lung function was assessed using TBA.

The following TBA parameters were significantly lower in the AD group than in the HC group (P < .05): time to peak tidal expiratory flow, exhaled volume to peak tidal expiratory flow, ratio of time to peak tidal expiratory flow to expiratory time, ratio of exhaled volume to peak tidal expiratory flow to total expiratory volume, expiratory flow when 25% of tidal volume remains in the lungs, respiratory rate, and minute ventilation. No difference was observed in the AD group when TBA parameters were compared according to disease severity, food sensitivity, and history of recurrent wheezing (P > .05). The receiver-operating characteristic curve demonstrated by the ratio of time to peak tidal expiratory flow to expiratory time yielded an area under the curve of 0.826 (CI, 0.772-0.879), with a cutoff value of 31.65 or higher in differentiating AD, with a sensitivity of 78.7% and a specificity of 77.5%.

TBA curves can be a useful tool for demonstrating expiratory airway obstruction in AD and for providing objective information for the clinician. Bronchial obstruction was detected in young children with AD irrespective of the severity of the disease, food sensitivity, and history of recurrent wheezing.

Atopic dermatitis often precedes the development of other atopic diseases, and the atopic march describes this temporal relationship in the natural history of these diseases. Although the pathophysiological mechanisms that underlie this relationship are poorly understood, epidemiologic and genetic data have suggested that the skin might be an important route of sensitization to allergens.

Review of recent studies on the role of skin barrier defects in systemic allergen sensitization.

Recent publications on the relationship between skin barrier defects and expression of epithelial cell–derived cytokines.

Animal models have begun to elucidate on how skin barrier defects can lead to systemic allergen sensitization. Emerging data now suggest that epithelial cell–derived cytokines, such as thymic stromal lymphopoietin, drive the progression from atopic dermatitis to asthma and food allergy. Skin barrier defects can lead to induction of epithelial cell–derived cytokines, which in turn leads to the initiation and maintenance of allergic inflammation and the atopic march.

Development of new biologic drug targeting type 2 cytokines provides novel therapeutic interventions for atopic dermatitis.

Optimal sleep is important for child growth, development, and immune function. We aimed to explore whether sleep disorders were associated with the risk of allergic diseases in Chinese toddlers.

This study included 566 children (aged 23.9 ± 0.7 months; 51.1% boys) in Shanghai, China. Sleep parameters (total sleep time, sleep onset latency, nocturnal awaking and snoring) were assessed by an expanded version of the Brief Infant Sleep Questionnaire (BISQ-expanded). Information on four allergic diseases (wheeze, eczema, food allergy, and allergic rhinitis) in the past year was collected via standard questionnaire and judged by pediatricians. We used logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for having any/and each of the four allergic diseases, based on sleep parameters, adjusting for children's age and gender, mode of delivery, any breastfeeding duration, children's body mass index (BMI), children's exposure to passive smoking, maternal education, family income, family allergic history, and children's antibiotic use.

There were 23.3% of children with at least one of the four allergic diseases. Snoring was significantly associated with increased odds of having any allergy (adjusted OR = 1.95; 95% CI: 1.17, 3.26), eczema (OR = 1.83, 95% CI: 1.03, 3.23) and food allergy (OR = 4.31, 95% CI: 1.23, 15.14), after adjustment for potential confounders. Nocturnal awaking ≥2 times per night was associated with higher risk of food allergy (OR = 3.92, 95% CI: 1.00, 15.35) and wheeze (OR = 6.16, 95% CI: 1.28, 29.74).

In this study, presence of certain sleep disorders was associated with higher risk of having allergic diseases in Chinese toddlers.

The increasing incidence of food allergy (FA) can be attributed to interactions between genes and the environment, but these interactions are not yet fully clear.

We aimed to evaluate the interaction between infant genetic variations and maternal dietary patterns to identify risk factors in the development of FA.

We used the Cohort for Childhood Origin of Asthma and allergic diseases birth cohort of 1628 infants, born between 2007 and 2015. Maternal dietary intakes were assessed at 26 weeks of pregnancy using a food frequency questionnaire and grouped according to 5 dietary patterns. Infant cord blood samples were genotyped at 12 loci.

Among 1628 infants, 147 (9.0%) were diagnosed with FA based on history. A maternal confectionery diet characterized by a higher intake of baked and sugary products during pregnancy was associated with a higher prevalence of FA (adjusted odds ratio [OR] = 1.517, P = .02); this dietary pattern tended to be higher in trans fat (r = 0.498, P < .001). Development of FA was associated with longer periods of breastfeeding (adjusted OR = 1.792, P = .03), and this dietary pattern was more significantly related to the development of FA in infants with the homozygous TT genotype of CD14 (rs2569190) and more than 1 copy of GSTM1 and GSTT1.

A maternal confectionery diet during pregnancy that majorly consists of baked and sugary products, combined with a longer ensuing period of breastfeeding, may lead to the development of FA, suggesting a harmful effect of trans fats in the infant. Polymorphisms in CD14 and GST in the infant influence FA susceptibility.