Atopic phenotypes identified with latent class analyses at age 2 years

Abstract

Background Atopic sensitization or atopy is the most commonly reported risk factor for asthma. Recent studies have begun to suggest that atopy, as conventionally defined, may be an umbrella term that obfuscates more specific allergic disease types. Objective To determine if distinct and meaningful atopic phenotypes exist within a racially diverse birth cohort using ten allergen-specific IgE (sIgE) measurements from children of age 2 years. Methods Using the WHEALS birth cohort (62% Black), we analyzed sIgE data from ten allergens (Der f, dog, cat, Timothy grass, ragweed, Alternaria alternata, egg, peanut, milk, and German cockroach) among 594 children measured at age 2 years. Conventional atopy was defined as at least one sIgE ≥ 0.35 IU/ml. Results A four-class solution (latent class model) was the best fit. Class types were labeled “Low to no sensitization (76.9% of sample)”, “Highly sensitized (2.7%)”, “Milk and egg dominated (15.3%)” and “Peanut and inhalant(s) (5.1%)”. Almost one-third (32.2%) of the “low to no sensitization” group met the criteria for conventional atopy. The “Highly sensitized” group was significantly associated with doctor diagnosis of asthma after age 4 years, odds ratio [OR]=5.3, 95% Cl, 1.6–17.4) while the “Milk and egg dominated” and “Peanut and inhalant(s)” groups were not, OR=1.6 (0.8–3.0) and OR=1.8 (0.6–4.9), respectively. Children of Black race were more likely to be in the three multi-sensitized groups, p=0.04. Conclusion Classification by sIgE patterns defined groups whose membership is more strongly associated, as compared to conventional atopy, with atopic dermatitis, wheeze, and asthma.

Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood

“…[19][20][21][22] In 2016, LCA method was also used to identify phenotypes of atopic sensitization. 23,24 To our knowledge, this is one of the first studies using the LCA method to evaluate different subtypes of atopic dermatitis in childhood. The strengths of this study are the large population design of the PASTURE study and the repeated data on atopic dermatitis symptoms, prospectively collected from birth to school age, which give the opportunity to use this method.…”

Influence and effect of the human microbiome in allergy and asthma

“…Although atopic children do not always develop asthma, recent data have indicated that allergic children who exhibit multiple early-life (age 2) sensitizations to a range of allergens, for example, dog, cat, cockroach, egg, peanut, are at a significantly higher risk for subsequently developing physician diagnosed asthma at age 4 (odds ratio, 5.3; 95% confidence interval, 1.6-17.4), compared with those who are either nonsensitized or sensitized to only one or two of these allergens [20]. Indeed, murine studies examining neonatal mice whose airways were sensitized with house dust mite (HDM) demonstrated more pronounced allergic airway inflammation compared with similarly challenged adult animals [21 & ].…”

The mechanism or mechanisms driving atopic asthma initiation: The infant respiratory microbiome moves to center stage

“…This balance ranges between the extremes of Treg cell dominance (absolute tolerance/no evidence of IgE production) and strong T H 2 memory dominance (ie, multiple sensitizations/high IgE/high asthma risk). 18,19 However, a very common outcome is an apparently ''mixed'' memory response in which sufficiently high levels of T H 2 memory persist to drive ongoing IgE production but not to mediate the repeated cycles of aeroallergen-induced acute-phase (IgE-FcR-mediated) plus late-phase (T H 2 effector-mediated) responses responsible collectively for the severe airways inflammation necessary to drive asthma pathogenesis. The existence of such balanced but seemingly ''benign'' T H 2 memory responses is evident from data from some of the large birth cohort studies exemplified in Fig 1. These data come from the 14-year respiratory follow-up of our RAINE cohort, 20 in which approximately 40% of the 1380 subjects assessed were sensitized to the perennial indoor allergen house dust mite but only a minority of these exhibit wheezing symptoms.…”