Evolution of Eczema, Wheeze, and Rhinitis from Infancy to Early Adulthood: Four Birth Cohort Studies

Abstract

Rationale: The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear.Objectives: To investigate within-individual patterns of morbidity of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood.Methods: We investigated onset, progression, and resolution of eczema, wheeze, and rhinitis using descriptive statistics, sequence mining, and latent Markov modeling in four population-based birth cohorts. We used logistic regression to ascertain if early-life eczema or wheeze, or genetic factors (filaggrin [FLG] mutations and 17q21 variants), increase the risk of multimorbidity.Measurements and Main Results: Single conditions, although the most prevalent, were observed significantly less frequently than by chance. There was considerable variation in the timing of onset/remission/persistence/intermittence. Multimorbidity of eczema1wheeze1rhinitis was rare but significantly overrepresented (three to six times more often than by chance). Although infantile eczema was associated with subsequent multimorbidity, most children with eczema (75.4%) did not progress to any multimorbidity pattern. FLG mutations and rs7216389 were not associated with persistence of eczema/wheeze as single conditions, but both increased the risk of multimorbidity (FLG by 2-to 3-fold, rs7216389 risk variant by 1.4-to 1.7-fold). Latent Markov modeling revealed five latent states (no disease/low risk, mainly eczema, mainly wheeze, mainly rhinitis, multimorbidity). The most likely transition to multimorbidity was from eczema state (0.21). However, although this was one of the highest transition probabilities, only one-fifth of those with eczema transitioned to multimorbidity.Conclusions: Atopic diseases fit a multimorbidity framework, with no evidence for sequential atopic march progression. The highest transition to multimorbidity was from eczema, but most children with eczema (more than three-quarters) had no comorbidities.

Dog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers

“…The larger heterogeneity of these ''intermediate'' classes, possibly coupled with smaller effect sizes in these groups, might have driven the observed lack of association. Future longitudinal wheezing classification strategies 34 will help elucidate whether a GxE exists for these classes. It is also to be noted that, because of the nature of the STELAR cohorts, which are restricted to participants with British ancestry, the generalizability of the results in other ethnicities will have to be investigated in future studies.…”

Gastroesophageal Reflux, Atopic Dermatitis, and Asthma: Finally Evidence for Causal Links?

“…On the one hand, this is not surprising given studies showing shared genetic risk between these diseases ( 13 ). The atopic march theory, however, supposes that some AD serves as a precursor to asthma ( 14 , 15 ), and mechanistic studies are needed to determine whether this is the case or whether this relationship reflects simply shared genetic risk. Furthermore, additional studies are needed to better understand the genetic influences on the risk of asthma among those with GERD and vice versa.…”

Revisiting the Atopic March Current Evidence

“…In this issue of the Journal , Haider and colleagues (pp. 950–960 ) aimed to evaluate the validity of the atopic march hypothesis using data from four birth cohort studies in the United Kingdom ( 8 ). They investigated the onset, progression, and resolution of eczema, wheeze, and rhinitis using sequence mining and Latent Markov modeling.…”

“…The broad definition of eczema as an itchy rash applied by Haider and colleagues ( 8 ) requires further scrutiny. Eczema encompasses a range of phenotypes, including both atopic and nonatopic dermatitis.…”

“…There is great potential to conduct in-depth investigations of multiple phenotypes of allergic disease using the rich birth cohort data sets as presented in the current manuscript ( 8 ) with the aim of better understanding risk trajectories for the development of allergic diseases. Such information will benefit efforts toward personalized patient care and may facilitate the development of novel tailored strategies to arrest an individual’s march toward further disease.…”