Early Life Atopy Research Articles

Association Between Asthma Control Trajectories in Preschoolers and Disease Remission

In few studies have researchers characterized the relationship between the frequency (and severity) of early events and long-term disease evolution in preschoolers with asthma. The purpose of this study was to investigate if asthma control trajectories 2 years postdiagnosis in preschoolers were associated with subsequent disease remission and recurrence.The study included a population cohort in 4 Canadian provinces consisting of 48 687 children with asthma diagnosed before 5 years of age and born between 1990 and 2013 who had prolonged disease activity postdiagnosis.Prolonged disease activity was defined as ≥1 medical visits or medications for asthma every 6-month period for at least 4 of the 6 periods postdiagnosis. Remission was defined as 2 consecutive years without drug claims or medical visits for asthma. Asthma control trajectories were classified by using the validated Pharmacoepidemiologic Pediatric Asthma Control Index. Cox regression models within each Canadian province were used to estimate associations between asthma control trajectories and time to remission or recurrence, with children controlled 2 years postdiagnosis as a reference control category. Province specific hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized by using random-effects meta-analysis.All suboptimal control trajectories were associated with a lower likelihood of remission, compared with that of children who were controlled throughout, with a pooled adjusted HR for remission of 0.51 (95% CI: 0.45 to 0.59) for those out of control throughout. An older age at diagnosis, atopy, and asthma diagnosis on the basis of hospitalization outside of the winter season were associated with a lower likelihood of remission. Suboptimal control trajectories were also associated with a higher likelihood of recurrence (HR: 1.17; 95% CI: 1.11 to 1.24), compared with children controlled throughout. Stratifying by sex or atopy did not significantly alter estimated HRs between trajectories. Girls in the study had higher recurrence rates than boys did. Children without atopy in early life were more likely to experience recurrence, compared with atopic children.In the 2 years after an asthma diagnosis in preschoolers, worse asthma control trajectories were associated with incrementally lower likelihoods of remission.With this study, the authors are the first to investigate the association between asthma control trajectories after a preschool diagnosis and remission. The asthma control trajectory in the 2 years after diagnosis in preschoolers appears to be an important predictor of both remission and recurrence, with poorer control associated with a lower likelihood of remission. With the study, the authors support previous studies in which researchers reported potential predictors of persistence, including older age at diagnosis, male sex, and diagnosis in a season other than winter.

Childhood atopy and mental health: a prospective, longitudinal investigation.

Prior studies have suggested a relationship between atopy and mental health, although methodological barriers have limited the generalizability of these findings. The objective of this study was to investigate the relationship between early-life atopy and vulnerability to mental health problems among youth in the community. Data were drawn from the Raine Study (N = 2868), a population-based birth cohort study in Western Australia. Logistic regression and generalized estimating equations were used to examine the relationship between atopy at ages 1-5 years [using parent report and objective biological confirmation (sera IgE)], and the range of internalizing and externalizing mental health problems at ages 5-17 years. Atopy appears to be associated with increased vulnerability to affective and anxiety problems, compared to youth without atopy. These associations remained significant after adjusting for a range of potential confounders. No relationship was evident between atopy and attention deficit hyperactivity disorder or externalizing problems. Findings are the first linking atopy (measured by both parent report and objective verification) with increased vulnerability to affective and anxiety problems. Therefore, replication is required. If replicated, future research aimed at understanding the possible biological and/or social and environmental pathways underlying these links is needed. Such information could shed light on shared pathways that could lead to more effective treatments for both atopy and internalizing mental health problems.

Anti-infective proteins in breast milk and asthma-associated phenotypes during early childhood.

The impact of breast milk feeding on susceptibility to asthma in childhood is highly controversial, due in part to failure of the majority of studies in the area to adequately account for key confounders exemplified by respiratory infection history, plus the effects of recall bias. As part of a prospective cohort study on the role of respiratory infections in asthma development in high-risk children, we measured the concentration of a panel of anti-infective proteins in maternal milk samples and analyzed associations between these and subsequent atopy-, infection-, and asthma-related outcomes prospectively to age 10 years. We observed significant but transient inverse associations between the concentration of milk proteins and susceptibility to upper respiratory infections in year 1 only, and parallel but positive transient associations with early lower respiratory infections and atopy. No associations were seen with asthma-related outcomes. Breast milk feeding may influence the expression of inflammatory symptoms associated with respiratory infections and atopy in early life, but these effects appear to be inconsistent and transient. The heterogeneous nature of breast-feeding effects suggests it may influence systemic immunoinflammatory function at several different levels.

Human Rhinovirus, Wheezing Illness, and the Primary Prevention of Childhood Asthma

Human Rhinovirus, Wheezing Illness, and the Primary Prevention of Childhood Asthma

Atopy phenotypes in the Childhood Asthma Prevention Study (CAPS) cohort and the relationship with allergic disease

Atopy in early life is heterogeneous in timing of onset, remission and persistence and in the nature of specific sensitization to allergens. However, this heterogeneity is not well characterized. Our aim was to define longitudinal phenotypes of atopy between ages 1.5 and 8years, and to assess the relationship of the atopy phenotypes to the risk of asthma, eczema and rhinitis at 8years of age. We used latent class analysis (LCA) to define atopy phenotypes using data from skin prick tests that were performed at 1.5, 3, 5 and 8years in participants in the Childhood Asthma Prevention Study (CAPS). Four phenotypes were defined: late mixed inhalant sensitization; mixed food and inhalant sensitization; house dust mite (HDM) monosensitized; and no atopy. All three atopic phenotypes were associated with asthma, eczema and rhinitis, but the strongest association, particularly for asthma, was with the mixed food and inhalant sensitization phenotype. We have used a LCA model to define atopy phenotypes empirically. The finding of a strong association between the mixed food and inhalant sensitization class and the presence of asthma and poor asthma control at age 8years implies that food sensitization in early life may be of greater significance for subsequent risk of asthma than previously thought.

Serum carotenoids and atopy among children of different ethnic origin living in Germany

The manifestation of atopy in early life is thought to be influenced by the diet. We hypothesized that the previously reported lower prevalence of atopy among Turkish immigrant children in Germany might be related to a different pattern of serum carotenoids. Serum carotenoid concentrations were measured in pre-school children of different ethnic origin from Berlin, D. German children (D, N = 49) were compared to Turkish children with well (TR-D, N = 32) or weak cultural adaptation (TR-TR, N = 41). Serum levels of pro-vitamin A carotenoids (α- and β-carotene, β-cryptoxanthin) and non-pro-vitamin A carotenoids (lutein, zeaxanthin, lycopene) were measured by high performance liquid chromatography. Serum IgE to common inhalant allergens was measured by immunoassay. Median levels of pro-vitamin A carotenoids were lower in Turkish children if compared to German children: D 135 μg/L, TR-D 100 μg/L (p = 0.025), TR-TR 82 μg/L (p = 0.001). By contrast, median levels of non-pro-vitamin A carotenoids were not higher in German children. The ratio of pro-vitamin A to non-pro-vitamin A carotenoid median levels was highest among D (2.05), lower among TR-D (1.32; p = 0.001) and lowest among TR-TR (1.26; p < 0.001)). A higher ratio was not significantly associated with atopy (atopic 1.79, non-atopic 1.36; p = 0.067). Pro-vitamin A carotenoids are higher in children originating from a cultural population with a higher prevalence of atopy, but atopy seems not to be directly related to the current carotenoid serum levels in children at school age. The distinct pattern of carotenoid levels among Turkish migrant and German children indicates changed nutrition patterns with acculturation.

Confirmed Moisture Damage at Home, Respiratory Symptoms and Atopy in Early Life: A Birth-Cohort Study

Most previous studies on the association between moisture or mold problems in the home and respiratory symptoms in children were cross-sectional and based on self-reported exposure. The aim of this study was to evaluate the impact of objectively observed moisture damage and visible mold in the homes on early-life respiratory morbidity and atopic sensitization in a birth cohort. Building inspection was performed by building engineers in the homes of 396 children, and the children were followed up with questionnaires from birth to the age of 18 months. Specific immunoglobulin E levels were measured at the age of 1 year. Doctor-diagnosed wheezing was associated with the severity of moisture damage in the kitchen and with visible mold in the main living area and especially in the bedroom of the child. The risk for parent-reported wheezing apart from cold increased with the severity of moisture damage in the kitchen. Moisture damage in the bathrooms or other interior spaces had no significant association with wheezing. No significant associations were observed for other end points, such as cough, or respiratory infections. There was a suggestion for an increased risk for sensitization to cat dander linked with moisture and mold exposure. This birth-cohort study supports previous observations that moisture mold problems in the kitchen and in the main living area increase the risk for wheezing in early childhood. The results underline the importance of assessing separately the health effects of moisture and mold problems in different areas of the home.

Cord Blood (CB) Progenitor Toll- Like Receptor (TLR) Expression: An Alternate Innate Immune Pathway In The Development Of Atopy

RATIONALE: Atopy in early life may be modulated by the expression and stimulation of TLRs on immunocompetent cells. Infants at high risk for developing atopy demonstrate phenotypic alterations of their CB progenitor cell hemopoietic cytokine receptors (HCR). Since hemopoietic mechanisms are involved in atopic development and maintenance, we investigated the co-expression of TLR and HCR on CB progenitors.

Wheezy babies—wheezy adults? Review on long‐term outcome until adulthood after early childhood wheezing

Population-based birth cohort studies have documented that about 30% of children suffer from wheezing during respiratory infection before their third birthday. Recurrent wheezing is common in early childhood, but most patients outgrow their symptoms by school age. However, recent long-term postbronchiolitis follow-up studies from Sweden and Finland have revealed that asthma is present in about 40% of young adults and over half of the cases are relapses after many symptom-free years. In population studies, the principal predictors for later asthma have been parental asthma, recurrent wheezing, atopy and eosinophilia. In the Swedish postbronchiolitis study, atopic diathesis through the development of clinical atopy, and early passive smoking through bronchial hyper-reactivity or later active smoking led to adult asthma. The Finnish postbronchiolitis follow-up stressed early recurrence of wheezing, wheezing induced by less invasive viruses than respiratory syncytial virus (RSV), early-life atopy and eosinophilia and parental asthma as predictors for adult asthma. The majority of wheezing infants and children outgrow their symptoms by school age, but based on recent long-term follow-up studies, asthma relapses are common in young adults. These studies have highlighted parental asthma, maternal smoking and wheezing induced by other viruses than RSV as predictive factors for later asthma.

Low-normal gestational age as a predictor of asthma at 6 years of age.

Perinatal factors, including gestational age and birth weight, influence the development of atopy in early life. However, the role of these factors in the development of asthma in later life among children who do not develop perinatal respiratory disease remains unclear. Four hundred fifty-four infants who had a history of allergy or asthma in at least 1 parent, were born in the 36th week of gestation or later, and did not develop perinatal respiratory distress were monitored for at least 6 years. Associations between predictor variables and asthma and wheeze were assessed with multivariate logistic regression and repeated-event analyses. Although we previously observed a relationship between low birth weight and persistent wheeze in the first 1 year of life, we did not observe similar associations between low birth weight and asthma at 6 years of age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 0.40-2.73). However, a strong relationship was found between low-normal gestational age and asthma at 6 years of age (OR: 4.7; 95% CI: 2.1-10.5). The effects of low-normal gestational age were significantly greater among boys than among girls (boys: OR: 8.15; 95% CI: 2.98-22.3; girls: OR: 1.90; 95% CI: 0.38-13.83). Longitudinal analysis of the relationship between gestational age and wheeze during the 6 years of observation confirmed these gender differences. Among children at high risk of developing atopic disease, late prematurity might be an important additional determinant of asthma later in life, and these effects are gender specific.

Predicting persistent disease among children who wheeze during early life.

This study sought to determine factors influencing the persistence of early life wheezing up to the age of 10 yrs and to create a score identifying those with the highest risk of persistent disease. Children were seen at birth, 1, 2, 4 and 10 yrs in a whole population birth cohort study (n=1,456). Information was collected prospectively on wheeze prevalence and subjects were classified into wheezing phenotypes. Early life genetic and environmental risk factors were recorded and skin-prick testing (SPT) was performed at 4 yrs. Independently significant factors for persisting wheeze were identified at logistic regression and used to create a score for persistence. Wheezing persistence from the first 4 yrs to the age of 10 yrs occurred in 37% of early life wheezers. Independent significance for persistence was associated with asthmatic family history, atopic SPT at 4 yrs and recurrent chest infections at 2 yrs, whilst recurrent nasal symptoms at 1 yr conferred reduced risk. A cumulative risk score using these factors identified wheezing persistence in 83% scoring 4 and transience in 80% scoring 0. Thus, a combination of genetic predisposition, early life atopy and recurrent chest infections favours the persistence of early life wheezing. Risk scores using such knowledge could provide prognostic guidance on the outcome of early wheeze.