Cord-blood respiratory syncytial virus antibodies and respiratory health in first 5 years of life.

Objective: To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2 years of life, RSV-NA at 3 years, and respiratory health to age 5 years.

Methods: Two community-based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV-NA levels were compared in cord blood and at age 3 years.

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children.

Background: Antigen-specific IgE binds the Fcε receptor I (FcεRI) expressed on several types of immune cells, including dendritic cells (DCs). Activation of FcεRI on DCs in atopics has been shown to modulate immune responses that potentially contribute to asthma development. However, the extent to which DC subsets differ in FcεRI expression between atopic children with or without asthma is currently not clear.

Trajectories of childhood immune development and respiratory health relevant to asthma and allergy.

Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear.

Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development.

Background: Virus-associated febrile lower respiratory tract infections (fLRIs) during infancy have been identified as risk factors for persistent wheeze development. We hypothesized that variations in innate immune defense capacity during this period, as exemplified by production of type 1 and 3 interferons (T1/3IFNs), might be an underlying determinant of risk.

Objective: We sought to investigate relationships between postnatal development of innate interferon response capacity and susceptibility to early infections and persistent wheeze.

Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease.

Repeated cycles of infection-associated lower airway inflammation drive the pathogenesis of persistent wheezing disease in children. In this study, the occurrence of acute respiratory tract illnesses (ARIs) and the nasopharyngeal microbiome (NPM) were characterized in 244 infants through their first five years of life. Through this analysis, we demonstrate that >80% of infectious events involve viral pathogens, but are accompanied by a shift in the NPM toward dominance by a small range of pathogenic bacterial genera.

Vitamin D over the first decade and susceptibility to childhood allergy and asthma.

Background: Vitamin D (25(OH)D) deficiency has been implicated as a possible risk factor for asthma development, but studies at selected time points measuring 25(OH)D levels during childhood have yielded conflicting findings. Prospective studies tracking 25(OH)D levels during the initiation phase of asthma in early childhood have not been reported.

Objective: We sought to elucidate relationships between 25(OH)D levels from birth to age 10 years and susceptibility to allergic sensitization, respiratory tract infections, and asthma.

Distinguishing benign from pathologic TH2 immunity in atopic children.

Background: Although most children with asthma and rhinitis are sensitized to aeroallergens, only a minority of sensitized children are symptomatic, implying the underlying operation of efficient anti-inflammatory control mechanisms.

Objective: We sought to identify endogenous control mechanisms that attenuate expression of IgE-associated responsiveness to aeroallergens in sensitized children.

Methods: In 3 independent population samples we analyzed relationships between aeroallergen-specific IgE and corresponding allergen-specific IgG (sIgG) and associated immunophenotypes in atopic children and susceptibility to asthma and rhinitis, focusing on responses to house dust mite and grass.

The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development.

The nasopharynx (NP) is a reservoir for microbes associated with acute respiratory infections (ARIs). Lung inflammation resulting from ARIs during infancy is linked to asthma development. We examined the NP microbiome during the critical first year of life in a prospective cohort of 234 children, capturing both the viral and bacterial communities and documenting all incidents of ARIs.

Vitamin D in fetal development: findings from a birth cohort study.

Birth cohort studies provide an invaluable resource for studies of the influence of the fetal environment on health in later life. It is uncertain to what extent maternal vitamin D status influences fetal development. Using an unselected community-based cohort of 901 mother-offspring pairs (the Western Australian Pregnancy Cohort [Raine] Study), we examined the relationship between maternal vitamin D deficiency at 18 weeks' pregnancy and long-term health outcomes of offspring who were born in Perth, Western Australia (32° South), in 1989-1991.

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

Background: 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.

Methods: 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.

Results: 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.

Low maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms.

Pregnancy is a time of vulnerability for vitamin D insufficiency, and there is an emerging literature associating low levels of 25(OH)-vitamin D with depressive symptoms. However, the link between 25(OH)-vitamin D status in pregnancy and altered risk of postnatal depressive symptoms has not been examined. We hypothesise that low levels of 25(OH)-vitamin D in maternal serum during pregnancy will be associated with a higher incidence of postpartum depressive symptoms.

Vitamin D deficiency at 16 to 20 weeks' gestation is associated with impaired lung function and asthma at 6 years of age.

Rationale: Vitamin D deficiency is associated with chronic lung disease. We have previously shown in an in vivo mouse model that maternal vitamin D deficiency is associated with alterations in early life lung structure and function. However, there are limited data to support a relationship between maternal vitamin D deficiency during the early stages of lung development and postnatal lung function in human populations.

Maternal vitamin D status during pregnancy and bone mass in offspring at 20 years of age: a prospective cohort study.

It is uncertain whether the vitamin D status of pregnant women influences bone mass of their children. Cohort studies have yielded conflicting results; none have examined offspring at skeletal maturity. This longitudinal, prospective study investigated the association between maternal vitamin D status and peak bone mass of offspring in 341 mother and offspring pairs in the Western Australian Pregnancy Cohort (Raine) Study.

Maternal vitamin D levels during pregnancy and offspring eating disorder risk in adolescence.

Objective: To determine if maternal vitamin D concentrations at 18 weeks gestation predict offspring eating disorder risk in adolescence.

Method: Participants were 526 Caucasian mother-child dyads from the Western Australian Pregnancy Cohort (Raine) Study. The Raine Study has followed participants from 18 weeks gestation to 20 years of age.

Respiratory impedance and bronchodilator responsiveness in healthy children aged 2-13 years.

Background: The forced oscillation technique (FOT) can be used in children as young as 2 years of age and in those unable to perform routine spirometry. There is limited information on changes in FOT outcomes in healthy children beyond the preschool years and the level of bronchodilator responsiveness (BDR) in healthy children. We aimed to create reference ranges for respiratory impedance outcomes collated from multiple centers.

Maternal vitamin D levels and the autism phenotype among offspring.

We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks' pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean.

Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development.

Objectives: To determine the association between maternal serum 25(OH)-vitamin D concentrations during a critical window of fetal neurodevelopment and behavioral, emotional, and language outcomes of offspring.

Methods: Serum 25(OH)-vitamin D concentrations of 743 Caucasian women in Perth, Western Australia (32°S) were measured at 18 weeks pregnancy and grouped into quartiles. Offspring behavior was measured with the Child Behavior Checklist at 2, 5, 8, 10, 14, and 17 years of age (n range = 412-652).

Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children.

Background: Infants who develop house dust mite (HDM) allergy and HDM-sensitised children with severe persistent asthma have low antibody responses to the P6 antigen of Haemophilus influenzae.

Objective: To measure the development of antibody to two ubiquitous bacteria of the respiratory mucosa in a prospective birth cohort at high risk of allergic disease and to assess which responses are associated with asthma and atopy.

Methods: IgG1 and IgG4 antibody to H influenzae (P4 and P6) and Streptoccocus pneumoniae (PspA and PspC) surface antigens was measured in yearly blood samples of children aged 1-5 years.

Exhaled breath temperature in healthy children is influenced by room temperature and lung volume.

Background: Exhaled breath temperature (EBT) has been proposed for the non-invasive assessment of airway inflammation. Previous studies have not examined the influence of room temperature or lung size on the EBT.

Objective: This study aimed to address these issues in healthy children.

Do early-life viral infections cause asthma?

Epidemiologic associations between viral lower respiratory infections (LRIs) and asthma in later childhood are well known. However, the question of whether such infections cause asthma or unmask asthma in a susceptible host has still not been settled. Most early evidence centered on the role of the respiratory syncytial virus; however, recent studies highlight a potential role for human rhinovirus as a risk factor for asthma.

Toward improved prediction of risk for atopy and asthma among preschoolers: a prospective cohort study.

Background: Atopy and asthma are commonly initiated during early life, and there is increasing interest in the development of preventive treatments for at-risk children. However, effective methods for assessing the level of risk in individual children are lacking.

Objective: We sought to identify clinical and laboratory biomarkers in 2-year-olds that are predictive of the risk for persistent atopy and wheeze at age 5 years.

Plasmacytoid dendritic cells during infancy are inversely associated with childhood respiratory tract infections and wheezing.

Background: It has been proposed that immune dysfunction during early childhood plays an important role in asthma pathogenesis. However, it is not known specifically whether changes in dendritic cells (DCs) during infancy antedate the development of respiratory tract infections, asthma, and related clinical phenotypes.

Objectives: We sought to assess the association between the level of blood DCs during the first year and the subsequent development of respiratory tract infections, wheezing, and allergic sensitization.

Management of childhood asthma in Western Australia.

Aims: The study aimed to determine how childhood asthma is managed in Western Australia by general practitioners (GPs) and specialist paediatricians.

Methods: A questionnaire survey was sent to 992 GPs and specialist paediatricians, asking about practice and preferences regarding maintenance management of childhood asthma and treatment of acute asthma. Questions about asthma in infants, pre-school and school-aged children were asked separately.

Interleukin-10/interleukin-5 responses at birth predict risk for respiratory infections in children with atopic family history.

Rationale: Respiratory infections in early life are associated with risk for wheezing bronchiolitis, especially in children at high risk of atopy. The underlying mechanisms are unknown, but are suspected to involve imbalance(s) in host defense responses against pathogens stemming from functional immaturity of the immune system in this age group.

Objectives: To assess the contribution of eosinophil-trophic IL-5, and the potent antiinflammatory cytokine IL-10, to risk for infection in early life.

Cord blood hemopoietic progenitor profiles predict acute respiratory symptoms in infancy.

Atopy is characterized by eosinophilic inflammation associated with recruitment of eosinophil/basophil (Eo/B) progenitors. We have previously shown that Eo/B progenitor phenotypes are altered in cord blood (CB) in infants at high risk of atopy/asthma, and respond to maternal dietary intervention during pregnancy. As respiratory tract viral infections have been shown to induce wheeze in infancy, we investigated the relationship between CB progenitor function and phenotype and acute respiratory illness (ARI), specifically wheeze and fever.