LPS binding protein and activation signatures are upregulated during asthma exacerbations in children.

Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children (n = 19) during acute virus-associated exacerbations and later during convalescence.

Cord Blood IL-12 Confers Protection to Clinical Malaria in Early Childhood Life.

Using a well-designed longitudinal cohort, we aimed to identify cytokines that were protective against malaria and to explore how they were influenced by genetic and immunological factors. 349 Mozambican pregnant women and their newborn babies were recruited and followed up for malaria outcomes until 24 months of age. Six Th1 cytokines in cord blood were screened for correlation with malaria incidence, of which IL-12 was selected for further analyses.

PCR screening of antimicrobial resistance genes in faecal samples from Australian and Chinese children.

Objectives: Recent public awareness campaigns on the risk of antibiotic resistance in pathogenic microbes has placed pressure on governments to enforce stricter antimicrobial stewardship policies on hospitals and the agricultural industry. In this study, faecal samples from Australian and Chinese children were screened for the presence of antimicrobial resistance genes (ARGs) in order to identify demographics at risk of carriage of these genes and to examine antimicrobial stewardship policies from the two countries that may influence carriage.

Methods: Faecal samples from 46 Australian and 53 Chinese children were screened by PCR for the presence of six clinically relevant ARGs.

Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes.

The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland.

No simple answers for the Finnish and Russian Karelia allergy contrast: Methylation of CD14 gene.

Background: Finnish and Russian Karelian children have a highly contrasting occurrence of asthma and allergy. In these two environments, we studied associations between total serum immunoglobulin E (IgE) with methylation levels in cluster of differentiation 14 (CD14).

Methods: Five hundred Finnish and Russian Karelian children were included in four groups: Finnish children with high IgE (n = 126) and low IgE (n = 124) as well as Russian children with high IgE (n = 125) and low IgE (n = 125).

Monitoring of Therapy for Mucopolysaccharidosis Type I Using Dysmorphometric Facial Phenotypic Signatures.

There is a pattern of progressive facial dysmorphology in mucopolysaccharidosis type I (MPS I). Advances in 3D facial imaging have facilitated the development of tools, including dysmorphometrics, to objectively and precisely detect these facial phenotypes. Therefore, we investigated the application of dysmorphometrics as a noninvasive therapy-monitoring tool, by longitudinally scoring facial dysmorphology in a child with MPS I receiving enzyme replacement therapy (ERT) and bone marrow transplantation (BMT).

Phenotyping: targeting genotype's rich cousin for diagnosis.

There are many current and evolving tools to assist clinicians in their daily work of phenotyping. In medicine, the term 'phenotype' is usually taken to mean some deviation from normal morphology, physiology and behaviour. It is ascertained via history, examination and investigations, and a primary aim is diagnosis.

Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With "Western or Eastern Environments/Lifestyles".

Purpose: We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children.

Methods: This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children.

Plasma advanced oxidative protein products are associated with anti-oxidative stress pathway genes and malaria in a longitudinal cohort.

Background: Advanced oxidation protein products (AOPP) are newly identified efficient oxidative stress biomarkers. In a longitudinal birth cohort the effects were investigated of genetic polymorphisms in five oxidative pathway genes on AOPP levels.

Methods: This study is part of a three-arm randomized, double-blind, placebo-controlled trial.

Epidemiology, etiology, x-ray features, importance of co-infections and clinical features of viral pneumonia in developing countries.

Pneumonia is still the number one killer of young children globally, accounting for 18% of mortality in children under 5 years of age. An estimated 120 million new cases of pneumonia occur globally each year. In developing countries, management and prevention efforts against pneumonia have traditionally focused on bacterial pathogens.

The facial evolution: looking backward and moving forward.

Three-dimensional (3D) facial analysis is ideal for high-resolution, nonionizing, noninvasive objective, high-throughput phenotypic, and phenomic studies. It is a natural complement to (epi)genetic technologies to facilitate advances in the understanding of rare and common diseases. The face is uniquely reflective of the primordial tissues, and there is evidence supporting the application of 3D facial analysis to the investigation of variation and disease including studies showing that the face can reflect systemic health, provides diagnostic clues to disorders, and that facial variation reflects biological pathways.

Interleukin-10 (IL-10) polymorphisms are associated with IL-10 production and clinical malaria in young children.

The role of interleukin-10 (IL-10) in malaria remains poorly characterized. The aims of this study were to investigate (i) whether genetic variants of the IL-10 gene influence IL-10 production and (ii) whether IL-10 production as well as the genotypes and haplotypes of the IL-10 gene in young children and their mothers are associated with the incidence of clinical malaria in young children. We genotyped three IL-10 single nucleotide polymorphisms in 240 children and their mothers from a longitudinal prospective cohort and assessed the IL-10 production by maternal peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs).

Prevalence of and risk factors for human rhinovirus infection in healthy aboriginal and non-aboriginal Western Australian children.

Background: Human rhinovirus (HRV) species C (HRV-C) have been associated with frequent and severe acute lower respiratory infections and asthma in hospitalized children. The prevalence of HRV-C among healthy children and whether this varies with ethnicity is unknown.

Objective: To describe the prevalence of HRV species and their associations with demographic, environmental and socioeconomic factors in healthy Aboriginal and non-Aboriginal children.

Disparity of innate immunity-related gene effects on asthma and allergy on Karelia.

Background: We investigated the interactive effects of 11 innate immunity-related genes (IL10, IL12b, IL8, TLR2, TLR4, CD14, IFNGR, CC16, IFNg, CMA1, and TGFB) and four IgE response genes (IL4, IL13, IL4RA, and STAT6) with 'Western' or 'Eastern' environments/lifestyles on asthma and allergy in Karelian children.

Methods: Karelian children (412 Finnish and 446 Russian) were recruited and assessed for a range of allergic conditions, with 24 single-nucleotide polymorphisms genotyped in 15 genes.

Results: The genotype-phenotype relationships differed in Finnish and Russian Karelian children.

The era of genome-wide association studies: opportunities and challenges for asthma genetics.

In the era of genome-wide association (GWA) studies, delineating pathogenic asthma genetic pathways has provided both challenges and opportunities. Initial GWA studies on asthma and asthma-like phenotypes provided some successes in terms of ascertaining new potential asthma candidate genes. However, due to asthma having a heterogeneous etiology, replications of these genotype-phenotype association studies are generally lacking.

Interactions between innate antiviral and atopic immunoinflammatory pathways precipitate and sustain asthma exacerbations in children.

Severe asthma exacerbations in children requiring hospitalization are typically associated with viral infection and occur almost exclusively among atopics, but the significance of these comorbidities is unknown. We hypothesized that underlying interactions between immunoinflammatory pathways related to responses to aeroallergen and virus are involved, and that evidence of these interactions is detectable in circulating cells during exacerbations. To address this hypothesis we used a genomics-based approach involving profiling of PBMC subpopulations collected during exacerbation vs convalescence by microarray and flow cytometry.

Inhaled mannitol improves lung function in cystic fibrosis.

Background: The airways in patients with cystic fibrosis (CF) are characterized by the accumulation of tenacious, dehydrated mucus that is a precursor for chronic infection, inflammation, and tissue destruction. The clearance of mucus is an integral component of daily therapy. Inhaled mannitol is an osmotic agent that increases the water content of the airway surface liquid, and improves the clearance of mucus with the potential to improve lung function and respiratory health.

Parental smoking impairs vaccine responses in children with atopic genotypes.

Background: Gene-environment interactions play central roles in controlling postnatal maturation of immune function, but their effects on infant vaccine responses are unknown. Genetic variants associated with atopy and the environmental factor of exposure to parental smoking (PS) of tobacco independently alter immune responses.

Objective: We sought to investigate the hypothesis that genetic variants associated with atopy and their interaction with PS influence infant vaccine responsiveness.

Acute asthma in children: Relationships among CD14 and CC16 genotypes, plasma levels, and severity.

Rationale: The majority of previous studies investigating asthma genetics have focused on cohorts with stable disease and have not defined mechanisms important during acute asthma. CD14 and CC16 each play a key role in biologically important inflammatory pathways and the gene of each has a functional promoter-region polymorphism.

Objectives: This study was designed to determine the influence of these polymorphisms on plasma levels of their products and clinical disease during acute asthma.

Clara cell protein 16 (CC16) gene polymorphism influences the degree of airway responsiveness in asthmatic children.

Background: Several studies have indicated linkage of chromosome 11q12-13 to asthma and associated traits. Among other candidate genes, the Clara cell protein 16 (CC16) gene maps to this region. CC16 is expressed in the bronchial epithelium and exhibits potent anti-inflammatory properties.

Comparison of subjective and objective measures in recurrently wheezy infants.

Objectives: The aim of this study was to compare subjective measures (overall health assessment both by the study physician and the child's mother) with objective measurements of forced expiratory volumes (FEV(t)) and maximal flow at functional residual capacity V(max)FRC) in recurrently wheezy infants.

Methods: Sixteen wheezy infants (12 boys) aged 8-26 months were studied. A clinical assessment at visit 1 was followed by the run-in period during which day- and nighttime asthma symptom scores were obtained.