A Respiratory Syncytial Virus Attachment Gene Variant Associated with More Severe Disease in Infants Decreases Fusion Protein Expression, Which May Facilitate Immune Evasion.

This study identified a genotype of respiratory syncytial virus (RSV) associated with increased acute respiratory disease severity in a cohort of previously healthy term infants. The genotype (2stop+A4G) consists of two components. The A4G component is a prevalent point mutation in the 4th position of the gene end transcription termination signal of the G gene of currently circulating RSV strains.

Using urine metabolomics to understand the pathogenesis of infant respiratory syncytial virus (RSV) infection and its role in childhood wheezing.

Background: Respiratory syncytial virus (RSV) infection in infants causes significant morbidity and is the strongest risk factor associated with asthma. Metabolites, which reflect the interactions between host cell and virus, provide an opportunity to identify the pathways that underlie severe infections and asthma development.

Objective: To study metabolic profile differences between infants with RSV infection, and human rhinovirus (HRV) infection, and healthy infants.

Association of newborn screening metabolites with risk of wheezing in childhood.

Background: There are critical gaps in our understanding of the temporal relationships between metabolites and subsequent asthma development. This is the first study to examine metabolites from newborn screening in the etiology of early childhood wheezing.

Methods: One thousand nine hundred and fifty one infants enrolled between 2012 and 2014 from pediatric practices located in Middle Tennessee in the population-based birth cohort study, the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE), were linked with metabolite data from the Tennessee Newborn Screening Program.

Infant Viral Respiratory Infection Nasal Immune-Response Patterns and Their Association with Subsequent Childhood Recurrent Wheeze.

Rationale: Recurrent wheeze and asthma are thought to result from alterations in early life immune development following respiratory syncytial virus (RSV) infection. However, prior studies of the nasal immune response to infection have assessed only individual cytokines, which does not capture the whole spectrum of response to infection.

Objectives: To identify nasal immune phenotypes in response to RSV infection and their association with recurrent wheeze.

Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood wheezing illnesses following acute respiratory syncytial virus infection in infancy.

Background: Early life acute respiratory infection (ARI) with respiratory syncytial virus (RSV) has been strongly associated with the development of childhood wheezing illnesses, but the pathways underlying this association are poorly understood.

Objective: To examine the role of the nasopharyngeal microbiome in the development of childhood wheezing illnesses following RSV ARI in infancy.

Methods: We conducted a nested cohort study of 118 previously healthy, term infants with confirmed RSV ARI by RT-PCR.

Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity.

Seasonal patterns of Asthma medication fills among diverse populations of the United States.

Objective: Nonadherence to controller and overuse of reliever asthma medications are associated with exacerbations. We aimed to determine patterns of seasonal asthma medication use and to identify time period(s) during which interventions to improve medication adherence could reduce asthma morbidity.

Methods: We conducted a retrospective cohort study of asthmatics 4-50 years of age and enrolled in three diverse health insurance plans.

Racial disparities in family-provider interactions for pediatric asthma care.

Objective: Black and Latino children experience significantly worse asthma morbidity than their white peers for multifactorial reasons. This study investigated differences in family-provider interactions for pediatric asthma, based on race/ethnicity.

Methods: This was a cross-sectional study of parent surveys of asthmatic children within the Population-Based Effectiveness in Asthma and Lung Diseases Network.

Interference Between Respiratory Syncytial Virus and Human Rhinovirus Infection in Infancy.

Background: Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are the most common viruses associated with acute respiratory tract infections in infancy. Viral interference is important in understanding respiratory viral circulation and the impact of vaccines.

Methods: To study viral interference, we evaluated cases of RSV and HRV codetection by polymerase chain reaction in 2 prospective birth cohort studies (the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure [INSPIRE] study and the Tennessee Children's Respiratory Initiative [TCRI]) and a double-blinded, randomized, controlled trial (MAKI), using adjusted multivariable regression analyses.

Clinical and Biological Insights Into Combined Post- and Pre-Capillary Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a common and morbid complication of left heart disease with 2 subtypes: isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Little is known about the clinical or physiological characteristics that distinguish these 2 subphenotypes or if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH).

Objectives: The goal of this study was to test the hypothesis that the hemodynamic and genetic profile of Cpc-PH would more closely resemble PAH than Ipc-PH.

Differences in the Nasopharyngeal Microbiome During Acute Respiratory Tract Infection With Human Rhinovirus and Respiratory Syncytial Virus in Infancy.

Respiratory viruses alter the nasopharyngeal microbiome and may be associated with a distinct microbial signature. To test this hypothesis, we compared the nasopharyngeal microbiome of 135 previously healthy infants with acute respiratory infection due to human rhinovirus (HRV; n = 52) or respiratory syncytial virus (RSV; n = 83). The nasopharyngeal microbiome was assessed by sequencing the V4 region of the 16S ribosomal RNA.

Variants in angiopoietin-2 (ANGPT2) contribute to variation in nocturnal oxyhaemoglobin saturation level.

Genetic determinants of sleep-disordered breathing (SDB), a common set of disorders that contribute to significant cardiovascular and neuropsychiatric morbidity, are not clear. Overnight nocturnal oxygen saturation (SaO2) is a clinically relevant and easily measured indicator of SDB severity but its genetic contribution has never been studied. Our recent study suggests nocturnal SaO2 is heritable.

Seasonal Timing of Infant Bronchiolitis, Apnea and Sudden Unexplained Infant Death.

Rates of Sudden Unexplained Infant Death (SUID), bronchiolitis, and central apnea increase in winter in temperate climates. Though associations between these three conditions are suggested, more work is required to establish if there is a causal pathway linking bronchiolitis to SUID through inducing central apnea. Utilizing a large population-based cohort of infants studied over a 20-year period (n = 834,595, from birth years 1989-2009)), we analyzed ecological associations between timing of SUID cases, bronchiolitis, and apnea healthcare visits.

Interaction of vitamin E isoforms on asthma and allergic airway disease.

Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population-based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms α-tocopherol and γ-tocopherol on asthma risk.

Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene.

Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion.

Mismatching Among Guidelines, Providers, and Parents on Controller Medication Use in Children with Asthma.

Background: Underuse of controller medicines among children with asthma remains widespread despite national guidelines.

Objectives: To (1) assess provider prescribing patterns for asthma controller medications; (2) assess how frequently parents' reports of their child's asthma controller medicine use were mismatched with their provider's recommendations; and (3) evaluate parent attitudes and demographic characteristics associated with these mismatches.

Methods: In this cross-sectional study, we conducted linked surveys of parents and providers of children with probable persistent asthma in a Medicaid program and 4 commercial health plans in 2011.

Identifying genetically driven clinical phenotypes using linear mixed models.

We hypothesized that generalized linear mixed models (GLMMs), which estimate the additive genetic variance underlying phenotype variability, would facilitate rapid characterization of clinical phenotypes from an electronic health record. We evaluated 1,288 phenotypes in 29,349 subjects of European ancestry with single-nucleotide polymorphism (SNP) genotyping on the Illumina Exome Beadchip. We show that genetic liability estimates are primarily driven by SNPs identified by prior genome-wide association studies and SNPs within the human leukocyte antigen (HLA) region.

Comparison of Heritability Estimation and Linkage Analysis for Multiple Traits Using Principal Component Analyses.

A disease trait often can be characterized by multiple phenotypic measurements that can provide complementary information on disease etiology, physiology, or clinical manifestations. Given that multiple phenotypes may be correlated and reflect common underlying genetic mechanisms, the use of multivariate analysis of multiple traits may improve statistical power to detect genes and variants underlying complex traits. The literature, however, has been unclear as to the optimal approach for analyzing multiple correlated traits.

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans.

Rationale: Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability.

A simple respiratory severity score that may be used in evaluation of acute respiratory infection.

Background: Acute respiratory infections are ubiquitous and may have long-term implications on respiratory health. There are many scoring systems used to objectively measure severity of respiratory infections in clinical and research settings. A respiratory severity score derived exclusively from physical exam components (RSS-HR) was studied as an objective measure of disease severity and was compared to a previously described score that uses pulse oximetry as a component of its score (RSS-SO).

Genes associated with RSV lower respiratory tract infection and asthma: the application of genetic epidemiological methods to understand causality.

Infants with respiratory syncytial virus (RSV) lower respiratory tract infections (LRIs) are at increased risk for childhood asthma. The objectives of this article are to review the genes associated with both RSV LRI and asthma, review analytic approaches to assessing shared genetic risk and propose a future perspective on how these approaches can help us to understand the role of infant RSV infection as both an important risk factor for asthma and marker of shared genetic etiology between the two conditions. The review of shared genes and thus pathways associated with severity of response to RSV infection and asthma risk can help us to understand mechanisms of disease and ultimately propose new and novel targets for primary prevention of both diseases.

Common variants in DRD2 are associated with sleep duration: the CARe consortium.

Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample.