Dysregulation of Airway and Systemic Interferon Responses Promote Asthma Exacerbations in Urban Children.

Background: Determining why some upper respiratory illnesses provoke asthma exacerbations remains an unmet need.

Objective: To identify transcriptome-wide gene expression changes associated with colds that progress to exacerbation.

Methods: 208 urban children (6-17 years) with exacerbation-prone asthma were prospectively monitored for up to two cold illnesses.

Rhinoconjunctivitis Symptoms in Children and Adolescents with Asthma: A Longitudinal Clustering Analysis.

Background: Rhinoconjunctivitis phenotypes are conventionally described based on symptom severity, duration and seasonality and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.

Objective: To identify phenotypes of rhinoconjunctivitis based on symptom intensity and seasonality using an unbiased approach and to compare their characteristics.

Caregiver worry about COVID-19 as a predictor of social mitigation behaviours and SARS-CoV-2 infection in a 12-city U.S. surveillance study of households with children.

Objective: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections.

Methods: Data were drawn from a surveillance study of households with children ( = 1913) recruited from 12 U.

Low Lung Function Is Associated with High Population Attributable Fraction for Cardiovascular Mortality.

Rationale: Chronic lung diseases are associated with increased risk of mortality due to coronary heart disease (CHD). Nonetheless, the population attributable fraction (PAF) of lung function impairment relative to other established cardiovascular risk factors is unclear.

Objective: To evaluate the PAF of low lung function for CHD mortality Methods: We harmonized and pooled lung function and clinical data across 8 US general population cohorts.

The Upper Limit of Normal Rate of Lung Function Decline in Healthy Adults in the Framingham Heart Study.

Background: Lung function declines over the course of adulthood; however, a consensus on the normal range of decline in an individual's lung function is lacking.

Research Question: What is the normal range and the upper limit of normal (ULN) decline in lung function in adults without prior tobacco use, occupational dust exposure, or a known diagnosis or symptoms of cardiopulmonary disease?

Study Design And Methods: A retrospective analysis of healthy individuals who have never smoked (N = 1,305) from the Framingham Heart Study with repeated lung function meeting standards for acceptability and reproducibility was conducted. Longitudinal change was derived using a linear mixed effects model and estimated to a 6-year interval.

Viral and non-viral episodes of wheezing in early life and the development of asthma and respiratory phenotypes among urban children.

Background: Viral wheezing is an important risk factor for asthma, which comprises several respiratory phenotypes. We sought to understand if the etiology of early-life wheezing illnesses relates to childhood respiratory and asthma phenotypes.

Methods: Data were collected prospectively on 429 children in the Urban Environment and Childhood Asthma (URECA) birth cohort study through age 10 years.

Airway Mucus Plugs in Community-Living Adults: A Study Protocol.

Introduction: Mucus pathology plays a critical role in airway diseases like chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). Up to 32% of community-living persons report clinical manifestations of mucus pathology (e.g.

Relationships between lung function, allergy, and wheezing in urban children.

Background: Allergic sensitization and low lung function in early childhood are risk factors for subsequent wheezing and asthma. However, it is unclear how allergic sensitization affects lung function over time.

Objective: We sought to test whether allergy influences lung function and whether these factors synergistically increase the risk of continued wheezing in childhood.

Genetically Predicted Body Mass Index and Mortality in Chronic Obstructive Pulmonary Disease.

Body mass index (BMI) is associated with chronic obstructive pulmonary disease (COPD) mortality, but the underlying mechanisms are unclear. The effect of genetic variants aggregated into a polygenic score may elucidate the causal mechanisms and predict risk. To examine the associations of genetically predicted BMI with all-cause and cause-specific mortality in COPD.

Early-life nasal microbiota dynamics relate to longitudinal respiratory phenotypes in urban children.

Background: Five distinct respiratory phenotypes based on latent classes of longitudinal patterns of wheezing, allergic sensitization. and pulmonary function measured in urban children from ages from 0 to 7 years have previously been described.

Objective: Our aim was to determine whether distinct respiratory phenotypes are associated with early-life upper respiratory microbiota development and environmental microbial exposures.

Preschool impulse oscillometry predicts active asthma and impaired lung function at school age.

Background: Asthmatic symptoms often start during early childhood. Impulse oscillometry (IOS) is feasible in preschool children who may be unable to reliably perform spirometry measurements.

Objective: We sought to evaluate the use of IOS in a multicenter, multiethnic high-risk asthma cohort titled the Vitamin D Antenatal Asthma Reduction Trial.

Comparative Effectiveness of Mepolizumab, Benralizumab, and Dupilumab among Patients with Difficult-to-Control Asthma: A Multicenter Retrospective Propensity-matched Analysis.

The comparative effectiveness of biologic agents used as add-on therapy in the management of difficult-to-control asthma is unclear. To compare the effectiveness of dupilumab, mepolizumab, and benralizumab among patients with difficult-to-control asthma. Retrospective multicenter cohort study of adult patients with difficult-to-control asthma starting treatment with dupilumab, mepolizumab, or benralizumab as documented in a multicenter electronic health record and claims-based database between October 19, 2018, and September 30, 2022.

Bik promotes proteasomal degradation to control low-grade inflammation.

Although chronic low-grade inflammation does not cause immediate clinical symptoms, over the longer term, it can enhance other insults or age-dependent damage to organ systems and thereby contribute to age-related disorders, such as respiratory disorders, heart disease, metabolic disorders, autoimmunity, and cancer. However, the molecular mechanisms governing low-level inflammation are largely unknown. We discovered that Bcl-2-interacting killer (Bik) deficiency causes low-level inflammation even at baseline and the development of spontaneous emphysema in female but not male mice.

Genome-wide association study of preserved ratio impaired spirometry (PRISm).

Background: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV) <80% predicted and FEV/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities.

Early life gut microbiome in children following spontaneous preterm birth and maternal preeclampsia.

The early life microbiome plays an important role in developmental and long-term health outcomes. However, it is unknown whether adverse pregnancy complications affect the offspring's gut microbiome postnatally and in early years. In a longitudinal cohort with a five-year follow-up of mother-child pairs affected by preeclampsia (PE) or spontaneous preterm birth (sPTB), we evaluated offspring gut alpha and beta diversity as well as taxa abundances considering factors like breastfeeding and mode of delivery.

Prenatal vitamin D supplementation to prevent childhood asthma: 15-year results from the Vitamin D Antenatal Asthma Reduction Trial (VDAART).

This article provides an overview of the findings obtained from the Vitamin D Antenatal Asthma Reduction Trial (VDAART) spanning a period of 15 years. The review covers various aspects, including the trial's rationale, study design, and initial intent-to-treat analyses, as well as an explanation of why those analyses did not achieve statistical significance. Additionally, the article delves into the post hoc results obtained from stratified intent-to-treat analyses based on maternal vitamin D baseline levels and genotype-stratified analyses.

Bronchial epithelial gene expression and interstitial lung abnormalities.

Introduction: Interstitial lung abnormalities (ILA) often represent early fibrotic changes that can portend a progressive fibrotic phenotype. In particular, the fibrotic subtype of ILA is associated with increased mortality and rapid decline in lung function. Understanding the differential gene expression that occurs in the lungs of participants with fibrotic ILA may provide insight into development of a useful biomarker for early detection and therapeutic targets for progressive pulmonary fibrosis.

Epigenome-wide DNA methylation association study of circulating IgE levels identifies novel targets for asthma.

Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases.

Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs).

A Polygenic Risk Score for Idiopathic Pulmonary Fibrosis and Interstitial Lung Abnormalities.

In addition to rare genetic variants and the locus, common genetic variants contribute to idiopathic pulmonary fibrosis (IPF) risk. The predictive power of common variants outside the locus for IPF and interstitial lung abnormalities (ILAs) is unknown. We tested the predictive value of IPF polygenic risk scores (PRSs) with and without the region on IPF, ILA, and ILA progression.

The relationship of fetal sex and maternal race and ethnicity with early and late pregnancy C-reactive protein and interleukin-8.

Problem: Promotion of a healthy pregnancy is dependent on a coordinated immune response that minimizes inflammation at the maternal-fetal interface. Few studies investigated the effect of fetal sex on proinflammatory biomarkers during pregnancy and whether maternal race could impact this association. We aimed to examine whether fetal sex could, independently of maternal race/ethnicity and the condition of pregnancy (normal vs.