- 11/11/2024 - 5 Formulaires, 2 Groupes Item, 20 Eléments de données, 1 Langue
Groupes Item: IG.0, IG.5
Principal Investigator: Gloria Pryhuber, University of Rochester Rochester, Rochester, NY, USA MeSH: Infant, Premature,Infant, Newborn,Premature Birth,Term Birth,Microbiota,Gastrointestinal Microbiome,T-Lymphocytes,Bronchopulmonary Dysplasia,Respiratory Tract Diseases https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001347 *Public health importance*: Babies born preterm, approximately 1 out of every 9 live births in the United States, have significant respiratory morbidity over the first two years of life, exacerbated by respiratory viral infections. Many (50%) return to pediatricians, emergency rooms and pulmonologists with symptoms of respiratory dysfunction (SRD): intermittent or chronic wheezing, poor growth and an excess of upper and lower respiratory tract infections (LRTI). SRD correlate inversely with gestational age and weight at birth and is more common in those with chronic lung disease of prematurity, yet its incidence and severity varies widely among both the prematurely born and those born at term. There is evidence from clinical studies and animal models that risks of LRTI and recurrent wheezing is influenced by gut and respiratory flora and by T cell responses to infection. Information gained from this study will be used to identify characteristics, risk factors and potential mechanisms for early and persistent lung disease in children born at term and born preterm. This Clinical Research Study will investigate the relationships between sequential respiratory viral infections, patterns of intestinal and respiratory bacterial colonization, and adaptive cellular immune phenotypes which are associated with increased susceptibility to respiratory infections and long term respiratory morbidity in preterm and full term infants. We hypothesize that the timing and acquisition of specific viral infections and bacterial species are directly related to respiratory morbidity in the first year of life as defined by SRD and by measures of pulmonary function. We hypothesize that cellular and molecular immuno-maturity are altered due to factors presented by premature birth in such a way as to promote chronic inflammatory and cytotoxic damage to the lung, with subsequent enhanced, damaging responses to infectious agents and environmental irritants. Our preliminary studies demonstrate both feasibility and expertise in mutiparameter immunophenotyping of small volume peripheral blood samples obtained from premature infants including gene expression arrays of flow cytometry sorted cells. We will use new technologies for known viral identification, as well as high-throughput metagenome sequencing of RNA and DNA virus like particles (VLP) to be used for viral discovery in infant respiratory sample and use of high-throughput pyrosequencing (454T) of bacterial 16S rRNA to determine shifts in bacterial community structure, occurring in pre-term (PT) as compared to full term (FT) infants, over the first year of life. Finally, we present statistical approaches to stratify disease risk predictors using multivariate logistic regression modeling approaches. We propose to evaluate T cell phenotypic and functional profiles relative to viral and predominant bacterial exposures according to highly complementary, but independent, Specific Objectives. *Objective 1*: To determine if viral respiratory infections and patterns of respiratory and gut bacterial community structure (microbiome) in prematurely born babies predict the rate and degree of immunologic maturation, and pulmonary dysfunction, measured from birth to 36 weeks corrected gestational age (CGA). *Objective 2*: To determine the relationship between respiratory viral infections and disease severity up to one year CGA, and the lymphocyte (Lc) phenotypes documented at term gestation (birth for term infants and 36 wks/NICU discharge in preterm infants) and at one year CGA. Three secondary outcomes of this objective will be to a) relate the quantity, type and severity of viral infections with pulmonary function at one and three years of life, b) relate the viral community structure to severity of viral infections and c) to seek evidence of modulation of viral susceptibility by bacterial respiratory and gut community structure (microbiome). The relationship of colonization with known and non-identified bacterial species in both the respiratory tract and the gut will be evaluated. Flow cytometry data corresponding to this study can be found within Immport study SDY1302. Positive and negative controls for microbiome samples are uploaded under SRA bioproject PRJNA474485. Microbiome samples corresponding to PRISM2 are distinguished from PRISM1 via "_PRISM2" appended to the sample name. Within the positive and negative controls, PRISM1 controls are uploaded as bam files and PRISM2 controls are uploaded as paired fastq. Samples ending in -08 correspond to TLDA qPCR results for a given sample. There is a column for each pathogen tested and a column to indicate where that pathogen was bacteria or virus.

pht006796.v3.p2

1 Groupe Item 32 Eléments de données

pht006794.v3.p2

1 Groupe Item 7 Eléments de données

pht006795.v3.p2

1 Groupe Item 2 Eléments de données

pht006797.v3.p2

1 Groupe Item 94 Eléments de données
- 29/06/2023 - 6 Formulaires, 1 Groupe Item, 5 Eléments de données, 1 Langue
Groupe Item: pht005915

Eligibility

1 Groupe Item 85 Eléments de données

pht005911.v1.p1

1 Groupe Item 2 Eléments de données

pht005912.v1.p1

1 Groupe Item 6 Eléments de données

pht005913.v1.p1

1 Groupe Item 4 Eléments de données

pht005914.v1.p1

1 Groupe Item 2 Eléments de données
- 12/10/2022 - 5 Formulaires, 1 Groupe Item, 5 Eléments de données, 1 Langue
Groupe Item: pht002336
Principal Investigator: Xiaobin Wang, MD, MPH, ScD, Zanvyl Krieger Professor, Director, Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, and Professor of Pediatrics, John Hopkins University School of Medicine, Baltimore, MD, USA MeSH: Infant, Premature,Premature Birth,Gestational Age https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000332 Preterm birth (PTB, born before 37 weeks of gestation) is a leading cause of neonatal mortality and post-natal morbidity. PTB affects one in nine all live births in the U.S. Notably, the highest rate of PTB occurs among African Americans (one in six). PTB is a complex trait, likely determined by multiple environmental and genetic factors and their interactions. We demonstrated strong familial aggregation of preterm and low birthweight in the US Blacks and Whites (Wang et al, NEJM, 1995) and conducted the largest candidate gene study of preterm birth at that time (Hao et al, HMG, 2004). We showed that a subset of mothers with certain metabolic gene variants are particularly vulnerable to the adverse effects of cigarette smoking on low birthweight and preterm births (Wang et al, JAMA, 2002). We also published a number of papers that examined the effect of maternal pre-pregnancy BMI, micronutrient status, stress and environmental toxins on the risk of preterm birth and related conditions. This project, supported by a grant from the NICHD (2R01HD41702, PI, Xiaobin Wang), aimed to conduct a genome-wide association study (GWAS) and apply advanced statistical methods to identify susceptibility loci of PTB in a predominantly urban low-income African American sample, a subset of the Boston Birth Cohort. PUBLIC HEALTH REVELANCE: We anticipate that this study will lead to the identification of novel genetic loci of PTB and gene-environment interactions. Such findings not only will provide important insights into mechanisms leading to PTB, but also may help identify women at high-risk of PTB, which in turn, may lead to the development of early and targeted interventions that can prevent PTB or mitigate the severity and consequences of PTB.

Eligibility

1 Groupe Item 5 Eléments de données

pht003739.v2.p2

1 Groupe Item 4 Eléments de données

pht002337.v3.p2

1 Groupe Item 5 Eléments de données

pht002338.v2.p2

1 Groupe Item 33 Eléments de données

Utilisez ce formulaire pour les retours, les questions et les améliorations suggérées.

Les champs marqués d’un * sont obligatoires.

Do you need help on how to use the search function? Please watch the corresponding tutorial video for more details and learn how to use the search function most efficiently.

Watch Tutorial