Track topics on Twitter Track topics that are important to you
Inherited deficiencies in any one of 3 genes (surfactant protein B, surfactant protein C, and ATP-binding cassette transporter A3) can cause neonatal respiratory distress syndrome by disrupting metabolism of the pulmonary surfactant. The investigators will use state of the art methods to link specific changes in the genetic code of each of these genes with disruption of discrete steps in the metabolism of the pulmonary surfactant in human newborn infants. These studies will lead to improved diagnostic capabilities and suggest novel strategies to correct surfactant deficiency in newborn infants.
Genetic regulation of neonatal pulmonary surfactant deficiency has been suggested by studies of gender, genetic linkage, recurrent familial cases, targeted gene ablation in murine lineages, and by racial disparity in risk of neonatal respiratory distress syndrome. Successful fetal-neonatal pulmonary transition requires production of the pulmonary surfactant, a phospholipid-protein film that lines alveoli and maintains alveolar patency at end expiration. Our goal is to understand the genetic mechanisms that disrupt pulmonary surfactant metabolism and cause neonatal respiratory distress syndrome. Studies in human newborn infants have demonstrated that 3 genes are critical for surfactant metabolism: surfactant protein B (SFTPB), surfactant protein C (SFTPC), and an ATP-binding cassette transporter, ABCA3 (ABCA3). To understand genetic regulatory mechanisms, we will investigate the contribution of variation in each of these genes to risk of neonatal respiratory distress syndrome by testing the hypothesis that genetic variants in the SFTPB, SFTPC, and ABCA3 disrupt pulmonary surfactant metabolism. Using high throughput automated sequencing to genotype, multidimensional protein identification technology to assess quantitative and qualitative differences in surfactant protein B and C expression, in vivo metabolic labeling with stable isotopically labeled precursors to estimate surfactant protein B and C and phospholipid metabolic rates, and cohort sizes that provide statistical power (0.8), we will use race-specific, severity-stratified case-control (N=480) and case comparison (N=250) designs to understand genetically regulated, metabolic mechanisms that cause surfactant deficiency by disrupting expression or altering processing of surfactant proteins B or C or by disrupting surfactant phospholipid composition in human newborn infants. Improved understanding of genetic regulation of surfactant deficiency will suggest novel diagnostic strategies to identify and categorize high risk infants and therapeutic strategies that target discrete steps in pulmonary surfactant metabolism to improve outcomes of infants with neonatal respiratory distress syndrome.
Observational Model: Case Control, Time Perspective: Prospective
Respiratory Distress Syndrome, Newborn
St. Louis Children's Hospital
Washington University School of Medicine
Published on BioPortfolio: 2014-07-10T14:18:30-0400
The object of this study is to determine the best way to care for infants with respiratory distress. The investigators are testing a method of feeding fluids to infants with respiratory di...
Preterm infants ranging from 29+0 to 36+6 weeks+days are randomly assigned to one of the following treatments as non invasive respiratory support if they develop mild to moderate Respirato...
During caesarean section, transient respiratory distress which occurs frequently (3%) with possible complications are at present managed by non invasive nasal continuous positive airway pr...
The best mode of delivery room stabilization for premature infants at high risk for respiratory distress syndrome is unknown. The protocol evaluates the impact of three distinct methods of...
The aim of Alizé is to describe a population of premature babies (gestational age, birth clinical characteristics and particularly the respiratory function) with a gestational age (GA) < ...
Acute respiratory distress syndrome (ARDS) threatens humans' health worldwide, causing huge labor and economic cost investment. This study aims to explore whether mesenchymal stem cells (MSCs) affect ...
Classification of patients with acute respiratory distress syndrome into hyper- and hypoinflammatory subphenotypes using plasma biomarkers may facilitate more effective targeted therapy. We examined w...
Respiratory distress syndrome is a common condition among preterm neonates and . Assessing lung aeration assists in diagnosing the disease and helping to guide and monitor treatment. We aimed to ident...
Infectious pneumonia is the most common cause of acute respiratory distress syndrome, with viruses frequently implicated as causative. However, the significance of viruses in pediatric acute respirato...
Response to PEEP in acute respiratory distress syndrome (ARDS) depends on recruitability. We propose a bedside approach to estimate recruitability accounting for the presence of complete airway closur...
A chronic lung disease developed after OXYGEN INHALATION THERAPY or mechanical ventilation (VENTILATION, MECHANICAL) usually occurring in certain premature infants (INFANT, PREMATURE) or newborn infants with respiratory distress syndrome (RESPIRATORY DISTRESS SYNDROME, NEWBORN). Histologically, it is characterized by the unusual abnormalities of the bronchioles, such as METAPLASIA, decrease in alveolar number, and formation of CYSTS.
A condition of the newborn marked by DYSPNEA with CYANOSIS, heralded by such prodromal signs as dilatation of the alae nasi, expiratory grunt, and retraction of the suprasternal notch or costal margins, mostly frequently occurring in premature infants, children of diabetic mothers, and infants delivered by cesarean section, and sometimes with no apparent predisposing cause.
A respiratory distress syndrome in newborn infants, usually premature infants with insufficient PULMONARY SURFACTANTS. The disease is characterized by the formation of a HYALINE-like membrane lining the terminal respiratory airspaces (PULMONARY ALVEOLI) and subsequent collapse of the lung (PULMONARY ATELECTASIS).
A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA.
A syndrome characterized by outbreaks of late term abortions, high numbers of stillbirths and mummified or weak newborn piglets, and respiratory disease in young unweaned and weaned pigs. It is caused by PORCINE RESPIRATORY AND REPRODUCTIVE SYNDROME VIRUS. (Radostits et al., Veterinary Medicine, 8th ed, p1048)
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...