Acute lung injury is a common and devastating illness that occurs in the context of sepsis and other systemic inflammatory disorders. Whether a clear genetic basis exists for susceptibility to sepsis, acute lung injury, and ventilator-induced lung injury remains unresolved. To address this critical question, we propose to employ high throughput genomic technologies to examine (i) the patterns of gene expression and (ii) candidate gene polymorphisms which explain susceptibility to ALl. SA #1will prioritize novel sepsis and sepsis/VALI candidate genes obtained by extensive temporal expression profiling conducted in conjunction with Project #1 personnel in a small, well phenotyped subset of patients with sepsis and ALl. These patterns of expression will be analyzed within each clinical and experimental condition, within each species and then across species. This approach will allow us to determine both concordantly and discordantly regulated gene clusters, link these gene clusters with physiological measurements of lung function, and determine the gene profiles responsible for the development and maintenance of either resistance or susceptibility to VALI. SA #2 will then validate the physiological importance of these genes and """"""""high risk"""""""" alleles in a large cohort of well phenotyped patients with sepsis/ALl. We will perform high throughput genotyping for positional candidate genes generated from a combination of (1) human and animal cDNA microarray expression profiles; (2) preliminary data; and (3) literature. In SA #3, we will determine whether the frequencies of functional polymorphisms associated with ALl and sepsis vary significantly in African Americans compared to Caucasians. For any """"""""high risk"""""""" alleles/genotypes/haplotypes identified in Specific Aim 2, frequencies will be obtained from the two population-based samples to test the hypothesis that the prevalence of these allelic variants differs according to ethnicity. Additional analyses will include associations between sepsis and 'no sepsis', regardless of ALl status, and associations between survivors of VALI and non-survivors (e.g. mortality resulting from VALI). We will utilize standard and novel haplotype analytical tools to specifically identify haplotypes, which address the enhanced morbidity and mortality from sepsis and sepsis/VALI. We will rely upon public SNP data as well as the development of novel SNPs. Priority will be given to polymorphisms in coding or regulatory regions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
1P50HL073994-01
Application #
6820156
Study Section
Special Emphasis Panel (ZHL1-CSR-R (M1))
Project Start
2003-09-30
Project End
2008-06-30
Budget Start
2003-09-30
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$348,352
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Bienvenu, O Joseph; Friedman, Lisa Aronson; Colantuoni, Elizabeth et al. (2018) Psychiatric symptoms after acute respiratory distress syndrome: a 5-year longitudinal study. Intensive Care Med 44:38-47
Chan, Kitty S; Mourtzakis, Marina; Aronson Friedman, Lisa et al. (2018) Evaluating Muscle Mass in Survivors of Acute Respiratory Distress Syndrome: A 1-Year Multicenter Longitudinal Study. Crit Care Med 46:1238-1246
Heins, Sara E; Wozniak, Amy W; Colantuoni, Elizabeth et al. (2018) Factors associated with missed assessments in a 2-year longitudinal study of acute respiratory distress syndrome survivors. BMC Med Res Methodol 18:55
Brodsky, Martin B; De, Ishani; Chilukuri, Kalyan et al. (2018) Coordination of Pharyngeal and Laryngeal Swallowing Events During Single Liquid Swallows After Oral Endotracheal Intubation for Patients with Acute Respiratory Distress Syndrome. Dysphagia 33:768-777
Chan, Kitty S; Mourtzakis, Marina; Aronson Friedman, Lisa et al. (2018) Upper arm anthropometrics versus DXA scan in survivors of acute respiratory distress syndrome. Eur J Clin Nutr 72:613-617
Brodsky, Martin B; Huang, Minxuan; Shanholtz, Carl et al. (2017) Recovery from Dysphagia Symptoms after Oral Endotracheal Intubation in Acute Respiratory Distress Syndrome Survivors. A 5-Year Longitudinal Study. Ann Am Thorac Soc 14:376-383
Ruhl, A Parker; Huang, Minxuan; Colantuoni, Elizabeth et al. (2017) Healthcare Resource Use and Costs in Long-Term Survivors of Acute Respiratory Distress Syndrome: A 5-Year Longitudinal Cohort Study. Crit Care Med 45:196-204
Dinglas, Victor D; Aronson Friedman, Lisa; Colantuoni, Elizabeth et al. (2017) Muscle Weakness and 5-Year Survival in Acute Respiratory Distress Syndrome Survivors. Crit Care Med 45:446-453
Chan, Kitty S; Aronson Friedman, Lisa; Bienvenu, O Joseph et al. (2016) Distribution-based estimates of minimal important difference for hospital anxiety and depression scale and impact of event scale-revised in survivors of acute respiratory failure. Gen Hosp Psychiatry 42:32-5
Bienvenu, O Joseph; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A et al. (2015) Cooccurrence of and remission from general anxiety, depression, and posttraumatic stress disorder symptoms after acute lung injury: a 2-year longitudinal study. Crit Care Med 43:642-53

Showing the most recent 10 out of 127 publications