Abstract

The goal of this project is to determine the role of neutrophils, proteases and immunologic mediators in damaging the lung and exacerbating infection in the chronic lung disease of cystic fibrosis. This information is obtained by systematic examination of inflammatory cells and epithelial lining fluid obtained from bronchoalveolar lavage of well characterized cystic fibrosis patients. The study population includes those with mold and moderate disease, as well as those participating in therapeutic trials. Prior studies in stable, clinically mild patients suggested the presence of ongoing infection and inflammation. Comparisons of cystic fibrosis patients and healthy subjects found elevated levels of immune mediators such as leukotriene B4 in the epithelial lining fluid, suggesting that this mediator may play a role in recruiting neutrophils to the airways and stimulating them to release their injurious products. Persistent neutrophil influx, which characterizes the inflammatory response to persistent infection in this disorder, contributes to lung damage by a variety of mechanisms.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR003655-11
Application #
5224654
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Elston, Robert C; Satagopan, Jaya; Sun, Shuying (2017) Statistical Genetic Terminology. Methods Mol Biol 1666:1-9
Thota, Prashanthi N; Zackria, Shamiq; Sanaka, Madhusudhan R et al. (2017) Racial Disparity in the Sex Distribution, the Prevalence, and the Incidence of Dysplasia in Barrett's Esophagus. J Clin Gastroenterol 51:402-406
Liang, Jingjing; Cade, Brian E; Wang, Heming et al. (2016) Comparison of Heritability Estimation and Linkage Analysis for Multiple Traits Using Principal Component Analyses. Genet Epidemiol 40:222-32
Wang, Chuchu; Wu, Manman; Qian, Jin et al. (2016) Identification of rare variants in TNNI3 with atrial fibrillation in a Chinese GeneID population. Mol Genet Genomics 291:79-92
Lemas, Dominick J; Klimentidis, Yann C; Aslibekyan, Stella et al. (2016) Polymorphisms in stearoyl coa desaturase and sterol regulatory element binding protein interact with N-3 polyunsaturated fatty acid intake to modify associations with anthropometric variables and metabolic phenotypes in Yup'ik people. Mol Nutr Food Res 60:2642-2653
Day, Kenneth; Waite, Lindsay L; Alonso, Arnald et al. (2016) Heritable DNA Methylation in CD4+ Cells among Complex Families Displays Genetic and Non-Genetic Effects. PLoS One 11:e0165488
Justice, Cristina M; Bishop, Kevin; Carrington, Blake et al. (2016) Evaluation of IRX Genes and Conserved Noncoding Elements in a Region on 5p13.3 Linked to Families with Familial Idiopathic Scoliosis and Kyphosis. G3 (Bethesda) 6:1707-12
Petrovic, Dusan; Pivin, Edward; Ponte, Belen et al. (2016) Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study. Psychoneuroendocrinology 67:76-85
Castiblanco, John; Sarmiento-Monroy, Juan Camilo; Mantilla, Ruben Dario et al. (2015) Familial Aggregation and Segregation Analysis in Families Presenting Autoimmunity, Polyautoimmunity, and Multiple Autoimmune Syndrome. J Immunol Res 2015:572353
Shetty, Priya B; Tang, Hua; Feng, Tao et al. (2015) Variants for HDL-C, LDL-C, and triglycerides identified from admixture mapping and fine-mapping analysis in African American families. Circ Cardiovasc Genet 8:106-13

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