The overall goal of this project is to identify genes that are involved in the development of airflow obstruction and airway inflammation in asthmatics, and to determine whether polymorphisms in these differentially expressed genes predispose individuals to develop asthma. In this project, we hypothesize that polymorphisms of genes expressed by the airway epithelia in asthmatics following specific airway challenges predispose individuals to the development of asthma.
Name: Lipopolysaccharide endotoxin
Description: Delivered in nebulized form expressed in activity units(endotoxin units -EU). Subjects receive each dose 30 min after completing the previous dose, dose duration is approximately 10 minutes: Challenge One first saline then 5000 EU 10,000 EU 20,000 EU Challenge 1 and 2 must be at least 2 weeks apart. Challenge 2 Saline 40,000 EU 80,000 EUType: BiologicalChallenge
Single Group Assignment
There are 2 SNPs
We hypothesize that individuals with the co-segregating Asp299Gly and Thr399Ile mutations in the TLR4 gene will exhibit a defective immune response to LPS, and that specific components of altered immunity in these individuals are linked to characteristic airway responses to LPS. Specific Aim 1: Approximately 1000 individuals will be genotyped in order to establish 3 study groups: 10 subjects homozygous for the TLR4 299/399 mutation; 10 subjects heterozygous for the TLR4 299/399 mutation; and 10 subjects homozygous for wild type TLR 4. Specific Aim 2: Ten individuals with wild type TLR4, 10 individuals heterozygous for mutant TLR4 and 10 individuals homozygous for mutant TLR4 will be phenotyped for airway responsiveness to inhaled LPS. --- Asp299Gly ---
We hypothesize that individuals with the co-segregating Asp299Gly and Thr399Ile mutations in the TLR4 gene will exhibit a defective immune response to LPS, and that specific components of altered immunity in these individuals are linked to characteristic airway responses to LPS. Specific Aim 1: Approximately 1000 individuals will be genotyped in order to establish 3 study groups: 10 subjects homozygous for the TLR4 299/399 mutation; 10 subjects heterozygous for the TLR4 299/399 mutation; and 10 subjects homozygous for wild type TLR 4. Specific Aim 2: Ten individuals with wild type TLR4, 10 individuals heterozygous for mutant TLR4 and 10 individuals homozygous for mutant TLR4 will be phenotyped for airway responsiveness to inhaled LPS. --- Asp299Gly --- --- Thr399Ile ---