The purpose of the study is to determine the role of nitric oxide (NO) in asthma and to characterize the symptoms associated with inhaled endotoxin (lipopolysaccharide [LPS]) in normal subjects. In this study, we will determine the effect of inhaled endotoxin on exhaled NO in healthy African Americans, with and without NOS2 promoter polymorphisms. The protocol described in this submission will involve the use of NIH Clinical Center Reference Endotoxin which has been approved by the FDA under IND BB-IND-10035.
Name: LPS endotoxin
Description: Low challenge: saline (diluent), 5000EU, 10,000EU and 20,000EU LPS endotoxin as tolerated High challenge: Saline (diluent), 40,000EU and 80,000EU as tolerated Diluent Challenge: 3 X Sterile saline inhalation (2 ml)Type: Biological1
Single Group Assignment
There are 2 SNPs
Because SNPs in the TLR4 gene result in a lack of airway obstruction in response to endotoxin, we will genotype the 1000 DNA samples for the Asp299Gly and Thr399Ile TLR4 polymorphisms in Phase 1 and exclude these individuals from the studies proposed in Phase 2. Likewise, CD14 serves as a coreceptor for endotoxin and polymorphisms in the CD14 gene and promoter have been associated with asthma and responsiveness to endotoxin. --- Asp299Gly ---
Because SNPs in the TLR4 gene result in a lack of airway obstruction in response to endotoxin, we will genotype the 1000 DNA samples for the Asp299Gly and Thr399Ile TLR4 polymorphisms in Phase 1 and exclude these individuals from the studies proposed in Phase 2. Likewise, CD14 serves as a coreceptor for endotoxin and polymorphisms in the CD14 gene and promoter have been associated with asthma and responsiveness to endotoxin. --- Asp299Gly --- --- Thr399Ile ---