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GENE EXPRESSION AFTER ENDOBRONCHIAL INSTILLATION OF ENDOTOXIN (LPS) AND HOUSE DUST MITE ANTIGEN (HDM) IN ASTHMATIC AND NON-ASTHMATIC SUBJECTS

Duke University Medical Center, Durham, NC

PURPOSE: Endotoxin (LPS) and house dust mite antigen (HDM) contribute to asthma development and are well-studied models of asthma pathogenesis. Though both LPS and HDM can induce asthmatic phenotypes in susceptible individuals, it is not clear as to what mechanisms are shared and which are different with these two agents. We believe that with simultaneous localized instillation of both agents we will gain insight into mechanisms of asthma development and pathogenesis.

METHODS: 11 atopic, mild asthmatic and 11 nonatopic, nonasthmatic adult subjects were identified by routine screening studies. Subjects underwent an initial bronchoscopy with instillation of saline, LPS, and house dust mite antigen (D farinae) in separate subsegmental bronchi. Four hours later, a repeat bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial brush biopsy was performed in each subsegmental bronchus. Inflammatory and epithelial cells from these specimens were separated, RNA was extracted, and microarray analysis was performed using the Agilent whole human genome array.

RESULTS: After instillation of LPS, there was increased inflammatory cell gene expression in both asthmatics and control subjects. Specifically, genes involved with innate immunity and other mechanisms of cell injury were upregulated. In contrast, after instillation of HDM we found much less dramatic changes in gene expression. However, we noted that genes involved in the adaptive immune response were upregulated both in atopic and nonatopic individuals after instillation of HDM.

CONCLUSION: We demonstrate that asthmatics and control subjects have similar gene expression changes in inflammatory cells following LPS installation. The changes after instillation of HDM do not appear as robust, but those genes that are upregulated may lead to fundamental understanding of mechanisms of asthma development based on different environmental exposures.

CLINICAL IMPLICATIONS: Asthma is a heterogeneous group of disorders with various inciting agents and a variety of responses to treatment. It is possible that gene expression technologies can serve as important clinical aides to phenotype patients with asthma and their response to treatment as well as lead to better understanding of the genetics of asthma susceptibility.

DISCLOSURE: Jaspal Singh, None.