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Human rhinovirus (HRV) infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE) modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRVinduced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes. [ABSTRACT FROM AUTHOR]

Recent advances in our understanding of the immune-mediated inflammatory pathways in asthma and other allergic diseases have resulted in the development of novel biological compounds for the treatment of these conditions. These compounds offer an advantage over glucocorticosteroid therapy by specifically targeting components of the immunologic cascade, thereby allowing patients to reduce or discontinue their glucocorticosteroid treatment. Another potential advantage of biological compounds is that they may provide additional anti-inflammatory benefits, over and above those provided by glucocorticosteroid therapy, for patients who continue to have evidence of refractory asthma. The anti-IgE monoclonal antibody omalizumab is already being used for the treatment of allergic asthma and a number of other biological therapies are currently in various stages of clinical development. The purpose of this review is to summarize the data from these studies and to provide a rationale for the use of these compounds in asthma and related allergic airway diseases. [ABSTRACT FROM AUTHOR]