Asthma is a complex disease since it involves genetic predisposition, environmental factors, and an interaction with the immune status in the development and progression of the disease. Over 15 million Americans are afflicted with this disease and despite the use of potent medications, between 16-17% of patients experience continuous daily and frequent nocturnal symptoms. One underappreciated and controversial factor in the etiology of asthma is the role that atypical bacterial infections, such as those caused by Mycoplasma pneumoniae, play in initiating, exacerbating and prolonging airway-related symptoms and pathologies. Multiple lines of evidence directly link M. pneumoniae to the pathogenesis of asthma beyond its role as a precipitating factor in acute exacerbation of asthma. In children, M. pneumoniae infections have been shown to induce chronic lung damage for prolonged periods after the resolution of respiratory tract symptoms. Studies have demonstrated abnormal pulmonary function tests in up to 50% of children and abnormalities of the lung in 37% of children months to years after an episode of M. pneumoniae respiratory infection. Mycoplasma pneumoniae is also known to induce a number of inflammatory mediators implicated in the pathogenesis of asthma. IgE, IL-4, and IL-5 have been shown to be significantly elevated in children with M. pneumoniae infections, suggesting that M. pneumoniae can induce a TH-2 like cytokine response. In adults, M. pneumoniae has been detected in a large percentage of patients with stable moderately severe chronic asthma. The significance of this finding was supported by a randomized, doubleblind study that demonstrated only PCR positive asthmatics improved their pulmonary function test when treated with antibiotic therapy directed against mycoplasmas. Recently, Drs. Baseman and Kannan discovered an ADP-ribosylating, vacuolating toxin of M. pneumoniae designated the Community Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX appears to be much more immunogenic than the P1 adhesin molecule in patients with both acute and chronic asthma, and cards fxgene PCR assays also appear to be a marked improvement over existing M. pneumoniae PCR assays in detecting M. pneumoniae in patient samples. This project is designed to evaluate the prevalence of antibodies to CARDS TX and detect cards tx DMA by PCR in nasal lavage, sputum, and serum in various groups of patients with acute and chronic asthma. Specifically, we will evaluate chronic stable asthmatics, patients with acute exacerbation of asthma, and a group of asthmatics with refractory asthma. We plan to compare the sensitivity of CARDS TX to the """"""""gold"""""""" standard P1 assay for M. pneumoniae and to evaluate the cellular and cytokine response in these groups of asthmatic patients.
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