Asthma is a complex disease since it involves genetic predisposition, environmental factors, and aninteraction with the immune status in the development and progression of the disease. Over 15 millionAmericans are afflicted with this disease and despite the use of potent medications, between 16-17% ofpatients experience continuous daily and frequent nocturnal symptoms. One underappreciated andcontroversial factor in the etiology of asthma is the role that atypical bacterial infections, such as thosecaused by Mycoplasma pneumoniae, play in initiating, exacerbating and prolonging airway-relatedsymptoms and pathologies. Multiple lines of evidence directly link M. pneumoniae to the pathogenesis ofasthma beyond its role as a precipitating factor in acute exacerbation of asthma. In children, M. pneumoniaeinfections have been shown to induce chronic lung damage for prolonged periods after the resolution ofrespiratory tract symptoms. Studies have demonstrated abnormal pulmonary function tests in up to 50% ofchildren and abnormalities of the lung in 37% of children months to years after an episode of M. pneumoniaerespiratory infection. Mycoplasma pneumoniae is also known to induce a number of inflammatory mediatorsimplicated in the pathogenesis of asthma. IgE, IL-4, and IL-5 have been shown to be significantly elevated inchildren with M. pneumoniae infections, suggesting that M. pneumoniae can induce a TH-2 like cytokineresponse. In adults, M. pneumoniae has been detected in a large percentage of patients with stablemoderately severe chronic asthma. The significance of this finding was supported by a randomized, doubleblindstudy that demonstrated only PCR positive asthmatics improved their pulmonary function test whentreated with antibiotic therapy directed against mycoplasmas.Recently, Drs. Baseman and Kannan discovered an ADP-ribosylating, vacuolating toxin of M. pneumoniaedesignated the Community Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TXappears to be much more immunogenic than the P1 adhesin molecule in patients with both acute andchronic 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 toevaluate 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 willevaluate chronic stable asthmatics, patients with acute exacerbation of asthma, and a group of asthmaticswith refractory asthma. We plan to compare the sensitivity of CARDS TX to the 'gold' standard P1 assay forM. pneumoniae and to evaluate the cellular and cytokine response in these groups of asthmatic patients.
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