Chronic sinonasal disease is associated with more severe asthma and contributes to poor asthma control. One possible mechanism for a proposed interaction between upper and lower airways includes a systemic `inflammatory response. The suggestion is that stimulus in one part of the airway leads to systemic release of cytokines and chemokines responsible for eosinophil trafficking to the respiratory tissues and thus inflammatory response occurs in other parts of the airway as well. The eotaxins are the key chemokines responsible for trafficking of eosinophils to the tissues. Eosinophilic cationic protein is the main marker of eosinophil activation in tissues. We are proposing to conduct an ancillary mechanistic study among the first 190 patients enrolled for the STAN trial to establish whether six months of intranasal steroids in poorly controlled allergic asthmatics with chronic sinonasal disease will lead to reduction in local nasal and systemic inflammatory mediators - eotaxins and ECP. We will also assess if decreasing levels of eotaxin and ECP levels correlate with improved asthma control. The ongoing Asthma Clinical Trials Center (ACRC) Study of Asthma and Nasal Steroids (STAN) trial will determine if six months of intranasal steroids compared to placebo will improve asthma control in 380 patients with poorly controlled asthma and chronic sinonasal disease. This ancillary study is important because it will provide answers relating to the possible mechanisms of interaction between disease in the upper and lower airways. If changes in serum and nasal lavage fluid levels correlate with improved asthma control, then we would have more targets for future therapeutic interventions.

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We are proposing to perform an ancillary study as part of a large multicenter randomized trial, the Study of Asthma and Nasal Steroids (STAN). The objective of our ancillary study is to determine if treating patients with poorly controlled asthma who have chronic rhinitis, chronic sinusitis or both with intranasal mometasone will lead to a reduction in the levels of nasal lavage fluid and blood markers that are associated with mobilizing and activation of specific allergy associated inflammatory cells called eosinophils. We will also determine if there is improvement in asthma control as measured by severity and frequency of symptoms and also by measurement of lung function. Finally we will determine if reduction in levels of these blood and nasal lavage fluid markers correlate with improvement in asthma control.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F10A-S (20))
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Prograis, Lawrence J
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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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