This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. [from CRISP website (edited)] Nightime exacerbations of asthma (severe wheezing, coughing, etc.) can be severe and possibly lead to death. Understanding their mechanism is critical to the treatment of asthma and likely provides a unique insight into this disease. It has been shown that increased airway inflammation at night contributes to airway obstruction in asthma. In addition, 24-hour variations in hormone levels such as epinephrine and cortisol are felt to influence the appearance of nightime asthma. How does circadian rhythm promote airway inflammation at night. Preliminary data suggest that fibronectin (FN), a protein that helps to make up the structure of the lung, is increased in lung fluid obtained from patients with nightime asthma (NA) subjects at 4:00 AM. Furthermore, FN levels in lung fluid obtained at 4:00 AM correlated with the severity of night time asthma symptoms.
The specific aims of this study are to: (1) Establish, in night time asthma, the variable night to day pattern of circulating and airway FN levels in relation to lung function; hormone levels (plasma epinephrine and cortisol), numbers and activation of airway and blood cells important in asthma (eosinophils); (2) Establish what efffects fibronectin protein has on eosinophils in the lung and in the blood; (3) Establish which cell is making the fibronectin and determine what signals that cell to make more or less fibronectin.
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