This is a bronchoalveolar lavage and mouth wash study to test the hypothesis that ibuprofen limits the inflammatory response in the CF lung by reducing persistent neutrophil influx due to limiting LTB4 production by neutrophils already recruited to the CF lung. Results from the BAL portion of the study revealed decreased inflammation in the airways of CF patients randomized to ibuprofen compared to those randomized to placebo. Mouthwash studies revealed that high-dose ibuprofen decreases PMN delivery to the oral mucosa, while low-dose ibuprofen increases PMN delivery, in both CF patients and healthy volunteers. Since the results of the 4-year trial suggest that ibuprofen should become a standard component of CF care, an expansion of the original study (enrollment beginning 9/95) has been designed to include intermediate doses of ibuprofen and a slightly longer duration of drug administration, and to obtain ibuprofen levels during the study.
The specific aims are 1) to determine the effect of ibuprofen on PMN delivery to a mucosal surface in CF patients and healthy controls and 2) to determine the duration of effect (and possible rebound effect) of ibuprofen on PMN delivery to a mucosal surface (the oral mucosa) in CF patients and healthy controls. To date 66 subjects have been enrolled (52 healthy and 14 CF). Results to date suggest that 1) high doses of ibuprofen appear to be required to decrease PMN migration, low and intermediate doses appear to increase PMN migration; 2) a dosing interval of 12 hours appears to be appropriate to achieve the desired effect on PMN migration (24 hours is too long); and 3) there might possibly be a rebound effect after discontinuing the drug. These results suggest that careful and sustained dosing of CF patients with ibuprofen is required to achieve the desired effect and to minimize adverse effects of ibuprofen on PMN migration. Recruitment continues with the goal of 11 more CF patients to be studied in the next year.

Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
37
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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