MUCOCILIARY CLEARANCE DURING AND AFTER ISOCAPNIC HYPERVENTILATION WITH DRY AIR IN THE PRESENCE OF FRUSEMIDE

We have previously shown that mucociliary clearance (MCC) decreased du ring and increased after isocapnic hyperventilation (ISH) with dry air , both in asthmatic and healthy subjects. Inhaled frusemide, an inhibi tor of the Na+/K+/2Cl(-) and NaCl co-transporters on the basolateral m embrane of the epithelial cell, prevents the airway narrowing provoked by ISH with dry air, The co-transport system controls epithelial cell volume and chloride secretion and, thus, frusemide has the potential to modify the rate of recovery of periciliary fluid volume during and after ISH with dry air, and hence affect MCC. Frusemide also blocks me diator release from mast cells, which may also modify the increase in MCC after ISH. Eleven asthmatic and 11 healthy subjects inhaled frusem ide (35.7+/-0.44 mg) or its vehicle, from a Fisoneb(TM) ultrasonic neb ulizer 30 min before ISH with dry air, on two separate occasions, MCC was measured using Tc-99m-sulphur colloid and a gamma camera. Frusemid e, compared to its vehicle, did not affect MCC during or 45 min after ISH. However, in the presence of frusemide, the onset of the increase of MCC after ISH was significantly delayed for approximately 10 min in the whole right lung (p<0.002) and central region (p<0.01) in the ast hmatic but not in the healthy subjects. These findings could be explai ned by frusemide delaying the recovery of the periciliary fluid volume after ISH with dry air and/or interfering with the stimulus that caus es the increase in MCC in the asthmatic subjects after ISH.