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Effects of terbutaline in combination with mannitol on mucociliary clearance

Depts of ¹ Respiratory and ² Positron Emission Tomography and Nuclear Medicine, Royal Prince Alfred Hospital, Camperdown, and ³ Depts of Pharmacy and ⁴ Pharmacology, University of Sydney, Sydney, Australia

CORRESPONDENCE: E. Daviskas, Respiratory Medicine, E11 South, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia. Fax: 61 295158196. E-mail: lily@nucmed.rpa.cs.nsw.gov.au

Keywords: hyperosmolarity, mannitol, mucociliary clearance, terbutaline

Received: December 10, 2001
Accepted June 11, 2002

The study was supported by a grant from the National Health and Medical Research Council of Australia. The application for the use of mannitol described in the paper is covered by US Patent No 5817028, an Australian Patent No 682756 and an International Patent PCT/AU 95/00086 held by Central Sydney Area Health Service.

ß₂-agonists and osmotic agents stimulate mucociliary clearance (MCC) via different mechanisms which could potentially interact.

The effects of inhaling terbutaline in combination with mannitol on MCC were investigated in nine healthy (aged 19±1 yrs) and 11 mild (aged 21±4 yrs) asthmatic subjects. Using ^99mTc-sulphur colloid radioaerosol and a gamma camera, MCC was studied on four separate days with each of the following interventions: 1) terbutaline or its placebo inhaled 10 min before mannitol (in random, double blind); 2) terbutaline inhaled 5 min after mannitol; and 3) terbutaline inhaled 10 min before the control for mannitol. Lung images were collected over a period of 120 min postintervention and over 150 min in total.

The mannitol-induced increase in clearance was transiently inhibited by terbutaline pretreatment and transiently enhanced when terbutaline was administered after mannitol both in asthmatic and healthy subjects. The order of administration of mannitol and terbutaline did not affect the total clearance of radioactive mucus over 140 min from the start of intervention in both groups.

The pathways through which terbutaline and mannitol increase mucociliary clearance may transiently interact in an inhibitory or synergistic way, depending on the order of administration. However, this did not affect the overall increase in mucociliary clearance over 140 min.