Challenge interval determines tachyphylaxis to aerosolized LTD4

Abstract

Leukotrienes (LK) play an important role in the inflammatory response found in the asthmatic airway and it is therefore of interest to explore the clinical value of agents which can either block the effect or inhibit the synthesis of leukotrienes. If tachyphylaxis does not develop, repeated LTD₄ challenges can be used for dose ranging studies.

Tachyphylaxis has been observed when LTD₄ challenge intervals are kept below 1 h, but the effect of prolonging the interval is uncertain. The aim of this study was therefore to investigate the interval between LTD₄ challenges necessary to avoid development of tachyphylaxis.

Ten stable adult asthmatics with moderate asthma were challenged seven times: a screening day to secure responsiveness to LTD₄, two challenges on three separate days with an interval of 2, 4 and 6h, respectively. No significant differences between mean PC₂₀-LTD₄ Values (P>0.5) was found. It was concluded that tachyphylaxis to repeated LTD₄ challenges of asthmatics does not develop when challenge intervals are prolonged above 2 h.