To better understand the role of leukotriene D4 (LTD4) in the pathogenesis of airway hyperreactivity, we administered aerosolized LTD4, on multiple occasions to 6 normal subjects and measured specific airway conductance (SGaw) by body plethysmography and the flow rate at 30% of vital capacity from partial forced expiratory maneuvers (V30P). Dose-response curves generated from standard bronchoprovocation tests revealed that LTD4, was 280 to 590 times more potent as a bronchoconstrictor than was methacholine. The airways response to single bronchoconstricting doses of LTD4, administered on separate days was reproducible for SGaw (r = 0.86, p < 0.05) and V30P (r = 0.95, p < 0.005). The response to 3 consecutive single-dose LTD4 challenges performed on the same day, allowing SGaw and V30P to return to > 90% of the control value between challenges, demonstrated tachyphylaxis: the response to the third dose was significantly less than the response to the first dose for SGaw (p < 0.001) and for V30P (p < 0.01). A single bronchoconstricting dose of LTD4, given before a standard methacholine dose-response challenge, lowered the concentration of methacholine needed to decrease V30P 30% (p < 0.05) and SGaw 35% (p = 0.09). A single bronchoconstricting dose of methacholine preceding a standard methacholine challenge did not have this effect. LTD4, and methacholine demonstrates a cumulative dose-effect when progressively higher concentrations were inhaled. In summary, the airway response to LTD4 is reproducible, exhibits tachyphylaxis, and a cumulative dose-effect occurs. As well, LTD4 increases the responsiveness of normal airways to methacholine.
|Original language||English (US)|
|Number of pages||6|
|Journal||American Review of Respiratory Disease|
|State||Published - 1986|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine