title: Characterization of the airway response to inhaled leukotriene D4 in normal subjects.
abstract: 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 airway response to single bronchoconstricting doses of LTD4 administered on separate days was reproducible for SGaw (r = 0.86, p less than 0.05) and V30P (r = 0.95, p less than 0.005). The response to 3 consecutive single-dose LTD4 challenges performed on the same day, allowing SGaw and V30P to return to greater than 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 less than 0.001) and for V30P (p less than 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 less than 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 demonstrated 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.
mesh_terms: D000328:Adult; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007114:Immunization; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D012016:Reference Values; D012137:Respiratory System / Q000187:drug effects*; D013189:SRS-A / Q000494:pharmacology*; D013618:Tachyphylaxis
chemical_list: D000336:Aerosols; D008688:Methacholine Compounds; D013189:SRS-A; D016210:Methacholine Chloride