In vivo and in vitro human airway responsiveness to leukotriene D4 in patients without asthma

We have examined the in vivo airway responsiveness to leukotriene (LT) D4 in 11 patients without asthma who were to undergo thoracotomy and compared this responsiveness with in vitro sensitivity and in vitro contractility of bronchial smooth muscle to LTD4. In vivo responses were measured by the provocation concentration producing a 10% fall in FEV1, a 30% fall in partial flow rate at 30% of total lung capacity from a partial forced expiratory maneuver, and a 35% fall in specific airway conductance. In vitro sensitivity was measured as the concentration of LTD4 producing a 50% of maximum contraction and maximum-induced tension. The smooth muscle content of the bronchial strip was estimated microscopically, and the absolute quantity of muscle strip was compared with the maximum tension generated by that bronchial smooth muscle sample. In vivo results varied over 2 log units, and in vitro sensitivity, over 1 log unit. The absolute amount of smooth muscle present in bronchial strips correlated with maximal LTD4-induced tension. There was no relationship between in vivo responsiveness and in vitro sensitivity nor between in vivo responsiveness and maximum tension generated, even when this was corrected for the proportion of smooth muscle present in each bronchial strip. These results suggest that in vivo airway responsiveness to LTD4 is not determined by airway smooth muscle sensitivity or its ability to generate tension alone. Other factors must be influencing the response of the airway to LTD4. Nevertheless, the finding of a positive correlation between the absolute amount of smooth muscle present in bronchial strips and maximal LTD4-induced tension suggests that hypertrophy and/or hyperplasia of airway smooth muscle may contribute to in vivo airway hyperresponsiveness.