Pulmonary gas exchange and sputum cellular responses to inhaled leukotriene D-4 in asthma

Inhalational challenges with inflammatory mediators may provoke lung functi on disturbances similar to those shown in spontaneous acute asthma. Cystein yl leukotrienes (CysLTs) have recently been established as mediators of bro nchoconstriction in asthma but their effects on pulmonary gas exchange in a sthma have not been assessed. We therefore investigated the effects of leuk otriene D-4 (LTD4) challenge resulting in a significant decrease in FEV1 (m ean +/- SE, by 32 +/- 3%) in 13 nonsmoking, mild asthmatics. Respiratory sy stem resistance (Rrs), and respiratory and inert gases were measured before and immediately after, and at 15 and 45 min after challenge. After broncho provocation, Rrs increased (by 106 +/- 12%), Pa-O2 decreased (by 25 +/- 4 m m Hg), and ventilation-perfusion distributions moderately to severely deter iorated, as shown by increases in the dispersions of pulmonary blood flow ( Log SDQ, by 59 +/- 12%) and alveolar ventilation (Log SDV, by 65 +/- 20%) ( p < 0.05 each). Sputum eosinophils (p < 0.05) and urinary LTE4 (p < 0.005) increased after challenge. Despite the lack of mathematical correlations be tween spirometric and Rrs changes and gas exchange indices, the pattern of improvement of the functional variables after challenge ran in parallel. Th ese findings support the evidence that CysLTs, in addition to being potent bronchoconstrictors, also provoke profound disturbances of pulmonary gas ex change in asthma.