THE EFFECT OF INHALED LEUKOTRIENE D-4 AND METHACHOLINE ON SPUTUM CELLDIFFERENTIALS IN ASTHMA

The cysteinyl leukotriene LTE(4) has been shown to induce airway eosin ophilia in asthmatics in vivo. This phenomenon has not yet been report ed for LTD(4). Hence, we examined the effect of inhaled LTD(4) and a c ontrol bronchoconstrictor agent, methacholine, on cell differentials i n hypertonic saline-induced whole sputum samples of 12 nonsmoking atop ic asthmatic subjects (three women, nine men; 21 to 29 yr of age; FEV( 1), 74 to 120% pred; PC(20)FEV(1) methacholine < 9.6 mg/ml). The study had a crossover, placebo-controlled design consisting of 4 d separate d by greater than or equal to 1 wk. On each randomized study day, the subjects inhaled five serial doses of either LTD(4) (mean cumulative c oncentration: 95.7 mu M) or methacholine (mean cumulative concentratio n: 542 mM) or five doses of their respective diluents (PBS/ethanol or PBS). The airway response was measured by FEV(1), followed by sputum i nduction with 4.5% NaCl, 4 h postchallenge. Inflammatory cells (greate r than or equal to 250) were counted twice on coded cytospins and expr essed as percentages of nonsquamous cells. There was no significant di fference in the maximal percent fall in FEV(1) from baseline between L TD(4) (mean +/- SEM, 49.5 +/- 4.4% fall) and methacholine (mean +/- SE M, 55.9 +/- 3.4% fall) (p = 0.11). LTD(4) induced a significant increa se in the percentage of sputum eosinophils as compared with its diluen t (mean +/- SD, 26.6 +/- 21.3% and 10.2 +/- 8.8%, respectively; p = 0. 025), whereas a similar trend for methacholine failed to reach signifi cance (mean +/- SD, 19.1 +/- 22.9% and 7.8 +/- 5.8%, respectively; p = 0.11). There was no significant difference in the changes in the perc entage of sputum eosinophils between LTD(4) and methacholine (mean dif ference +/- SD, 7.5 +/- 12.5% eosinophils; p = 0.09). We conclude that LTD(4) induces eosinophilia in sputum of asthmatic subjects 4 h after inhalation. Our data suggest that LTD(4) recruits eosinophils into th e airways of asthmatics in vivo, possibly by virtue of direct or indir ect chemotactic properties, whereas an additional effect of vigourous airway narrowing per se cannot be excluded.