89708
document
The effect of inhaled leukotriene D4 and methacholine on sputum cell differentials in asthma . The cysteinyl leukotriene LTE4 has been shown to induce airway eosinophilia in asthmatics in vivo . This phenomenon has not yet been reported for LTD4 . Hence , we examined the effect of inhaled LTD4 and a control bronchoconstrictor agent , methacholine , on cell differentials in hypertonic saline-induced whole sputum samples of 12 nonsmoking atopic asthmatic subjects ( three women , nine men ; 21 to 29 yr of age ; FEV1 , 74 to 120 % pred ; PC20FEV1 methacholine < 9.6 mg/ml ) . The study had a cross-over , placebo-controlled design consisting of 4 d separated by > or = 1 wk . On each randomized study day , the subjects inhaled five serial doses of either LTD4 ( mean cumulative concentration : 95.7 microM ) or methacholine ( mean cumulative concentration : 542 mM ) or five doses of their respective diluents ( PBS/ethanol or PBS ) . The airway response was measured by FEV1 , followed by sputum induction with 4.5 % NaCl , 4 h postchallenge . Inflammatory cells ( > or = 250 ) were counted twice on coded cytospins and expressed as percentages of nonsquamous cells . There was no significant difference in the maximal percent fall in FEV1 from baseline between LTD4 ( mean +/- SEM , 49.5 +/- 4.4 % fall ) and methacholine ( mean +/- SEM , 55.9 +/- 3.4 % fall ) ( p = 0.11 ) . LTD4 induced a significant increase in the percentage of sputum eosinophils as compared with its diluent ( mean +/- SD , 26.6 +/- 21.3 % and 10.2 +/- 8.8 % , respectively ; p = 0.025 ) , whereas a similar trend for methacholine failed to reach significance ( 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 percentage of sputum eosinophils between LTD4 and methacholine ( mean difference +/- SD , 7.5 +/- 12.5 % eosinophils ; p = 0.09 ) . We conclude that LTD4 induces eosinophilia in sputum of asthmatic subjects 4 h after inhalation . Our data suggest that LTD4 recruits eosinophils into the airways of asthmatics in vivo , possibly by virtue of direct or indirect chemotactic properties , whereas an additional effect of vigourous airway narrowing per se can not be excluded .
89709
Intervention_Pharmacological
leukotriene D4
89710
Intervention_Pharmacological
methacholine
89711
Intervention_Pharmacological
cysteinyl leukotriene LTE4
89712
Intervention_Pharmacological
LTD4
89713
Intervention_Pharmacological
LTD4
89714
Intervention_Pharmacological
methacholine
89715
Intervention_Pharmacological
( PBS/ethanol
89716
Outcome_Physical
sputum cell differentials
89717
Outcome_Physical
airway eosinophilia
89718
Outcome_Physical
cell differentials
89719
Outcome_Physical
airway response
89720
Outcome_Physical
maximal percent fall in FEV1 from baseline
89721
Outcome_Physical
percentage of sputum eosinophils
89722
Outcome_Physical
percentage of sputum eosinophils
89723
Outcome_Physical
eosinophilia in sputum
89724
Outcome_Physical
eosinophils
89725
Outcome_Physical
vigourous airway narrowing
89726
Participant_Condition
asthma .