Urinary leukotriene E4 (LTE4) concentrations have been measured in six asthmatic patients with aspirin sensitivity and in five asthmatic subjects tolerant of aspirin, before and after provocation with aspirin or placebo. Aspirin-sensitive subjects showed an average 21% fall in FEV1 after aspirin challenge whereas control individuals had a 2% fall in FEV1 after ingestion of 100 mg aspirin. The resting urinary LTE4 concentrations in asthmatic subjects sensitive to aspirin were 243 pg/mg creatinine (range 50 to 1,041), and these were on average sixfold greater than those in control asthmatic subjects. Further, there was a mean fourfold increase in urinary LTE4 levels at 3 to 6 h after aspirin, but not placebo, challenge in aspirin-sensitive asthmatic subjects that was not seen in the control asthmatic individuals. Leukotriene release may play a central role in the mechanisms of asthmatic attacks produced by aspirin ingestion.

Seven weight-trained males performed both light resistance with partial occlusion (LRO: 30% 1 RM) and moderate resistance (MR: 70% 1 RM) to failure to ascertain whether blood protein carbonyls (PC) and glutathione status was altered compared to partial occlusion (PO) in a counterbalanced fashion. PO was identical in duration to the LRO session and all sessions were on separate days. PC did not differ for the three conditions at PRE (0.05 nM mg protein(-1)). PC significantly increased for PO and MR over time and was greater than the LRO treatment at POST (0.13 nM mg protein(-1)). The GSSG/TGSH ratio at PRE did not differ across treatments (8%) whereas the ratio at POST was significantly elevated for PO and MR treatments (17%). In contrast, no change occurred for the LRO session at any time. These results indicate that MR to failure and PO can significantly increase blood oxidative stress but LRO did not elicit oxidative stress.

The time course of leukotriene generation in the adult respiratory distress syndrome (ARDS) was investigated by measurement of urinary leukotriene E4 (LTE4) excretion, the major urinary LT metabolite in humans. Sequential measurements were made in nine subjects entered into the study within 48 h of the onset of ARDS, defined by an arterial/alveolar PO2 ratio of less than 0.3 and radiographic evidence of diffuse bilateral pulmonary edema. Initial urinary LTE4 excretion was significantly elevated (1.250 +/- 0.050 ng/mg creatinine sulphate; n = 7) compared with a non-ARDS postoperative group (0.254 +/- 0.114 ng/mg; n = 5) and normal control subjects (0.035 +/- 0.010 ng/mg; n = 12). LTE4 excretion in the first 24 h was estimated to be 6.9 micrograms, representing a release of 0.1 micrograms/kg/h of peptido leukotrienes into the bloodstream. These values were physiologically important based on a comparison with the increased urinary LTE4 excretion observed after antigen-induced bronchoconstriction in allergic asthmatics (baseline LTE4, 0.06 +/- 0.04 ng/mg; postantigen, 0.56 +/- 0.14 ng/mg; 0.17 micrograms LTE4/24 h; n = 8). In subjects with ARDS, this pathologic LTE4 excretion persisted during a subsequent 5-day study period. Leukotriene E4 excretion was associated with persistent abnormalities in gas exchange, pulmonary edema, and lung compliance, suggesting an important role for peptido leukotrienes in the pathophysiology of ARDS.

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Eosinophil Major Basic Protein (MBP) may be a potent effector in damaging airway epithelium and inducing acute (2-3 h) hyperresponsiveness to agonists in primates. Accordingly, interactions between human eosinophil MBP and guinea-pig airway epithelium were quantitated biochemically. MBP was extracted from human eosinophils and purified by size-exclusion HPLC. This resulted in a single protein band on electrophoresis, which cross-reacted with antisera raised to peptides derived from the predicted sequence of human MBP. This human MBP caused modest, but statistically significant, damage to respiratory epithelium (16.4% increase in efflux of 51Cr from guinea-pig tracheal rings) after 3 h of incubation with 10(-4) M concentration, but not with lower concentrations. These data demonstrates that MBP cytotoxicity to intact epithelium can be rapidly measured in vitro, and suggests that rodent airway epithelium may be relatively resistant to the cytotoxic effects of MBP.