Effect of aspirin in "aspirin sensitive" patients.

Eighteen patients with a history of urticaria or asthma, or both, induced by aspirin were studied before and after provocation of symptoms with aspirin. The plasma prostaglandin F2 alpha concentration, which was characteristically raised before challenge, fell significantly at the time of adverse reactions. Repeated administration of aspirin up to a dose of 650 mg daily induced tolerance in most of the patients, and several developed bronchodilator responses to aspirin. Although median total IgE concentrations may be raised in patients with aspirin sensitivity, it appears likely that pharmacological rather than immunological mechanisms are chiefly responsible for the phenomena of aspirin sensitivity and desensitisation.     

Effect of aspirin on nasal resistance to airflow.

The effect of aspirin on nasal resistance to airflow was investigated by rhinomanometry in 25 healthy subjects before and after ingestion of aspirin or vitamin C in a double blind crossover trial. Aspirin caused a significant increase in nasal resistance compared with vitamin C. The effect of aspirin may be due to its inhibition of the synthesis of prostaglandins.     

Aquagenic pruritus.

Three patients were studied in whom brief contact of the skin with water at any temperature evoked intense itching without visible changes in the skin. The patients were otherwise apparently healthy, and this chronic and disabling disorder tended to attract a "psychogenic" label. Pharmacological studies showed that the condition was associated with local release of acetyl choline in the skin, mast-cell degranulation, and raised blood histamine concentrations. It responded well to antihistamines in two of the three patients. Aquagenic pruritus is probably common, but it is generally unrecognised and may be misdiagnosed. Antihistamines may induce a good therapeutic response.     

Cholestyramine in uraemic pruritus.

In a patient with longstanding severe uraemic pruritus who was undergoing chronic haemodialysis cholestyramine caused the pruritus to disappear completely within a few days. A four-week randomised controlled double-blind study was therefore performed in 10 other patients with uraemic pruritus who were on chronic haemodialysis. The pruritus improved considerably in four of the five treated patients, whereas only one of those treated with placebo experienced relief. The patient who had no relief while on cholestyramine showed a considerable improvement when the dose subsequently doubled. One of the five patients receiving cholestyramine experienced mild and easily reversible constipation, and another suffered nausea. Neither of these complications prevented the patients from continuing treatment. Cholestyramine seems to be useful in treating uraemic pruritus, although it is not known how it acts.     

Effect of aspirin on the pressor activity of endothelin

To examine the inhibition of prostaglandins to the pressor activity of endothelin, hemodynamic changes of dogs pretreated with aspirin in response to endothelin were compared with those of control. In control dogs, endothelin rose blood pressure due to vasoconstriction, with a transient vasodilation in some dogs in the initial phase. In dogs treated with aspirin, the initial vasodilation and the subsequent vasoconstriction were also noted, but the zenith of the total peripheral resistance was observed earlier, compared with control dogs. Thus, prostaglandins do not appear to have a role in the initial vasodilatory action of endothelin, but may modify the long lasting vasoconstriction in the late phase.     

Effect of aspirin on cysteinyl leukotrienes production by eosinophils co-cultured with epithelial cells.

Eosinophils have long been considered to play solely crucial role in the pathogenesis of aspirin-induced asthma, however increasing evidence suggest that the bronchial epithelium is also involved in the initiation and maintenance of allergic inflammation. Epithelial cells and eosinophils retained within airways interact reciprocally to mount and sustain inflammatory response. Recently, we have shown that eosinophil-epithelial cell interactions are capable of amplifying the production of cysteinyl leukotrienes (Cys-LTs). The aim of this study was to investigate if there is any influence of aspirin (ASA) on Cys-LTs and prostaglandin E2 (PGE(2)) production in the model of co-cultured human epithelial cells (line BEAS-2B) and human eosinophils. Synthesis of Cys-LTs in eosinophils was increased after incubation with ASA. At the same time the production of PGE(2) was decreased by aspirin (n=32). BEAS-2B cells barely formed Cys-LTs; addition of ASA increased this production, while production of PGE(2) was inhibited by aspirin (n=32). Synthesis of Cys-LTs by eosinophils co-incubated with BEAS-2B was nearly 7-fold higher than that of activated eosinophils alone (1631.5 pg/ml +/- 154 vs. 258 pg/ml +/- 31; p<0.05; n=32). Surprisingly, in the eosinophil-epithelial cell co-culture, aspirin inhibited both augmentation of Cys-LTs synthesis (from 1631.5 pg/ml +/- 154 to 1458 pg/ml +/- 137; p<0.05; n=32) and the production of PGE2 (from 2640 pg/ml +/- 231 to 319 pg/ml +/- 27; p<0.05; n=32). In summary, we have demonstrated that interactions between non-atopic eosinophils and epithelial cells result in augmentation of Cys-LTs production, and this augmentation could be inhibited by aspirin.     

Effect of aspirin on prostaglandin synthesis by human platelets

When platelet rich plasma is exposed to N-ethylmaleimide, a ten fold increase in measurable prostaglandin E synthesis occurs. This effect is almost completely abolished within 2 hours of ingestion of 600 mg of aspirin by human volunteers. Recovery of this platelet function is slow for the first two days, returning sharply to normal over the next six days and plateauing approximately 8 days following initial removal from aspirin. It is suggested from these studies that platelet prostaglandin E production following NEM may be a useful test of platelet function.