Oral aspirin challenges in asthmatic patients: a study of plasma histamine

Abstract

Summary Under carefully controlled conditions, seven aspirin‐intolerant asthmatic patients were challenged with oral aspirin and experienced respiratory tract reactions with a decline in forced expiratory volume in 1 sec (FEV1), ranging from 26 to 64%. Venous blood samples, which were collected during the challenges, showed a rise in plasma histamine in all seven patients. The increase in plasma histamine occurred at the onset of their respiratory reactions and those patients with the most severe asthmatic responses were found to have the highest and most prolonged levels of plasma histamine. The same aspirin‐intolerant asthmatic patients were able to ingest Maalox® or sodium salicylate without untoward effects, decline in FEV1 values or changes in plasma histamine levels. Ten non‐asthmatic individuals and eight out of ten asthmatic control patients were able to ingest aspirin without any reactions or changes in their plasma histamine levels. However, two asthmatic control individuals, with severe asthma requiring treatment with moderate dosages of corticosteroids, were found to have elevated pre‐challenge plasma histamine levels which increased during their ASA challenges despite the absence of respiratory reactions or changes in FEV1 values. It is possible that these two individuals were unsuspected aspirin‐intolerant asthmatics. These studies demonstrate that asthmatic reactions to acetylsalicylates are associated with release of histamine into plasma in the subgroup of asthmatic patients with the aspirin‐intolerance syndrome. Such a finding suggests that histamine may be one of the mediators of bronchospasm in aspirin‐induced asthma.

Analgesics, allergy and asthma.

“…Indeed, prostaglandins of the E type are not only bronchodilators, but stabilize histamine stores in mastocytes. In aspirin-sensitive asthmatics, aspirin challenge results in a significant increase in plasma histamine (Stevenson, Arroyave, Bhat & Tan, 1976). Furthermore, aspirin-induced bronchoconstriction can be diminished or even prevented by drugs which either stabilize the mast-cell membranes (Basomba, Romar, Villamanzo & Campos, 1976) or block HI-histamine receptors (Szczeklik & Serwoniska, 1979).…”

Definition and classification of the histamine-release response to drugs in anaesthesia and surgery: Studies in the conscious human subject

“…Before reliable and practicable [20] histamine assays in human plasma became available for routine use [4,26,27] a histamine-release response to drugs could not be estimated in clinical conditions with an acceptable accuracy [9,10,28,29,34,36,45,51,58,62]. But even one decade after the discovery of H2-receptor antagonists [5] and the development of these highly sensitive and specific asays [4,26] histamine was still not generally recognized as an important mediator of any pathological and clinical phenomenon [63].…”

Challenge of Isolated Sputum Cells Supports in vivo Origin of Intolerance Reaction to Aspirin/Non-Steroidal Anti-Inflammatory Drugs in Asthma

“…Thus, the aspirin/NSAID-induced asthmatic reaction is associated with the release of histamine [28,29,30], tryptase [9,29,30,39], PGD 2 [9,10,11,12,30] and CysLTs [7,8,9,10,11,12,13]. There are also histological findings [32] supporting the participation of mast cells in the intolerance reaction.…”

“…Suggestions of aspirin-induced activation of platelets from patients with AIA [27] have not been replicated [18]. Moreover, despite in vivo evidence that mast cell activation occurs during aspirin-induced bronchoconstriction [9,10,11,28,29,30,31,32], Wang et al [33] could not trigger activation of blood-derived mast cells from subjects with AIA by ex vivo exposure to aspirin. The present study therefore gives support to the concept that aspirin/NSAID intolerance is a unique and not yet completely understood in vivo reaction in which presumably many cells interact in a complex fashion that, however, requires contact with the target tissue in the airways.…”