Altered platelet function associated with the bronchial hyperresponsiveness accompanying nocturnal asthma

Abstract

Background: Nocturnal awakening is a common feature of bronchial asthma, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether nocturnal awakening is associated with changes in platelet function with the use of a variety of markers of platelet activation. Methods: Ten patients with a history of nocturnal asthma and 10 age- and sex-matched healthy control subjects were studied at 10:00 PM, 4:00 AM, and 10:00 AM on 2 consecutive days. The following parameters were tested: forced expiratory volume in 1 second (FEV 1), log dose of methacholine inducing a 20% fall in FEV 1, platelet count and volume, platelet aggregation induced by collagen or activating factor, and plasma and intraplatelet levels of β-thromboglobulin and platelet factor 4. Results: We have demonstrated that altered platelet function and platelet activation occurs at 4:00 AM in patients with nocturnal asthma and is associated with the maximum increases in bronchial reactivity. Such changes were not observed in 10 control subjects. Platelet dysfunction has been detected as a reduced aggregatory response of platelets to collagen and platelet activating factor such that up to 5 times more platelet activating factor and 1.5 times more collagen were required to elicit a threshold aggregatory response in asthmatic subjects when compared with control subjects; this difference was evident at all time points tested. Furthermore, at 4:00 AM there were significantly lower levels of intraplatelet β-thromboglobulin corresponding to the maximum reduction in peak expiratory flow and to the maximal increase in bronchial responses to inhaled methacholine. Conclusions: These results suggest that platelet activation accompanies nocturnal asthma and further suggest that platelets may play a role in this common clinical condition.