Bronchoalveolar lavage fluid mediator levels 5 minutes after allergen challenge in atopic subjects with asthma: Relationship to the development of late asthmatic responses

Abstract

Inflammatory mediators have been implicated in the pathogenesis of human asthma and have been demonstrated to increase in bronchoalveolar lavage fluid during the time of the immediate asthmatic response (IAR) after allergen instillation in the lungs. However, the relationship of these mediators, measured early to the late asthmatic response (LAR), airway reactivity, and clinical asthma, is unknown. In the present study, we evaluated mediator levels in bronchoalveolar lavage fluid before and 5 minutes after allergen challenge from three subject groups: atopic subjects without asthma (N = 7), atopic subjects with asthma and without LAR ((−) LAR) (N = 6), and atopic subjects with asthma and with LAR ((+) LAR) (N = 6). subjects with asthma were differentiated into subjects with and without LARs based on at least a 15% decrease in FEV 1 between 3 to 8 hours postallergen inhalation. The mediators, prostaglandin D 2, thromboxane B 2, leukotriene C 4 (LTC 4), and histamine, were measured both before and after allergen instillation. Baseline prechallenge levels were similar, except in the case of LTC 4, LTC 4 was detectable at baseline significantly more frequently in the atopic subjects with asthma with and without LAR when these subjects were compared to the atopic subjects without asthma (nine of 12 detectable versus one of seven detectable). In all groups, significant increases in mediator levels were observed in the groups with asthma postallergen challenge, compared to the atopic subjects without asthma. Atopic subjects with asthma and without LAR had significantly higher levels of all four mediators after challenge than atopic subjects with asthma and with LAR and atopic subjects without asthma. No correlation was found between the mediator levels and airway physiology among any of the three groups. Although atopic subjects with asthma and with LAR were more reactive to methacholine than the other two groups, the difference did not reach significance. In addition, no correlation was observed with cell counts, differentials, or proteins. It is hypothesized from these findings that multiple factors are involved in the production of an LAR. These factors most likely include mediator levels and underlying airway reactivity, with the more reactive airways requiring less mediators for bronchoconstriction to occur. This finding implies that therapeutic options in asthma should focus not only on blockage of mediator activity but also on reversal of underlying airway hyperreactivity.