Absence of a late-phase response or increase in histamine responsiveness after bronchial provocation with adenosine 5′-monophosphate in atopic and non-atopic asthma

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Abstract
AMP causes bronchoconstriction in atopic and non-atopic asthma by a mechanism believed to involve histamine release from airway mast cells. To determine whether preformed mast cellmediators, principally histamine, can initiate a late-phase bronchoconstriction we have investigated the effect on the airways over a 24 h period of a single bronchial challenge with AMP. Six atopic asthmatic subjects (all late responders to inhaled allergen) and six non-atopic asthmatic subjects were studied on two occasions for a 24 h period after inhalation of the provocation concentration of AMP required to produce a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline (PC20) and 0.9% (w/v) sodium chloride placebo, respectively. The atopic asthmatic subjects were studied on a further occasion after challenge with the PC20 allergen. Inhalation of the PC20 AMP resulted in an immediate fall in FEV1to a mean maximal 25.5% below baseline without resulting in any late decrease in airway calibre. No significant increase in non-specific bronchial responsiveness as determined by measuring the PC20 histamine before, and at 3, 9 and 24 h after, AMP challenge, occurred. Inhalation of the PC20 allergen caused a reproducible late-phase bronchoconstriction and increase in non-specific bronchial responsiveness in all the atopic asthmatic subjects studied. These results suggest that preformed mast cell mediators, principally histamine, play no role in the initiation of the late-phase reaction in allergen-provoked asthma, although they may contribute to the inflammatory changes involved.