Absence of a late-phase response or increase in histamine responsiveness after bronchial provocation with adenosine 5'-monophosphate in atopic and non-atopic asthma.
1. Adenosine 5'-monophosphate (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 cell mediators, 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. 2. 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. 3. Inhalation of the PC20 AMP resulted in an immediate fall in FEV1 to a mean maximum 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. 4. 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.
Phillips
G D
GD
Immunopharmacology Group, Southampton General Hospital, U.K.
Holgate
S T
ST
D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000249:Adenosine Monophosphate