The Effect of Oral Terfenadine Alone and in Combination with Flurbiprofen on the Bronchoconstrictor Response to Inhaled Adenosine 5′-Monophosphate in Nonatopic Asthma

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Abstract
Inhaled adenosine and adenosine 5 ′-monophosphate (AMP) cause bronchoconstriction in atopic and nonatopic asthmatics by a mechanism believed to involve histamine release from airway mast cells and an interaction with neural reflexes. In the present study, we have investigated the effect of oral terfenadine 180 mg, flurbiprofen 100 mg, and the drug combination on AMP-induced bronchoconstriction in eight nonatopic asthmatic subjects with a mean age of 53.8 ± 5.6 yr. The provocation concentrations of histamine and AMP required to produce a 20% decrease in FEV1 (PC20) were determined to be 2.5 (range, 0.2 to 16.3) and 50.1 (range, 1.5 to 841) mg/ml, respectively, representing a potency difference of 17.8-fold on a molar basis. In subsequent time-course studies, the bronchoconstrictor response to inhalation of the PC20 histamine was suppressed completely by terfenadine and the drug combination, but unaffected by flurbiprofen. Terfenadine alone and flurbiprofen alone inhibited bronchoconstriction provoked by the PC20 AMP by 49.8 ± 5.5% (p < 0.01) and 31.9 ± 7.9% (p < 0.01), respectively, when areas under the FEV1 time curves were compared with placebo, the difference between the two treatments not being significant (p = 0.06). The drug combination inhibited the response to AMP by 60.0 ± 8.3% (p < 0.01), this being significantly greater than with flurbiprofen (p < 0.01), but not with terfenadine alone. These data implicate both histamine and cyclooxygenase products in the bronchoconstrictor response to AMP.