Mediator Release in an Isolated Airway Segment in Subjects with Asthma

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Abstract
To determine if mediator release would occur in the airways of human subjects after exposure to a hyperosmolar stimulus, we challenged isolated airway segments in vivo with 900 mosmol sodium chloride using a specially designed double-balloon catheter. In order to determine if differences in mediator concentrations correlated with airway responsiveness or with atropy, we studied 3 separate groups: 6 atopic, asthmatic subjects; 6 atopic, nonasthmatic subjects; and 6 nonatopic, nonasthmatic normal subjects. In addition, to determine if the presence of the catheter itself was a stimulus, we studied 6 atopic, asthmatic subjects after exposure to isotonic sodium chloride alone (sham exposure). Lavage specimens were assayed for PGD2, PGF2.alpha., PGE2, TxB2, LTC4, and LTB4 by radioimmunoassay and for histamine and for histamine by the modified single isotope enzymatic assay. The histamine concentration of the baseline lavage samples (bronchoalveolar lavage and isoalted airway segment lavage) for the subjects with asthma were significantly greater than for the atopic of normal subjects (P < 0.05). There was a significant negative correlation between histamine concentration in the lavage samples and the airway responsiveness of the subjects (r = -0.53, p < 0.0001). There was a marked correlation among the concentrations of histamine, PGD2, PGF2.alpha., and TxB2 in all the lavage fluids for the subjects with asthma (p < 0.03 for all comparisons and p < 0.0001 for overall concordance). As a result of hyperosmolar challenge, there was a significant increase in the concentration of histamine, PGD2, and PGF2.alpha. in the subjects with asthma. However, there was also an increase in PGD2 and histamine concentration with the sham exposure, suggesting that the presence of the catheter itself resulted in some mediator release. We conclude that there is more histamine present in the airways of subjects with asthma at baseline and that stimulus of the airways (catheter and hyperosmolar solution) results in further increase in histamine, PGD2, and PGF2.alpha.