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 atopy, 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 by the modified single
isotope enzymatic assay. The
histamine concentration of the baseline lavage samples (bronchoalveolar lavage and isolated airway segment lavage) for the subjects with
asthma were significantly greater than for the atopic or normal subjects (p less than 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 less than 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 less than 0.03 for all comparisons and p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)