Differences in airway responsiveness to leukotriene D4 in allergic sheep with and without late bronchial responses.

Allergic sheep respond to inhaled Ascaris suum antigen with either acute and late bronchial obstructions (dual responders) or only acute bronchoconstriction (acute responders). In this study we tested the hypothesis that one factor which may distinguish between these two populations is the difference in sensitivity to a specific mediator of airway anaphylaxis, leukotriene (LT) D4 (a major component of slow reacting substance of anaphylaxis). We postulated that if the hypothesis was correct then dual responders should demonstrate increased airway responses to inhaled LTD4 and that this increased responsiveness should also be reflected by a more severe response to inhaled antigen. To test this we used animals from both groups with the same degree of non-specific airway responsiveness to carbachol and determined their airway responses to controlled inhalation challenges with synthetic LTD4 and Ascaris suum antigen. Airway responsiveness to carbachol was determined by measuring the change in specific lung resistance (SRL) to increasing concentrations of carbachol aerosol, and then identifying, by linear interpolation, the provocative carbachol concentration which produced a 150% increase (PC150) in SRL. Airway responses to LTD4, and antigen were determined by measuring the percentage change in SRL after a controlled inhalation challenge with either aerosol. Airway responsiveness to carbachol was not different between the two groups. There was, however, a difference (p less than 0.05) in the airway response to the same dose of LTD4 in the two groups. Dual responders showed a 297 +/- 72% increase in SRL as compared to a 90 +/- 13% increase in SRL in the acute responders. Dual responders also showed a greater immediate and more prolonged response to antigen than did acute responders. These results suggest that increased responsiveness to LTD4 may be one factor which may distinguish dual responders from acute responders.