The temporal relationship between increases in airway responsiveness to histamine and late asthmatic responses induced by occupational agents

The temporal relationship between increases in airway responsiveness and the late asthmatic response was assessed in nine patients challenged with occupational agents toluene diisocyanate (one patient), carmine (one patient), maleic anhydride (two patients), colophony (four patients), and trimellitic anhydride (one patient). The provocation concentration of histamine causing a 20% decrease in FEV 1 (PC 20) was measured before challenge and at approximately 3 hours and 24 hours on control and active-challenge days. Thirteen active challenges provoked eight definite late asthmatic responses (maximum fall in FEV 1 > 15% at 3 to 11 hours). At 3 hours after the challenges that provoked late responses, there was a significant ( p < 0.02) decrease in PC 20 that was more ( p < 0.03) than that observed for the five tests provoking early (late FEV 1 fall 0% to 5%) or equivocal late (FEV 1 fall 6% to 15%) responses. At 24 hours, PC 20 remained decreased ( p < 0.05), although it was less so than at 3 hours ( p < 0.05) and not significantly when compared with challenge tests causing single early or equivocal late responses. The 3-hour decreases in PC 20 were identified when FEV 1 (five of seven observations) was >90% of prechallenge values. For the nine independent tests, the 3-hour decreases in PC 20 correlated (r = 0.72; p < 0.05,) with the magnitude of the late falls in FEV 1, whereas this was not observed at 24 hours (r = 0.35; p, not significant). These results demonstrate that in subjects challenged with occupational agents, increases in histamine airway responsiveness precede the late asthmatic response, occur independently of changes in airway caliber, and correlate with the magnitude of the subsequent late response. We suggest that in subjects with occupational asthma, the late asthmatic response depends on the tissue events, possibly airway inflammation, that underlie the preceding increase in airway responsiveness.