Hexamethylene diisocyanate induction of transient airway hyperresponsiveness in guinea pigs

The induction of lung injury and the development of airway hyperresponsiveness (AHR) by exposure to hexamethylene diisocyanate (HDI) were studied in a guinea pig model of occupational lung diseases. In addition to an unexposed control group of 16 guinea pigs (A), two groups (B, C) of 8 animals inhaled HDI atmospheres in the range of the threshold limit value (TLV) of 10 ppb for 6 h/day on 5 days/week over a period of 8 weeks. Airway responses to aerosols of 0.125, 0.25, 0.5, 1.0 and 2.0% acetylcholine (ACH) were measured in exposed as well as in unexposed animals. Basal values of respiratory mechanical and cardiovascular parameters were not significantly altered after 8 weeks of HDI inhalation (group B). Furthermore, additional acute challenge by 10 ppb HDI for a period of 60 min, performed under continuous registration of respiratory and cardiovascular parameters, did not cause any significant changes in functional parameters. After 8 weeks of HDI exposure, the amplitude of airway constriction as a response to 2.0% ACH, indicated by the changes in dynamic elastance (Edyn) rose significantly to almost 5 times the ACH response in group A(p < 0.0005). In group C of 8 guinea pigs, ACH response was evaluated after a latency period of 8 weeks. In this group, changes of airway responsiveness to ACH were significantly smaller than in group B without a latency period. They were comparable to those of group A. In summary, HDI-induced airway hyperresponsiveness to ACH in the guinea pig is reversible within 8 weeks of HDI avoidance. It is assumed that the augmented airway responsiveness indicates an increased risk of developing isocyanate-induced obstructive lung diseases.