Role of acetylcholinesterase inhibition in toluene diisocyanate (TDI) induced bronchoconstriction.

Two groups of subjects (ten controls and 13 with a clinical history of bronchial asthma attributed to TDI exposure in industry), underwent a specific bronchial stimulation test with TDI at concentrations around the MAC. Five other subjects not exposed to TDI, underwent an a specific bronchial stimulation test with carbachol. AChE and CHE activity and respiratory function (FEV1 and V max 50%) were determined before, immediately after and 4 h after exposure. In vitro, the ID50 and ID90 of TDI on AChE activity is very high (7.2 x 10−5 and 6.8 × 10−4 mol/l, respectively). In vivo, AChE activity of the control group and of the group exposed to carbachol is not inhibited, while in TDI professionally exposed subjects, five show only a fall of ACNE activity after 4 h (6% lower than the base, P < 0.005), without respiratory impairment, five show a “late” response with AChE inhibition of 13% (P < 0.001); three show a “dual” response with AChE activity inhibition of 16% (P < 0.001) after 4h. There was no variation of CHE activity in any subject. The authors hypothesized a “biochemical” effect mediated by an immune mechanism due to the presence of antibodies against acetylcholinesterase-TDI complex with a threshold effect on respiratory impairment due to acetylcholinesterase inhibition.