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Aims of this study were to define (1) whether toluene diisocyanate (TDI) bronchial hyper-responsiveness persists in subjects with occupational asthma after long-term cessation of exposure; (2) whether evolution of specific bronchial TDI sensitization and symptoms and functional abnormalities of asthma were coincident, and (3) the determinants at the time of diagnosis of patients’ outcome. Twenty-five nonatopic spray painters with occupational asthma due to TDI were re-examined 58 ± 7 (46–73) months after removal from exposure. On both examinations, the severity of asthmatic symptoms and the need for antiasthma treatment over the past 12 months were graded and lung function tests, measurement of airway responsiveness to methacholine (PD20), circulating total IgE and TDI-HSA specific IgE, skin tests with common inhalant allergens and specific bronchial challenge with TDI were carried out. Seven subjects were still TDI-reactors and 18 lost reactivity to it. All persistent reactors had still asthma and their symptom score, medication score, FEV1, PD20 and serum IgE were unchanged between assessments. In the 18 subjects no longer responsive to TDI, 8 had still features of asthma: their symptom and medication score had improved significantly, but FEV1, PD20 and serum IgE had not significantly changed; the other ten patients no longer reactors to TDI were also asymptomatic and their PD20 had become normal. The duration of symptomatic exposure to TDI was the only feature at diagnosis that differentiated patients with persistent TDI airway hyper-responsiveness and asthma from those who were no longer responsive to TDI but still asthmatic and those who were no longer responsive to TDI and no longer asthmatic (4 ± 1. 6; 2. 1 ± 0. 8; 0. 6 ± 0. 3 years, respectively; p < 0. 001). Our study demonstrates that airway sensitization to TDI and symptoms and functional airway abnormalities of asthma can persist for years after cessation of exposure and may have different outcome. If avoidance of the offending agent takes place within few months after the development of symptoms, remission of asthma and of TDI bronchial hyper-responsiveness can occur, whereas waiting for years makes it too late to cure asthma and, in the end, to reverse specific sensitization. [ABSTRACT FROM AUTHOR]