The prevalence studies on specific IgE to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate in TDI-induced asthma have shown variable results. In this study, we attempted to compare specific IgE bindings to TDI-HSA conjugate and its specificity using 3 different conjugates. Sera were collected from 20 TDI-induced asthma and 10 controls. Specific IgE were measured by ELISA using three TDI-HSA conjugates; two from Carnegie Mellon (CM; 98 and 99 CM conjugates) and one from Ajou University. To evaluate specificity and cross-reactivity, ELISA inhibition tests were applied. Positive and negative predictive values between Ajou conjugate and 98 CM conjugate were 75% and 100%. Those between Ajou and 99 CM were 100% and 93.8%. One patient showed an isolated positive response to the Ajou with negative responses to the other two conjugates. ELISA inhibition test using this patient's serum revealed the significant inhibitions by the Ajou and minimal inhibitions by the others. On the other hand, another patient showed an isolated positive response to 99 CM with negative responses to the others, and ELISA inhibition test showed significant inhibition by 99 CM with minimal inhibitions by the others. These results suggest that specific IgE bindings to a new antigenic determinant of TDI-HSA conjugate can be heterogeneous and differ from one individual to another.
Asthma/immunology ; Asthma/chemically induced* ; Enzyme-Linked Immunosorbent Assay ; Human ; IgE/biosynthesis* ; Serum Albumin/immunology* ; Toluene 2,4-Diisocyanate/immunology* ; Toluene 2,4-Diisocyanate/adverse effects

OBJECTIVE: To explore the effect of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice. METHODS: Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated. RESULTS: TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05). CONCLUSION Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.
Animals ; Asthma/chemically induced* ; Inflammation ; Macrophages ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases ; Respiratory System ; Toluene 2,4-Diisocyanate/adverse effects*

Isocyanate is the most prevalent agent in occupational asthma(OA) in Korea. We analyzed 43 toluene diisocyanate(TDI) induced OA patients of whom 81% were found to be spray painters. The bronchial sensitivity of all subjects was confirmed by TDI-bronchial challenge test. Serum-specific IgE antibodies to isocyanate-human serum albumin(HSA) conjugate were detected by RAST technique(Pharmacia, Sweden). Bronchial challenge test results revealed 21(57%) early, 5 late only, 4 dual, and 12 atypical responders(5 prolonged immediate, 6 square-shaped, 1 progressive). Four(9%) subjects had negative results on the methacholine bronchial challenge test. High levels of serum specific IgE antibody to isocyanate-HSA were found in 17(40%) patients. The prevalence of a specific IgE antibody was not associated with a type of TDI-bronchial challenge test response, smoking and atopic status, presence of rhino-sinusitis and systemic symptoms, or a degree of airway hyperresponsiveness to methacholine(p> 0.05). The period of latency, ranging from 3 to 132 months, was significantly longer in high specific IgE responders (p< 0.05). These data suggest that 40% of isocyanate-induced occupational asthma patients had high specific IgE antibody to isocyanate-HSA conjugate. The presence of specific IgE antibody does not seem to correlate with clinical parameters.
Allergens/adverse effects/*immunology ; Asthma/chemically induced/*immunology ; Female ; Human ; Immunoglobulin E/blood/*immunology ; Male ; Occupational Exposure/*adverse effects ; Toluene 2,4-Diisocyanate/adverse effects/*immunology

Adult ; Air Pollutants, Occupational ; adverse effects ; Health Status ; Humans ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Toluene 2,4-Diisocyanate ; adverse effects ; Young Adult

OBJECTIVETo investigate the effect of long-term exposure to toluene diisocyanate (TDI) on the lung function of TDI-exposed workers.

METHODSA factory was selected for this occupational epidemiological investigation. The workers who were exposed to TDI and had complete physical examination records in recent 3 years were the exposed group (n = 45), while the company's administrative staff, logistics staff, and other non-TDI-exposed workers who had complete physical examination records in recent 3 years were the control group (n = 47). The two groups were compared in terms of lung function indices.

RESULTSCompared with the control group, the 2009 exposure group had significantly lower forced expiratory volume in one second (FEV1.0), FEV1.0/forced vital capacity (FVC), and maximal expiratory flow at 25% of FVC (MEF25) (P < 0.05), the 2010 exposure group had significantly lower FEV1.0, FEV1.0/FVC,maximum voluntary ventilation (MVV), and maximal expiratory flow at 50% of FVC (MEF50) (P < 0.05), and the 2011 exposure group had significantly lower FEV1.0, FEV1.0/FVC, peak expiratory flow (PEF), MEF25, and MEF50 (P < 0.05).

CONCLUSIONLong-term exposure to TDI can lead to certain impairment of lung function in workers, which may be reflected by decreased lung function indices such as vital capacity, FVC, FEV1.0, FEV1.0/FVC, PEF, and MVV.

Case-Control Studies ; Forced Expiratory Volume ; Humans ; Lung ; drug effects ; physiopathology ; Male ; Occupational Exposure ; Toluene 2,4-Diisocyanate ; adverse effects ; Vital Capacity ; drug effects

Isocyanates are the most significant cause of occupational asthma in our country. To evaluate the prevalence of work-related respiratory symptoms and immunologic sensitization to it, we performed a questionnaire survey, allergy skin test, radioallergosorbent test (RAST) to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate and methacholine bronchial challenge test on 23 isocyanate-exposed employees and 9 unexposed controls working in a zipper factory. Six employees (26.1%) complained of work-related respiratory symptoms and three symptomatic workers showed significant bronchoconstrictions on TDI-bronchoprovocation test. Three (13%) asymptomatic workers had high specific IgE antibodies to TDI-HSA and none of the TDI-sensitive asthmatic workers had specific IgE antibody. One of the TDI-sensitive asthmatic workers showed a negative result on the initial methacholine bronchial challenge test, but bronchial hyperresponsiveness developed after the TDI challenge. It was suggested that TDI-sensitive asthma was noted in three (13%) of 23 exposed workers and that asymptomatic workers could have high specific IgE antibody. Measurement of the changes in bronchial hyperresponsiveness after the TDI challenge could be helpful to diagnose TDI-sensitive asthma.
Adult ; Asthma/*chemically induced/diagnosis ; Bronchial Provocation Tests ; Humans ; Immunoglobulin E/analysis ; Occupational Diseases/*chemically induced/diagnosis ; Occupational Exposure ; Serum Albumin/immunology ; Toluene 2,4-Diisocyanate/*adverse effects/immunology

OBJECTIVETo investigate the effect of occupational exposure to toluene diisocyanate (TDI) on the workers' health.

METHODSA total of 76 workers exposed to TDI (exposure group) and 64 management staff members (control group) were selected from a factory as the study subjects. Area sampling was performed for the place with exposure to TDI according to the method in GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace, and gas chromatography was applied to measure the concentration of TDI in workplace air. The workers' personal information was collected with questionnaire, pulmonary ventilation function was determined with a portable spirometer, hematological parameters were analyzed by automatic blood analyzer and blood chemistry analyzer, and the indicators of oxidative damage and energy metabolism were measured by the reagent kit provided by Nanjing Jiancheng Bioengineering Institute. SPSS 17 software was applied for statistical analysis.

RESULTSThe exposure group had significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second(FEV1.0), and FEV1.0/FVC ratio than the control group (P <0.05). Compared with the control group, the exposure group had significantly higher red blood cell count, platelet distribution width, mean platelet volume, lymphocyte count, and neutrophil count(P<0.01), and significantly lower activities of lactate dehydrogenase(LDH), superoxide dismutase, and succinodehydrogenase (SDH)(P <0.01). In the exposure group, the length of exposure was negatively correlated with the activities of SDH and LDH in the serum (r=-0.319, P <0.05; r=-0.239, P <0.05), and the length of exposure was not found to be correlated with the activity of SOD and pulmonary function indices.

CONCLUSIONTDI can induce inflammatory response and lung ventilation function impairment in workers exposed to TDI, as well as oxidative stress and imbalance of energy metabolism. Therefore, it can cause damage to workers' health, and protective measures should be enhanced.

Case-Control Studies ; Erythrocyte Count ; Forced Expiratory Volume ; Humans ; Inflammation ; physiopathology ; L-Lactate Dehydrogenase ; blood ; metabolism ; Leukocyte Count ; Lung ; physiopathology ; Occupational Exposure ; adverse effects ; Pulmonary Ventilation ; Succinate Dehydrogenase ; blood ; metabolism ; Superoxide Dismutase ; metabolism ; Toluene 2,4-Diisocyanate ; adverse effects ; Vital Capacity

Current asthma is often diagnostically excluded by the presence of normal bronchial responsiveness. We report on a TDI-induced occupational asthma patient with normal bronchial responsiveness. He had suffered from shortness of breath during and after TDI exposure for several months. His initial methacholine bronchial challenge test showed a negative response. The bronchoprovacation test with TDI showed an isolated immediate bronchoconstriction. The following methacholine bronchial challenge tests revealed that the bronchial hyperresponsiveness developed seven hours after the TDI challenge (methacholine PC20:5.1 mg/ml), progressed up until 24 hours, and returned to normal on the seventh day. This case provides evidence that the response of the airway to TDI may not always be accompanied by bronchial hyperresponsiveness to methacholine. Screening programs utilizing methacholine challenges may not always identify TDI-sensitized asthmatic workers.
Adult ; Asthma/*chemically induced/diagnosis ; Bronchial Provocation Tests ; Bronchoconstriction/*drug effects ; Humans ; Male ; Methacholine Chloride/*diagnostic use ; Occupational Diseases/*chemically induced ; Skin Tests ; Time Factors ; Toluene 2,4-Diisocyanate/*adverse effects

BACKGROUND: An appreciable number of patients with toluene diisocyanate (TDI)-induced asthma have high serum levels of specific IgE (sIgE) antibody to TDI-human serum albumin conjugate (HSA). A recent investigation suggested a role of specific IgG (sIgG) in the development of TDI asthma. METHODS: We observed the changes in the levels of specific IgE and IgG antibodies to TDIHSA conjugate in TDI-induced asthmatic patients during seven years avoidance. RESULTS: Six subjects with high sIgE and five with high sIgG were enrolled. All of them had taken anti-asthmatic medications with complete avoidance. Serum levels of sIgE and sIgG to TDI-HSA conjugate were detected by ELISA. The level of sIgE continued to decline up to 7 years and the mean half-life was 3.9 years. The mean half-life of sIgG was 4.5 yrs. CONCLUSION: These findings suggest that both sIgE and sIgG to TDI-HSA conjugate may persist for several years after the last exposure to TDI.
Adult ; Asthma/*chemically induced/immunology ; Biological Markers/blood ; Human ; Immunoglobulin E/blood/*immunology ; Immunoglobulin G/blood/*immunology ; Longitudinal Studies ; Male ; Middle Aged ; Serum Albumin/*immunology ; Support, Non-U.S. Gov't ; Toluene 2,4-Diisocyanate/adverse effects/*immunology

BACKGROUND: Plastic resins are complex chemicals that contain toluene diisocyanate (TDI) and/or trimellitic anhydride (TMA), which cause occupational allergies (OA), including respiratory allergies. Serum IgGs against TDI and TMA have been suggested as potential markers of the exposure status and as exploring cause of OA. Although TDI-specific IgG has been examined for suspected OA, TMA-specific IgG is not commonly evaluated in a urethane foam factory. This study therefore investigated both TDI- and TMA-specific IgGs in suspected OA patients and to evaluate the usefulness of the measurement of multiple chemical-specific IgG measurement for practical monitoring. METHODS: Blood samples were collected from two male workers who developed respiratory allergies supposedly caused by occupational exposure to TDI and/or TMA for the presence of TDI- and TMA-specific IgGs. In addition, blood samples from 75 male workers from a urethane foam factory, along with 87 male control subjects, were collected in 2014 and tested for the same IgGs in 2014. The presence and levels of TDI- and TMA-specific serum IgGs were measured using dot blot assays. RESULTS: We found that controls had mean concentrations of TDI- and TMA-specific IgGs of 0.98 and 2.10 μg/mL, respectively. In the two workers with respiratory allergies, the TDI-specific IgG concentrations were 15.6 and 9.51 μg/mL, and TMA-specific IgG concentrations were 4.56 and 14.4 μg/mL, which are clearly higher than those in controls. Mean concentrations of TDI- and TMA-specific IgGs in the factory workers were 1.89 and 2.41 μg/mL, respectively, and are significantly higher than those of the controls (P < 0.001 and P < 0.026 for TDI- and TMA-specific IgGs, respectively). CONCLUSION The workers suspected of OA showed an evidently high level of TDI- and TMA-specific IgG, and these levels in workers at the urethane foam factory were also significantly higher than those in controls. In conclusion, the measurement of TDI- and TMA-specific IgG among workers using plastic resins is helpful to monitor their exposure status.
Adult ; Air Pollutants, Occupational ; adverse effects ; immunology ; Environmental Monitoring ; Humans ; Immunoglobulin G ; blood ; immunology ; Japan ; Male ; Manufacturing and Industrial Facilities ; statistics & numerical data ; Middle Aged ; Occupational Diseases ; blood ; chemically induced ; Occupational Exposure ; adverse effects ; statistics & numerical data ; Phthalic Anhydrides ; immunology ; toxicity ; Respiratory Hypersensitivity ; blood ; chemically induced ; Toluene 2,4-Diisocyanate ; immunology ; toxicity ; Workforce