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Hae-sim Park - One of the best experts on this subject based on the ideXlab platform.
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epithelial folliculin is involved in airway inflammation in workers exposed to Toluene Diisocyanate
Experimental and Molecular Medicine, 2017Co-Authors: Duy Le Pham, Tu Hk Trinh, Gayoung Ban, Seunghyun Kim, Hae-sim ParkAbstract:Long-term exposure to Toluene Diisocyanate (TDI) triggers asthma by enhancing levels of a protein found in airway cells. TDI is a compound used in paints, varnishes and upholstery foam. Workers exposed to TDI can develop occupational asthma, but precisely why this happens is unclear. Hae-Sim Park at Ajou University in South Korea and co-workers examined the involvement of a protein called folliculin in the development of TDI-induced asthma. Folliculin is expressed by airway tissue cells to help maintain healthy tissue structures. The researchers analyzed serum samples from 212 TDI-exposed individuals, 93 of whom had occupational asthma, and compared these with samples from control groups. Levels of folliculin were considerably higher in the TDI-exposed group than the controls. TDI appears to be a strong inducer of folliculin production, and disrupts the control of airway inflammation.
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serum specific igg response to Toluene Diisocyanate tissue transglutaminase conjugate in Toluene Diisocyanate induced occupational asthmatics
Annals of Allergy Asthma & Immunology, 2014Co-Authors: Le Duy Pham, Miae Kim, Moon Gyung Yoon, Seung Ihm Lee, Yoo Seob Shin, Hae-sim ParkAbstract:Abstract Background Tissue transglutaminase (tTG) is a post-translational modifying enzyme located in airway epithelial cells. A potential contribution of serum specific IgG (sIgG) to tTG in airway inflammation of Toluene Diisocyanate (TDI)-induced occupational asthma (OA) has been suggested. Objective To prepare a TDI-tTG conjugate and detect serum specific antibodies in sera of patients with TDI-OA to understand this mechanism. Methods Ninety-nine patients with TDI-OA, 76 asymptomatic exposed controls, 208 patients with non-OA, and 74 unexposed controls were enrolled for this study. The TDI-tTG conjugate was prepared and confirmed by a native gel. Serum sIgG and/or sIgE antibodies to tTG, TDI-tTG, TDI conjugated to human serum albumin, cytokeratin 19, and serum cytokine levels, such as interleukin-8, transforming growth factor-β1, and tissue inhibitor of metalloproteinase-1, were measured by enzyme-linked immunosorbent assay. The level of interleukin-8 produced from airway epithelial cells (A549) treated with tTG was evaluated to investigate the inflammatory effect of tTG and TDI-tTG. Results In the TDI-OA group, the prevalence of serum sIgG to TDI-tTG (17.2%) was higher than that of sIgG to tTG (11.1%), which were significantly higher than those of the 3 control groups ( P Conclusion These findings suggest that TDI exposure in the workplace binds to tTG to form a conjugate that can induce serum sIgG antibody production, airway inflammation, and airway remodeling in patients with TDI-OA.
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biophysical determinants of Toluene Diisocyanate antigenicity associated with exposure and asthma
The Journal of Allergy and Clinical Immunology, 2006Co-Authors: Young-min Ye, Dong-ho Nahm, Carrie A Redlich, Hae-sim Park, Adam V WisnewskiAbstract:Background Toluene Diisocyanate (TDI), a widely used aromatic Diisocyanate with the potential to cause asthma, reacts with albumin in the airway fluid, which acts as a carrier protein for chemical presentation to the immune system. Structural elucidation of TDI-albumin conjugates is crucial to understanding the human immune response to TDI exposure. Objective Investigate the dependence of TDI's antigenicity on the biophysics of exposure and its association with TDI asthma. Methods Toluene Diisocyanate–albumin conjugates were generated by exposing albumin to TDI in liquid or vapor phase (liquid or vapor TDI-albumin, respectively). Conjugates were characterized by native gel electrophoresis and matrix-assisted laser desorption/ionization-mass spectrometry, and used as antigens in ELISA assays for serum specific-IgE and IgG. Results The physical phase of TDI (vapor vs liquid) affects the formation of TDI-albumin conjugates, with measurable differences in the amount of TDI per albumin molecule, migration in native gels, matrix-assisted laser desorption/ionization-mass spectrometry mass/charge spectra, and antigenicity. Vapor TDI-albumin conjugates were recognized by IgE from 44% of subjects with TDI asthma, whereas liquid TDI-albumin conjugates are recognized by IgE from only 17% of these patients. A significant ( P Conclusion Biophysics of TDI exposure substantially affects formation of TDI-albumin conjugates recognized by the immune system in association with exposure and asthma. Clinical implications The data suggest that serology may help identify TDI asthmatics and exposed workers if the appropriate form of TDI is used as the antigenic basis for analysis.
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longitudinal study of specific antibodies to Toluene Diisocyanate tdi human serum albumin hsa conjugate in patients with tdi induced asthma
The Korean Journal of Internal Medicine, 2002Co-Authors: Hae-sim Park, Dong-ho NahmAbstract: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.
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specific immunoglobulin e and immunoglobulin g antibodies to Toluene Diisocyanate human serum albumin conjugate useful markers for predicting long term prognosis in Toluene Diisocyanate induced asthma
Clinical & Experimental Allergy, 2002Co-Authors: Hae-sim Park, Dong-ho NahmAbstract:Summary Background Our previous study reported that more than 50% of Toluene Diisocyanate (TDI)-induced asthma patients had persistent asthmatic symptoms even after complete avoidance. Although specific IgE (sIgE) has been detected in a portion of patients with TDI-asthma, a recent investigation suggests that the presence of serum specific IgG (sIgG), not sIgE, is more closely associated with positive bronchoprovocation test (BPT) results. Objective To evaluate the possible role of sIgE and sIgG in predicting long-term prognosis of TDI-asthma. Materials and methods Forty-one TDI-asthma patients whose diagnosis was confirmed by TDI-BPT, and 20 unexposed healthy controls were enrolled. Both sIgE and sIgG to TDI-human serum albumin (HSA) conjugate were detected by ELISA. All patients with persistent asthmatic symptoms took anti-asthmatic medications during the follow-up period (mean: 67.5 months) and were instructed to avoid exposure to TDI. Airway hyper-responsiveness to methacholine (AHM) was monitored every year during the study period. The patients were classified into three groups according to changing patterns of AHM and asthmatic symptoms as follows: group I, no improvement with persistent asthmatic symptoms (n = 12); group II, partial improvement with persistent asthmatic symptoms (n = 13); group III, in remission (n = 16). Results Favourable prognosis was associated with a mild degree of AHM at initial diagnosis (P 0.05), prevalence of sIgG in group I tended to be higher than in group II (0.05 0.05). Conclusion This study confirmed that a favourable outcome is related to a mild degree of AHM and to low levels of sIgG to predict persistent asthmatic symptoms, it also suggested that the presence of high serum-specific IgE at initial diagnosis may represent a better prognosis.
Dong-ho Nahm - One of the best experts on this subject based on the ideXlab platform.
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biophysical determinants of Toluene Diisocyanate antigenicity associated with exposure and asthma
The Journal of Allergy and Clinical Immunology, 2006Co-Authors: Young-min Ye, Dong-ho Nahm, Carrie A Redlich, Hae-sim Park, Adam V WisnewskiAbstract:Background Toluene Diisocyanate (TDI), a widely used aromatic Diisocyanate with the potential to cause asthma, reacts with albumin in the airway fluid, which acts as a carrier protein for chemical presentation to the immune system. Structural elucidation of TDI-albumin conjugates is crucial to understanding the human immune response to TDI exposure. Objective Investigate the dependence of TDI's antigenicity on the biophysics of exposure and its association with TDI asthma. Methods Toluene Diisocyanate–albumin conjugates were generated by exposing albumin to TDI in liquid or vapor phase (liquid or vapor TDI-albumin, respectively). Conjugates were characterized by native gel electrophoresis and matrix-assisted laser desorption/ionization-mass spectrometry, and used as antigens in ELISA assays for serum specific-IgE and IgG. Results The physical phase of TDI (vapor vs liquid) affects the formation of TDI-albumin conjugates, with measurable differences in the amount of TDI per albumin molecule, migration in native gels, matrix-assisted laser desorption/ionization-mass spectrometry mass/charge spectra, and antigenicity. Vapor TDI-albumin conjugates were recognized by IgE from 44% of subjects with TDI asthma, whereas liquid TDI-albumin conjugates are recognized by IgE from only 17% of these patients. A significant ( P Conclusion Biophysics of TDI exposure substantially affects formation of TDI-albumin conjugates recognized by the immune system in association with exposure and asthma. Clinical implications The data suggest that serology may help identify TDI asthmatics and exposed workers if the appropriate form of TDI is used as the antigenic basis for analysis.
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longitudinal study of specific antibodies to Toluene Diisocyanate tdi human serum albumin hsa conjugate in patients with tdi induced asthma
The Korean Journal of Internal Medicine, 2002Co-Authors: Hae-sim Park, Dong-ho NahmAbstract: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.
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specific immunoglobulin e and immunoglobulin g antibodies to Toluene Diisocyanate human serum albumin conjugate useful markers for predicting long term prognosis in Toluene Diisocyanate induced asthma
Clinical & Experimental Allergy, 2002Co-Authors: Hae-sim Park, Dong-ho NahmAbstract:Summary Background Our previous study reported that more than 50% of Toluene Diisocyanate (TDI)-induced asthma patients had persistent asthmatic symptoms even after complete avoidance. Although specific IgE (sIgE) has been detected in a portion of patients with TDI-asthma, a recent investigation suggests that the presence of serum specific IgG (sIgG), not sIgE, is more closely associated with positive bronchoprovocation test (BPT) results. Objective To evaluate the possible role of sIgE and sIgG in predicting long-term prognosis of TDI-asthma. Materials and methods Forty-one TDI-asthma patients whose diagnosis was confirmed by TDI-BPT, and 20 unexposed healthy controls were enrolled. Both sIgE and sIgG to TDI-human serum albumin (HSA) conjugate were detected by ELISA. All patients with persistent asthmatic symptoms took anti-asthmatic medications during the follow-up period (mean: 67.5 months) and were instructed to avoid exposure to TDI. Airway hyper-responsiveness to methacholine (AHM) was monitored every year during the study period. The patients were classified into three groups according to changing patterns of AHM and asthmatic symptoms as follows: group I, no improvement with persistent asthmatic symptoms (n = 12); group II, partial improvement with persistent asthmatic symptoms (n = 13); group III, in remission (n = 16). Results Favourable prognosis was associated with a mild degree of AHM at initial diagnosis (P 0.05), prevalence of sIgG in group I tended to be higher than in group II (0.05 0.05). Conclusion This study confirmed that a favourable outcome is related to a mild degree of AHM and to low levels of sIgG to predict persistent asthmatic symptoms, it also suggested that the presence of high serum-specific IgE at initial diagnosis may represent a better prognosis.
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diverse profiles of specific ige response to Toluene Diisocyanate tdi human serum albumin conjugate in tdi induced asthma patients
Journal of Korean Medical Science, 2001Co-Authors: Hae-sim Park, Dong-ho NahmAbstract: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.
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specific igg but not specific ige antibodies to Toluene Diisocyanate human serum albumin conjugate are associated with Toluene Diisocyanate bronchoprovocation test results
The Journal of Allergy and Clinical Immunology, 1999Co-Authors: Hae-sim Park, Dong-ho NahmAbstract:Abstract Background: The role of specific IgG to Toluene Diisocyanate (TDI) in the pathogenesis of TDI-induced asthma still remains unclear. Objective: We sought to evaluate the clinical significance of serum-specific IgG to TDI-human serum albumin (HSA) conjugate in subjects with TDI-induced asthma compared with specific IgE antibody. Methods: One hundred three subjects were enrolled and divided into 4 groups according to specific bronchoprovocation test (BPT) results: 50 subjects with TDI-induced asthma with positive results on TDI BPT were defined as group 1, 13 symptomatic workers exposed to TDI with negative results on TDI BPT were defined as group 2, 20 unexposed patients with allergic asthma were defined as group 3, and 20 unexposed healthy control subjects were defined as group 4. Serum-specific IgG and IgE antibodies to TDI-HSA conjugate were detected by means of ELISA. Results: The prevalence of specific IgG antibody to TDI-HSA conjugate was significantly higher in group 1 than in group 2 (46% vs 7.7%, P = .01) or group 3 (0%, P P > .05). However, the prevalence of specific IgE antibody to TDI-HSA conjugate was not significantly different between group 1 and group 2 (14% vs 7.7%, P > .05) or group 2 and group 3 (7.7% vs 0%, P > .05). There was no significant difference in prevalence of specific IgE or specific IgG according to the type of asthmatic response during the TDI BPT ( P > .05). Overall, statistically significant association was noted between the prevalence of specific IgE and IgG antibodies in 103 subjects ( P P > .05). Conclusion: These findings demonstrate that the presence of serum-specific IgG is closely related to TDI BPT results, and it may contribute to the development of TDI-induced asthma. (J Allergy Clin Immunol 1999;104:847-51.)
Sebastien Gagne - One of the best experts on this subject based on the ideXlab platform.
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quantitative determination of hexamethylene Diisocyanate hdi 2 4 Toluene Diisocyanate 2 4 tdi and 2 6 Toluene Diisocyanate 2 6 tdi monomers at ppt levels in air by alkaline adduct coordination ionspray tandem mass spectrometry
Journal of Environmental Monitoring, 2005Co-Authors: Jacques Lesage, Yves Cloutier, Sebastien Gagne, Claude Ostiguy, Huu Van TraAbstract:Occupational exposures to isocyanates can lead to occupational asthma. Once sensitized, some workers could react to isocyanate monomers at concentrations below 1% of the Permissible Exposure Limit of 5 ppb in air. Currently available methods are not sufficiently sensitive to adequately evaluate isocyanates present at these levels in workplace air. This article describes a novel method for isocyanate determination allowing the ultratrace quantification in workplace air of hexamethylene Diisocyanate, 2,4-Toluene Diisocyanate and 2,6-Toluene Diisocyanate monomers. Sampling is performed during a complete workshift at a flow rate of 1 L min−1 with a cassette containing a 1-(2-methoxyphenyl)piperazine-impregnated 25 mm filter. Analysis is performed using liquid chromatography hyphenated with coordination ionspray tandem mass spectrometry. The analytical method’s linearity was measured for a concentration range varying from the limit of detection of 0.04–0.13 ng mL−1, depending on the monomer, up to approximately 32 ng mL−1 for every isocyanate monomer, all with correlation coefficients (R2) greater than 0.999. The analytical method’s lower limit of quantification combined with an adapted sampling strategy allow the quantification of isocyanate monomers down to 0.04 ppt for an 8 h work shift when a lithium adduct is used, which is more than 300 times lower than the most sensitive method currently available. This novel method can be used to confirm the very low level of isocyanate monomers for the safe reassignment of sensitized workers and it is also useful for charting the isocyanate dispersion tail in workplace environments.
Hakan Tinnerberg - One of the best experts on this subject based on the ideXlab platform.
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Toluene Diisocyanate exposure and autotaxin lysophosphatidic acid signalling
Toxicology and Applied Pharmacology, 2018Co-Authors: Julia M Brostrom, Aram Ghalali, Huiyuan Zheng, Johan Hogberg, Ulla Stenius, Margareta Littorin, Hakan Tinnerberg, Karin BrobergAbstract:Abstract Toluene Diisocyanate (TDI) is a reactive chemical used in manufacturing plastics. TDI exposure adversely affects workers' health, causing occupational asthma, but individuals differ in susceptibility. We recently suggested a role for signalling mediated by the enzyme autotaxin (ATX) and its product, lysophosphatidic acid (LPA), in TDI toxicity. Here we genotyped 118 TDI-exposed workers for six single-nucleotide polymorphisms (SNPs) in genes encoding proteins implicated in ATX–LPA signalling: purinergic receptor P2X7 (P2RX7), C C motif chemokine ligand 2 (CCL2), interleukin 1β (IL1B), and caveolin 1 (CAV1). Two P2RX7 SNPs (rs208294 and rs2230911) significantly modified the associations between a biomarker of TDI exposure (urinary 2,4-Toluene diamine) and plasma LPA; two IL1B SNPs (rs16944 and rs1143634) did not. CAV1 rs3807989 modified the associations, but the effect was not statistically significant (p = 0.05–0.09). In vitro, TDI-exposed bronchial epithelial cells (16HBE14o-) rapidly released ATX and IL-1β. P2X7 inhibitors attenuated both responses, but confocal microscopy showed non-overlapping localizations of ATX and IL-1β, and down-regulation of CAV1 inhibited the ATX response but not the IL-1β response. This study indicates that P2X7 is pivotal for TDI-induced ATX–LPA signalling, which was modified by genetic variation in P2RX7. Furthermore, our data suggest that the TDI-induced ATX and IL-1β responses occur independently.
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Toluene Diisocyanate induction of the autotaxin lysophosphatidic acid axis and its association with airways symptoms
Toxicology and Applied Pharmacology, 2015Co-Authors: Julia M Brostrom, Aram Ghalali, Huiyuan Zheng, Ulla Stenius, Margareta Littorin, Hakan Tinnerberg, Christian H Lindh, Anna Axmon, Bo Jonsson, Johan HogbergAbstract:Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of Toluene Diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to <5ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose-response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting "sneezing", the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity.
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development validation and characterization of an analytical method for the quantification of hydrolysable urinary metabolites and plasma protein adducts of 2 4 and 2 6 Toluene Diisocyanate 1 5 naphthalene Diisocyanate and 4 4 methylenediphenyl Diisocyanate
Biomarkers, 2003Co-Authors: Carl Johan Sennbro, Margareta Littorin, Hakan Tinnerberg, Christian H Lindh, Cecilia Gustavsson, Hans Welinder, Bo A G JonssonAbstract:Occupational exposure to Diisocyanates within the plastic industry causes irritation and disorders in the airway. The aim of this study was to develop, validate and characterize a method for the determination of 2,4-Toluenediamine (2,4-TDA), 2,6-Toluenediamine (2,6-TDA), 1,5-diaminonaphthalene (1,5-NDA) and 4,4′-methylenedianiline (4,4′-MDA) in hydrolysed urine and plasma, and to study the correlation between the plasma and urinary levels of these potential biomarkers of 2,4-Toluene Diisocyanate (2,4-TDI), 2,6-Toluene Diisocyanate (2,6-TDI), 1,5-naphthalene Diisocyanate (1,5-NDI) and 4,4′-methylenediphenyl Diisocyanate (4,4′-MDI), respectively. Samples were hydrolysed with 0.3 M NaOH at 100°C for 24 h. The diamines were extracted, derivatized with pentafluoropropionic acid anhydride, and quantified by selected ion monitoring on gas chromatography-mass spectrometry. The repeatability and reproducibility of the method were 7-18% and 7-19%, respectively. Dialysis experiments showed that the metabolites of 2,...
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determination of complex mixtures of airborne isocyanates and amines part 2 Toluene Diisocyanate and aminoisocyanate and Toluenediamine after thermal degradation of a Toluene Diisocyanate polyurethane
Analyst, 1996Co-Authors: Hakan Tinnerberg, Marten Spanne, Marianne Dalene, Gunnar SkarpingAbstract:An LC–MS method is presented for the determination of thermal decomposition products of polyurethane. The method is based on the collection of air samples in midget impinger flasks containing 0.01 mol l–1 dibutylamine (DBA) dissolved in Toluene. DBA reacts with isocyanates to give urea derivatives. The amines simultaneously collected were derivatized with ethyl chloroformate (ET) to give urethane derivatives. Two isomers of Toluene Diisocyanate (2,4-and 2,6-TDI), Toluene-2,4-and-2,6-diamine (TDA), three isomers of Toluene aminoisocyanates and oligomers with two and three aromatic rings were determined in air containing thermal decomposition products of TDI–polyurethane. LC with gradient elution, at 0.5 ml min–1 starting with acetonitrile–water (46 + 54) and ending after 14 min with acetonitrile–water (77.5 + 22.5) and atmospheric pressure ionization monitoring of positive ions demonstrated highly sensitive and selective determinations. Quantification was performed by monitoring the molecular ion [M + 1]+ of TDI–DBA and TDA–ET derivatives. The instrumental detection limit was 1 nmol l–1 of TDI–DBA and 2 nmol l–1 of TDA–ET. Linear calibration curves were obtained and the correlation coefficient was 0.9981–0.9996 for 50–500 nmol l–1(n= 14). The over-all precision for samples spiked at a concentration of 500 nmol l–1 of 2,4-and 2,6-TDA–ET and 2,4-and 2,6-TDI–DBA was 1.7, 1.6, 1.8 and 1.9%(n= 11), respectively.
C E Mapp - One of the best experts on this subject based on the ideXlab platform.
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lack of association of hla class i genes and tnf alpha 308 polymorphism in Toluene Diisocyanate induced asthma
Allergy, 2004Co-Authors: B Beghe, M Padoan, C T Moss, Sheila J Barton, J W Holloway, S T Holgate, W M Howell, C E MappAbstract:Background: Toluene Diisocyanate (TDI)-induced asthma is a common cause of occupational asthma and it affects 5–15% of the exposed population suggesting an underlying genetic susceptibility. Methods: To investigate the role of genetic factors in the development of TDI-induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)-α A-308G polymorphism in 142 patients with TDI-induced asthma and in 50 asymptomatic exposed subjects. Results: Neither the distribution of HLA class I antigens nor the distribution of TNF-α A-308G polymorphism was different between patients with TDI-induced asthma and asymptomatic exposed subjects. Conclusions: These results suggest that HLA class I antigens and TNF-α A-308G are not associated with susceptibility or resistance to the development of TDI-induced asthma.
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long term follow up of Toluene Diisocyanate induced asthma
European Respiratory Journal, 2003Co-Authors: Michele Padoan, Piero Maestrelli, Valeria Pozzato, M Simoni, Luciana Zedda, G Milan, Ilaria Bononi, C Piola, Piera Boschetto, C E MappAbstract:Eighty-seven cases of occupational asthma induced by Toluene Diisocyanate (TDI) were diagnosed by an inhalation challenge with TDI and methacholine. After an average follow-up interval of 11 yrs, all subjects were re-examined. Of the 87 subjects examined, 13 (15%) had remained in the same job, 44 (50.5%) had been removed from exposure for 10 yrs. The proportion of subjects who experienced symptoms of asthma and those who were hyperresponsive to methacholine was significantly lower. Of the patients, 59% used short-acting bronchodilators, 8% long-acting bronchodilators and 18% were on regular inhaled glucocorticoids. Thus, multiple regression analysis showed a positive correlation between forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1 ) at follow-up and FVC and FEV 1 at diagnosis, and a negative correlation with smoking and with therapy with bronchodilators. Stepwise logistic regression showed that the follow-up provocative dose causing a 20% fall in the FEV 1 (PD 20 ) could be predicted from baseline PD 20 . These results indicate that respiratory symptoms and airway hyperresponsiveness to methacholine persist in subjects removed from exposure to TDI for >10 yrs. A more favourable prognosis was associated with a better lung function and a lower degree of airway hyperresponsiveness to methacholine at diagnosis.
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association between hla genes and susceptibility to Toluene Diisocyanate induced asthma
Clinical & Experimental Allergy, 2000Co-Authors: C E Mapp, Michele Padoan, B Beghe, A Balboni, G Zamorani, Laura Jovine, Olavio R Baricordi, Leonardo M FabbriAbstract:Background Only a small proportion of subjects exposed to isocyanates develop occupational asthma, suggesting individual predisposition. The human leucocyte antigen (HLA) class II molecules may play a crucial role in the development of the immune response to isocyanates. Objectives To investigate the role of HLA class II molecules in the development of Toluene Diisocyanate (TDI)-induced asthma. Subjects Sixty-seven asthmatic subjects and 27 asymptomatic exposed subjects (controls) were typed at the HLA class II DQA1, DQB1 and DRB1 loci by polymerase chain reaction (PCR)-based techniques. Results The frequencies of DQA1*0104 and DQB1*0503 were significantly increased in asthmatics compared with asymptomatic exposed subjects, while DQA1*0101 and DQB1*0501 were significantly increased in asymptomatic exposed subjects. No significant difference was found in the distribution of DRB1 alleles between asthmatics and controls. Conclusions The results of this study indicate that HLA-regulated immune mechanisms are involved in TDI-induced asthma and that, in exposed subjects, specific factors may increase or decrease the risk of developing disease.
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eosinophil cationic protein ecp histamine and tryptase in peripheral blood before and during inhalation challenge with Toluene Diisocyanate tdi in sensitized subjects
Clinical & Experimental Allergy, 1994Co-Authors: C E Mapp, Marina Saetta, Piero Maestrelli, Diego Faggian, P G Calcagni, Franco Borghesan, Leonardo M FabbriAbstract:Summary To determine whether the measurement of specific markers of inflammatory cells in peripheral blood might be used to detect the inflammatory activity in the airways in asthma induced by Toluene Diisocyanate (TDI). we measured the levels of eosinophil cationic protein (ECP), histamine and tryplase in peripheral blood before and during inhalation challenge with TDI or methacholine in two groups of subjects who exhibited or did not exhibit an asthmatic reaction after exposure to Toluene Diisocyanate in the laboratory. When the subjects developed a late asthmatic reaction after exposure to TDI, the\ showed an increase in their ECP serum levels. By contrast, there were no signilicam changes in serum ECP levels after exposure to TDI in the control group or after methacholine challenge in either group. Tryptase levels in serum were not detectable before or during inhalation challenge with TDI or methacholinc. There was no significant increase in plasma histamine levels during inhalation challenge with TDJ or methacholine. These results suggest that eosinophils arc ‘activated’ in subjects who develop a late asthmatic reaction after exposure to TDI and that the measurement of ECP levels in peripheral blood may be a useful marker to monitor airway inflammation.
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predictive value of airways hyperresponsiveness and circulating ige for identifying types of responses to Toluene Diisocyanate inhalation challenge
American Journal of Respiratory and Critical Care Medicine, 1994Co-Authors: M H Karol, Leonardo M Fabbri, Marina Saetta, Piero Maestrelli, Dj Tollerud, Tp Campbell, C E MappAbstract:Development of asthma after exposure to Toluene Diisocyanate (TDI) has been recognized in a variety of occupational settings. However, the pathogenesis of isocyanate-induced asthma remains controversial. In particular, the role of IgE in the development of TDI-induced asthma has remained uncertain. To investigate predictive factors for response to inhalation challenge with TDI, we analyzed data from 63 subjects referred for evaluation of respiratory symptoms thought to be related to TDI sensitization. All subjects underwent interview, routine phlebotomy, spirometry, methacholine challenge, and allergy skin testing prior to TDI challenge. Spirometry and methacholine challenge were repeated 1 day after TDI challenge. The cumulative dose of methacholine needed to produce a 20% decrease in FEV1 (PD20) was determined. A PD20 of 1.4 mg or more was considered normal. Subjects were challenged by exposure to 5 to 10 ppb TDI for up to 30 min in a 9 m3 exposure chamber. A positive response was a 20% or more decrease in FEV1 within 1 h (early) or beyond 1 h (late) after TDI exposure. Thirty-four subjects (54%) had a positive response, of whom 12 (35% of responders) had isolated early responses, 13 (38%) had isolated late responses, and the remainder had dual responses. Thirty-two individuals (51%) had a positive response to methacholine (AR+) prior to TDI challenge. AR+ was strongly associated with a positive TDI challenge: 23 AR+ subjects (72%) had a positive TDI challenge, compared with only 11 AR- subjects (35%) (p < 0.01). AR positivity did not predict the time of onset of TDI response.(ABSTRACT TRUNCATED AT 250 WORDS)