Abstract
Diisocyanate-induced asthma is difficult to diagnose since the immunopathological mechanisms and exposure determinants at the workplace are not well defined. The aim of this study was to evaluate the non-invasive methods of nasal lavage fluid (NALF) and induced sputum (IS) to enhance the diagnostic efficiency. Sixty-three diisocyanate-exposed workers with work-related shortness of breath underwent a standardized 4-steps-1-day-whole body exposure test with diisocyanates used at work up to 30 ppb. NALF and IS were collected before, 0.5, and 19 h after the end of exposure. Cellular composition and soluble inflammatory biomarkers were studied in the samples. In addition, ten controls with bronchial hyperresponsiveness, but without prior occupational diisocyanate exposure, were also examined. Twelve out of the 63 subjects (19 %) showed a significant asthmatic reaction (pulmonary responders) after challenge (FEV1 decrease >20 %). NALF samples did not demonstrate significant effects either on cellular composition or on mediator concentrations in the responders, non-responders, or controls at any time point. In contrast, in the IS samples of the pulmonary responders collected 19 h after challenge, the percentage of eosinophils was higher (p = 0.001) compared with baseline before challenge. Eosinophils were also increased 30 min and 19 h after challenge in IS samples of the responders compared with the non-responders or controls. In addition, 19 h after challenge the eosinophilic cationic protein (ECP) concentration was significantly higher in the responders than non-responders (p < 0.04) or controls (p < 0.002). In conclusion, positive asthmatic reactions to diisocyanates are accompanied by an influx of eosinophils into lower airways. Analysis of induced sputum should be implemented in the diagnostic procedure of diisocyanate-related airway diseases.
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References
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72, 248–254.
Fisseler-Eckhoff, A., Bartsch, H., Zinsky, R., & Schirren, J. (2011). Environmental isocyanate-induced asthma: morphologic and pathogenetic aspects of an increasing occupational disease. International Journal of Environmental Research and Public Health, 8, 3672–3687.
Lemière, C., Romeo, P., Chabboillez, S., Tremblay, C., & Malo, J. L. (2002). Airway inflammation and functional changes after exposure to different concentrations of isocyanates. The Journal of Allergy and Clinical Immunology, 110, 641–646.
Marczynski, B., Merget, R., Mensing, T., Rabstein, S., Kappler, M., Bracht, A., Haufs, M. G., Käfferlein, H. U., & Brüning, T. (2005). DNA strand breaks in the lymphocytes of workers exposed to diisocyanates: Indications of individual differences in susceptibility after low-dose and short-term exposure. Archives of Toxicology, 79, 355–362.
Merget, R., Marczynski, B., Chen, Z., Remberger, K., Raulf-Heimsoth, M., Willrot, P. O., & Baur, X. (2002). Haemorrhagic hypersensitivity pneumonitis due to naphthylene-1,5-diisocyanate. European Respiratory Journal, 19, 377–380.
Merget, R., Heinze, E., Korn, M., Raulf-Heimsoth, M., Marczynski, B., & Brüning, T. (2004). Diagnostische Validität und Sicherheit eines 4-Stufen-1-Tagesexpositionstests mit Diisocyanaten. Atemwegs- und Lungenkrankheiten, 30, 380–381.
Palikhe, N. S., Kim, J. H., & Park, H. S. (2011). Biomarkers predicting isocyanate-induces asthma. Allergy, Asthma & Immunology Research, 3, 21–26.
Paris, C., Ngatchou-Wandji, J., Luc, A., McNamee, R., Bensefa-Colas, L., Larabi, L., Telle-Lamberton, M., Herin, F., Bergeret, A., Bonneterre, V., Brochard, P., Choudat, D., Dupas, D., Garnier, R., Pairon, J. C., Agius, R. M., Ameille, J., & Members of the RNV3P. (2012). Work-related asthma in France: Recent trends for the period 2001–2009. Occupational and Environmental Medicine, 69, 391–397.
Park, H., Jung, K., Kim, H., Nahm, D., & Kang, K. (1999). Neutrophil activation following TDI bronchial challenges to the airway secretion from subjects with TDI-induced asthma. Clinical and Experimental Allergy, 29, 1395–1401.
Pronk, A., Preller, L., Raulf-Heimsoth, M., Jonkers, I. C., Lammers, J. W., Wouters, I. M., Doekes, G., Wisnewski, A. V., & Heederik, D. (2007). Respiratory symptoms, sensitization, and exposure response relationships in spray painters exposed to isocyanates. American Journal of Respiratory and Critical Care Medicine, 176, 1090–1097.
Quirce, S., Lemière, C., de Blay, F., Del Pozo, V., Gerth Van Wijk, R., Maestrelli, P., Pauli, G., Pignatti, P., Raulf-Heimsoth, M., Sastre, J., Storaas, T., & Moscato, G. (2010). Noninvasive methods for assessment of airway inflammation in occupational settings. Allergy, 65, 445–458.
Raulf-Heimsoth, M., & Baur, X. (1998). Pathomechanisms and pathophysiology of isocyanate-induced diseases – Summary of present knowledge. American Journal of Industrial Medicine, 34, 137–143.
Raulf-Heimsoth, M., Wirtz, C., Papenfuss, F., & Baur, X. (2000). Nasal lavage mediator profile and cellular composition of nasal brushing material during latex challenge tests. Clinical and Experimental Allergy, 30, 110–121.
Raulf-Heimsoth, M., Pesch, B., Kendzia, B., Spickenheuer, A., Bramer, R., Marczynski, B., Merget, R., & Brüning, T. (2011). Irritative effects of vapours and aerosols of bitumen on the airways assessed by non-invasive methods. Archives of Toxicology, 85, S41–S52.
Vandenplas, O., Lantin, A. C., D’Alpaos, V., Larbanois, A., Hoet, P., Vandeweerdt, M., Thimpont, J., & Speybroeck, N. (2011). Time trends in occupational asthma in Belgium. Respiratory Medicine, 105, 1364–1372.
Wisnewski, A. V., Redlich, C. A., Mapp, C. E., & Bernstein, D. I. (2006). Polyisocyanates and their prepolymers. In I. L. Bernstein, M. Chan-Yeung, J.-L. Malo, & D. I. Bernstein (Eds.), Asthma in the workplace (3rd ed., pp. 481–504). New York: Taylor & Francis Group, LLC.
Acknowledgements
This study is part of a doctor thesis of R. Liebig and part of the IPA-projects All/Imm-D and Med-D funded by the DGUV (German Social Accident Insurance).
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The authors declare no conflicts of interest in relation to this article.
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Raulf-Heimsoth, M. et al. (2013). Implementation of Non-invasive Methods in the Diagnosis of Diisocyanate-Induced Asthma. In: Pokorski, M. (eds) Neurobiology of Respiration. Advances in Experimental Medicine and Biology, vol 788. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6627-3_40
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