title: Implementation of non-invasive methods in the diagnosis of diisocyanate-induced asthma.
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.
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany, raulf@ipa-dguv.de.
authors.forename: M
authors.initials: M
authors.lastname: Raulf-Heimsoth
authors.forename: R
authors.initials: R
authors.lastname: Liebig
authors.forename: B
authors.initials: B
authors.lastname: Marczynski
authors.forename: G
authors.initials: G
authors.lastname: Borowitzki
authors.forename: S
authors.initials: S
authors.lastname: Bernard
authors.forename: S
authors.initials: S
authors.lastname: Freundt
authors.forename: E
authors.initials: E
authors.lastname: Heinze
authors.forename: T
authors.initials: T
authors.lastname: Brüning
authors.forename: R
authors.initials: R
authors.lastname: Merget
mesh_terms: D000328:Adult; D001249:Asthma / Q000139:chemically induced* / Q000175:diagnosis*; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001985:Bronchial Provocation Tests / Q000379:methods*; D047150:Eosinophil Cationic Protein / Q000097:blood; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D017953:Isocyanates / Q000009:adverse effects*; D008297:Male; D017817:Nasal Lavage Fluid; D009784:Occupational Diseases / Q000139:chemically induced* / Q000175:diagnosis*; D016273:Occupational Exposure; D012907:Smoking; D013997:Time Factors
chemical_list: D015415:Biomarkers; D017953:Isocyanates; D047150:Eosinophil Cationic Protein