Isocyanates are increasingly being used for manufacturing polyurethane foam, elastomers, adhesives, paints, coatings, insecticides, and many other products. At present, they are regarded as one of the main causes of occupational asthma. The large number of workers who are exposed to these chemicals have a concentration-dependent risk of developing chronic airway disorders, especially bronchial asthma. Different pathophysiologic mechanisms are involved. Immunoglobulin E (IgE)-mediated sensitization and irritative effects have been clearly demonstrated in both exposed subjects and animals. Presumably, neural inflammation due to neuropeptide release of capsaicin-sensitive afferent nerves is crucial. We collected data on 1780 isocyanate workers who had been examined by our groups. Of them 1095 (including subjects from outpatient departments) had work-related symptoms, predominantly of the respiratory tract. Specific IgE antibodies were found in 14% of the 1095 subjects. The methacholine challenge test was shown to be an inadequate predictor of the results of inhalative isocyanate provocation tests in workers and in asthmatic controls. Isocyanate (toluene diisocyanate TDI) air concentrations of 10 ppb (0.07 mg/m3) and 20 ppb (0.14 mg/m3), respectively, did not cause significant bronchial obstruction in the majority of previously unexposed asthmatics with bronchial hyperreactivity. IgG-mediated allergic alveolitis, a rare disease among isocyanate workers, was found in approximately 1% of the symptomatic subjects. Experimental studies exhibit dose-dependent toxic effects and give evidence for tachykinin-mediated bronchial hyperreactivity after exposure to isocyanates. The clinical role of genotoxic effects of isocyanates and their by-products demonstrated here in vitro and in vivo has yet to be clarified.

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Inhalative methacholine challenge (MC) was performed in 229 subjects presumed to suffer from occupational asthma due to exposure to airborne latex allergens (n = 62), flour (n = 28), isocyanates (n = 114), or irritants in hairdressers' salons (n = 25). They were also subjected to specific challenges with the occupational agents they were exposed to, completed a questionnaire using an abbreviated version of the ATS‐DLD, and were interviewed by an experienced physician. Bronchial hyperresponsiveness in MC was defined by the results obtained in a previous study with 81 healthy volunteers. The threshold in these controls was set at a cumulative MC dose of 0.3 mg, corresponding to a sensitivity of 95%. The main purpose of the study was to investigate whether the MC and/or the occupational asthma case history are reliable predictors of the specific challenge test outcomes. In 40–72% of examined subjects, workplace‐related asthma complaints occurred, with bronchial hyperreactivity in the MC ranging from 48% to 61%. However, only 12–25% demonstrated a significant bronchoconstructive reaction in the specific challenge test. MC results are only moderately associated with workplace‐related asthma case histories. Positive outcomes of challenges with occupational agents are well correlated with positive MC results plus occupational asthma case histories. The combination of MC and occupational asthma case history shows a relatively high specifity (62%, 86%, 80%), but the sensitivity was moderately low (83%, 71%, 52%). MC sensitivities were 92%, 71%, and 62% (case histories of hairdressers were not available). We conclude that in most cases, occupational asthma (as defined by a specific challenge test response) is combined with bronchial hyperresponsiveness and workplace‐related asthmatic symptoms. However, subjects of each exposure group demonstrated bronchial hyperresponsiveness and complained of workplace‐related asthmatic symptoms, but occupational asthma could not be proved in the specific challenge test. In subjects with a positive occupational asthma case history, a negative MC test result can almost rule out a positive specific challenge test result. Hence, the MC test can reduce performance of the laborious specific challenge test. Am. J. Ind. Med. 33:114–122, 1998. © 1998 Wiley‐Liss, Inc.

Radioimmunoimaging of bone marrow was performed for non-invasive detection of skeletal involvement in 15 patients with carcinoma of the breast and 17 patients with malignant lymphomas. Bone marrow scans were performed by means of a monoclonal 99mTc-labelled antibody, directed against NCA-95 and CEA. The presence and extent of skeletal involvement were controlled by skeletal scintigraphy, plain radiographs and CT; bone marrow biopsies were obtained in 19 patients as well. 20 subjects without suspected malignant disease served as controls. Haematopoietic bone marrow was imaged homogeneously and with high contrast in all controls. 15/15 patients with carcinoma of the breast and 10/17 patients with malignant lymphomas had multifocal bone marrow defects due to skeletal metastases. Bone marrow scans revealed significantly more lesions than skeletal scintigraphy both in carcinoma of the breast (p = 0.027) and malignant lymphomas (p = 0.015). Thus, radioimmunoscintigraphy of bone marrow may provide a new, sensitive approach for non-invasive detection of metastatic spread to the skeletal system.