Associations have been observed between exposure to isocyanates, consisting mainly of oligomers, and respiratory symptoms and isocyanate specific sensitisation in spray painters. The aim of the present study was to assess associations between isocyanate exposure and more objective respiratory effect measures such as bronchial hyperresponsiveness (BHR), baseline spirometry and exhaled nitric oxide (eNO) in a subset of spray painters.Methacholine challenge and eNO measurements were performed in 229 workers. Questionnaires and blood samples were obtained. Specific immunoglobulin (Ig)E and IgG to hexamethylene di-isocyanate were assessed in serum using various assays. Personal exposure was estimated by combining personal task-based inhalatory exposure measurements and timeactivity information.Workers with higher isocyanate exposure were more often hyperresponsive (prevalence ratio comparing the 75th versus 25th percentile of exposure 1.8). In addition, significant exposurerelated decreased forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio and flow-volume parameters independent of BHR were found. BHR was more prevalent among sensitised workers. This was statistically significant for only IgG-ImmunoCAP (Phadia, Uppsala, Sweden) positive workers. eNO was not associated with exposure although slightly elevated eNO levels in specific IgG positive subjects were found.The current study provides evidence that exposure to isocyanate oligomers is related to asthma with bronchial hyperresponsiveness as a hallmark, but also shows independent chronic obstructive respiratory effects resulting from isocyanate exposure.KEYWORDS: Bronchial hyperresponsiveness, hexamethylene di-isocyanate, oligomer, sensitisation, spirometry, spray painter D i-isocyanates are among the most common causes of occupational asthma [1][2][3]. Although asthma is considered the major health effect, hypersensitivity pneumonitis and accelerated lung function decline have also been related to di-isocyanate exposure [4]. Di-isocyanate monomers are characterised by two highly reactive isocyanate (NCO) groups and are used as polymerising agents in polyurethane products [5]. Most of the evidence regarding health effects from di-isocyanates involves these monomers. Lately, isocyanate oligomers or poly-isocyanates, with lower vapour pressure, have been introduced to reduce inhalatory exposure. These are increasingly being used and currently many workers are exposed to complex mixtures of isocyanate oligomers. Exposure assessment for these agents is challenging [6] and few epidemiological studies incorporated an exposure assessment component. As a result, exposure-response information for isocyanate oligomers is extremely limited.The present authors recently demonstrated an association between exposure and (work-related) respiratory symptoms and isocyanate-specific sensitisation in a population of 581 spray painters exposed to mainly hexamethylene di-isocyanate (HDI) oligomers [7]. To further investigate the nature of respirato...