Occup Environ Med 71:415-422 doi:10.1136/oemed-2013-101672
  • Workplace
  • Original article

Exhaled nitric oxide in spray painters exposed to isocyanates: effect modification by atopy and smoking

  1. Dick Heederik1
  1. 1Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, The Netherlands
  2. 2Arak University of Medical Sciences, Arak, Iran
  3. 3TNO, Zeist, The Netherlands
  1. Correspondence to Dr Dick Heederik, Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80178, Utrecht3508 TD, The Netherlands; d.heederik{at}
  • Received 18 June 2013
  • Revised 24 February 2014
  • Accepted 9 March 2014
  • Published Online First 28 March 2014


Background Isocyanate asthma is one of the most frequently identified forms of occupational asthma in industrialised countries. The underlying mechanisms have not been clarified. There is only limited information about the relationship between exhaled nitric oxide (eNO) and occupational exposure to isocyanates and asthma.

Objectives To investigate the association between isocyanate exposure and eNO levels in isocyanate-exposed workers and to elucidate whether eNO acts as a marker of airway inflammation controlling for smoking and atopy in an industry-wide survey.

Methods Information on estimated personal isocyanate exposure, measured eNO levels, health effects and sensitisation were analysed in 229 workers from a cross-sectional study. Univariate and multiple regression analyses were used to explore the exposure–response relationships between isocyanate exposure and eNO, stratified by smoking and atopy.

Results A marginally significant exposure–response relationship was found between isocyanate exposure and eNO in atopic, non-smokers (p=0.054). eNO was significantly associated with atopy and smoking, bronchial hyper-responsiveness (BHR), work-related conjunctivitis and rhinitis after adjustment for age, gender, atopy and smoking (p<0.05). A borderline significant association was found between eNO and asthma-like symptoms after adjustment for age, gender, atopy and current smoking (p=0.055). In a small group of isocyanate-exposed workers with positive serum-specific immunoglobulin E (IgE) antibodies to hexamethylene diisocyanate (HDI), elevated eNO levels were clearly exposure related. eNO was associated with the positive specific IgG antibodies to HDI in non-atopic, non-smokers (p=0.03).

Conclusions Increased eNO levels may indicate increased airway inflammation in atopic, non-smokers exposed to isocyanates especially at higher levels of isocyanate exposure.

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