title: Isocyanate exposure and occupational asthma: a case-referent study.
abstract: OBJECTIVE
  To examine the quantitative relation between exposure to isocyanates and occupational asthma, and to explore the role of atopy and smoking in occurrence of the disease.
  
  
  METHODS
  A case-referent study was undertaken of cases from two manufacturing companies (A and B) from which referents without disease could be selected and reliable exposure measurements were available. In company A, 27 cases mainly attributed to toluene diisocyanate (TDI) were matched to 51 referents on work area, start and duration of employment, sex, and age. Exposures were estimated from existing measurements by job category. In company B there were seven cases attributed to 4,4'-diphenylmethane diisocyanate (MDI) in two areas of the plant; 12 non-cases from the same areas were used as referents. Personal exposure measurements were available for all cases and 11 referents.
  
  
  RESULTS
  No difference in peak exposures between cases and referents was found in either plant; but in both, time weighted average (TWA) exposures at the time of onset of asthma were higher for cases. In A, the mean TWA exposure for cases was 1.5 (95% confidence interval (95% CI) 1.2 to 1.8) ppb compared with 1.2 (1.0 to 1.4) ppb for referents. From a matched analysis, the odds ratio (OR) associated with 8 hour TWA exposure to isocyanates greater than 1.125 ppb (the median concentration for the referent group) was 3.2 (95% CI 0.96 to 10.6; p=0.06). Occupational asthma was associated with a pre-employment history of atopic illness (OR 3. 5, p=0.04) and, less strongly, with smoking (OR 2.1, p=0.14). In B, small numbers limited analysis, but three of seven cases had at least one TWA exposure measurement greater than 5 ppb compared with one of 11 referents (OR 7.5, p=0.09).
  
  
  CONCLUSIONS
  Asthma can occur at low concentrations of isocyanates, but even at low concentrations, the higher the exposure the greater the risk. By contrast with other studies, smoking and atopy seemed to increase the odds of occupational asthma due to isocyanates, but did not affect the estimate of risk associated with exposure.
authors.affiliation: MRC Clinical Trials Unit, 222 Euston Road, London NW1 2DA, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Meredith
authors.forename: J
authors.initials: J
authors.lastname: Bugler
authors.forename: R L
authors.initials: RL
authors.lastname: Clark
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects; D001249:Asthma / Q000139:chemically induced* / Q000209:etiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications; D017953:Isocyanates / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced* / Q000209:etiology; D016273:Occupational Exposure; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000485:Allergens; D017953:Isocyanates; D014051:Toluene 2,4-Diisocyanate