Airway inflammation and functional changes after exposure to different concentrations of isocyanates.
BACKGROUND
Isocyanates are a common cause of occupational asthma (OA).


OBJECTIVE
We sought (1) to examine whether asthmatic reactions to isocyanates could be induced at concentrations as low as 1 ppb in subjects with OA caused by isocyanates previously diagnosed in our center and (2) to compare the inflammatory and functional changes after exposure to 1 and 15 ppb of isocyanates with similar total doses (concentration of isocyanates x duration of exposure).


METHODS
Specific inhalation challenges were performed in 12 asthmatic subjects with previously confirmed OA caused by isocyanates. Eight subjects were exposed to 1 ppb at 10% of the dose of isocyanates that induced an asthmatic reaction at the time of the diagnosis. Seven subjects were exposed to the same total dose of isocyanates by using concentrations of 1 and 15 ppb 1 month apart.


RESULTS
Exposure to 1 ppb at 10% of the dose that had induced functional changes at the time of diagnosis induced an asthmatic reaction in 3 of 8 subjects. There was a significant correlation between the percentage of maximum decrease in FEV(1) after exposure to 1 ppb and the increase in sputum neutrophils (rho = 0.8). By keeping the total dose (concentration of isocyanates x duration of exposure) of isocyanates similar, 4 of 7 subjects experienced an asthmatic reaction after exposure to 1 ppb, whereas only one subject experienced an 18.5% decrease in FEV(1) after exposure to 15 ppb.


CONCLUSIONS
Isocyanates can induce functional and inflammatory changes (mainly neutrophilic) at concentrations as low as 1 ppb. For the same total dose of exposure, low concentrations of isocyanates are as harmful as or even more harmful than higher concentrations for subjects with OA to isocyanates.
Lemière
Catherine
C
Department of Chest Medicine, Hôpital du Sacré-Coeur de Montréal, 5400 West Gouin Boulevard, Montreal, Quebec, Canada H4J 1C5.
Romeo
Philippe
P
Chaboillez
Simone
S
Tremblay
Caroline
C
Malo
Jean-Luc
JL
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001249:Asthma / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D017953:Isocyanates / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D009784:Occupational Diseases / Q000473:pathology / Q000503:physiopathology; D009994:Osmolar Concentration; D013183:Sputum / Q000166:cytology
D017953:Isocyanates