Atropine does not inhibit late asthmatic responses induced by toluene-diisocyanate in sensitized subjects.
To determine whether early and/or late asthmatic responses induced by toluene diisocyanate (TDI) are caused by a reflex mechanism involving stimulation of muscarinic receptors, we studied the effect of the muscarinic antagonist atropine on early and late airway response induced by TDI. A preliminary study was conducted in asthmatics to assess whether the selected dose of atropine provided adequate muscarinic blockade. On different days we measured the provocation dose (in milligrams) of carbachol causing a 15% decrease in FEV1 (PD15FEV1) without and with atropine premedication (0.008 or 0.012 mg/kg subcutaneous atropine 30 or 90 min before carbachol challenge test). We found that 0.008 to 0.012 mg/kg subcutaneous atropine increased the PD15FEV1 carbachol by 6- to 10-fold, inducing a consistent and prolonged decrease in nonspecific bronchial hyperresponsiveness to cholinergic agent. Then we examined 10 subjects with a history of sensitization to TDI in 2 sets of experiments. In the first set of experiments, we studied the subjects before and after exposure to TDI (0.04 ppm; 30 min) after no treatment. In the second set of experiments, carried out 1 to 2 wk later, we repeated the same procedure after treatment with atropine (0.008 to 0.012 mg/kg atropine sulfate administered subcutaneously 30 min before TDI challenge, and then at 90-min intervals after TDI exposure); all patients showed symptoms of atropine effect (dryness of mouth, cycloplegia, increased heart rate).(ABSTRACT TRUNCATED AT 250 WORDS)
Paggiaro
P
P
Second Medical Clinic, University of Pisa, Pisa, Italy.
Bacci
E
E
Talini
D
D
Dente
F L
FL
Rossi
O
O
Pulerá
N
N
Fabbri
L M
LM
Giuntini
C
C
D000280:Administration, Inhalation; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology*; D002217:Carbachol / Q000037:antagonists & inhibitors; D003485:Cyanates / Q000037:antagonists & inhibitors*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced / Q000503:physiopathology; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects / Q000037:antagonists & inhibitors*
D003485:Cyanates; D014051:Toluene 2,4-Diisocyanate; D001285:Atropine; D002217:Carbachol