Cross refractoriness between bradykinin and hypertonic saline challenges in asthma.
BACKGROUND
Repeated inhalation of bradykinin and hypertonic saline leads to refractoriness of the bronchoconstrictor response in asthma. It is not known whether cross-refractoriness exists between these stimuli.


OBJECTIVE
We postulated that repeated bradykinin and hypertonic saline bronchial challenges might reduce the airway response to subsequent hypertonic saline and bradykinin challenges, respectively.


METHODS
Eleven atopic asthmatic subjects underwent two concentration-response studies, separated by 1 hour, with either inhaled histamine or bradykinin. After recovery, a hypertonic saline challenge was performed. During the next phase, nine subjects underwent two concentration-response studies, separated by 1 hour, with hypertonic saline. After recovery, a bradykinin challenge was performed.


RESULTS
On the histamine study day, the mean provocative volume of agonist required to produce 20% drop in forced expiratory volume in 1 second (PD20) hypertonic saline was 220.7 L (+/- 42.7 L) and this was not significantly different from that measured at baseline. On the bradykinin study day, the geometric mean provocative concentration of agonist required to produce a 20% drop in forced expiratory volume in 1 second (PC20) was 0.39 mg/ml (0.01 to 11.73 mg/ml) for the first test and significantly higher at 1.38 mg/ml (0.01 to > 16.0 mg/ml) for the second test (p = 0.006). The hypertonic saline PD20 increased significantly from a baseline of 159.2 L (+/- 27.3 L) to 377.6 (+/- 64.7 ) (p = 0.003). On the hypertonic saline study day, the mean PD20 was 152.8 L for the first test, and 337.7 L for the second test (p = 0.01). PC20 bradykinin increased significantly from a baseline of 0.57 to 2.56 mg/ml (p = 0.02). A significant correlation was found between loss of response to bradykinin and to hypertonic saline (rs, 0.63 and 0.76).


CONCLUSIONS
Refractoriness produced by repeated exposure of the airways to bradykinin and hypertonic saline results in loss of responsiveness to hypertonic saline and bradykinin respectively, suggesting a shared mechanism for refractoriness produced by these stimuli.
Rajakulasingam
K
K
Immunopharmacology Group, University of Southamptom, Southamptom General Hospital, England.
Makker
H K
HK
Howarth
P H
PH
Holgate
S T
ST
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D001920:Bradykinin; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D012462:Saline Solution, Hypertonic
D012462:Saline Solution, Hypertonic; D006632:Histamine; D001920:Bradykinin