Cross refractoriness between bradykinin and hypertonic saline challenges in asthma

• Published in: Journal of allergy and clinical immunology Vol. 96; no. 4; pp. 502 - 509
• Main Authors: Rajakulasingam, K., Makker, H.K., Howarth, P.H., Holgate, S.T.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.1995; Elsevier
• Subjects: Adolescent; Adult; Asthma - diagnosis; Asthma - physiopathology; Biological and medical sciences; Bradykinin; Bronchial Provocation Tests; cross refractoriness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Tolerance; Female; Forced Expiratory Volume - drug effects; Histamine; Humans; hypertonic saline; Investigative techniques of respiratory function; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Osmolar Concentration; Saline Solution, Hypertonic; Tachyphylaxis; Tachyphylaxis; cross refractoriness; FEV 1; hypertonic saline; bradykinin; HS; PD 20; PC 20; Human; Respiratory disease; Bronchus; Exploration; Refractoriness; Asthma; Induced bronchoconstriction; Lung function; Bradykinin; Cross reaction; Obstructive pulmonary disease; Hypertonic solution; Saline solution; Provocation test
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/S0091-6749(95)70294-6

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 (PD 20) 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 (PC 20) 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 PD 20 increased significantly from a baseline of 159.2 L (±27.3 L) to 377.6 (±64.7 L) ( p = 0.003). On the hypertonic saline study day, the mean PD 20 was 152.8 L for the first test, and 337.7 L for the second test ( p = 0.01). PC 20 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 (r s, 0.63 and 0.76). Conclusion: 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. ( J Allergy Clin Immunol 1995;96:502-9.)