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Cross refractoriness between bradykinin and hypertonic saline challenges in asthma
K Rajakulasingam1, H K Makker, P H Howarth
1Immunopharmacology Group, University of Southamptom, Southamptom General Hospital, England.
The Journal of Allergy and Clinical Immunology
|October 1, 1995
Summary
Repeated exposure to bradykinin or hypertonic saline causes airway refractoriness in asthma. This study shows that refractoriness to one stimulus reduces the response to the other, suggesting a shared underlying mechanism.
Area of Science:
- Pulmonary Medicine
- Respiratory Physiology
- Pharmacology
Background:
- Repeated inhalation of bradykinin and hypertonic saline induces refractoriness in asthma.
- The existence of cross-refractoriness between these stimuli in asthma was previously unknown.
Purpose of the Study:
- To investigate if repeated bradykinin and hypertonic saline bronchial challenges reduce airway responsiveness to subsequent challenges with the same or different stimuli.
- To explore potential shared mechanisms of airway refractoriness.
Main Methods:
- Eleven atopic asthmatic subjects underwent paired concentration-response studies with histamine or bradykinin, followed by hypertonic saline challenge.
- Nine subjects underwent paired concentration-response studies with hypertonic saline, followed by bradykinin challenge.
- Airway responsiveness was assessed by measuring the provocative concentration or volume required to cause a 20% drop in forced expiratory volume in 1 second (PD20 or PC20).
Main Results:
- Repeated bradykinin challenge led to refractoriness to subsequent bradykinin (p=0.006) and hypertonic saline (p=0.003) challenges.
- Repeated hypertonic saline challenge led to refractoriness to subsequent hypertonic saline (p=0.01) and bradykinin (p=0.02) challenges.
- Significant correlations were observed between the loss of response to bradykinin and hypertonic saline, indicating cross-refractoriness.
Conclusions:
- Refractoriness induced by repeated bradykinin or hypertonic saline inhalation results in diminished airway responsiveness to both stimuli.
- These findings suggest a shared underlying mechanism for airway refractoriness to bradykinin and hypertonic saline in asthma.
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