Related Experiment Videos
Adenosine monophosphate and histamine induced bronchoconstriction: repeatability and protection by terbutaline
E Egbagbe1, I D Pavord, P Wilding
1Division of Respiratory Medicine, University of Nottingham City Hospital, UK.
Background:
Inhaled adenosine monophosphate (AMP) is thought to cause bronchoconstriction in asthmatic patients indirectly through mast cell mediator release. It may therefore be a more sensitive marker of airway inflammation in asthma and hence more specific for epidemiological surveys of asthma than challenges that act directly on airway smooth muscle such as histamine. There is some uncertainty as to how repeatable the measurement is and this is important if it is to be used for epidemiological studies.
Methods:
The response to histamine and AMP challenges and the protection afforded by terbutaline (500 micrograms) against these two challenges was measured on two occasions two weeks apart in 20 subjects with asthma (19 completed the study). The response to histamine and AMP was measured as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20) and the protection afforded by terbutaline in doubling doses (DD). Repeatability was assessed as the limits of agreement.
Results:
Although terbutaline had a slightly greater protective effect against AMP than histamine on both the first (delta PD20 = 2.66 versus 2.11 DD) and second occasion (2.56 and 2.15 DD), the differences were not statistically significant. The limits of agreement for the two histamine and two AMP challenges after placebo were from 3.06 to -3.5 and from 3.78 to -4.54 DD respectively, and these values did not differ significantly. The agreement limits between the first PD20 histamine and PD20 AMP values after placebo were similar, being from 3.73 to -3.72 DD after allowing for the 17.8-fold higher PD20 values for AMP compared with histamine.
Conclusions:
Terbutaline caused a slightly greater inhibition of the bronchoconstrictor response to AMP than histamine but the differences were small and non-significant. Any differences in repeatability between AMP and histamine challenges are small and in this study were not significant. The fact that the agreement between histamine and AMP PD20 values was similar to the agreement between repeat histamine or repeat AMP PD20 values suggests that, within an asthmatic population, PD20 AMP may not be providing different information from that provided by PD20 histamine.
Insights
Adenosine monophosphate (AMP) and histamine challenges show similar repeatability in asthma studies. Terbutaline offered comparable protection against both, suggesting AMP may not provide unique information compared to histamine for epidemiological surveys.
Area of Science:
- Pulmonary Medicine
- Respiratory Physiology
- Clinical Immunology
Background:
- Inhaled adenosine monophosphate (AMP) may indicate airway inflammation in asthma via mast cell mediators.
- AMP challenges could be more sensitive and specific for asthma epidemiology than direct smooth muscle agonists like histamine.
- Repeatability of AMP challenge measurements is crucial for its epidemiological use.
Purpose of the Study:
- To assess the repeatability of adenosine monophosphate (AMP) and histamine airway challenges in asthma.
- To compare the protective effects of terbutaline against AMP and histamine-induced bronchoconstriction.
- To determine if AMP challenges offer distinct information from histamine challenges for asthma research.
Main Methods:
- Twenty subjects with asthma underwent histamine and AMP challenges twice, two weeks apart.
- Response measured as provocative dose causing a 20% fall in FEV1 (PD20).
- Terbutaline's protective effect assessed using doubling doses (DD); repeatability by limits of agreement.
Main Results:
- Terbutaline showed a slightly greater, but not statistically significant, protective effect against AMP compared to histamine.
- Repeatability (limits of agreement) for both histamine and AMP challenges were similar and not significantly different.
- Agreement between histamine and AMP PD20 values was comparable to repeat measurements of the same challenge.
Conclusions:
- Differences in terbutaline's inhibitory effect on AMP versus histamine bronchoconstriction were minimal and non-significant.
- Repeatability of AMP and histamine challenges in asthmatic subjects is similar.
- PD20 measurements for AMP and histamine may not provide substantially different information in asthmatic populations.