The role of airway inflammation, induced by
weekly antigen challenge, in the airway hyperresponsiveness to vagal (whole and NANC
components) nerve stimulation and to neurotransmitters (acetylcholine and selective
agonists for tachykinin NK1 and NK2 receptors) has been studied in the guinea-pig.
Primarily, the time course (3, 7 and 14 days following the last challenge) of the effects
of repeated aerosol antigen challenge on airway inflammation and bronchoalveolar fluid
cellular composition was investigated. At 7 days following the last antigen challenge a
maximal (as compared to 3 and 14 days) inflammatory response, in terms of a diffuse mild
to marked infiltration of eosinophils, neutrophils and lymphocytes, was evident throughout
pulmonary tissues. Only at this time some evidence of eosinophilia and neutropenia was
detectable in BAL fluids. In these animals there was a normal bronchial responsiveness to
iv administration of acetylcholine, selective synthetic agonists for the tachykinin NK2
receptors and capsaicin. On the other hand a remarkable airways hyperresponsiveness to iv
administration of selective agonists for tachykinin NK1 receptors, as well as electrical
stimulation of the vagal nerves (in presence and in absence of atropine), was detected. As
a whole, these data indicate that at the peak of the inflammatory airway response
following multiple antigen challenge there is a selective hyperresponsiveness to
stimulation of vagal (mainly the non-adrenergic, non-cholinergic component) nerves
associated with an increase in tachykinins (NK-1)-mediated bronchospasm.
When my office
lease expired at the end of 2004, I decided to turn it into a
"sabbatical" from my private practice. Many years ago, in my
grandfather's 89th year of life, he told me, "John, it is important
to smell the roses while you can still smell them." His life
gave living a very good reputation. It is also true that the
pursuit of that philosophy required my grandfather to to re-open his
assay office/ore market in Wickenburg, Arizona as a 75-year-old because
he had run a little short of retirement money. Thus, if blessed with his
luck and health, I'll be back.. --jjh
