TransMEM Gas Exchange -- Project 1, Aim 2

The set of four experiments described here is a subcomponent of one Project included in a
Clinical Research Center Grant Program focused on the physiology and pathophysiology of
middle-ear (ME) pressure-regulation in children and adults. These experiments are designed to
measure the rate of transME mucosal (transMEM) inert gas exchange in adults and determine if
nasal inflammatory reactions experimentally provoked by intranasal histamine or allergen
challenge increase the rate transMEM inert gas exchange and if nasal or oral treatment with
an adrenergic agonist decreases that rate. Four cohorts of 20 otherwise healthy adults will
be identified and one cohort assigned to each of the four experiments. All subjects will have
a x-ray in Schuller projection to estimate mastoid volume. The transMEM inert gas exchange
rate is measured by repeatedly recording ME pressure by tympanometry while the subject
breathes a mixture of 50%N2O/ 50%O2, and then regressing ME pressure on time and dividing the
slope of the function by the estimated N2O driving gradient to yield an exchange constant.
For each experiment, the transMEM N2O exchange rate is measured twice at separate visits
(active and placebo). The four experimental conditions are: (1) intranasal ragweed and
placebo challenges; (2) intranasal histamine and placebo challenges; (3) oral pseudoephedrine
and placebo; (4) intranasal oxymetazoline and placebo. Experiments 2-4 require two visits,
while Experiment 1 will require an additional visit to obtain blood for RAST testing to
verify ragweed allergy. The paired exchange constants measured in each experiment will be
compared for a significant difference using a Student's Paired t test and the results
interpreted as supporting or refuting the possibility of modulating the transMEM N2O exchange
rate by the different procedures.

Inclusion Criteria:

- healthy

- no evidence of otitis media at entry

- bilaterally intact tympanic membranes

- ragweed arm: history of symptomatic ragweed allergy and Class 2 positive on RAST
testing with or without other allergic sensitivities by history

Exclusion Criteria:

- craniofacial syndrome (ef, cleft palate)

- Use of prescription medications (except for birth control) in the 1 month prior to
entry;

- Use of over-the-counter allergy medication within 2 weeks before challenge
(Experiments 1, 2 only);

- Use of over-the-counter decongestants (nasal or oral) within 2 weeks before challenge
(Exp 3,4 only)

- Elevated blood pressure (>140/90);

- Individuals with any pulmonary or cardiac problems, including asthma;

- Individuals who are pregnant or who are planning to become pregnant during the period
of study;

- Individuals who had immunotherapy for ragweed allergy at any time (Experiment 1 only);

- Individuals who used any experimental medication or treatment within 3 months of
screening;

- Individuals with extant unilateral or bilateral otitis media as documented by otoscopy
or tympanometry;

- Individuals with abnormally low tympanic membrane mobility, eg Type B tympanogram;

- Individuals reporting a previous adverse experience with breathing gas mixtures
containing N2O (e.g. during dental procedures);

- Individuals who have upper respiratory ("cold") symptoms or allergic rhinitis symptoms
(may be rescheduled);

- Individuals with single or multiple allergic sensitivities by screening history
(Experiment 2 only)