TransMEM Gas Exchange -- Project 1, Aim 2
Condition: Middle Ear Disease; Nasal Allergy
MeSH terms: Ear Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will determine if exposure to an allergy material (ragweed) or exposure to an
      allergic-symptom-provoking substance (histamine) and medications typically used to decongest
      the nose changes the rate of blood-flow in the lining of the middle-ear. Otitis media (the
      build-up of water-like fluid in the middle-ear airspace) may occur if the blood flow in the
      lining of the middle-ear is too high and may be prevented if a way could be found to lower
      the blood flow in persons susceptible to the disease. Middle-ear blood flow is measured
      indirectly by measuring the change in middle-ear pressure while a person breathes a gas
      mixture containing nitrous oxide ("laughing gas"). In this study, 4 groups of subjects will
      be entered and middle-ear pressure in persons breathing a mixture of 50% Oxygen, 50% Nitrous
      Oxide ("laughing gas")will be measured after exposure to one of four substances (ragweed,
      histamine,an oral decongestant, a decongestant nasal spray) and a fake medication (placebo)
      at separate test sessions. All subjects will have one set of 2 x-rays of the middle ears and
      mastoids. The group exposed to ragweed will require 3 study visits while the other 3 groups
      will have 2 study visits. From this information middle-ear blood flow will be calculated.
      This will help determine the relationship between what happens in the nose and what happens
      in the middle ear.
    

Detailed description: 
      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.
    

Intervention name(s): ragweed; histamine; pseudoephedrine; Oxymetazoline
Intervention type(s): Biological; Biological; Drug; Drug
Intervention description(s): ragweed arm only; histamine arm only; pseudoephedrine arm only; oxymetazoline arm only
Other intervention name(s): Sudafed; Afrin
Intervention MeSH terms: Phenylephrine; Pseudoephedrine; Oxymetazoline; Ephedrine; Histamine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: middle ear; allergy; nose