Hydrolytic enzymes have been shown to be present in middle ear effusions recovered from children with both persistent and acute otitis media. In the present study, we investigated the effect of ampicillin therapy on the expression of hydrolytic enzyme activity in acute middle ear effusions using the chinchilla animal model. The median values of enzyme activities were lower for the ampicillin-treated animals when compared with the nontreated control animals. For the ampicillin-treated animals, eight of 12 assayed activities were characterized by a time-dependent decay of enzymatic activity. For the untreated animals, the majority of assayed activities (seven of 12) showed an increase in activity with time. These results show that sterilization of the middle ear cleft and elimination of the hydrolytic enzyme activity may be benefits of antimicrobial therapy and prerequisite to the healing of the inflamed mucosa.

Acute Disease↗

PubMed1988

Inflammatory mediators in chronic otitis media with effusion.

Otitis media with effusion (OME) is a common middle ear inflammatory disease in the pediatric population. This article determines concentrations of three functionally and metabolically distinct inflammatory mediators in middle ear effusions (MEE) and corresponding plasma of children with OME. One hundred two patients (mean age, 4.9 years) with persistent OME were studied. Middle ear effusions were collected from all subjects and plasma from a subset at the time of tympanostomy tube insertion. Histamine was assayed radioisotopically, 13,14-dihydro-15-keto-prostaglandin F2 alpha (stable PGF2 alpha metabolite) by radioimmunoassay, and neutrophil chemotactic factor of anaphylaxis by modified Boyden chamber. Mean MEE levels of the mediators (39 +/- 13 ng/mL, 462 +/- 179 pg/mL, and 264% +/- 57% positive control, respectively) were markedly higher than those of corresponding plasma (0.5 +/- 0.1 ng/mL, 285 +/- 127 pg/mL, and 47% +/- 5% positive control, respectively). The mean histamine content of mucoid effusions (43.2 +/- 56.9 ng/mL) was significantly higher than that of purulent (22.5 +/- 10.5 ng/mL) and serous (17.9 +/- 16.8 ng/mL) effusions. Higher histamine levels were observed in effusions positive for Haemophilus influenzae when compared with those with other pathogenic isolates. The high concentrations of these mediators in MEE and their potential for inducing or sustaining the inflammatory process supports a role in the pathogenesis of OME.

Adolescent↗

PubMed1988

Efficacy of a new macrolide (azithromycin). For acute otitis media in the chinchilla model.

The efficacy of an investigational macrolide, azithromycin, in the treatment of acute otitis media consequent to an infection by a strain of beta-lactamase-producing Haemophilus influenzae, was evaluated using the chinchilla animal model. The results indicate that the azithromycin high-dosage (30 mg/kg/d) group has a significantly higher rate for effusion sterilization and resolution as compared with the other treatment groups. Unique pharmacokinetic properties of this investigational antimicrobial were demonstrated. Clinical trials using azithromycin for the treatment of upper respiratory tract infections, including otitis media, are warranted.

Acute Disease↗

PubMed1988

Anatomy and physiology of eustachian tube and middle ear related to otitis media.

The middle ear is part of a functional system composed of the nasopharynx and the eustachian tube (anteriorly) and the mastoid air cells (posteriorly). The only active muscle that opens the eustachian tube is the tensor veli palatini, which promotes ventilation of the middle ear. The eustachian tube also functions to protect the middle ear from excessive sound pressure, and nasopharyngeal secretions. The eustachian tube helps drain the middle ear during opening and closing by pumping secretions from the middle ear; clearance of secretions also occurs. An understanding of the anatomy and physiology of the system can aid the clinician in understanding the role of eustachian tube dysfunction in the cause and pathogenesis of middle ear disease and the possible contribution of allergy to this disease.

Adult↗

PubMed1988

A double-blind, placebo-controlled clinical trial of the effect of chlorpheniramine on the response of the nasal airway, middle ear and eustachian tube to provocative rhinovirus challenge.

This paper presents the results of a randomized, double-blind, placebo-controlled study of the efficacy of chlorpheniramine in relieving the symptoms and attenuating the pathophysiologic correlates of a rhinovirus "common cold." Forty healthy, adult, nonatopic subjects were randomly assigned to one of two treatment groups: active drug and placebo. On study Day 0, all subjects were challenged intranasally with rhinovirus type 39 (dose = 100 TCID50). Subjects were cloistered from Day 2 to Day 7, at which time they were treated with either chlorpheniramine or placebo. From 3 days before challenge to study Day 19, subjects had nasal patency assessed by rhinomanometry, eustachian tube function assessed by the 9-step test and sonotubometry, middle ear pressure assessed by tympanometry and nasal clearance assessed by the dyed-saccharin technique. Symptom diaries were maintained throughout the period of follow-up. During cloister, symptoms also were scored by interview, nasal secretions were quantified and nasal washings were performed for viral culture. Results showed that 19 (95%) subjects in the active-treatment group and 18 (90%) subjects in the placebo-treatment group shed virus. Symptomatic colds were observed in 63% of the active-treated and 83% of the placebo-treated subjects. Symptoms increased on Day 1 and peaked at Days 4 to 5. Detrimental changes in other measured functions consistent with those previously reported were observed. During the period of treatment, significant differences in the average symptom scores favoring the active-treatment group were observed for sneezing. Also, weight of expelled secretions was greater and mucociliary clearance rate less on some cloister days for the placebo-treated group. No significant differences between treatment groups in the objective measures of nasal congestion or the response of the middle ear and eustachian tube were documented.

Acoustic Impedance Tests↗

PubMed1988

Evaluation of noninvasive eustachian tube function tests in normal adults.

A causal association between eustachian tube (ET) dysfunction and otitis media (OM) has been documented. We present normative data for eustachian tube function (ETF) in an otologically normal population of 107 college-age subjects using two noninvasive methods: nine-step tympanometric testing and sonotubometry. The results show a 78% agreement between the two methods when one test session was performed. The nine-step test showed a 52% repeatability rate on three sequential test sessions while the sonotubometry test showed a 34% repeatability rate. The combined tests showed a 34% agreement for the three sequential tests. The findings reveal that the combination of the two tests identify 96% of normal subjects as having at least some tubal function present. Although both tests provide similar information regarding the presence of tubal opening, the sonotubometry method is more physiologic. Additional information shows that the average category of the nine-step test in a normal population was category 2, the mean duration of tubal dilation was 0.40 seconds, and the mean middle-ear pressure was -12 mm H2O.

Acoustic Impedance Tests↗

PubMed1987

Efficacy of a new cephalosporin for acute otitis media.

The efficacy of a new third-generation cephalosporin, cefixime, in the treatment of acute otitis media resulting from infection with ampicillin-resistant, beta-lactamase-producing nontypable Haemophilus influenzae, was evaluated using the chinchilla animal model. The results showed that cefixime, administered in moderately low doses (8 mg/kg of body weight, two times per day), readily penetrated the chinchilla middle ear and rapidly sterilized the effusion. The data also suggest that the effusions were resolved more quickly in the cefixime-treated group compared with a group of animals treated with ampicillin or an untreated control group. No adverse side effects were noted in the cefixime-treated animals. The results of this study warrant the testing of cefixime for acute otitis media in the clinical setting.

Ampicillin↗

PubMed1987

Eustachian tube obstruction (ETO) after histamine nasal provocation--a double-blind dose-response study.

Eustachian tube obstruction (ETO) has been reported to develop more frequently in subjects with allergic rhinitis (AR) than in subjects without AR after a single intranasal histamine challenge. The present double-blind crossover study was designed to confirm and extend this observation. In a pilot study, nebulization was demonstrated to be superior to insufflation in provoking ETO. Five subjects with AR and five subjects without AR were repeatedly challenged intranasally with nebulized normal saline or increasing doses of histamine (0.01, 0.1, 0.5, 1.0, 5, and 10 mg per nostril). Subjects with AR were selected on the basis of AR symptoms and IgE antibodies to allergens and were challenged in their nonallergy seasons. ETO was assessed by nine-step tympanometry and nasal airway resistance by anterior rhinomanometry before and after each challenge. Of nine ears in subjects with AR, ETO developed in five ears at 0.1 mg and in four ears at 0.5 mg. In contrast, in 10 ears of subjects without AR, ETO developed in two ears at 5 mg but did not develop in eight ears at doses as large as 10 mg. This test effectively discriminated subjects with AR from subjects without AR, groups that could not be similarly differentiated by nasal or skin responsiveness to histamine challenge. Saline challenges provoked ETO in three of nine ears of subjects with AR and in one of 10 ears of subjects without AR. These data suggest a hyperresponsiveness of the nasopharyngeal and/or tubal mucosa to histamine in subjects with AR that may predispose these patients to otitis media with effusion.

Adult↗

PubMed1987

Effect of an antihistamine/decongestant on nasal and eustachian tube function following intranasal pollen challenge.

Ten adult subjects with documented ragweed allergic rhinitis underwent progressive intranasal allergen challenge following pretreatment with either an antihistamine/decongestant or placebo in a double-blind crossover fashion. Objective measurements of nasal and Eustachian tube (ET) function were made following each challenge dose using posterior rhinomanometry and sonotubometry. The percent decrease in nasal airway function, expressed as a change in conductance, was significantly less in the drug pretreatment tests when compared with placebo pretreatment. Eustachian tube function was also significantly improved by antihistamine/decongestant pretreatment as 13 of the 20 ET were obstructed at a higher antigen dose following drug pretreatment when compared with placebo. These results demonstrate a role for antihistamine/decongestant preparations in the treatment of allergic rhinitis as well as for potential allergen-induced ET dysfunction.

Adult↗

PubMed1987

The relationship between the nasal cycle and axillary sweat production.

Mean inspiratory nasal resistances and mean axillary sweating rates were recorded bilaterally every 30 minutes for a 5-7 hour period in seven subjects. One subject performed the experiment twice. Nasal resistance was measured using either anterior (n = 5) or posterior (n = 2) rhinomanometry and sweating rate was determined using a filter paper technique. The results for seven of the experiments showed that both nasal resistance and axillary sweating rate exhibited periodic reversals in side dominance. The cyclic patterns for nasal resistance and sweating rate were synchronized in phase in two experiments and 180 degrees out of phase in five experiments. These results support the concept of a central governing cycle with peripheral expression effected by the autonomic nervous system.

Adult↗

PubMed1987

Relationship between nasal patency and clearance.

Nasal airway patency and nasal clearance were measured bilaterally on six different test days in ten subjects. Nasal patency was evaluated using anterior rhinomanometry and clearance was measured using a dyed saccharin method. The results showed large intra- and inter-subject variances in the clearance times. Clearance times determined by the saccharin taste method were shorter than those determined by the dye method, but these measures were positively correlated. Also, the mean clearance rate was directly related to the mean nasal conductance. In seven of ten subjects, the clearance rate for a given side of the nasal passage was relatively faster when that side was the more patent. These results suggest that the clearance rate is a function of the patency of the nasal passage and may also exhibit alternating cyclic fluctuations.

Airway Resistance↗

PubMed1986

Eustachian tube obstruction after intranasal challenge with house dust mite.

Past studies have shown that provocative intranasal pollen challenge in allergic subjects results in signs and symptoms of allergic rhinitis, nasal obstruction, and eustachian tube obstruction. The study presented herein extends these observations to challenges with a perennial antigen, house dust mite. Twenty-three adult volunteers with confirmed sensitivity to Dermatophagoides farinae were challenged by intranasal inhalation of antigen in doses that were incremented from 0.5 to 10.0 mg. Eustachian tube function by the nine-step pressure-swallow test and nasal airway resistance by anterior rhinomanometry were evaluated before and after challenge. Twenty-two of the 40 ears showing normal tubal function before challenge were abnormal after challenge. Sixteen of the 23 subjects developed a nasal obstruction after challenge. The median specific serum IgE antibody titer for those individuals responding to the challenge was significantly greater than that of the individuals exhibiting no response. These results show that intranasal challenge with D farinae can provoke immune-mediated nasal obstruction and eustachian tube dysfunction in sensitized subjects.

Adolescent↗

PubMed1986

Fetal development of the auditory tube and paratubal musculature.

The purpose of this study was to describe the prenatal development of the human auditory tube and paratubal musculature. Twenty prenatal specimens, 8 to 36 weeks of age postconception were embedded in celloidin, sectioned, and stained with hemotoxylin eosin. Qualitative data on the initial appearance and development were obtained using light microscopy (Plates I-VI). Linear and angular measurements were obtained from traced sections. The analysis showed the following: morphological differentiation of this area occurs between 8 and 16 weeks menstrual age; tubal structures develop in anterior-posterior and medial-lateral gradients; the tubal lumen of the perinatal fetus is cylindrical and lacks an isthmus; the allometric growth of the cartilaginous portion of the lumen between 16 and 28 weeks is responsible for the greatest increase in the tubal length during the fetal period.

Cartilage↗

PubMed1986

Effect of palatoplasty on the function of the Eustachian tube in children with cleft palate.

Eustachian tube function of 24 children with cleft palate (37 ears) was evaluated longitudinally utilizing the inflation-deflation and forced-response tests before and after palatoplasty. Our results for children in this longitudinal study showed that the passive function of the tube was improved following palatoplasty. Active tubal function, which measures the muscle-induced tubal dilations, was little affected by the procedure. The majority of ears tested both before and after palatoplasty demonstrated tubal dilations with swallowing. In contrast, cross-sectional data conducted on the children with a history of otitis media and repaired cleft palates, documented a severe defect in this active tubal function with 70 percent of the tests evidencing a tubal constriction. These data suggest that the results of Eustachian tube function tests may be prognostic of the future course of ear disease in these children.

Child, Preschool↗