Gut microbiota in multiple sclerosis and animal models.

Multiple sclerosis (MS) is a chronic central nervous system (CNS) neurodegenerative and neuroinflammatory disease marked by a host immune reaction that targets and destroys the neuronal myelin sheath. MS and correlating animal disease models show comorbidities, including intestinal barrier disruption and alterations of the commensal microbiome. It is accepted that diet plays a crucial role in shaping the microbiota composition and overall gastrointestinal (GI) tract health, suggesting an interplay between nutrition and neuroinflammation via the gut-brain axis. Unfortunately, poor host health and diet lead to microbiota modifications that could lead to significant responses in the host, including inflammation and neurobehavioral changes. Beneficial microbial metabolites are essential for host homeostasis and inflammation control. This review will highlight the importance of the gut microbiota in the context of host inflammatory responses in MS and MS animal models. Additionally, microbial community restoration and how it affects MS and GI barrier integrity will be discussed.

Farnesol brain transcriptomics in CNS inflammatory demyelination.

BACKGROUND: Farnesol (FOL) prevents the onset of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). OBJECTIVE: We examined the transcriptomic profile of the brains of EAE mice treated with daily oral FOL using next-generation sequencing (RNA-seq). METHODS: Transcriptomics from whole brains of treated and untreated EAE mice at the peak of EAE was performed. RESULTS: EAE-induced mice, compared to naïve, healthy mice, overall showed increased expression in pathways for immune response, as well as an increased cytokine signaling pathway, with downregulation of cellular stress proteins. FOL downregulates pro-inflammatory pathways and attenuates the immune response in EAE. FOL downregulated the expression of genes involved in misfolded protein response, MAPK activation/signaling, and pro-inflammatory response. CONCLUSION: This study provides insight into the molecular impact of FOL in the brain and identifies potential therapeutic targets of the isoprenoid pathway in MS patients.

Gut microbiome-modulated dietary strategies in EAE and multiple sclerosis.

Over the last few decades, the incidence of multiple sclerosis has increased as society's dietary habits have switched from a whole foods approach to a high fat, high salt, low dietary fiber, and processed food diet, termed the "Western diet." Environmental factors, such as diet, could play a role in the pathogenesis of multiple sclerosis due to gut microbiota alterations, gut barrier leakage, and subsequent intestinal inflammation that could lead to exacerbated neuroinflammation. This mini-review explores the gut microbiome alterations of various dietary strategies that improve upon the "Western diet" as promising alternatives and targets to current multiple sclerosis treatments. We also provide evidence that gut microbiome modulation through diet can improve or exacerbate clinical symptoms of multiple sclerosis, highlighting the importance of including gut microbiome analyses in future studies of diet and disease.

The immunomodulatory roles of the gut microbiome in autoimmune diseases of the central nervous system: Multiple sclerosis as a model.

The gut-associated lymphoid tissue is a primary activation site for immune responses to infection and immunomodulation. Experimental evidence using animal disease models suggests that specific gut microbes significantly regulate inflammation and immunoregulatory pathways. Furthermore, recent clinical findings indicate that gut microbes' composition, collectively named gut microbiota, is altered under disease state. This review focuses on the functional mechanisms by which gut microbes promote immunomodulatory responses that could be relevant in balancing inflammation associated with autoimmunity in the central nervous system. We also propose therapeutic interventions that target the composition of the gut microbiota as immunomodulatory mechanisms to control neuroinflammation.

Farnesol induces protection against murine CNS inflammatory demyelination and modifies gut microbiome.

Farnesol is a 15­carbon organic isoprenol synthesized by plants and mammals with anti-oxidant, anti-inflammatory, and neuroprotective activities. We sought to determine whether farnesol treatment would result in protection against murine experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis (MS). We compared disease progression and severity in C57BL/6 mice treated orally with 100 mg/kg/day farnesol solubilized in corn oil to corn-oil treated and untreated EAE mice. Farnesol significantly delayed the onset of EAE (by ~2 days) and dramatically decreased disease severity (~80%) compared to controls. Disease protection by farnesol was associated with a significant reduction in spinal cord infiltration by monocytes-macrophages, dendritic cells, CD4+ T cells, and a significant change in gut microbiota composition, including a decrease in the Firmicutes:Bacteroidetes ratio. The study suggests FOL could protect MS patients against CNS inflammatory demyelination by partially modulating the gut microbiome composition.

A formal description of middle ear pressure-regulation.

INTRODUCTION: Middle ear (ME) pressure-regulation (MEPR) is a homeostatic mechanism that maintains the ME-environment pressure-gradient (MEEPG) within a range optimized for "normal" hearing. OBJECTIVE: Describe MEPR using equations applicable to passive, inter-compartmental gas-exchange and determine if the predictions of that description include the increasing ME pressure observed under certain conditions and interpreted by some as evidencing gas-production by the ME mucosa. METHODS: MEPR was modeled as the combined effect of passive gas-exchanges between the ME and: perilymph via the round window membrane, the ambient environment via the tympanic membrane, and the local blood via the ME mucosa and of gas flow between the ME and nasopharynx during Eustachian tube openings. The first 3 of these exchanges are described at the species level using the Fick's diffusion equation and the last as a bulk gas transfer governed by Poiseuille's equation. The model structure is a time-iteration of the equation: PMEg(t=(i+1)Δt) = ∑s(PMEs(t=iΔt)+(1/(ßMEsVME)∑P(ҚPs(PCs(t=(iΔt)-PMEs(t=(iΔt))). There, PMEg(t=iΔt) and PMEs(t=iΔt) are the ME total and species-pressures at the indexed times, PCs(t=iΔt) is the species-pressure for each exchange-compartment, ßMEsVME is the product of the ME species-capacitance and volume, ҚPs is the pathway species-conductance, and ∑S and ∑P are operators for summing the expression over all species or exchange pathways. RESULTS: When calibrated to known values, the model predicts the empirically measured ME species-pressures and the observed time-trajectories for total ME pressure and the MEEPG under a wide variety of physiologic, pathologic and non-physiologic conditions. CONCLUSIONS: Passive inter-compartmental gas exchange is sole and sufficient to describe MEPR.

Offspring of parents who were separated and not speaking to one another have reduced resistance to the common cold as adults.

Exposure to parental separation or divorce during childhood has been associated with an increased risk for physical morbidity during adulthood. Here we tested the hypothesis that this association is primarily attributable to separated parents who do not communicate with each other. We also examined whether early exposure to separated parents in conflict is associated with greater viral-induced inflammatory response in adulthood and in turn with increased susceptibility to viral-induced upper respiratory disease. After assessment of their parents' relationship during their childhood, 201 healthy volunteers, age 18-55 y, were quarantined, experimentally exposed to a virus that causes a common cold, and monitored for 5 d for the development of a respiratory illness. Monitoring included daily assessments of viral-specific infection, objective markers of illness, and local production of proinflammatory cytokines. Adults whose parents lived apart and never spoke during their childhood were more than three times as likely to develop a cold when exposed to the upper respiratory virus than adults from intact families. Conversely, individuals whose parents were separated but communicated with each other showed no increase in risk compared with those from intact families. These differences persisted in analyses adjusted for potentially confounding variables (demographics, current socioeconomic status, body mass index, season, baseline immunity to the challenge virus, affectivity, and childhood socioeconomic status). Mediation analyses were consistent with the hypothesis that greater susceptibility to respiratory infectious illness among the offspring of noncommunicating parents was attributable to a greater local proinflammatory response to infection.

Histamine Applied Topically to the Nasal Mucosa Increases the Transmucosal Nitrous Oxide Exchange for the Middle Ear.

OBJECTIVE: Determine if the middle ear transmucosal nitrous oxide (N2O) exchange rate is affected by nasal inflammation caused by topical application of histamine. METHODS: In a randomized, double-blind, crossover study, 20 adults were challenged intranasally with histamine (5 mg) and placebo on separate occasions. At each session, the subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes, 50% N2O:50% O2 for 20 minutes, and 100% O2 for 10 minutes. Throughout, heart rate, blood pressure, and blood O2 saturation were monitored, and bilateral middle ear pressure was recorded by tympanometry every minute. The primary outcome measure was the slope of the middle ear pressure-time function for the 50% N2O:50% O2 breathing period, which is a measure of the transmucosal N2O exchange-constant. The effects of challenge substance, session, and period on the measured vital signs and of treatment, session, ear disease history, and test ear on the pressure-time slopes were evaluated using repeated measures ANOVAs. RESULTS: The post-challenge total symptom score and the slope of the middle ear pressure-time function were greater after histamine when compared to placebo challenge. Of the signs, only heart rate was affected, responding to challenge substance and study period. CONCLUSION: The transmucosal N2O exchange rate for the middle ear is increased during inflammation caused by nasal histamine exposure.

Dispositional Affect Moderates the Stress-Buffering Effect of Social Support on Risk for Developing the Common Cold.

OBJECTIVE: The aim was to examine whether trait positive and negative affect (PA, NA) moderate the stress-buffering effect of perceived social support on risk for developing a cold subsequent to being exposed to a virus that causes mild upper respiratory illness. METHOD: Analyses were based on archival data from 694 healthy adults (Mage = 31.0 years, SD = 10.7 years; 49.0% female; 64.6% Caucasian). Perceived social support and perceived stress were assessed by self-report questionnaire and trait affect by aggregating responses to daily mood items administered by telephone interview across several days. Subsequently, participants were exposed to a virus that causes the common cold and monitored for 5 days for clinical illness (infection + objective signs of illness). RESULTS: Two 3-way interactions emerged-Support × Stress × PA and Support × Stress × NA. The nature of these effects was such that among persons with high trait PA or low trait NA, greater social support attenuated the risk of developing a cold when under high but not low perceived stress; this stress-buffering effect did not emerge among persons with low trait PA or high trait NA. CONCLUSIONS: Dispositional affect might be used to identify individuals who may be most responsive to social support and support-based interventions.

Resolution of Otitis Media With Effusion in Children With Cleft Palate Followed Through Five Years of Age.

OBJECTIVE: To describe the temporal pattern of otitis media with effusion (OME) resolution for a cohort of nonsyndromic cleft palate children enrolled before palatoplasty and followed through 5 years of age. DESIGN: This is a prospective, longitudinal study of the time course for OME resolution in infants and children with palatal clefts. SETTING: Cleft Palate Craniofacial Center of a tertiary care pediatric hospital. PARTICIPANTS: This study included 52 children with cleft palate (29 boys, 45 white, Veau 1 through 4) who had a Furlow-type palatoplasty between 10 and 24 months of age performed by one of six surgeons. INTERVENTIONS: Standard cleft palate management was supplemented with study visits to the research clinic pre- and postpalatoplasty and then yearly to 6 years of age for assessments of middle ear status by interval history, otoscopy, and tympanometry. MAIN OUTCOME MEASURE: The main outcome measure was age at otitis media resolution defined as the age in years at the first in a sequence of "disease-free" diagnoses not interrupted or followed by any other diagnosis. RESULTS: The cumulative percent OME resolution for ears/children at ages <1, 1, 2, 3, 4, 5 years was 4.1/4.4, 14.3/10.9, 31.6/21.7, 45.9/37.0, 56.1/50.0, and 70.4/60.9%. OME resolution followed a simple linear time curve with slopes of 13.5% (confidence interval [CI] = 12.2% to 14.8%, r(2) = .99) and 11.9% (CI = 10.1% to 13.6%, r(2) = .99) resolutions per year for ears and children, respectively. CONCLUSIONS: There is a natural, age-related pattern of resolution for persistent OME that affects most infants and young children with cleft palate that is not affected by palatoplasty.

Information on co-morbidities collected by history is useful for assigning Otitis Media risk to children.

OBJECTIVES: Determine if a 2-Step multivariate analysis of historical symptom/sign data for comorbid diseases can abstract high-level constructs useful in assigning a child's "risk" for different Otitis Media expressions. METHODS: Seventeen items related to the symptom/sign expression of hypothesized Otitis Media comorbidities were collected by history on 141 3-year-old children. Using established criteria, the children were assigned to 1 of 3 groups: Control (no significant past Otitis Media, n=45), Chronic Otitis Media with Effusion (n=45) and Recurrent Acute Otitis Media (n=51). Principal Component Analysis was used to identify factors representing the non-redundant shared information among related items and Discriminant Analysis operating on those factors was used to estimate the best predictor equation for pairwise group assignments. RESULTS: Six multivariate factors representing the assignable comorbidities of frequent colds, nasal allergy, gastroesophageal disease (specific and general), nasal congestion and asthma were identified and explained 81% of the variance in the 17 items. Discriminant Analysis showed that, for the Control-Chronic Otitis Media with Effusion comparison, a combination of 3 factors and, for the Control-Recurrent Acute Otitis Media comparison, a combination of 2 factors had assignment accuracies of 74% and 68%, respectively. For the contrast between the two disease expressions, a 2-factor combination had an assignment accuracy of 61%. CONCLUSION: These results show that this analytic methodology can abstract high-level constructs, comorbidities, from low-level data, symptom/sign scores, support a linkage between certain comorbidities and Otitis Media risk and suggest that specific comorbidity combinations contain information relevant to assigning the risk for different Otitis Media expressions.

Basal salivary cortisol secretion and susceptibility to upper respiratory infection.

The immunosuppressive effects of glucocorticoids (GCs) are well-established. However, whether the net effect of GC-elicited alterations in immune function is sufficient to influence a clinically relevant outcome in healthy adults has yet to be shown. The aim of the present study was to investigate whether inter-individual differences in basal salivary cortisol production are associated with increased risk and severity of infection and subsequent illness following experimental exposure to a virus that causes the common cold. The present analyses combine archival data from three viral-challenge studies. Participants were 608 healthy adults, aged 18 to 55 years (49.2% female; 65.8% white), who each completed a three-day saliva collection protocol; was subsequently exposed to a virus that causes the common cold; and monitored for 5 days for objective signs of infection (presence of challenge virus in nasal secretions) and clinical illness (mucus weight, mucociliary clearance time). Basal cortisol production (operationalized as the calculated area-under-the-curve averaged across the 3 days) showed a graded association with infection risk, with those producing higher levels of cortisol being at greater risk. Cortisol also showed a continuous association with duration of viral shedding, an indicator of viral replication and continuing infection, such that higher cortisol concentrations predicted more days of shedding. Cortisol was not, however, related to severity of objective illness. These findings are the first to demonstrate in healthy adults an association between basal cortisol production and an objectively measured and clinically relevant infectious disease outcome.

Oxymetazoline Applied Topically to the Nasal Mucosa Decreases Trans-Mucosal Nitrous Oxide Exchange for the Middle Ear.

OBJECTIVE: Determine if the middle ear (ME) trans-mucosal nitrous oxide (N2O) gas exchange rate can be pharmacologically modulated by the nasal application of a vasoconstrictor. METHODS: In a randomized, double-blind, crossover study, 20 adults received a nasal spray challenge containing either oxymetazoline or saline (placebo). At each session, subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes, 50% N2O:50% O2 for 20 minutes, and 100% O2 for 10 minutes. Throughout, heart rate, blood pressure (BP), and blood O2 saturation were monitored, and bilateral ME pressure was recorded by tympanometry every minute. The primary outcome measure was the slope of the ME pressure-time function for the experimental period, a direct measure of the transMEM N2O exchange constant. The effects of treatment, session, and period on the measured vital signs and of treatment, session, disease history, and ear on the ME pressure-time slopes were evaluated for statistical significance using repeated measures ANOVAs. RESULTS: The analysis documented a significant effect of period on O2 saturation (N2O > room air, P = .03) and of treatment on blood pressure (oxymetazoline > placebo, P < .02) and the ME pressure-time slope (placebo > oxymetazoline, P = .05). CONCLUSION: The exchange rate across the ME mucosa of inert gases can be decreased by topical treatment of the nasal mucosa with oxymetazoline.

Eustachian Tube Function in 6-Year-Old Children with and without a History of Middle Ear Disease.

OBJECTIVE: To test the hypothesis that eustachian tube opening efficiency, measured as the fractional gradient equilibrated (FGE), is lower in 6-year-old children with no middle ear disease but a well-documented history of recurrent acute otitis media, as compared with children with a negative disease history (control). STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care pediatric hospital. SUBJECTS AND METHODS: Bilateral eustachian tube function was evaluated in 44 healthy 6-year-old children (19 boys, 29 white). None had middle ear disease at the time of testing, but 23 had a history of recurrent acute otitis media. Twenty-one had no significant past otitis media. Eustachian tube function was measured with a pressure chamber protocol that established negative middle ear gauge pressures (referenced to the chamber pressure) and recorded that pressure before and after a swallow. FGE was calculated as the change in middle ear gauge pressure with swallowing divided by the preswallow pressure. Between-group comparisons of the preswallow pressures and FGEs were made with a 2-tailed Student's t test. RESULTS: FGE was independent of the preswallow middle ear gauge pressure. For the 39 and 44 evaluable ears in the control and recurrent acute otitis media groups, the mean preswallow pressures were -194 daPa (95% confidence interval [95% CI] = -211 to -177) versus -203 (95% CI = -216 to -190; P > .40), and FGEs were 0.32 (95% CI = 0.21-0.43) vs 0.16 (95% CI = 0.08-0.24; P = .016), respectively. CONCLUSION: In children with past recurrent acute otitis media, residual eustachian tube opening inefficiency is maintained after they have "outgrown" their middle ear disease.

Self-Rated Health in Healthy Adults and Susceptibility to the Common Cold.

OBJECTIVES: To explore the association of self-rated health (SRH) with host resistance to illness after exposure to a common cold virus and identify mechanisms linking SRH to future health status. METHODS: We analyzed archival data from 360 healthy adults (mean [standard deviation] age = 33.07 [10.69] years, 45.6% women). Each person completed validated questionnaires that assessed SRH (excellent, very good, good, fair, poor), socioemotional factors, and health practices and was subsequently exposed to a common cold virus and monitored for 5 days for clinical illness (infection and objective signs of illness). RESULTS: Poorer SRH was associated in a graded fashion with greater susceptibility to developing clinical illness (good/fair versus excellent: odds ratio = 3.21, 95% confidence interval = 1.47-6.99; very good versus excellent: odds ratio = 2.60, 95% confidence interval = 1.27-5.32), independent of age, sex, race, prechallenge immunity (specific antibody), body mass, season, education, and income. Greater illness risk was not attributable to infection, but to increased likelihood of developing objective signs of illness once infected. Poorer SRH also correlated with poorer health practices, increased stress, lower positive emotions, and other socioemotional factors. However, none of these (alone or together) accounted for the association between SRH and host resistance. Additional data (separate study) indicated that history of having colds was unrelated to susceptibility and hence also did not account for the SRH link with immunocompetence. CONCLUSIONS: Poorer SRH is associated with poorer immunocompetence, possibly reflecting sensitivity to sensations associated with premorbid immune dysfunction. In turn, poorer immune function may be a major contributing mechanism linking SRH to future health.

Oral pseudoephedrine decreases the rate of transmucosal nitrous oxide exchange for the middle ear.

OBJECTIVES/HYPOTHESIS: Determine if oral treatment with a vasoconstrictor decreases the blood to middle ear exchange rate of the perfusion-limited gas, nitrous oxide (N2O). STUDY DESIGN: Randomized, double-blind, crossover study. METHODS: Ten adult subjects with and 10 without past middle ear disease completed paired experimental sessions, identical except for oral treatment with either pseudoephedrine hydrochloride or lactose placebo. At each session, subjects were fitted with a nonrebreathing mask and breathed room air for 20 minutes (acclimation period), 50% N2O:50% O2 for 20 minutes (experimental period), and 100% O2 for 10 minutes (recovery period). Throughout, heart rate, blood pressure, and O2 saturation were monitored, and bilateral middle ear pressures were recorded by tympanometry every minute. The primary outcome was the slope of the middle ear pressure-time function for the experimental period, which estimates the volume N2O exchange rate. Using repeated measures analysis of variance, the effects of group (disease history), treatment (active vs. placebo), and period (1 vs. 2) on the recorded vital signs, and of group, treatment, and ear (left/right) on the middle ear pressure-time slope were evaluated for statistical significance. RESULTS: Statistically significant effects of period on O2 saturation (period 2 > period 1) and of treatment on heart rate (active > placebo) were documented. Only treatment was statistically significant for the middle ear pressure-time slope, with a shallower slope characterizing the active treatment session. CONCLUSIONS: The volume exchange rate across the middle ear mucosa of perfusion-limited gases can be modulated pharmacologically. Theoretically, similar drugs can be used to reduce the requisite eustachian tube opening efficiency for adequate middle ear pressure regulation. LEVEL OF EVIDENCE: 1b.

Quantitative description of eustachian tube movements during swallowing as visualized by transnasal videoendoscopy.

IMPORTANCE: Eustachian tube (ET) dysfunction predisposes ears to otitis media, tympanic membrane retraction, retraction pocket and perforation, or cholesteatoma. OBJECTIVE: To develop a method to quantitatively measure the eustachian tube (ET) component movements and their interactions captured by transnasal videoendoscopy of the ET during swallowing. DESIGN, SETTING, AND PARTICIPANTS: A blinded analysis of ET mechanics in 33 adults, aged 18 to 54 years, with no middle ear disease at present but without (group 1 [n = 16]) or with (group 2 [n = 17]) history of disease, conducted at a clinical research laboratory. INTERVENTIONS: Videoendoscopy of the ET orifice at the nasopharynx. MAIN OUTCOMES AND MEASURES: Eustachian tube component translations and structural interactions during a swallow and the between-group differences in those variables. After topical anesthesia of the nose, a 45° telescope was introduced unilaterally and focused on the ipsilateral ET orifice. A video recording of ET component movements was made during 3 swallows. Swallow and ET opening durations and times to selected events were calculated. Images at 3 time points were analyzed by measuring the apex angle, the medial-lateral luminal width, and the medial angles between a frame-normal horizontal line through the apex and fixed points on the torus and medial and lateral luminal walls. Linear and angular variables during a swallow were expressed as change from baseline. RESULTS: Luminal opening was driven by soft palate elevation-related medial rotation of the torus and medial wall, coupled with lateral wall fixedness. The magnitude of the change from baseline for most variables was statistically greater than 0. Swallow time, palatal elevation time, time interval between maximum palatal elevation, and maximum eustachian tube opening time were not different between groups 1 and 2. Opening time was longer (mean [SD], 0.49 [0.28] vs 0.67 [0.51] seconds; P = .03) in group 2. Higher magnitude of torus rotation (mean [SD], 36.05° [12.96°] vs 27.72° [9.45°]; P = .002) with maximum soft palate elevation in group 1 resulted in greater degree of eustachian tube orifice widening (mean [SD], 0.34% [0.47%] vs -0.02% [0.49%]; P = .001) compared with the resting position in that group. CONCLUSIONS AND RELEVANCE: This methodology has application in developing quantitative descriptions of ET mechanics in groups of persons without and with history or suspected ET dysfunction. A lesser degree of soft palate elevation during swallow that derives the ET medial lamina rotation and widening of the ET orifice may be associated with poor ET function and higher risk for otitis media. Videoendoscopic evaluation of the ET orifice may assist in diagnosing presence and mechanism of ET dysfunction.

Does hugging provide stress-buffering social support? A study of susceptibility to upper respiratory infection and illness.

Perceived social support has been hypothesized to protect against the pathogenic effects of stress. How such protection might be conferred, however, is not well understood. Using a sample of 404 healthy adults, we examined the roles of perceived social support and received hugs in buffering against interpersonal stress-induced susceptibility to infectious disease. Perceived support was assessed by questionnaire, and daily interpersonal conflict and receipt of hugs were assessed by telephone interviews on 14 consecutive evenings. Subsequently, participants were exposed to a virus that causes a common cold and were monitored in quarantine to assess infection and illness signs. Perceived support protected against the rise in infection risk associated with increasing frequency of conflict. A similar stress-buffering effect emerged for hugging, which explained 32% of the attenuating effect of support. Among infected participants, greater perceived support and more-frequent hugs each predicted less-severe illness signs. These data suggest that hugging may effectively convey social support.

A method to assess the accuracy of sonotubometry for detecting Eustachian tube openings.

Sonotubometry is a simple test for Eustachian tube (ET) opening during a maneuver. Different sonotubometry configurations were suggested to maximize test accuracy, but no method has been described for comparing sonotubometry test results with those for a definitive measure of ET opening. Here, we present such a method and exemplify is use by an accuracy assessment of a simple sonotubometry configuration. A total of 502 data-sequences from 168 test sessions in 103 adult subjects were analyzed. For each session, subjects were seated in a pressure chamber and relative middle ear over- and under-pressures created by changing chamber pressure. At each pressure, the test sequence of bilateral tympanometry, bilateral sonotubometry while the subject swallowed twice, and bilateral tympanometry was done. Tympanometric data were expressed as the fractional gradient equilibrated (FGE) by swallowing and sonotubometric signals were analyzed to record the shape of detected sound signals. Tympanometric and sonotubometric tubal opening assignments were analyzed by cross-correlation. For the data sequences with FGE = 0 (n = 32) evidencing no tubal opening and one (n = 249) evidencing definitive tubal opening, detection of a sonotubometry sound signal during a swallow had a sensitivity and specificity of 74.2 and 65.6 % for identifying ET openings and an accuracy of 73.3 % for assigning ET opening/non-opening by swallowing. Measures of sound signal shape were significantly different between those groups. This protocol allows a sonotubometry accuracy assessment for detecting ET openings. For the test configuration used, accuracy was moderate, but this should improve as more sophisticated sonotubometry test configurations are evaluated.

Eustachian tube function in young children without a history of otitis media evaluated using a pressure chamber protocol.

CONCLUSIONS: Protocol limitations were identified and accounted for in the analysis. Percent gradient equilibrated (PGE) was affected by driving gradient direction in a similar manner to other efficiency measures. A finer resolution of possible age-related changes in eustachian tube opening efficiency is expected with the application of more sophisticated statistical models to the complete dataset at study end. OBJECTIVE: To report the results of an interim analysis for an ongoing study designed to characterize the age-related changes in eustachian tube opening efficiency measured using a pressure chamber protocol in children without a history of middle ear disease. METHODS: To date, 41 children aged 3 years without a history of otitis media have been enrolled in a longitudinal study of the age-related changes in eustachian tube function and evaluated at yearly intervals between 3 and 7 years of age. Eustachian tube opening efficiency, the percent of the applied pressure gradient equilibrated by swallowing, was measured by repeat tympanometry during a pressure chamber protocol. Data (120 tests) were analyzed using an ANOVA with variance partitioned by age (3 through 6 years), gradient direction (positive/negative), and ear (left/right). RESULTS: PGE was higher for left ears and positive driving gradients, but was not different among age groups.