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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.

The gut-microbiota-brain axis has emerged as a critical pathway in the regulation of neuroinflammation. The gut microbiome regulates the severity of many experimental models of autoimmune central nervous system (CNS) demyelinating inflammatory diseases. Our most recent findings demonstrate that the microbiota of mice from different sources affects the severity of CNS inflammatory demyelination. Neuroinflammation triggered in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, modified the gut microbiota composition. The disease progression resulted in a significant reduction in the relative abundances of members of lactic acid bacteria when compared to healthy control mice. Among the altered taxa, bacteria producing gamma-aminobutyric acid (GABA) were significantly reduced. We hypothesized that modifying the microbiota with a probiotic while increasing intestinal GABA levels would reduce EAE’s severity. We genetically engineered a Lactococcus lactis probiotic that produces excessed levels of GABA. Real-time quantitative PCR analysis demonstrated an elevated expression of glutamic acid decarboxylase (GAD). GABA-specific ELISA showed a significant increase in neurotransmitter production when exposed to increasing concentrations of glutamic acid and time. In vivo, five times/week oral gavages with 5 × 108 CFU/mouse of GAD L. lactis but not with empty-plasmid carrier L. lactis protects against EAE in mice compared with sham-treated mice and prevents weight loss of animals while modulating the microbiome’s composition. Our results show that the increase of GABA at the intestinal level with the oral treatment with a probiotic strain protects against neuroinflammation in the CNS. Supported by grant from NIH (R15 NS107743)

Farnesol is a 15‑carbon 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.

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.

ObjectiveTo 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.DesignThis is a prospective, longitudinal study of the time course for OME resolution in infants and children with palatal clefts.SettingCleft Palate Craniofacial Center of a tertiary care pediatric hospital.ParticipantsThis 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.InterventionsStandard 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 MeasureThe 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.ResultsThe cumulative percent OME resolution for ears/children at ages 2= .99) and 11.9% (CI = 10.1% to 13.6%, r2= .99) resolutions per year for ears and children, respectively.ConclusionsThere 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.

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.

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 Laryngoscope, 125:2181–2186, 2015

We measured affect in 334 healthy adults on each of 7 days over a 3-week period. On the last day, salivary cortisol was assessed 14 times yielding scores for total concentration, morning rise amplitude, and slope of the time function. Trait negative affect (NA) was associated with higher total cortisol concentrations and greater morning rise in men. Cortisol levels for men low in trait positive affect (PA) did not decrease in the afternoon, resulting in a relatively high, flat rhythm. In contrast, women high in trait PA had low morning cortisol resulting in a low flat rhythm. State (person-centered) NA was not associated with same-day cortisol measures. State PA was associated with decreased total cortisol concentration in women. These are the first results showing associations between cortisol and trait PA. Differences in rhythmicity found here are noteworthy given the possible role of cortisol dysregulation in disease incidence, morbidity, mortality, and severity.

There is considerable evidence that social relationships can influence health, but only limited evidence on the health effects of the personality characteristics that are thought to mold people's social lives. We asked whether sociability predicts resistance to infectious disease and whether this relationship is attributable to the quality and quantity of social interactions and relationships. Three hundred thirty-four volunteers completed questionnaires assessing their sociability, social networks, and social supports, and six evening interviews assessing daily interactions. They were subsequently exposed to a virus that causes a common cold and monitored to see who developed verifiable illness. Increased sociability was associated in a linear fashion with a decreased probability of developing a cold. Although sociability was associated with more and higher-quality social interactions, it predicted disease susceptibility independently of these variables. The association between sociability and disease was also independent of baseline immunity (virus-specific antibody), demographics, emotional styles, stress hormones, and health practices.

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: P ME g(t=(i+1)Δt) = ∑ s (P ME s(t=iΔt) +(1/(β ME s V ME )∑ P (Қ P s (P C s(t=(iΔt) -P ME s(t=(iΔt) )). There, P ME g(t=iΔt) and P ME s(t=iΔt) are the ME total and species-pressures at the indexed times, P C s(t=iΔt) is the species-pressure for each exchange-compartment, β ME s V ME is the product of the ME species-capacitance and volume, Қ P s 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.

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.

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.

Objectives/Hypothesis Test the hypothesis that the eustachian tube (ET) function measured using standard manometric test methods is different between groups of ears with tympanostomy tubes inserted for recurrent acute otitis media (RAOM) and for chronic otitis media with effusion (COME). Study Design A cross-sectional study of ET function in populations of young children with different otitis media expressions. Methods The results for forced-response testing of ET function were compared using a general linear model between 37 ears of 26 children and 34 ears of 26 children, aged 3 and 4 years, with ventilation tubes inserted for COME and RAOM, respectively. Results There were no significant between-group differences in either the active measure of ET opening function, dilatory efficiency, or in the passive measures reflecting the magnitude of the forces that tend to hold the ET lumen closed, the opening and closing pressures, and passive trans-ET conductance. Conclusions The results do not support the hypothesis that ET closing forces are less in ears with RAOM when compared to ears with COME, and from the results of earlier studies, ears without disease. Both groups were characterized by a low ET opening efficiency (referenced to ears of adults with no disease history). Because both disease expressions present the same pattern of ET dysfunction, other factors are required to explain why a subset of ears with that type of dysfunction develop RAOM, as opposed to the default expression of COME. Level of Evidence 2b Laryngoscope, 124:2619–2623, 2014

Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different dimensions of childhood experience—those pertaining to socioeconomic status (SES), physical environment, or family relationships, relate differentially to CMV serostatus and reactivation during adulthood. Participants were 140 healthy adults, aged 18–55 years (41% female; 64% white). Childhood environments were assessed retrospectively and included family SES (parental housing tenure); childhood neighborhood environment (urban residence; physical conditions; safety; and social atmosphere); residential exposures (parental smoking and physical condition of home); and family relationships (parental divorce; warmth; harmony; dysfunction; parental bonding). Approximately 39% (n = 53) of participants were CMV+. In individual analyses controlling for age, sex, race, body mass, current adult SES and smoking status, fewer years of parental home ownership, having a parent who smoked, and living in a poorly maintained or unsafe neighborhood each were associated with greater odds of infection with CMV. By comparison, in individual analyses limited to CMV+ participants, less family warmth, less harmony, greater dysfunction, and suboptimal parental bonding each were related to higher antibody levels, independent of the aforementioned covariates. Findings were not attributable to current adult perceptions of psychological stress or relative levels of emotional stability. These results suggest that different types of childhood adversity may be associated with differential effects on CMV infection and latency.

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.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.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).PGE was higher for left ears and positive driving gradients, but was not different among age groups.

Test the hypothesis that active Eustachian tube opening efficiency as measured by sonotubometry is higher in adults with no extant middle-ear disease and no history of previous otitis media (Group-1) when compared to adults with no middle-ear disease but a positive history for otitis media (Group-2).Eustachian tube function for 1 ear of 33 otherwise healthy adult subjects, 16 assigned to Group-1 and 17 to Group-2, was tested by sonotubometry using a standard protocol. For each test, the sound envelopes for 3 swallows were abstracted independently by 2 observers from the data stream and 7 descriptive parameters related to sound envelope "shape" were calculated. Inter-relatedness among the values for the parameters was explored using correlation analysis. The contributions of swallow, observer and group to the variance in each parameter were evaluated for significance using a General Linear Model.The shape parameters reflecting envelope height, area and rise and fall rates were highly inter-correlated, but those reflecting envelope widths were not. There was no effect of "swallow" on any of the parameters; but there was a significant "observer" effect on all measures of envelope width, greater for observer-2, and a significant "group" effect for 5 of the 7 shape parameters, all greater in Group-1.Quantifiable measures of the sound signal "shape" recorded by sonotubometry during swallowing were significantly different between the 2 groups of subjects. This is interpretable as evidencing a more efficient Eustachian tube opening-function in adults with healthy middle ears who do not have a previous history of otitis media when compared to similar adults with a history of prior otitis media. Inefficient Eustachian tube function as children may not be completely resolved by adulthood increasing adult otitis media risk when Eustachian tube function is down-graded by extant upper respiratory diseases that provoke nasopharyngeal inflammation.

Low socioeconomic status (SES) during childhood and adolescence has been found to predict greater susceptibility to common cold viruses in adults. Here, we test whether low childhood SES is associated with shorter leukocyte telomere length in adulthood, and whether telomere length mediates the association between childhood SES and susceptibility to acute upper respiratory disease in adulthood. At baseline, 196 healthy volunteers reported whether they currently owned their home and, for each year of their childhood, whether their parents owned the family home. Volunteers also had blood drawn for assessment of specific antibody to the challenge virus, and for CD8+CD28− T-lymphocyte telomere length (in a subset, n = 135). They were subsequently quarantined in a hotel, exposed to a virus (rhinovirus [RV] 39) that causes a common cold and followed for infection and illness (clinical cold) over five post-exposure days. Lower childhood SES as measured by fewer years of parental home ownership was associated with shorter adult CD8+CD28− telomere length and with an increased probability of developing infection and clinical illness when exposed to a common cold virus in adulthood. These associations were independent of adult SES, age, sex, race, body mass, neuroticism, and childhood family characteristics. Associations with infections and colds were also independent of pre-challenge viral-specific antibody and season. Further analyses do not support mediating roles for smoking, alcohol consumption or physical activity but suggest that CD8+CD28− cell telomere length may act as a partial mediator of the associations between childhood SES and infection and childhood SES and colds.

Objectives/Hypothesis: In children with ventilation tubes (VTs) inserted for chronic otitis media with effusion (COME), the authors sought to determine whether any parameter of Eustachian tube (ET) function measured by the forced response test (FRT) predicts disease recurrence after the VT becomes nonfunctional. Study Design: Prospective study of those factors that predict disease recurrence in children with VTs inserted for COME. Methods: Forty-nine subjects (73 ears; 28 male, 34 white, aged 5.3 6 1.2 years) with COME had VTs inserted and were evaluable for disease status after the VT(s) became nonfunctional. The FRT was done when the VTs were patent, and results for the last test before the VT became nonfunctional were used in the analysis. After each VT became nonfunctional, the children were followed for disease recurrence over a 12-month period. Logistic regression was used to determine whether the ET opening pressure, closing pressure, and/or dilatory efficiency predicted disease recurrence. That model was expanded to include age, sex, race, history of adenoidectomy, previous VTs, and duration of VT patency as potential predictive factors. Results: Twenty-nine (40%) ears had recurrence of significant disease within 12 months after the VT became nonfunctional. For the complete logistic regression model, male gender (P 5.03), nonwhite race (P 5.02), shorter period of VT patency (P 5.01), and low dilatory efficiency (P 5.01) were significant predictors of disease recurrence. Conclusions: A measure of active ET function, dilatory efficiency, but not measures of passive function predicted disease recurrence within the 12 months after the VT became nonfunctional in children with COME.

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.Analyses were based on archival data from 694 healthy adults (MTwo 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.Dispositional affect might be used to identify individuals who may be most responsive to social support and support-based interventions.

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.

Objective To characterize Eustachian tube function using the forced response test in young children with cleft palate with or without cleft lip after palatoplasty with tympanostomy tubes inserted prepalatoplasty and compare these results with those of a 1986 study that evaluated a similar population using identical methods. Setting Outpatient research clinic. Patients/Participants A total of 34 children with cleft palate were tested at an average age of 18.6 ± 4.0 months. Main Outcome Measures Passive and active measures for the forced response test. Results Of the sample, 13 ears could not be tested, and tests on 24 ears were incomplete. The forced response test showed that the passive Eustachian tube function parameters were similar to those of normal adults and children. The percentage of ears that showed tubal dilation with swallowing was 60%. The active resistance and dilatory efficiency were similar to those of a normal adult population. Conclusions A 1986 study of Eustachian tube function in postpalatoplasty subjects with cleft palate (37 ears) aged 15 to 26 months documented Eustachian tube dilation with swallowing in 84% of the ears. In the present study, which focused on a similar population, the frequency of tubal dilation was 60%. Nonetheless, both frequencies are significantly greater than the dilation frequency of 27% reported for 56 ears of subjects with cleft palate tested between 3 months and 18 years with tympanostomy tubes inserted for persistent otitis media with effusion. This suggests that dilation during the forced response test may be a prognostic marker for those children with cleft palate who will resolve their ear disease at an early age.

One past study conducted in 1986 reported Eustachian tube dilation with swallowing during the forced response test (FRT) in a very high percentage (80%) of cleft palate patients both before and after palatoplasty. The present study was designed to determine the reproducibility of those results.The FRT was used to evaluate Eustachian tube function in a cohort of cleft palate children before and after palatoplasty. Pre-palatoplasty FRT data were available for 25 ears and post-palatoplasty data were available for 31 ears; 14 ears had paired pre-post palatoplasty test data. The results for the FRT tests were compared between the pre- and post-palatoplasty groups for the cross-sectional data and for the paired subset of ears.The 3 passive function measures of the FRT, the opening pressure, closing pressure and passive resistance were not different before and after palatoplasty for either data set. Similarly, 2 of the 3 active function measures, active resistance and dilatory efficiency, were not different pre- and post-palatoplasty, but the percent of ears evidencing tubal dilation for the cross-sectional data was 39% and 62% (p=NS) and for the paired subset was 33% and 83% (p=0.04) at the pre- and post-palatoplasty tests.Palatoplasty had no effect on most measures of the FRT, but may have had a positive effect on the ability to dilate the Eustachian tube during swallowing. The high frequency of ears with tubal dilation before palatoplasty reported in the 1986 study was not reproduced but that frequency after palatoplasty was similar.

This study describes the changes in mastoid air cell system (MACS) geometry with age in ears with a history of otitis media (OM), without (GR-I) or with (GR-II) middle ear fluid on the CT scan.Thirty-seven (74 MACSs) CT scans were selected to approximate 4 MACSs/year between 1 and 18 years. For each MACS, the volume, surface area and surface area/volume ratio were reconstructed using standard procedures. Correlation analysis was used to define the left-right relatedness for the geometric parameters, and regression analysis was used to determine the effect of age on those parameters for each group.Twenty scans were from female and 17 from males. Fluid was observed in 12 left, 4 right and 10 bilateral MACSs. The MACS volume and surface area of GR-I increased with age, were significantly greater than those for age-matched MACSs in GR-II, but show large variability. Those measures in GR-II were independent of age and a large percentage of these MACS volumes was5 ml. The surface-area/volume ratio for MACSs in both groups was independent of age and group assignment. The left-right correlations for the three geometric parameters of the MACS were significant for all MACS in the two groups, and for bilateral MACS concordant for group assignment. The left-right correlations for surface area and volume were not significant for bilateral MACSs discordant for group assignment.These results suggest that: the growth of MACS volume and surface area is genetically programmed but that this is disrupted by long-lasting OM; the effect of OM on MACS growth may depend on the duration and timing of the disease, and the MACS surface area/volume ratio does not explain the effect of MACS volume on the rate of gas exchange between middle ear and blood.

When used to test 3-year-old children within 3 months of tympanostomy tube placement for recurrent acute otitis media (rAOM) or chronic otitis media with effusion (cOME) the forced response test (FRT) showed relatively minor differences in the active and passive functions of the eustachian tube. While the sample size was small, the high variability in all test parameters suggests that the FRT alone is not capable of distinguishing between children with different expressions of otitis media.The FRT was designed to measure the passive and active properties of the eustachian tube. We evaluated the ability of that test to discriminate groups of children with rAOM or cOME.Twenty-two ears (15 children) with a confirmed history of rAOM and 24 ears (17 children) with a confirmed history of cOME were tested at 3 years of age within 3 months of ventilation tube placement. The parameters of the FRT were compared between these groups using a two-tailed Student's t test and the frequencies of ears evidencing eustachian tube dilation with swallowing were compared between groups using a χ(2) test.Passive resistance and one measure of active function were significantly higher in the rAOM group. The frequency of tubal dilation was not significantly different between groups. There were no differences in any of the FRT measures between cOME ears that did and did not have acute otitis media by history.

Objectives: We sought to develop normative values for 5 eustachian tube function (ETF) test protocols in adults without otitis media (OM). Methods: Twenty adults (19 to 48 years of age) without a recent history of OM (5 had OM in childhood) underwent unilateral myringotomy and were evaluated for ETF by use of the forced response, inflation, deflation, forcible “sniff,” and Valsalva test protocols. When possible, these tests were repeated on a second day. Results: Normative values for the parameters of these protocols in adult subjects without a recent history of OM were developed. Between-day data for the forced response test were highly correlated. A percentage of these tests showed eustachian tube “constriction” during swallowing — An abnormal condition. The percent reduction in applied pressures for the inflation and deflation tests was high, indicative of good ETF. Few subjects had a positive “sniff” test, whereas most had a positive Valsalva test, and the results for both tests were effort-dependent. Conclusions: Results of ETF tests in adults with and without recent OM have not been published. Normative data are now available for comparison with ETF test results in adults with OM. These protocols will be used to evaluate the efficacy of surgical procedures designed to improve ETF.

Past in vivo studies in humans showed that the tympanic membrane (TM) is permeable to physiological gases. Animal studies show that transTM CO(2) conductance is increased by TM pathology. The objective of the study was to determine if transTM CO(2) exchange in humans is affected by atrophic and sclerotic pathologies. The study used an ear canal (EC) probe (ECP) constructed from a custom-fitted acrylic body, a glass capillary tube enclosing an oil meniscus to maintain ambient ECP + EC pressure and a silica glass microtube linked to a mass spectrometer (MS) for measuring gas composition that was hermetically sealed within the ear canal of the test ear. ECP + EC volume was measured and gas samples taken at 10 min intervals for 1 h. The fractional CO(2) pressure measured in the ECP + EC for each sample was regressed on time and the slope of the function multiplied by the ECP + EC volume and divided by the estimated transTM CO(2) gradient at the start of the experiment to yield transTM CO(2) conductance (microL/min/Pa). Data were complete for 15 normal, 13 sclerotic and 9 atrophic TMs. The average (+std) transTM CO(2) conductances were 1.76 × 10(-4) + 7.27 × 10(-5), 2.26 × 10(-4) + 1.5 × 10(-4) and 2.36 × 10(-4) + 1.14 × 10(-4) microL/min/Pa/TM for the normal, sclerotic and atrophic TMs, respectively. A pairwise comparison of data for the normal and atrophic TMs under the directional hypothesis of a greater CO(2) exchange rate for thinner TMs approached statistical significance (P = 0.07). A similar pairwise comparison for the sclerotic and normal TMs did not approach statistical significance (P = 0.28). The effect of TM pathologies on CO(2) conductance was limited.

The middle ear (ME) surface area/volume ratio (SA/V) is greater than that of the tympanum. The rate of ME pressure decrease is proportional to the ME SA/V. The mastoid air-cell system (MACS) will not function as an ME gas reserve unless the blood perfusion/surface area is much greater for the tympanum than the MACS and decreases as MACS volume increases.To measure the MACS and tympanum surface areas and volumes and ascertain whether the MACS could function as an ME gas reserve.Twenty adult subjects with a wide range of MACS volumes underwent CT of their MEs. The left and right surface areas and volumes of the tympanum and MACS were reconstructed and entered into a simple perfusion-limited model of transmucosal gas exchange. In this model the MACS would be a gas reserve if ME SA/V was less than the tympanum SA/V or equivalently, if their ratio was less than a critical value of 1.Both MACS and tympanum SA were linearly related to their volumes. MACS SA/V and the ME SA/V were significantly greater than those for the tympanum. Inputting the measured values into the model yielded a critical value of 1.4, which was significantly greater than 1.

Objective Tympanometry is a relatively simple method to assess middle ear (ME) status and pressure. Daily, serial tympanometric measurements may contain information on the constitutional efficiency of Eustachian tube function (ETF). A study was conducted to determine family compliance with an effort-intensive protocol that requires daily tympanometry done on each child, daily symptom recording by a parent and weekly visits with study personnel and to abstract measures that summarize the data as they relate to ETF. Methods Longitudinal 6-month, daily follow-up on 249 children from 123 families by parent-recorded bilateral tympanometry and cold-like illnesses. Results Study attrition was minimal with 90% of the enrolled families completing 90% of the study period. Parental compliance with daily tympanometry was less. Overall, 67% of the families were 80% compliant and 51% were 90% compliant. Two measures (aMEP, average middle ear pressure; vMEP, standard deviation of MEP) were evaluated for summaries of the longitudinal tympanometric results. These measures were not bilaterally independent or mutually independent and were affected by cold-burden and age. The best summary measure of constitutional ET efficiency may be a dimensional map of vMEP on aMEP with subsequent subdivision of the dimensional space into zones with functional interpretations. Conclusion Long-term studies that require daily parental recording of tympanometry and the presence/absence of cold-like illness are feasible. It is expected that compliance with the required procedures can be increased substantially by pre-selection of candidate families. Preliminary data analyses suggest that the longitudinal tympanometric data contains important information on constitutional ETF.

Background Guidelines recommend treatment with intranasal corticosteroids for patients with allergic rhinitis (AR), but concerns remain about possible adverse effects. Objective To present the 1- and 2-year growth results for children with AR treated with triamcinolone acetonide aqueous nasal spray. Methods Thirty-nine children (aged 6.1–14.3 years at study entry) were treated with triamcinolone acetonide aqueous for 1 year, and a subset of 30 children completed a second year of treatment. The dose was physician titered to achieve control over AR symptoms. For each child, statural heights at baseline and at the 1- and 2-year (where available) visits, together with growth rates, were measured and were compared with predicted values. Results There were no significant differences between measured and predicted heights at the 1- and 2-year visits. The mean (SD) measured − predicted difference was 0.3 (2.2) cm (95% confidence interval, −0.4 to 1.0 cm) at the 1-year visit and 0.5 (3.0) cm (95% confidence interval, −0.6 to 1.6 cm) at the 2-year visit. Mean differences in measured and predicted growth rates were nonsignificant at the 1- and 2-year visits. Conclusions Triamcinolone acetonide aqueous titered to control AR symptoms and given for 1 or 2 years had no significant effect on statural growth in children with AR.

Streptococcus pneumoniae , a leading cause of otitis media (OM), undergoes spontaneous intra-strain variations in colony morphology. Transparent (T) variant is more efficient in colonizing the nasopharynx while the opaque (O) variant exhibits greater virulence during systemic infections. We hypothesized that changes in middle ear (ME) gas pressure/composition during Eustachian tube (ET) dysfunction and the treatment of that dysfunction, e.g., tympanostomy tube (TT) insertion, play a role in selecting the S. pneumoniae variant that can efficiently colonize/infect the ME mucosa. Human ME epithelial cells were preconditioned for 24 h under one of three conditions that simulated (1) normal ME, (2) ME with ET obstruction (ETO) and (3) ME with TT; subsequently exposed to a dose (∼10 7 CFU/ml) of either T or O variant of S. pneumoniae , and then incubated for 1 h and 3 h. Under the simulated ETO and TT conditions, T variant exhibited a higher growth rate and greater epithelial adherence and killing than did O variants. Attachment of T variant to epithelial cells was documented by scanning electron microscopy. These results suggest that the T variant is more highly adapted to various ME environments than the O variants.

Previous studies suggested that the otitis media (OM) complication rate of viral upper respiratory infection (vURI) is conditioned by genes affecting cytokine production. Two hundred and thirty children (114 male; 187 White, 25 Black; aged 1–9.3 years, average = 3.6 ± 1.6 years) were prospectively followed over the typical cold season for cold-like illness and OM. Nasopharyngeal secretion samples collected during cold-like illness and OM were assayed for upper respiratory viruses and buccal samples were assayed for TNFα (−308), IL-10(−1082, −819, −592), IL-6 (−174) and IFN-γ (+874) polymorphisms. Logistic regression was used to identify genotypes that predict OM coincident with RSV and rhinovirus (RV) infection. Of the 157 children with RV detection (79 male; 132 White, 13 Black, 12 Other; aged 3.6 ± 1.5 years), simple logistic regression identified age (B = −0.34, Z = −2.8, P < 0.01, OR = 0.71), IL-6 (B = −0.76, Z = −3.3, P < 0.01, OR = 0.47) and IL-10 (B = 0.49, Z = 2.0, P = 0.05, OR = 1.6) as significant predictors of OM coincidence. A more complex logistic regression model for RV detection that included selected OM risk factors identified these factors as well as the TNFα genotype, OM history, breastfeeding history and daily environment as significant predictors of OM coincidence. Of the 43 children with RSV detection (21 male; 35 White, 5 Black, 3 Other, aged 3.9 ± 1.7 years), logistic regression identified IL-10 (B = 1.05, Z = 2.0, P = 0.05, OR = 2.9) as a significant predictor of OM coincidence. New OM episodes coincident with evidence of RSV and RV infection were significantly more frequent in children with high production IL-10 phenotypes. The low production IL-6 and high production TNFα phenotypes also contributed to OM risk during RV detection. Cytokine polymorphisms may be one of an expectedly large number of genetic factors contributing to the known heritability of OM.

Summary Background There is a continuing interest in defining the incidence, prevalence and burden of otitis media (OM) in the individual and population for purposes of assigning “risk factors”. Often overlooked in past studies are the contributions of cold-like illnesses (CLIs) and sampling interval to those estimates. Objective Describe the incidence of symptomatic (AOM) and asymptomatic (OME) OM, the prevalence of OM, the contribution of CLI incidence, burden and other OM “risk factors” to the incidence and burden of OM, and the effect of sampling interval on those measures in children. Methods 148 children (74 male; 131 white, aged 1.0–8.6 years) were followed from November 1 to April 30 by weekly pneumatic otoscopy to diagnose OM presence/absence and by daily parental diary to assign CLI episodes. Data for previously identified OM “risk factors” were collected on 127. Results were summarized using standard measures of incidence, prevalence and burden, and multiple regression techniques were used to identify OM “risk factors”. Results The basal OM prevalence was 20% with peaks in December and March and the temporal pattern was correlated with CLI prevalence. The incidence of OME (per 27232 child-days) was 317, AOM was 74 and CLI was 456. The seasonal pattern of AOM and OME incidences tracked and was correlated with that for CLIs. New OM episodes were usually of short duration (≤7 days in 40%, ≤4 weeks in 75–90%) and the usual OM burden was low (median = 12%). OM and breastfeeding histories and CLI incidence/prevalence were significant predictors of OME and AOM incidence and OM burden. Longer sampling intervals were less efficient in capturing AOM and OME durations and incidences, but not OM burden. Conclusions These results demonstrate a high incidence and prevalence of OM, most OM episodes were of short duration and longer sampling intervals introduced biases into some parameter estimates. There was a significant relationship between OM and CLI incidence, prevalence and burden suggesting that CLI experience should be controlled for in assessing independent “risk factors” for AOM and OME.

Background: New otitis media (OM) episodes are most frequently a complication of cold-like illnesses (CLIs) which are often virus infections that can be exchanged within the family unit. Interference with intrafamily CLI transmission may present a strategy for OM prophylaxis in high risk children. This study estimated factors relevant to strategy efficiency. Methods: Two siblings (ages, 1.0-4.3 and 1.7-6.1 years) from 69 families were followed for 193 days beginning in October using daily parental diaries focused on CLI signs and weekly pneumatic otoscopy to diagnose OM presence/absence. An algorithm converted the signs to presence/absence of a cold-day; cold-days were grouped into CLI episodes, and episodes were examined for intersib transmission and OM complications. Results: We identified 267 CLIs in the younger siblings and 221 in the older siblings. Twenty-seven percent of the CLI episodes in one sibling occurred after CLI onset in the other with a median interval of 3 days. Sixty-two percent of newly diagnosed OM episodes occurred during a CLI and 27% of CLIs were complicated by OM. Analysis of factors that could affect CLI incidence documented significant contributions of gender, age, daily environment and the CLI burden in the sibling with expected directionalities. Conclusion: The results document intrafamily transmission of CLIs that is often associated with the development of OM as a complication. These observations and the measured interval between primary and secondary CLI onsets support the possibility of preventing OM by strategies that target intrafamily CLI transmission.

The physiological function of the mastoid air cell system (MACS) with respect to middle ear (ME) pressure-regulation remains controversial because predictive mathematical models and experimental data to formulate and test hypotheses are lacking.A mathematical description of MACS volume effects on the rate of ME pressure change is presented; the agreement between published data and model prediction is examined for consistency with the hypothesis that the MACS acts as a functional rate-limiter of ME pressure change, and an explanation for the relationship between MACS volume and otitis media is discussed.The mathematical description shows that the value of a single, free parameter, termed the "MACS buffering efficiency" (M) determines if MACS volume affects the rate of ME pressure change caused by diffusive gas exchange. The MACS serves no rate-limiting function for M=0, acts as a gas sink for M1 and acts as a gas reserve (rate-limiter) for M1.Fitting the model equation to published adult human data yielded an estimate for M of 0.2. This implies that larger MACS volumes are associated with lesser rates of change in ME pressure caused by diffusive gas exchange and lesser required frequencies of effective Eustachian tube openings to maintain near ambient ME pressures.If well-controlled studies confirm M1 for children and adults, larger MACS volumes will increase the time required to develop sufficient ME underpressures to cause otitis media by hydrops ex vacuo during transient or prolonged periods of Eustachian tube dysfunction.

The mechanisms that control Streptococcus pneumoniae's ability to colonize the nasopharynx or to invade the middle ear and cause acute otitis media are not understood. Focused study of these mechanisms requires efficient methods for the extraction of microbial RNA from minute clinical samples. Several lysis/extraction methods were tested and compared to determine the optimal conditions for isolating intact total RNA from pneumococcal cells. The sensitivity and efficiency of the extractions were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Compared to other methods, mechanical homogenization in TRIZOL was the most efficient for releasing microbial RNA, and addition of polyinosinic acid (Poly I) as an RNA carrier increased the assay sensitivity to 10(2) colony forming units when detected by RT-PCR amplification of 16S ribosomal RNA or messenger RNA for penicillin binding protein 2b. Quantitative results were confirmed using a ribonuclease protection assay. Penicillin binding protein 2b was also detected in rat middle ear mucosa recovered 5 weeks after middle ear challenge with S. pneumoniae. This study describes a useful core methodology for use in identifying pneumococcal virulence genes from small titer samples and has promising applications in clinical studies of pneumococcal nasopharyngeal colonization and otitis media pathogenesis.

Objectives: Simple, 2-compartment mathematical models of middle ear (ME) transmucosal gas exchange reproduce observed ME pressure behavior. These models require input of an experimentally determined, lumped-parameter exchange constant for each represented gas species. Previous model applications assumed directional asymmetry for those parameters, which has not been experimentally validated. Methods: As a surrogate for the inert gas nitrogen (N2), for which exchange is too slow to be measurable, the nitrous oxide (N2O) transmucosal exchange constant for 16 ears of 8 monkeys was measured for positive and negative ME blood N2O gradients. Results: The paired exchange constants for each ear were highly correlated, but the ME-blood/blood-ME exchange constant ratio was approximately 13. Modeling shows this asymmetry to depend on the value of the arterial-venous/arterial-ME ratio, a variable in the exchange constant for perfusion-limited gases. Conclusions: These results support an asymmetric rate of transmucosal N2O and, by extension, N2 exchange for the ME. Because the primary controlling parameter for ME pressure behavior in the absence of eustachian tube opening is the rate of transmucosal N2 exchange, this effect needs to be incorporated into the simple 2-compartment exchange models for predictive accuracy. The gradient ratio dependence suggests that parameter-free modeling may require treating the ME mucosa as having a distributed gradient for certain gas species.

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).Cross-sectional study.Tertiary care pediatric hospital.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.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.In children with past recurrent acute otitis media, residual eustachian tube opening inefficiency is maintained after they have "outgrown" their middle ear disease.

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.

Objective: In an earlier study, positive emotional style (PES) was associated with resistance to the common cold and a bias to underreport (relative to objective disease markers) symptom severity. This work did not control for social and cognitive factors closely associated with PES. We replicate the original study using a different virus and controls for these alternative explanations. Methods: One hundred ninety-three healthy volunteers ages 21 to 55 years were assessed for a PES characterized by being happy, lively, and calm; a negative emotional style (NES) characterized by being anxious, hostile, and depressed; other cognitive and social dispositions; and self-reported health. Subsequently, they were exposed by nasal drops to a rhinovirus or influenza virus and monitored in quarantine for objective signs of illness and self-reported symptoms. Results: For both viruses, increased PES was associated with lower risk of developing an upper respiratory illness as defined by objective criteria (adjusted odds ratio comparing lowest with highest tertile 2.9) and with reporting fewer symptoms than expected from concurrent objective markers of illness. These associations were independent of prechallenge virus-specific antibody, virus type, age, sex, education, race, body mass, season, and NES. They were also independent of optimism, extraversion, mastery, self-esteem, purpose, and self-reported health. Conclusions: We replicated the prospective association of PES and colds and PES and biased symptom reporting, extended those results to infection with an influenza virus, and “ruled out” alternative hypotheses. These results indicate that PES may play a more important role in health than previously thought. Key words: emotions, influenza, disease susceptibility, common cold, rhinovirus, affect.

Summary Introduction Past studies suggest that the majority of new otitis media (OM) diagnoses is a complication of a colds/flu. A prospective format was used to determine the coincidence of otitis media and parent diagnosed cold/flu episodes in young children followed over a typical cold/flu season. Methods Eighteen families with children aged 1–8 years were followed from October 1 to April 30 using parent-completed daily diaries focused on cold/flu signs and weekly examinations using pneumatic otoscopy for diagnosis of the presence/absence of otitis media. Results Overall, 108 cold episodes were documented in 36 enrolled children with 20 colds (19%) occurring during a pre-existing OM episode and 40 colds (37%) complicated by a new OM episode. Conversely, there were 82 new OM episodes, 40 (49%) were associated with a cold in the individual child and 18 (22%) with a concurrent cold in a family member. The median duration of the OM episodes was approximately 2 weeks but this was longer for OM episodes where earache was reported. Conclusion The results confirm past observation relating new OM episodes to a concurrent cold/flu but show these episodes to usually be of short duration. Two sources of potential bias were identified for point prevalence study formats: the presence of a pre-existing OM for a new onset cold/flu and the possibility of subclinical colds in patients with new OM episodes. These biases reinforce the need for longitudinal study formats to address this important relationship.

Middle ear barotrauma during flight is a painful disorder experienced by passengers who cannot properly regulate their middle ear pressure in response to the changing cabin pressures during ascent and descent. Previous reports emphasized the important role of poor eustachian tube function in disease pathogenesis but paid little attention to other moderating factors. Here we describe a mathematical model of middle ear pressure regulation and simulate the pressure response to the changes in cabin pressure experienced over typical flights. The results document buffering mechanisms that decrease the requisite efficiency of active, muscle-assisted eustachian tube opening for disease-free flight. These include the relative difference between destination and departure elevations and the ratio of maximum tympanic membrane volume displacement to middle ear volume, where greater absolute values require lesser efficiencies for disease-free flight. Also, the specific type of functional deficit is important since ears with a completely obstructed eustachian tube can be less susceptible to barotrauma than those with a eustachian tube that passively opens but fails to dilate in response to muscle activity. These buffering systems can explain why some children and adults with poor eustachian tube function do not experience middle ear barotrauma.

Identification of a pharmacologically targeted mediator of the common cold is a desirable, but, to date, elusive goal of current research. The roles of various mediators, such as histamine, leukotrienes, bradykinin, and, more recently, chemokines and cytokines, in the pathophysiology and development of complications of the common cold are the subject of previous and current investigations. Establishing causality of a mediator in the common cold has been difficult for a number of reasons, including the limitations of our research tools and protocols and the complexity of the inflammatory and immune pathways that participate during the common cold. The available evidence for mediation of the common cold is the subject of this manuscript.

Several physiological functions, such as regulating middle ear (ME) pressure and clearing ME fluid into the nasopharynx, require an opening of the collapsed eustachian tube (ET). The ability to perform these functions has been related to several mechanical properties of the ET: opening pressure (Popen), compliance (ETC), and hysteresis (η). These global properties may be influenced by the mechanics of the surrounding tissue and/or the mucosa-air interface. In this study, we investigated the influence of tissue mechanics by paralyzing the right tensor veli palatini (TVP) muscle in 12 cynomolgus monkeys via botulinum toxin injection. A previously developed modified forced-response protocol was used to measure Popen, ETC, and η under normal conditions and after muscle paralysis. The loss of muscle tone and/or stiffness resulted in a significant decrease in Popen (p < .01) and a significant increase in ETC (p < .01). In addition, muscle paralysis reduced the viscoelastic properties of the TVP muscle and therefore resulted in a significant decrease in η (p < .05). A comparison with previous measurements on the influence of surface tension mechanics indicates that the ET's compliance is primarily determined by tissue elastic properties. The ET hysteresis, however, is equally affected by viscoelastic tissue properties and surface tension hysteretic properties. Knowledge of how these physical components affect the global mechanical environment may lead to improved treatments for ET dysfunction that target the underlying mechanical abnormality.

Background Few studies have examined the relationship between subject-reported allergy and results of allergy skin testing in large unselected or unbiased cohorts. The objective of this study was to compare the results of self-reported allergy via verbal questioning with the results of allergy skin testing by the puncture method in 237 healthy adult subjects enrolled in a common cold study. Methods On enrollment, all subjects were verbally asked if they had a history of allergy and then underwent puncture skin testing to 19 relevant aeroallergens, as well as appropriate positive and negative controls. A skin test was considered positive if its wheal diameter was at least 3 mm larger than that obtained with the negative control. Results Forty-eight (20%) subjects reported a history of allergy and 124 (52%) subjects had at least one positive skin test response. A history of allergy was reported in 40 (32%) of the skin test-positive subjects and 8 (7%) of the skin test-negative subjects. At least one positive skin test response was found in 40 (83%) of those subjects reporting a history of allergy and 84 (44%) of those subjects denying a history of allergy. Conclusion These data indicate that there is a relatively poor correlation between self-reported history of allergy and skin test results in subjects enrolled in a common cold study. These results have implications in both clinical practice and research settings.

Illness severity and frequency of complications in infants with respiratory syncytial virus (RSV) infection may be influenced by the local elaboration of cytokines. Cytokine gene polymorphisms moderate severity of illness in various inflammatory and infectious diseases. We performed cytokine genotyping on 77 infants hospitalized with confirmed RSV infection to determine whether specific cytokine gene polymorphisms are associated with illness severity or complications. DNA was extracted from buccal brushings and assayed for tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-6 and IL-10, and transforming growth factor (TGF)-beta1 genotypes using polymerase chain reaction-sequence-specific primer technology. Clinical outcomes consisted of severity scores of lower respiratory illness, blood oxygen saturation, lengths of oxygen supplementation, and intensive care unit (ICU) and hospital stays, and the presence or absence of pneumonia and otitis media. IFN-gamma genotype was related to severity of lower respiratory illness, duration of ICU stay, and frequency of otitis media. Additionally, IL-6 genotype was related to the length of oxygen (O(2)) supplementation and hospital stay, IL-10 genotype to the frequency of pneumonia, and TGF-beta1 genotype to O(2) saturations at presentation. There were no associations between TNF-alpha genotype and any of the outcome parameters. These results demonstrate that certain cytokine gene polymorphisms contribute to illness severity and complications during RSV infection in infants. If future prospective studies confirm these observations, cytokine genotyping may be a useful tool for identifying "at risk" infants who may benefit from the selective use of preventive or early intervention treatments for RSV.

Otitis media (OM) imposes significant morbidity on the pediatric age group and a large financial burden on the general population. Because standard medical treatments are not highly efficacious in resolving the accompanying middle ear (ME) inflammation, a goal of current research is OM prevention. Past studies show that new episodes of OM are usually a complication of viral upper respiratory infection (vURI), and therefore, a rational approach to achieving that goal is to develop intervention strategies that target vURI-associated OM. However, past experiences with antibiotics show that, in the absence of well-defined treatment protocols that maximize expected efficacy, the adoption of prophylactic or active treatments for OM can have negative consequences for the patient and for the general population. In this review, we discuss the hypothesized mechanisms by which a vURI is translated into an acute OM episode and describe different strategies for aborting that process. Limitations to deployment of each strategy are outlined.