Dissecting eustachian tube dysfunction: From phenotypes to endotypes.

OBJECTIVE: A broad spectrum of complaints, symptoms and manifestations has been assigned to Eustachian tube (ET) dysfunction (ETD). While such presentations may manifest as ETD phenotypes, underlying mechanisms are defined as endotypes. Our goal is to develop a diagnostic approach to differentiate the endotypes and guide clinicians in the workup and selection of treatments targeting the mechanism of ETD. STUDY DESIGN: Retrospective. SETTING: Tertiary care. SUBJECTS AND METHODS: Children and adults with suspected ETD were evaluated with a thorough examination, otomicroscopy, otoendoscopy, trans-nasal videoendoscopy and testing of passive and active ET dilatory properties. Degree of weakness in soft palate elevation and ET orifice widening (muscular weakness, ETD-M), presence of inflammation (ETD-I) and/or adenoid tissue impinging and restricting the ET opening (ETD-R) were assessed with video-endoscopy. The Forced Response Test, Inflation-Deflation Test and Pressure Chamber Test were used as applicable to quantify the degree and type of difficulty (Stricture, ETD-S or adhesive, ETD-A) or ease (patulous or semi-patulous, ETD-P/SP) in opening the ET, and degree of active muscular strength/weakness (ETD-M) was measured. Ears with normal function (ETF-N) findings were also identified. RESULTS: Video-endoscopic and ETF test results were obtained for 71 ears of 40 subjects (22 males, 18 females; 38 white, 2 black), with an average age of 22.9 ± 16.5 years (min:6.2, max:64.1). Videoendoscopy (21, 13, 33, 16, 13, 0, 0 ETs) and ETF testing analysis (20, 24, 0, 38, 0, 3, 13 ears) were categorized as ETF-N and the ETD endotypes ETD-S, ETD-R, ETD-M, ETD-I, ETD-A, and ETD-P/SP, respectively. Some phenotypes had features consistent with more than one endotype. CONCLUSION: A systematic approach of examination and testing may differentiate the specific underlying mechanisms, lead to a treatment targeted to the ETD endotype and may establish novel ways to diagnose and treat ETD.

Presentation and eustachian tube function test results in children evaluated at a specialty clinic.

OBJECTIVES/HYPOTHESIS: Interest in eustachian tube (ET) dysfunction (ETD) has increased with the recent Food and Drug Administration approval of a new device for balloon dilation of the ET (BDET) in adults. However, children have been receiving BDET treatment with ET-specific or sinus balloons around the world and off-label in the United States for years. It is important, therefore, to understand the manifestations of and methods to verify ETD in children. STUDY DESIGN: Retrospective cross-sectional study. METHODS: This is a retrospective study of clinical presentations and results of ET function (ETF) tests in children referred to the ETD clinic. An otorhinolaryngology exam, nasopharyngeal videoendoscopy of the ET orifices during swallow and maneuvers, and ETF tests, including inflation deflation, forced response test, and pressure chamber tests, were performed as applicable. RESULTS: Data for 30 children aged 6.2 to 17.3 years (mean = 12.9 ± 2.8 years) were analyzed. Of 60 ears, 19 (31.7%) had an intact tympanic membrane (TM), 16 (26.7%) had a patent and two had a blocked ventilation tube, and 23 (38.3%) had a TM perforation. Endoscopy of the nasopharynx revealed a large amount of secretions in 19/45 (42.2%); ET orifices and mucosal inflammation in 22/45 (48.8%); a large amount of adenoid tissue in the fossa of Rosenmuller was noted in 21/45 (46.7%). ETF tests revealed abnormal active function in 43/54 ears (79.6%) and abnormal passive function in 40/54 ears (74.1%). CONCLUSIONS: ETD in children is often associated with residual or regrowth of adenoids and inflammation. Caution should be taken assigning a uniform phenotype and treatment prior to thorough evaluation and testing. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1218-1228, 2019.

Accuracy of the ETDQ-7 for Identifying Persons with Eustachian Tube Dysfunction.

Objective To compare the accuracy of the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) in identifying people with eustachian tube (ET) dysfunction based on symptoms and an objective ET function test. Study Design Cross-sectional study. ObjSettingective Tertiary referral center. Subjects and Methods Fifty-five subjects with and without symptoms suggestive of ET dysfunction completed the ETDQ-7 and had their ET function evaluated by the percentage of middle ear pressure equilibrated after 5 swallows (PEq5) either during a pressure chamber test (intact tympanic membranes) or by the inflation-deflation test (nonintact tympanic membranes). ETDQ-7 score ≥14.5 and PEq5 <60% were used to define ET dysfunction, and sensitivity, specificity, and receiver operating characteristic curves were used to assess the level of association between ETDQ-7 scores and PEq5. Results Twenty-five asymptomatic subjects (group 1 = 15 females, 15 white; mean ± SD age, 32 ± 12.8 years) and 30 subjects with ET dysfunction symptoms (group 2 = 17 females, 25 white; age, 27 ± 16.3 years) were included in the analysis. ETDQ-7 sensitivity and specificity regarding correct group assignment were 70% and 100%, respectively, and with respect to predicting PEq5<60%, 54% and 78%. An area under the curve (AUC) of 0.68 (95% CI, 0.53-0.83) at the participant level and 0.64 (95% CI, 0.50-0.77) at the ear level indicated a moderate level of association that was lower, though not statistically significant, for nonintact tympanic membranes (AUC = 0.63 at the participant level and AUC = 0.49 at the ear level). Conclusion The ETDQ-7 score had a higher correlation with the ET dysfunction symptoms than with an objective measure of ET function.

Panel 2: Anatomy (Eustachian Tube, Middle Ear, and Mastoid-Anatomy, Physiology, Pathophysiology, and Pathogenesis).

Objective In this report, we review the recent literature (ie, past 4 years) to identify advances in our understanding of the middle ear-mastoid-eustachian tube system. We use this review to determine whether the short-term goals elaborated in the last report were achieved, and we propose updated goals to guide future otitis media research. Data Sources PubMed, Web of Science, Medline. Review Methods The panel topic was subdivided, and each contributor performed a literature search within the given time frame. The keywords searched included middle ear, eustachian tube, and mastoid for their intersection with anatomy, physiology, pathophysiology, and pathology. Preliminary reports from each panel member were consolidated and discussed when the panel met on June 11, 2015. At that meeting, the progress was evaluated and new short-term goals proposed. Conclusions Progress was made on 13 of the 20 short-term goals proposed in 2011. Significant advances were made in the characterization of middle ear gas exchange pathways, modeling eustachian tube function, and preliminary testing of treatments for eustachian tube dysfunction. Implications for Practice In the future, imaging technologies should be developed to noninvasively assess middle ear/eustachian tube structure and physiology with respect to their role in otitis media pathogenesis. The new data derived from these structure/function experiments should be integrated into computational models that can then be used to develop specific hypotheses concerning otitis media pathogenesis and persistence. Finally, rigorous studies on medical or surgical treatments for eustachian tube dysfunction should be undertaken.

Diagnostic accuracy of tubomanometry R value in detecting the Eustachian tube pressure equalizing function.

Tubomanometry is a relatively novel Eustachian tube (ET) function testing method. A number of recent studies have utilized the R value of Tubomanometry as the main objective measure in reporting their outcome in balloon dilation of ET. There is, however, a lack of evidence concerning the reliability or validity of Tubomanometry measurements. The objectives of this study are to determine the accuracy of Tubomanometry for detecting ET opening as compared to tympanometry and determine its usefulness as a measure of ET function. Healthy subjects between ages 8 and 76 years with an intact tympanic membrane and no middle ear (ME) effusion were prospectively tested. Primary outcomes were the ET opening as determined by the Tubomanometry R value and the increase in ME pressure with tympanometry-measured in relation to a swallow at a nasopharyngeal pressure of 300 daPa. The accuracy of the tubomanometry R value for identifying a successful ET opening was made in reference to the change of ME pressure. A total of 280 measurements were available from 258 ears in 137 subjects. The presence of tubomanometry R value showed high sensitivity of detecting ET opening for the criteria of >5 daPa ME pressure increase (187/202) but low specificity for detecting ET non-opening (34/78). The R value criterion described in the original manuscripts on Tubomanometry is sensitive but not specific for ET opening. The need for validation of the tubomanometry test obviates its use as the main objective outcome measure for the balloon dilation of ET procedure.

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.

Idiopathic intervertebral disc calcification in childhood: an atypical case of an uncommon entity for pediatric pathologists.

Calcification of the intervertebral disc is a common occurrence in the adult population, but it is rare in children. However, its radiological and clinical findings are well described in the pediatric age group, with close to 150 publications on record. In contrast, little information is available regarding the histological features of this entity, which may prove to be challenging to surgical pathologists. Here we provide a detailed description of a young patient with an inflammatory retropharyngeal mass originating in a calcified intervertebral disc. A review of the pathological features described in the literature in English, with pathogenic considerations, is presented.

Sensitivity and specificity of eustachian tube function tests in adults.

IMPORTANCE: The study demonstrates the utility of eustachian tube (ET) function (ETF) test results for accurately assigning ears to disease state. OBJECTIVES: To determine if ETF tests can identify ears with physician-diagnosed ET dysfunction (ETD) in a mixed population at high sensitivity and specificity and to define the interrelatedness of ETF test parameters. DESIGN, SETTING, AND PARTICIPANTS: Through use of the forced-response, inflation-deflation, Valsalva, and sniffing tests, ETF was evaluated in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). Data were analyzed using logistic regression including each parameter independently and then a step-down discriminant analysis including all ETF test parameters to predict group assignment. Factor analysis operating over all parameters was used to explore relatedness. EXPOSURES: ETF testing. MAIN OUTCOMES AND MEASURES: ETF parameters for the forced response, inflation-deflation, Valsalva, and sniffing tests measured in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). RESULTS: The discriminant analysis identified 4 ETF test parameters (Valsalva, ET opening pressure, dilatory efficiency, and percentage of positive pressure equilibrated) that together correctly assigned ears to group 2 at a sensitivity of 95% and a specificity of 83%. Individual parameters representing the efficiency of ET opening during swallowing showed moderately accurate assignments of ears to their respective groups. Three factors captured approximately 98% of the variance among parameters: the first had negative loadings of the ETF structural parameters; the second had positive loadings of the muscle-assisted ET opening parameters; and the third had negative loadings of the muscle-assisted ET opening parameters and positive loadings of the structural parameters. CONCLUSIONS AND RELEVANCE: These results show that ETF tests can correctly assign individual ears to physician-diagnosed ETD with high sensitivity and specificity and that ETF test parameters can be grouped into structural-functional categories.

Panel 8: Complications and sequelae.

BACKGROUND AND OBJECTIVES: Although serious complications of otitis media (OM) such as brain abscess are rare, sequelae of OM such as tympanic membrane perforation and atelectatic tympanic membrane are quite common. Inner ear sequelae can cause hearing loss and speech and language problems. The objectives of this article are to provide a state-of-the-art review on recent articles on complications and sequelae of OM in different anatomic locations, from the tympanic membrane to intracranial sites, as well as hearing loss and speech and language development. DATA SOURCES: Primarily PubMed supplemented by Ovid MEDLINE and the Cochrane Database. REVIEW METHODS: All types of articles related to OM complications and sequelae published in English between January 2007 and June 2011 were identified. A total of 127 relevant quality articles are summarized and included in this report. RESULTS: Key findings are summarized based on the following major anatomic locations and categories: tympanic membrane; cholesteatoma; ossicular problems; mucosal sequelae; inner ear sequelae; speech and language development; extracranial areas, including mastoiditis and facial nerve paralysis; intracranial complications; and future research goals. New information and insights were gained to prevent complications and sequelae. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Over the past 4 years, progress has been made in advancing the knowledge on the complications and sequelae of OM, which can be used to prevent and treat them effectively. Areas of potential future research have been identified and outlined.

Panel 2: Eustachian tube, middle ear, and mastoid--anatomy, physiology, pathophysiology, and pathogenesis.

OBJECTIVE: This report reviews the literature to identify the advances in our understanding of the middle ear (ME)-Eustachian tube (ET) system during the past 4 years and, on that basis, to determine whether the short-term goals elaborated in the last report were achieved and propose updated goals to guide future otitis media (OM) research. DATA SOURCES: Databases searched included PubMed, Web of Science (1945-present), Medline (1950 to present), Biosis Previews (1969-present), and the Zoological Record (1978 to present). The initial literature search covered the time interval from January 2007 to June 2011, with a supplementary search completed in February 2012. REVIEW METHODS: The panel topic was subdivided; each contributor performed a literature search and provided a preliminary report. Those reports were consolidated and discussed when the panel met on June 9, 2011. At that meeting, the progress was evaluated and new short-term goals proposed. CONCLUSIONS: Progress was made on 16 of the 19 short-term goals proposed in 2007. Significant advances were made in the characterization of ME gas exchange pathways, modeling ET function, and preliminary testing of treatments for ET dysfunction. IMPLICATIONS FOR PRACTICE: In the future, imaging technologies should be developed to noninvasively assess ME/ET structure and physiology with respect to their role in OM pathogenesis. The new data derived from form/function experiments should be integrated into the finite element models and used to develop specific hypotheses concerning OM pathogenesis and persistence. Finally, rigorous studies of treatments, medical or surgical, of ET dysfunction should be undertaken.

Cytokine responses in the common cold and otitis media.

Cytokines are a group of diverse molecules that influence the function of every organ system. They are most well studied in their effects on the immune system and their integral role in mediating inflammation. The common cold and otitis media are two such disease states, and much has been learned about the various effects of cytokines in each disease. Most often the viruses isolated include rhinovirus (RV), respiratory syncytial virus (RSV), adenovirus, coronavirus, and picornavirus. Otitis media, sinusitis, bronchiolitis, pneumonia, and asthma exacerbation are commonly accepted as complications of viral upper respiratory tract infections. Furthermore, otitis media and upper respiratory infections are inextricably linked in that the majority (>70 %) of cases of acute otitis media occur as complications of the common cold. Cytokine polymorphisms have been associated with the severity of colds as well as the frequency of otitis media. This article attempts to update the reader on various studies that have recently been published regarding the role of cytokines in these two disease entities.

Relationship between the electromyographic activity of the paratubal muscles and eustachian tube opening assessed by sonotubometry and videoendoscopy.

OBJECTIVE: To determine the role played by the tensor veli palatini and levator veli palatini muscles (mTVP and mLVP, respectively) in eustachian tube (ET) opening. DESIGN: Prospective study. SETTING: Research laboratories at a tertiary care hospital. PATIENTS: Fifteen healthy adults with normal middle ears and documented ET openings. INTERVENTIONS: Submental and ground surface electrodes were placed. After anesthetizing and decongesting the nasal passages, paired electromyographic needle electrodes were inserted into both the mTVP and mLVP on the test side. A microphone was placed into the ipsilateral ear canal and the probe from a sound generator was introduced into the opposite nostril. A 45° telescope was used on the test side to video-record the soft palate and ET movements while the individual swallowed. MAIN OUTCOME MEASURES: Concurrent recordings of the ET openings by sonotubometry, the electromyographic activity for the LVP, TVP, and submental muscles, and video of the nasopharyngeal orifice of the ET during swallowing. RESULTS: During swallowing, the median peak amplitude and duration of ET openings by sonotubometry were 30.6 mV and 196 milliseconds, respectively. For the mLVP and mTVP, the median peak amplitudes were 0.33 and 0.82 mV, and peak durations were 131 and 85 milliseconds, respectively. The mean onsets of muscle activity referenced to the sonotubometry peak amplitude were -0.28, -0.24, and -0.14 milliseconds for the mLVP, mTVP, and submental muscles, respectively. Video recording of ET movements were consistent with the timing of these events. CONCLUSIONS: The mTVP activity had a shorter duration but greater amplitude than the mLVP activity and was associated with peak ET opening by sonotubometry. The mLVP activity occurred before that of the mTVP, the submental muscle group, and peak ET opening. The mLVP contractions were associated with movements of the soft palate, anterior ET orifice, and rotation of the ET cartilage.

Nasal secretion concentrations of IL-5, IL-6, and IL-10 in children with and without upper respiratory tract viruses.

OBJECTIVE: To determine if levels of interleukin (IL) 5, IL-6, and IL-10 or their ratios in nasal secretion are diagnostic of viral upper respiratory tract infections (vURTIs) and coldlike illnesses (CLIs) in children. DESIGN: Longitudinal study of children for vURTIs, CLIs, and concentrations and ratios of nasal cytokines. SETTING: Outpatient assessments of children. PARTICIPANTS: A total of 224 children, aged 1 to 9 years. MAIN OUTCOME MEASURES: Concentrations of IL-5, IL-6, and IL-10 in nasal secretions, vURTIs diagnosed by polymerase chain reaction (PCR) detection of upper respiratory tract viruses, and concurrent CLIs diagnosed by parents. RESULTS: Of 1269 secretion samples, 552 (43.5%) were collected during a vURTI (PCR findings positive for an assayed virus [PCR(+)]). A concurrent CLI was diagnosed for 34% of the PCR(+) samples and for 18% of the samples found to be negative by PCR analysis (PCR(-)). Cytokine concentrations and ratios were highly variable and skewed to the lower values. The significance of the cytokine concentrations and ratios as discriminators of groups defined by the presence or absence of virus and of subgroups defined by the presence or absence of a CLI was evaluated using receiver operating characteristic curves. All measures were significant discriminators of the PCR(+) vs PCR(-) groups, and most were significant discriminators of the paired CLI subgroups. The concentration of IL-6 and the IL-5/IL-6 ratio were the best discriminators across all groups and subgroups. However, the sensitivities and specificities of those discriminators at the best cutoff values were on the order of 0.7 for the most extreme pairwise comparison (PCR(+)CLI(+) vs PCR(-)CLI(-)) and lower for the other comparison groups. CONCLUSION: The low sensitivities and specificities for cytokine-based assignment of specimens to the paired groups and subgroups limit their usefulness for diagnosis of infection or illness.

Rate of concurrent otitis media in upper respiratory tract infections with specific viruses.

OBJECTIVE: To estimate the coincidence of new otitis media (OM) for first nasopharyngeal detections of the more common viruses by polymerase chain reaction (PCR). New OM episodes are usually coincident with a viral upper respiratory tract infection (vURTI), but there are conflicting data regarding the association between specific viruses and OM. DESIGN: Longitudinal (October-March), prospective follow-up of children for coldlike illness (CLI) by diary, middle ear status by pneumatic otoscopy, and vURTI by PCR. SETTING: Academic medical centers. PARTICIPANTS: A total of 102 families with at least 2 children aged between 1 and 5 years (213 children; mean [SD] age, 3.7 [1.5] years; 110 male; and 176 white) were recruited from the local communities at 2 study sites by advertisement. MAIN OUTCOME MEASURES: New OM and CLI episodes and nasopharyngeal virus detections. RESULTS: A total of 176 children (81%) had isolated PCR detection of at least 1 virus. The OM coincidence rates were 62 of 144 (44%) for rhinovirus, 15 of 27 (56%) for respiratory syncytial virus, 8 of 11 (73%) and 1 of 5 (20%) for influenza A and B, respectively, 6 of 12 (50%) for adenovirus, 7 of 18 (39%) for coronavirus, and 4 of 11 (36%) for parainfluenza virus detections (P = .37). For rhinovirus, new OM occurred in 50% of children with and 32% without a concurrent CLI (P = .15), and OM risk was predicted by OM and breastfeeding histories and by daily environment outside the home. CONCLUSIONS: New OM was associated with nasopharyngeal detection of all assayed viruses irrespective of the presence or absence of a concurrent CLI. Differences among viruses were noted, but statistical significance was not achieved, possibly because of the low power associated with the small number of nonrhinovirus detections.

Cytokine polymorphisms predict the frequency of otitis media as a complication of rhinovirus and RSV infections in children.

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 TNFalpha (-308), IL-10(-1082, -819, -592), IL-6 (-174) and IFN-gamma (+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 TNFalpha 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 TNFalpha 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.

Upper respiratory virus detection without parent-reported illness in children is virus-specific.

BACKGROUND: Viral upper respiratory tract infection (vURI) may or may not present with a cold/flu-like illness (CFLI). OBJECTIVES: For common upper respiratory viruses that cause vURIs, to determine the relative frequencies of virus detection by PCR in subjects with and without CFLIs. STUDY DESIGN: Prospective follow-up of 170 children aged 1-8.6 years through the CFLI season by daily parental diary for CFLI episodes and nasal secretion sampling using PCR assays for adenovirus, coronavirus (types 229E and OC43), influenza virus (types A and B), parainfluenza (types 1-3) virus, rhinovirus, and respiratory syncytial virus (RSV). RESULTS: Virus was detected in 415 of 956 independent assays: 425 CFLI episodes and 531 non-CFLI periods were sampled; samples from 270 (64%) CFLI episodes and 145 (27%) non-CFLI periods contained virus detected by PCR. Rhinovirus was most frequently detected at 64%, followed by mixed viruses at 12%, RSV at 7%, and the other viruses at 3-5% of all detections. About 85% of RSV, influenza A and adenovirus detections were associated with a CFLI, whereas less than 62% of other virus detections were associated with CFLI. CONCLUSIONS: The frequency of PCR virus detection without CFLI was different among viruses. This introduces virus-specific biases to estimating the frequencies of specific complications attributable to a vURI when ascertained by CFLI identification.

Directional asymmetry in the measured nitrous oxide time constant for middle ear transmucosal gas exchange.

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 N20 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/arterialME ratio, a variable in the exchange constant for perfusion-limited gases. CONCLUSIONS: These results support an asymmetric rate of transmucosal N20 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.

Rate of nitrous oxide exchange across the middle ear mucosa in monkeys before and after blockage of the mastoid antrum.

OBJECTIVES: We tested the hypothesis that mastoid volume buffers the rate of change in middle ear pressure caused by transmucosal, inert gas exchange. STUDY DESIGN: Twelve monkeys were randomly assigned to group 1 or group 2. Right ears of group 1 had sham surgery and of group 2 had obstruction of the mastoid antrum. Before and after surgery, the time constant for transmucosal N(2)O exchange was estimated from N(2)O breathing experiments. The hypothesis predicts that the postoperative time constant measured for right ears of group 2 but not group 1 is greater than that measured before surgery. RESULTS: Mastoid antrum block significantly decreased right middle ear volume but did not affect the time constant for transmucosal N(2)O exchange. CONCLUSION: A mastoid gas-reserve function is not supported by the experimental data. SIGNIFICANCE: These results for monkeys and the theory developed to explain the effect of mastoid volume on transmucosal inert gas exchange suggest that the results for previous experiments in humans interpreted as evidencing a mastoid gas-reserve function are consistent with alternative explanations.