Association between Asthma and Chronic Rhinosinusitis Severity in the Context of Asthma Control.

Objective Comorbid asthma is associated with decreased quality of life (QOL) in chronic rhinosinusitis (CRS). It is unclear whether this association is independent of the patients' clinical asthma status. We therefore sought to determine if asthma is associated with lower QOL in CRS, independent of asthma control. Study Design Cross-sectional cohort study of 350 patients with CRS. Setting Tertiary academic rhinology clinic. Subjects and Methods In total, 350 participants with CRS were recruited and 28.3% were asthmatic. CRS-specific QOL was measured using the 22-item Sinonasal Outcome Test (SNOT-22). Asthma control was assessed with the Asthma Control Test (ACT). General health-related QOL was assessed with the EuroQoL 5-dimensional general health-related quality of life survey visual analog scale (EQ-5D VAS). Associations were sought between SNOT-22 and EQ-5D VAS (dependent variables) and asthma (independent variable), while controlling for ACT. ACT score for patients with CRS without asthma was set at 25 (indicating completely controlled, asymptomatic asthma). Results Comorbid asthma was associated with SNOT-22 (ß = 11.8; 95% confidence interval [CI], 6.2-17.3; P < .001) and EQ-5D VAS (ß = -6.2; 95% CI, -11.2 to -1.3; P = .014). After controlling for ACT, asthma was no longer associated with SNOT-22 ( P = .147) or EQ-5D VAS ( P = .994). Instead, ACT score was associated with SNOT-22 (ß = -2.1; 95% CI, -3.2 to -1.1; P < .001) and EQ-5D VAS (ß = 2.1; 95% CI, 1.1 to 3.0; P < .001). ACT score completely drove the association between asthma and worse QOL. Conclusion Comorbid asthma is not necessarily reflective of decreased QOL in CRS. The association of comorbid asthma with lower QOL in CRS is related to the clinical status (eg, control) of asthma.

Periostin as a Biomarker for Nasal Polyps in Chronic Rhinosinusitis.

Objective Periostin is an extracellular matrix protein that is elevated in the sinonasal tissues of patients with chronic rhinosinusitis (CRS). The purpose of this study was to determine whether serum periostin could serve as a molecular biomarker of nasal polyp burden in sinonasal disease. Study Design Prospective cohort study. Setting Academic medical center. Subjects and Methods Serum periostin levels were measured by ELISA on blood samples collected from patients undergoing sinus surgery for CRS (n = 71), further stratified by phenotype as defined by nasal polyps and asthma. Results were compared with assays performed on control subjects (n = 62). Results Mean serum periostin levels were markedly elevated in patients with CRS versus controls (66.1 ng/mL [95% CI, 51.6-80.6] vs 38.7 ng/mL [95% CI, 34.4-42.9], respectively, P = .004). In addition, mean periostin levels were significantly higher in CRS patients with nasal polyps as compared with those without polyps (94.8 ng/mL [95% CI, 67.3-122.4] vs 41.1 ng/mL [95% CI, 35.2-47.0], respectively, P < .001). Periostin levels did not correlate with sex ( P = .473), smoking history ( P = .748), aspirin-exacerbated respiratory disease status ( P = .136), oral steroid use within 1 month of surgery ( P = .281), use of topical steroid nasal spray ( P = .864), or number of prior sinus operations ( P = .973). Conclusion Serum periostin appears to be a novel molecular biomarker for the presence of nasal polyps and may serve as an indicator of CRS endotypes.

Association between systemic antibiotic and corticosteroid use for chronic rhinosinusitis and quality of life.

OBJECTIVE: We sought to establish the significance of querying chronic rhinosinusitis (CRS) patients about their past CRS-related oral antibiotic and corticosteroid usage by determining the association between these metrics and patients' quality of life (QoL). STUDY DESIGN: Cross-sectional study. METHODS: A total of 157 patients with CRS were prospectively recruited. CRS-specific QoL was measured using the 22-item Sinonasal Outcome Test (SNOT-22). General health-related QoL was measured using the EuroQoL five-dimensional questionnaire visual analog scale. Associations were sought between these measures of QoL and frequency of CRS-related oral antibiotic and corticosteroid usage reported by the participants in the prior 3 and 12 months. RESULTS: More frequent antibiotic and corticosteroid use was significantly associated with worse CRS-specific and general health-related QoL, whether querying medication use over the prior 3 months or over the prior 12 months (P < 0.001 in all cases). The effect size of CRS-related antibiotic use during the prior 3 months on CRS-specific QoL (SNOT-22 score) was significantly greater than for use during the prior 12 months. However, there was no other statistically significant difference in effect size for association between QoL and CRS-related antibiotic or corticosteroid use in the prior 3 months versus prior 12 months. These results were independent of the presence or absence of polyps. CONCLUSION: More frequent past CRS-related oral antibiotic and corticosteroid use, regardless of time period queried (3 months or 12 months) is associated with significant decrease in CRS-specific and general health-related QoL. CRS-related systemic medication use is an important indicator of CRS patients' QOL that easily can be queried and utilized in both clinical and research settings. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:37-42, 2018.

A validated model for the 22-item Sino-Nasal Outcome Test subdomain structure in chronic rhinosinusitis.

BACKGROUND: Previous studies have identified subdomains of the 22-item Sino-Nasal Outcome Test (SNOT-22), reflecting distinct and largely independent categories of chronic rhinosinusitis (CRS) symptoms. However, no study has validated the subdomain structure of the SNOT-22. This study aims to validate the existence of underlying symptom subdomains of the SNOT-22 using confirmatory factor analysis (CFA) and to develop a subdomain model that practitioners and researchers can use to describe CRS symptomatology. METHODS: A total of 800 patients with CRS were included into this cross-sectional study (400 CRS patients from Boston, MA, and 400 CRS patients from Reno, NV). Their SNOT-22 responses were analyzed using exploratory factor analysis (EFA) to determine the number of symptom subdomains. A CFA was performed to develop a validated measurement model for the underlying SNOT-22 subdomains along with various tests of validity and goodness of fit. RESULTS: EFA demonstrated 4 distinct factors reflecting: sleep, nasal, otologic/facial pain, and emotional symptoms (Cronbach's alpha, >0.7; Bartlett's test of sphericity, p < 0.001; Kaiser-Meyer-Olkin >0.90), independent of geographic locale. The corresponding CFA measurement model demonstrated excellent measures of fit (root mean square error of approximation, <0.06; standardized root mean square residual, <0.08; comparative fit index, >0.95; Tucker-Lewis index, >0.95) and measures of construct validity (heterotrait-monotrait [HTMT] ratio, <0.85; composite reliability, >0.7), again independent of geographic locale. CONCLUSION: The use of the 4-subdomain structure for SNOT-22 (reflecting sleep, nasal, otologic/facial pain, and emotional symptoms of CRS) was validated as the most appropriate to calculate SNOT-22 subdomain scores for patients from different geographic regions using CFA.

Association between Nasal Obstruction and Risk of Depression in Chronic Rhinosinusitis.

Objective Chronic rhinosinusitis (CRS) is associated with an increased risk for depression. Since nasal obstruction is a symptom of CRS that is treatable, we sought to characterize its impact on the risk for depression in CRS. Study Design Prospective cross-sectional cohort of 94 patients with CRS. Setting Academic tertiary care rhinology clinic. Subjects and Methods Patients with CRS without vasculitis, cystic fibrosis, sarcoidosis, immunodeficiency, or sinonasal malignancy. Risk for depression was assessed with the 2-item Patient Health Questionnaire (PHQ-2) while nasal obstruction was assessed with the Nasal Obstruction Symptom Evaluation (NOSE) instrument. Multivariate logistic regressions were performed to seek association between NOSE and PHQ-2 scores. Analysis of receiver operating characteristic (ROC) curves defined a NOSE threshold for detecting participants with PHQ-2 greater than 1. Results Of the 94 participants, the mean NOSE score was 47.3, and 29.8% of patients had a PHQ-2 score greater than 1. We found an elevated NOSE score was associated with having a PHQ-2 score greater than 1 (adjusted odds ratio, 1.03; 95% CI, 1.01-1.05; P = .001). Alternatively, a 23-point increase in NOSE score was associated with a 1.5-fold increase in PHQ-2 score (adjusted relative risk, 1.02; 95% CI, 1.01-1.03; P < .001). ROC analysis identified an optimal NOSE threshold of 42.5 for detecting participants with PHQ-2 greater than 1, with 82.1% sensitivity and 50.0% specificity. Conclusions The impact of nasal obstruction is associated with an increased risk for depression in patients with CRS. Assessing for severe nasal obstruction may help to identify those patients with CRS with the highest risk for depression.

Smoking: An independent risk factor for lost productivity in chronic rhinosinusitis.

OBJECTIVES/HYPOTHESIS: Chronic rhinosinusitis (CRS) is associated with a significant loss of patient productivity that costs billions of dollars every year. Smoking is associated with worsening sinonasal symptoms, but its effect on lost productivity in CRS patients has yet to be described. Therefore, we sought to determine the association between smoking and productivity in patients with CRS. STUDY DESIGN: Prospective cross-sectional cohort study of 140 patients with CRS. METHODS: Sinonasal symptom severity was measured using the 22-item Sino-Nasal Outcomes Test. Lost productivity was assessed by asking participants how many days of work and/or school they missed in the last 3 months due to CRS. Associations were sought between lost productivity and smoking. RESULTS: Participants missed a mean of 3.0 days (standard deviation = 12.8 days) of work or school due to CRS. Having any history of smoking was associated with 6 days of lost productivity due to CRS (adjusted ß = 6.20, 95% confidence interval [CI]: 0.64 to 11.77, P = .031). Although the number of active smokers in our study cohort was very small (N = 6), we performed a univariate association between smoking status, considering former smokers and active smokers separately, and found that active smoking (ß = 11.75, 95% CI: 2.11 to 21.40, P = .018) had a much larger impact on CRS-related productivity loss than that experienced by former smokers (ß = 4.45, 95% CI: -0.32 to 9.23, P = .070). CONCLUSIONS: Smoking (likely driven by active smoking) is independently associated with missed days of work or school in patients with CRS. Further study is needed to determine whether interventions directed at smoking may impact CRS-related productivity loss. LEVEL OF EVIDENCE: 2c Laryngoscope, 127:1742-1745, 2017.

Depression symptoms and lost productivity in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is associated with significant losses of patient productivity that cost billions of dollars every year. The causative factors for decreases in productivity in patients with CRS have yet to be determined. OBJECTIVE: To determine which patterns of CRS symptoms drive lost productivity. METHODS: Prospective, cross-sectional cohort study of 107 patients with CRS. Sinonasal symptom severity was measured using the 22-item Sinonasal Outcomes Test, from which sleep, nasal, otologic or facial pain, and emotional function subdomain scores were calculated using principal component analysis. Depression risk was assessed with the 2-item Patient Health Questionnaire (PHQ-2), whereas nasal obstruction was assessed with the Nasal Obstruction Symptom Evaluation (NOSE) instrument. Lost productivity was assessed by asking participants how many days of work and/or school they missed in the last 3 months because of CRS. Associations were sought between lost productivity and CRS symptoms. RESULTS: A total of 107 patients were recruited. Patients missed a mean (SD) of 3.1 (12.9) days of work or school because of CRS. Lost productivity was most strongly associated with the emotional function subdomain (ß = 7.48; 95% confidence interval [CI], 5.71-9.25; P < .001). Reinforcing this finding, lost productivity was associated with PHQ-2 score (ß = 4.72; 95% CI, 2.62-6.83; P < .001). Lost productivity was less strongly associated with the nasal symptom subdomain score (ß = 2.65; 95% CI, 0.77-4.52; P = .007), and there was no association between lost productivity and NOSE score (ß = 0.01; 95% CI, -0.12 to 0.13; P = .91). CONCLUSION: Symptoms associated with depression are most strongly associated with missed days of work or school because of CRS. Further treatment focusing on depression-associated symptoms in patients with CRS may reduce losses in productivity.

The Relationship Between Cochleovestibular Orientation, Age, and Sensorineural Hearing Loss: Implications for Cochlear Implantation.

OBJECTIVES: To determine if spatial orientation of the cochlea within the temporal bone is related to age or sensorineural hearing loss (SNHL) and describe the implications for cochlear implantation. METHODS: Five angles of cochlear orientation were determined from computed tomography (CT) imaging of the temporal bones in adults with (n = 55) and without (n = 27) sensorineural hearing loss (SNHL) and children with (n = 45) and without (n = 12) SNHL: facial recess versus basal turn, posterior semicircular canal versus basal turn, round window versus basal turn (axial view), round window versus basal turn (coronal view), and the cochlear axis versus the mastoid facial nerve. RESULTS: All angles showed substantial variation between subjects and between ears. The angles between the round window and basal turn (coronal view) and the posterior semicircular canal and basal turn were significantly correlated with age for all subjects with SNHL (r = 0.22, P = .002 and r = 0.15, P = .03, respectively). Patients with SNHL had significantly more acute angles (46.6° vs 55.8°) between the round window versus basal turn (axial orientation) compared to controls (P < .001). CONCLUSIONS: Cochlear orientation within the temporal bone changes with age and the degree of SNHL. These results suggest that the approach to the round window for electrode insertion might differ between children and adults.

Intracochlear electrocochleography during cochlear implantation.

OBJECTIVE: Electrophysiologic responses to acoustic stimuli are present in nearly all cochlear implant recipients when measured at the round window (RW). Intracochlear recording sites might provide an even larger signal and improve the sensitivity and the potential clinical utility of electrocochleography (ECoG). Thus, the goal of this study is to compare RW to intracochlear recording sites and to determine if such recordings can be used to monitor cochlear function during insertion of a cochlear implant. METHODS: Intraoperative ECoG recordings were obtained in subjects receiving a cochlear implant from the RW and from just inside scala tympani (n = 26). Stimuli were tones at high levels (80-100 dB HL). Further recordings were obtained during insertions of a temporary lateral cochlear wall electrode (n = 8). Response magnitudes were determined as the sum of the first and second harmonics amplitudes. RESULTS: All subjects had measurable extracochlear responses at the RW. Twenty cases (78%) showed a larger intracochlear response, compared with three (11%) that had a smaller response and three that were unchanged. On average, signal amplitudes increased with increasing electrode insertion depths, with the largest increase between 15 and 20 mm from the RW. CONCLUSION: ECoG to acoustic stimuli via an intracochlear electrode is feasible in standard cochlear implant recipients. The increased signal can improve the speed and efficiency of data collection. The growth of response magnitudes with deeper intrascalar electrode positions could be explained by closer proximity or favorable geometry with respect to residual apical signal generators. Reductions in magnitude may represent unfavorable geometry or cochlear trauma.

Round window electrocochleography just before cochlear implantation: relationship to word recognition outcomes in adults.

HYPOTHESES: Electrocochleography (ECoG) to acoustic stimuli can differentiate relative degrees of cochlear responsiveness across the population of cochlear implant recipients. The magnitude of the ongoing portion of the ECoG, which includes both hair cell and neural contributions, will correlate with speech outcomes as measured by results on CNC word score tests. BACKGROUND: Postoperative speech outcomes with cochlear implants vary from almost no benefit to near normal comprehension. A factor expected to have a high predictive value is the degree of neural survival. However, speech performance with the implant does not correlate with the number and distribution of surviving ganglion cells when measured postmortem. We will investigate whether ECoG can provide an estimate of cochlear function that helps predict postoperative speech outcomes. METHODS: An electrode was placed at the round window of the ear about to be implanted during implant surgery. Tone bursts were delivered through an insert earphone. Subjects included children (n = 52, 1-18 yr) and postlingually hearing impaired adults (n = 32). Word scores at 6 months were available from 21 adult subjects. RESULTS: Significant responses to sound were recorded from almost all subjects (80/84 or 95%). The ECoG magnitudes spanned more than 50 dB in both children and adults. The distributions of ECoG magnitudes and frequencies were similar between children and adults. The correlation between the ECoG magnitude and word score accounted for 47% of the variance. CONCLUSION: ECoGs with high signal-to-noise ratios can be recorded from almost all implant candidates, including both adult and pediatric populations. In postlingual adults, the ECoG magnitude is more predictive of implant outcomes than other nonsurgical variables such as duration of deafness or degree of residual hearing.

A gerbil model of sloping sensorineural hearing loss.

OBJECTIVE: The goal of the overall project is to develop knowledge about cochlear physiology during cochlear implantation and develop procedures for assessing its status during hearing preservation surgery. As a step toward this goal, for this study, we established an animal model of sloping high frequency sensorineural hearing loss that mimics the hearing condition of candidates for combined electric-acoustic stimulation. METHODS: Mongolian gerbils were exposed to band-pass noise using various cutoff frequencies, intensities, exposure times, and survival times. Hearing loss was assessed in far-field recording using preexposure and postexposure auditory brainstem responses (ABRs), and in acute, near-field recordings of the cochlear microphonic and compound action potential from an electrode on the round window. Anatomic loss of hair cells was assessed from dissections. RESULTS: Postexposure ABRs and near-field recordings from the round window revealed sensorineural hearing loss that varied with the overall noise exposure. Loss of hair cells ranged from relatively sparse to large areas of complete absence depending on the noise exposure. Cases with high intensity (120 dB SPL) and long exposure times (3 h) showed sloping patterns of hearing loss with profound high-frequency loss and mild-to-moderate low-frequency loss. These cases showed complete loss of hair cells in the basal cochlea and preserved hair cells in the apical cochlea. The frequencies comprising the slope in the ABRs and the location of the transition zone between preserved and lost hair cells varied according to the cutoff frequency used. CONCLUSION: We were able to reliably induce sensorineural hearing loss and loss of hair cells in the gerbil that is comparable to candidates for hearing preservation surgery. This model can be used to evaluate the effects of electrode introduction in a system with a hearing condition similar to that in cases of hearing preservation operations.

Large vestibular aqueduct syndrome: anatomic and functional parameters.

OBJECTIVES/HYPOTHESIS: To correlate imaging and audiologic findings in patients with large vestibular aqueduct syndrome (LVAS). STUDY DESIGN: Retrospective analysis. METHODS: Thirty-eight patients with LVAS evident on magnetic resonance imaging with available clinical and audiometric data were selected from the databases of the study institution. Images were analyzed for endolymphatic sac and duct size, evidence of incomplete cochlear partitioning, and endolymphatic sac signal heterogeneity. The endolymphatic duct was measured in two different locations: near the vestibular aperture (ED(VA)) and at the midpoint between the common crus and the operculum (ED(MID)). Imaging data were correlated with audiologic variables. RESULTS: There was significant correlation between ears for the audiologic and anatomic variables collected. Twenty-one (62%) patients had a fluctuating or progressive hearing loss, and 13 (38%) remained stable (four were not evaluable). At the time of the analysis, 41% of ears had a profound loss. Significant correlation was identified between the presence of endolymphatic signal heterogeneity and worse pure tone average (PTA). ED(VA) measures were significantly larger among ears with a progressive pattern of hearing loss when compared to those that were stable. Also, ED(VA) correlated with PTA and the presence of progressive hearing loss, but ED(MID) had no such a relationship. CONCLUSIONS: Evidence of endolymphatic sac signal heterogeneity and larger measures of endolymphatic width when measured near the vestibule (ED(VA)) are markers of poorer hearing in these patients. By contrast, midpoint measures of the endolymphatic duct (ED(MID)) have no correlation with audiometric parameters.

Intracochlear recordings of electrophysiological parameters indicating cochlear damage.

OBJECTIVE: : The pathophysiologic mechanisms resulting in hearing loss during electrode implantation are largely unknown. To better understand the functional implications of electrode implantation, we recorded the effects of cochlear damage on acoustically evoked intracochlear measurements using normal-hearing gerbils. METHODS: : A metal electrode was placed on the surface of the round window, and recordings of the cochlear microphonic (CM) and compound action potential (CAP) were made in response to stimulation with tone-bursts at various frequencies in 1-octave intervals and at intensities of 15 to 72 dB sound pressure level. The electrode was then advanced incrementally, with CM and CAP measurements obtained at each step. These data were compared with data obtained at the round window, and the electrode was withdrawn when a significant change was observed. After electrophysiological analysis, the cochlea was examined histologically. RESULTS: : Results show that on electrode insertion, loss of amplitude in the CM and CAP occurs after damage to cochlear structures. Loss of activity was typically first apparent in the CAP rather than the CM. CONCLUSION: : These results suggest that a reduction of the CAP can be an early marker of interaction of the electrode with cochlear structures. Such measurements are potentially available with slight modifications to current cochlear implant technology.

Correlation of early auditory potentials and intracochlear electrode insertion properties: an animal model featuring near real-time monitoring.

OBJECTIVE: The goal of this work was to assess electrophysiologic response changes to acoustic stimuli as an intracochlear electrode impacted cochlear structures in an animal model of hearing preservation cochlear implantation. The ultimate goal is to develop efficient procedures for assessing the status of cochlear physiology for intraoperative use. METHODS: Sixteen gerbils and 18 ears were tested. A rigid electrode was inserted through a basal turn cochleostomy and directed toward the basilar membrane/osseous spiral lamina complex. We recorded acoustically evoked early auditory potentials including cochlear microphonics (CMs) and compound action potentials (CAPs) to a short stimulation sequence consisting of one stimulus frequency and intensity as the electrode was advanced. A microendoscope was used to visualize the electrode insertion progress and to identify the site of electrode impact. After each experiment, the site of intracochlear trauma was confirmed using whole mount preparations. RESULTS: Electrophysiologic changes correlated well with the degree and location of trauma. We observed four distinct patterns. In addition, the endoscope in conjunction with the short recording sequence allowed for the detection of response changes that were reversible when the electrode was retracted. These cases were associated with less than full-thickness damage on histology. CONCLUSION: The short recording sequence to obtain acoustically evoked intracochlear potentials and the microendoscope allowed us to detect various levels of cochlear trauma including minor and reversible damage. Recordings of this type are potentially available using current implant technology. Future improvements in the measurements can be expected to improve the efficiency of the recording paradigm to produce a clinically useful tool.

Flexible cochlear microendoscopy in the gerbil.

OBJECTIVES/HYPOTHESIS: To validate the scientific utility of flexible cochlear microendoscopy in the gerbil. This model is currently being developed to study the effects of intracochlear electrode positioning on functional parameters. STUDY DESIGN: Animal experiments. METHODS: A flexible fiberoptic microendoscope featuring a light channel and an outer diameter of 0.4 mm was specially modified to allow intracochlear visualization. Specifically, the focus distance was reduced to 1 mm and the optical properties were modified so that visualization was adequate when submerged in perilymphatic fluid. This endoscope was used to view intracochlear contents and monitor the progress of electrode insertions in 11 gerbils. The endoscopic data estimating the site of damage were compared to postmortem microdissections. RESULTS: The endoscope allowed for adequate visualization of intracochlear content in all animals. The site of electrode contact seen in the endoscope was confirmed in the microdissected cochleae in 10 of 11 cases, indicating the endoscope's ability to correctly identify the site of intracochlear trauma in this animal model. CONCLUSIONS: The current report demonstrates the feasibility of intracochlear microendoscopy in an animal model of hearing preservation cochlear implantation.