Faculty Bibliography

Purpose: Age-related loss of muscle bulk and strength has been documented in the tongue and geniohyoid. Our goal was to explore this phenomenon in the pharynx, specifically by measuring pharyngeal wall thickness (PWT) and pharyngeal lumen area (PLA) in a sample of young vs older women. Method(s): MRI scans of the neck were retrospectively reviewed from 60 women equally stratified by 3 age groups (20s, 60s, 70+). Exclusion criteria included dysphagia, c-spine surgery, neurological illness, head and neck malignancy and obstructive sleep apnea. Three de-identified axial slices were extracted per scan for randomized, blinded analysis: at the levels of the anterior inferior border of C2 and C3, and at the pit of the vallecula (Vpit). Pixel-based measures of PWT and PLA were completed using ImageJ and converted to metric units using the calibration markers on the original images. Measures of PWT and PLA (at three levels) were compared between age groups with one-way ANOVAs using Sidak adjustments for post-hoc pairwise comparisons. Result(s): A significant main effect of age was observed for all variables whereby PWT decreases and PLA increases with advancing age (Table 1). Pairwise comparisons revealed significant differences between 20s vs 70+ for all variables and 20s vs 60s for all variables except PWT and PLA at C2. Effect sizes ranged from 0.56-1.34. Conclusions (Including Clinical Relevance): Consistent with the existing sacropenia literature, the pharyngeal muscles appear to atrophy with age and consequently, PLA increases as well. Future work should explore the relationship between pharyngeal muscle size/ atrophy and functional swallowing outcomes. (Table Presented)

Purpose: Dynamic MRI has been used to examine swallowing in sagittal and axial planes with good temporal resolution. However, few studies have examined temporal measures and none have compared upright vs. supine swallowing in both positions with the MBSImP. We report physiologic variables and swallow safety upright and supine with MBSImP and Penetration/Aspiration scales in healthy subjects. Method(s): Twenty healthy subjects (mean = 28 years) underwent VFS study upright and supine with a C-Arm. Subjects were viewed in the sagittal plane and swallowed 5 mL liquid and pudding barium. Pen/Asp scores and 14 MBSImP variables were analyzed (overall Impression score) in both positions, with means and ranges across subjects upright and supine. Paired t-tests compared MBSImP scores upright vs. supine. Level of significance: p<.05. Result(s): All subjects tolerated the supine position while swallowing. Mean MBSImP scores were WNL across subjects for both positions, except Component 6, Initiation of the Pharyngeal Swallow (Table 1). Nosignificant differences were found for MBSImP scores upright vs. supine. Although the range of Pen/Asp scores was higher for supine, 3 subjects penetrated upright only, 1 penetrated supine only, and 1 aspirated on 1 supine swallow. Pearson coefficients for inter/intra-judge reliability:0.94, 0.91. Conclusions (Including Clinical Relevance): Physiologic measurse revealed a pharyngeal delay in both positions with scores not significantly different. Although Pen/Asp range was higher in supine, more subjects penetrated upright. Future research should examine swallow physiology in both positions in dysphagic and older healthy subjects. (Table Presented)

OBJECTIVES/HYPOTHESIS: To determine oral human papilloma virus (HPV) colonization in patients with adult-onset recurrent respiratory papillomatosis (AO-RRP) and their long-term partners. STUDY DESIGN: Prospective, cohort study METHODS: Patients with pathology-confirmed AO-RRP and a small cohort of their long-term partners were subjected to a standardized oral rinse and swab protocol to obtain oral epithelial cells. DNA from these samples was extracted and subjected to both qualitative analyses via multiplex polymerase chain reaction as well as to a commercially available linear array assay for the determination of specific HPV subtypes. RESULTS: Samples were collected from 27 patients with AO-RRP and six long-term sexual partners. Qualitative analysis of agarose gel products using a multiple genotype primer cocktail suggested the presence of HPV DNA in oral rinse or swabs in 26 patients (96%) and four partner samples (67%). A subset of these positive patient samples was then subjected to genotyping; a spectrum of HPV subtypes was observed. Interestingly, HPV81 was identified in many samples. CONCLUSION: Recent data suggest that less than 7% of the general population is HPV positive in the oral cavity. Our data suggest that the oral colonization rate is much higher in patients with AO-RRP. Additionally, long-term sexual partners of patients with RRP had a much higher rate of HPV positivity. These preliminary data may have implications for viral transmission and provide a framework for enhanced patient education as well as further investigation. LEVEL OF EVIDENCE: 4. Laryngoscope, 2014.

The human vocal fold is a complex structure made up of distinct layers that vary in cellular and extracellular matrix composition. Elucidating the mechanical properties of vocal fold tissues is critical for the study of both acoustics and biomechanics of voice production, and essential in the context of vocal fold injury and repair. Both quasistatic and dynamic behavior in the 10-300Hz range was explored in this preliminary investigation. The resultant properties of the lamina propria were compared to that of the nearby thyroarytenoid muscle. Er, quantified via quasistatic testing of the lamina propria, was 609+/-138MPa and 758+/-142MPa in the muscle (p=0.001). E' of the lamina propria as determined by dynamic testing was 790+/-526MPa compared to 1061+/-928MPa in the muscle. Differences in E' did not achieve statistical significance via linear mixed effect modeling between the tissue types (p=0.95). In addition, frequency dependence was not significant (p=0.18).

OBJECTIVE: The effortful swallow was designed to improve posterior mobility of the tongue base and increase intraoral pressures. We characterized the effects of this maneuver via dynamic magnetic resonance imaging (dMRI) in healthy patients. METHODS: A 3-T scanner was used to obtain dMRI images of patients swallowing pudding using normal as well as effortful swallows. Ninety sequential images were acquired at the level of the oropharynx in the axial plane for each swallow; 3 series were obtained for each swallow type for each patient. Images were acquired every 113 ms during swallowing. The images were analyzed with respect to oropharyngeal closure duration, anteroposterior and transverse distance between the oropharyngeal walls, and oropharyngeal area before and after closure. RESULTS: Preswallow reduced pharyngeal area was observed (P = .02; mean = 212.61 mm2 for effortful, mean = 261.92 mm2 for normal) as well as prolonged pharyngeal closure during the swallow (P < .0001; mean = 742.18 ms for effortful, mean = 437.31 ms for normal). No other differences were noted between swallow types. Interrater and intrarater reliability of all measurements was excellent. CONCLUSION: This preliminary investigation is the first to evaluate the effects of effortful swallows via dMRI. In our cohort, consistent physiologic changes were elicited, consistent with clinical dogma regarding this maneuver.

Objective. To determine the efficacy of small interfering RNA (siRNA) targeting Smad3 to mediate fibroplasia in vitro, to investigate the temporal regulation of Smad3 following vocal fold (VF) injury, and to determine the local and distal effects of Smad3 siRNA vocal fold injection. Study Design. In vitro and in vivo Methods. In vitro, Smad3 regulation was examined at both the level of transcription and translation in a human VF cell line in response to Smad3 siRNA +/- TGF-beta.Collagen transcription was also examined. In vivo, Smad3 mRNA expression was quantified as a function of time following rabbit VF injury. Also, the effects of injected Smad3 siRNA were assessed at local and distal sites. Results. Smad3 siRNA knocked down Smad3 transcription and translation and limited TGF-beta mediated collagen mRNA expression with minimal cytotoxicity in vitro. In vivo, Smad3 mRNA increased 1 day following VF injury and remained elevated through day 7. Smad3 siRNA injection into the uninjured vocal fold had no local or distant effect on Smad3 mRNA at multiple organ sites. Conclusion. These data provide a foundation for further investigation regarding the development of novel RNA-based therapeutics for the VF, specifically locally-delivered siRNA for challenging fibrotic conditions of the VF.

Objective. To evaluate risk factors strongly associated with Adult-Onset Recurrent Respiratory Papillomatosis (AO-RPP). Study Design. Prospective, age and sex-matched, case-control Methods. Patients with AO-RRP and controls completed a computer-based, 89-item questionnaire across three academic institutions. Results. Forty-eight AO-RRP patients were compared to 73 controls; 43 of the 48 AO-RRP patients were male (89.5%). The difference in the median number of lifetime sexual partners between AO-RRP (15) and controls (10) was significant (p=0.0387). Additionally, an increased number lifetime sexual partners (>/=26) was associated with AO-RRP. No significant difference for the number of lifetime oral sex partners was observed between groups. Increased comorbidity, as quantified by the Charleson Comorbidity Index, was observed in patients with AO-RRP. AO-RRP and control groups were similar across many other variables including birth history, smoking history, alcohol use, drug use, education, income, and SF-36 scores. Conclusion. AO-RRP was not associated with previously-proposed risk factors for juvenile-onset RRP and may be associated with an increased number of lifetime sexual partners.

OBJECTIVES/HYPOTHESIS: To provide the otolaryngologist an evidence-based sound review of glucocorticoid use for laryngeal pathology. STUDY DESIGN: Review of contemporary peer-reviewed literature as well as review articles. METHODS: A review of the literature regarding glucocorticoids as a therapeutic intervention for the treatment of benign laryngeal pathology and laryngeal manifestations of systemic disease was performed. Review included both systemic administration as well as local injection. RESULTS: Glucocorticoids, administered in the critical care setting for planned extubation, markedly reducing the risk of reintubation and remain a rudimentary pharmacologic adjunct in laryngeal manifestations of common autoimmune and inflammatory disorders. Intralesional injection has reduced the rate of surgical intervention for benign inflammatory primary laryngeal pathology. CONCLUSIONS: Glucocorticoids are effective in the treatment of a number of laryngeal pathologies, through both systemic and intralesional administration. However, a clear consensus for utilization of glucocorticoids in the treatment of specific laryngeal disorders has yet to be published. LEVEL OF EVIDENCE: NA Laryngoscope, 2014.

The present study aimed to characterize the mechanical response of beagle sartorius muscle fibers under strain rates that increase logarithmically (0.1mm/min, 1mm/min and 10mm/min), and provide an analysis of the fracture patterns of these tissues via scanning electron microscopy (SEM). Muscle tissue from dogs' sartorius was excised and test specimens were sectioned with a lancet into sections with nominal length, width, and thickness of 7, 2.5 and 0.6mm, respectively. Trimming of the tissue was done so that the loading would be parallel to the direction of the muscle fiber. Samples were immediately tested following excision and failures were observed under the SEM. No statistically significant difference was observed in strength between the 0.1mm/min (2.560+/-0.37MPa) and the 1mm/min (2.702+/-0.55MPa) groups. However, the 10mm/min group (1.545+/-0.50MPa) had a statistically significant lower strength than both the 1mm/min group and the 0.1mm/min group with p<0.01 in both cases. At the 0.1mm/min rate the primary fracture mechanism was that of a shear mode failure of the endomysium with a significant relative motion between fibers. At 1mm/min this continues to be the predominant failure mode. At the 10mm/min strain rate there is a significant change in the fracture pattern relative to other strain rates, where little to no evidence of endomysial shear failure nor of significant motion between fibers was detected.

OBJECTIVES/HYPOTHESIS: To characterize the videoendoscopic laryngeal findings in patients with a prior established diagnosis of laryngopharyngeal reflux disease (LPR) as the sole etiology for their chief complaint of hoarseness. We hypothesized that many, if not all, of these patients would present with discrete laryngeal pathology, divergent from LPR. STUDY DESIGN: Prospective, nonintervention. METHODS: Patients presenting to a tertiary laryngology practice with an established diagnosis of LPR as the sole etiology of their hoarseness were included. All subjects completed the Voice Handicap Index and Reflux Symptom Index, in addition to a questionnaire regarding their reflux diagnosis and prior treatment. Laryngoscopic examinations were reviewed by the laryngologist caring for the patients. Reliability of findings was assessed by interpretation of videoendoscopic findings by three outside laryngologists not involved in the care of the patients. RESULTS: Laryngeal pathology distinct from LPR was identified in all 21 patients felt to be causative of the chief complaint of dysphonia. Specifically, the most common findings were benign mucosal lesions and vocal fold paresis (29% each), followed by muscle tension dysphonia (14%). Two patients were found to have vocal fold leukoplakia, of which one was confirmed to be a microinvasive carcinoma upon removal. CONCLUSION: LPR may be overdiagnosed; other etiologies must be considered for patients with hoarseness who fail empiric LPR treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 2013.