Faculty Bibliography

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.

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.

OBJECTIVES/HYPOTHESIS: Recent data have suggested that in-office potassium titanyl phosphate (KTP) laser treatment for benign vocal fold lesions yields significant reduction in lesion size with favorable effects on both mucosal wave and glottic closure. However, these previous studies omitted voice-related outcomes. We sought to compliment these previous data with voice-related outcomes in a cohort of patients undergoing KTP ablation of vocal fold polyps. STUDY DESIGN: Retrospective outcomes study. METHODS: Voice Handicap Index (VHI)-10 and acoustic measures were reviewed for 31 consecutive patients with benign vocal fold polyps treated with in-office KTP laser surgery. All data were analyzed statistically via a mixed model fit to analyze the data from each of three clinical visits. RESULTS: Across all patients, the mean VHI-10 scores decreased at first follow-up from 19.7 to 9.7 (P < .0001). At subsequent follow-up visits, the VHI-10 scores remained stable (mean, 8.3). This shift in VHI scores was accompanied by favorable improvements in both noise-to-harmonic ratio and speaking fundamental frequency in both males and females. CONCLUSIONS: In-office KTP ablation of vocal fold polyps had a favorable effect on patient-reported handicap as determined by the VHI-10. This treatment also slightly altered physiologic measures of voice; however, these measures did not achieve statistical significance. LEVEL OF EVIDENCE: 4. Laryngoscope, 2013.

OBJECTIVES/HYPOTHESIS: To provide insight into the demographics and vocal habits of current Broadway musical theater performers. STUDY DESIGN: Prospective, Questionnaire. METHODS: Adult musical theater performers in Broadway Productions as defined by the League of American Theater Producers and the Actors' Equity Association were asked to complete a survey collecting demographic information, vocal health and habits, alcohol, tobacco, and drug use and information regarding their level of vocal comfort and threshold to miss performances based on their voice. Data were subjected to descriptive and statistical analysis based on sex and role type (lead vs ensemble). RESULTS: One hundred thirty-five performers completed the survey from seven actively running shows. Ensemble members were younger and had not been in the business as long as performers in lead roles. Over 25% of respondents had been diagnosed with a vocal injury, yet the number of days missed per year due to voice problems was relatively low (1.7-4.7). Across all respondents, only approximately 54.8% reported consistently warming up before a performance and 7.4% reported consistently cooling down afterward. Nearly 91% of respondents reported regular alcohol consumption and tobacco use was 10.4%; 23.0% reported illicit drug use. CONCLUSIONS: This study marks the first time that vocal health has been addressed in this elite group of vocal professionals. The performer's low self-reported numbers of missed days is interesting particularly given that they appear to participate in harmful vocal health activities at the same rate as the general public.

OBJECTIVES/HYPOTHESIS: Currently, no standard exists for reporting treatment results for the potassium titanyl phosphate (KTP) laser. The goal of this study was to establish a validated classification schema for reporting immediate tissue effects after laser treatment. STUDY DESIGN: Evaluation of KTP laser video sequences by academic laryngologists with use of the rating system. METHODS: A five-point classification system was developed; this included noncontact angiolysis, epithelial blanching, epithelial disruption, contact epithelial ablation, and contact epithelial ablation with tissue removal. Video recordings were made prospectively for each treatment effect. Ten treatment recordings, with two repeated recordings, were presented to seven academic laryngologists, who were asked to categorize each based on the given classification scheme. RESULTS: Overall accuracy for the combined reviewers in rating the treatments was 82%. Six of seven reviewers showed perfect intrarater reliability. Accuracy in rating clips did not correlate with the previous number of 532-nm KTP or 585-nm pulsed dye laser procedures performed but showed a trend toward correlating with total years in practice. This study reveals that standardized reporting of effects of the KTP laser is feasible. CONCLUSIONS: We believe that results of KTP treatment should be reported using a validated classification system of immediate laser effect, along with specific laser settings. This classification system allows for future systematic evaluation of long-term treatment results prospectively from single laser treatments.