Faculty Bibliography

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.

OBJECTIVE/HYPOTHESIS: Currently, no clinical standards exist with regard to antireflux medications in the perioperative period for patients undergoing surgery for benign vocal fold lesions. The present study sought to determine the clinical yield of these medications on operative outcomes in patients who underwent surgical treatment for benign vocal fold lesions. STUDY DESIGN: Retrospective, outcomes study. METHODS: Medical records were reviewed from a single surgeon database between January 2011 and June 2012 to quantify outcomes in patients taking antireflux medications compared with subjects not taking medications at the time of surgery. Voice Handicap Index (VHI)-10 and Reflux Symptom Index (RSI) scores were the primary dependent variables. The t test analyses were conducted to compare VHI-10 and RSI scores. Additional multivariate regression analyses were conducted to evaluate medication effects on VHI and RSI, adjusting for potential confounds. RESULTS: A total of 51 patients met inclusion criteria. Of these patients, 12 (23.5%) were using antireflux medication(s) at the time of surgery and 39 (76.5%) were not. The mean shifts in VHI-10 and RSI after surgery for the antireflux therapy (ART) group were -14.75 and -7.5, respectively. For the non-antireflux therapy (non-ART) group, mean DeltaVHI-10 and DeltaRSI values were -9.87 and -5.05, respectively. Both t test and regression analyses confirmed no statistical difference between the ART and non-ART groups for both DeltaVHI-10 and DeltaRSI. Additional regression analysis revealed a positive correlation between preoperative RSI score and DeltaRSI score. CONCLUSION: Antireflux medications did not significantly alter postoperative outcomes in this preliminary cohort of patients.

IMPORTANCE Current approaches to the diagnosis and subsequent management of specific voice disorders vary widely among primary care physicians (PCPs). In addition, sparse literature describes current primary care practice patterns concerning empirical treatment for vocal disorders. OBJECTIVE To examine how PCPs manage patients with dysphonia, especially with regard to laryngopharyngeal reflux. DESIGN, SETTING, AND PARTICIPANTS Prospective, questionnaire-based study by an academic laryngology practice among academic PCPs from all major US geographic regions. MAIN OUTCOMES AND MEASURES A 16-question web-based survey, distributed via e-mail, concerning management and possible empirical treatment options for patients with dysphonia. RESULTS Of 2441 physicians who received the e-mail broadcast, 314 (12.9%) completed the survey. Among those who completed the survey, 46.3% were family practitioners, 46.5% were trained in internal medicine, and 7.2% identified as specialists. Among all respondents, 64.0% preferred to treat rather than immediately refer a patient with chronic hoarseness (symptoms persisting for >6 weeks) of unclear origin. Reflux medication (85.8%) and antihistamines (54.2%) were the most commonly selected choices for empirical treatment. Most physician respondents (79.2%) reported that they would treat chronic hoarseness with reflux medication in a patient without evidence of gastroesophageal reflux disease. CONCLUSIONS AND RELEVANCE Most PCPs who responded to our survey report empirically treating patients with chronic hoarseness of unknown origin. Many physician respondents were willing to empirically prescribe reflux medication as primary therapy, even when symptoms of gastroesophageal reflux disease were not present. These data suggest that PCPs strongly consider reflux a common cause of dysphonia and may empirically treat patients having dysphonia with reflux medication before referral.

OBJECTIVE/HYPOTHESIS: Glucocorticoids (GCs) are commonly used in the treatment of laryngeal disorders despite the absence of clear guidelines regarding their use. We sought to assess clinical practice patterns regarding GC use for various vocal fold diseases and to ascertain factors underlying the selection of particular GCs for different vocal fold pathology. STUDY DESIGN: Prospective, survey. METHODS: A web-based 20-question survey querying clinical indications for GC use and other factors influencing decision making in GC administration was distributed to 5280 otolaryngologists via e-mail using a commercially available database. RESULTS: The overall response rate for the survey was 4% (212/5280). Of the respondents, 99% reported GCs to be valuable in their practice. Previous experience/results, familiarity, and use in practice (68%, 54%, and 37%, respectively) were the most commonly cited reasons for choosing a particular GC; pharmacokinetic profile and academic literature were infrequently cited reasons. Fifty-four percent of respondents were more likely to prescribe GCs for vocal performers compared with other patients. Additionally, most respondents stated that the potential for side effects only occasionally prevented GC utilization. CONCLUSIONS: GC prescription practices vary greatly among otolaryngologists. Drug choice appears to be driven primarily by clinician preference and personal experience rather than by specific pharmacologic or physiologic rationale. These findings likely reflect the current lack of well-constructed studies in the laryngology literature to guide GC selection and administration for benign disorders of the larynx and highlight an important potential area for future studies.