Elizabeth DiRenzo, PhD

All Publications

• Establishing a Mouse Model of Surgical Vocal Fold Injury. The Laryngoscope Kimura, A., Khan, M. I., Easwaran, M., Soo, J., Golchin, A., Erickson-DiRenzo, E. 2024

  Abstract

  Animal models of vocal fold (VF) surgical injury and scar formation provide insight into the wound healing process. The purpose of this study was to establish an alternative model of surgical injury to the mouse VF using materials commonly available in most research laboratories or for purchase and to investigate wound healing of the epithelium (EP) and lamina propria (LP).Mice were anesthetized by isoflurane gas delivery and positioned on a platform so that the larynx could be observed using a laryngoscope and dissection microscope. Unilateral VF injury was created using a wire brush. Mice were euthanized and the larynx evaluated 1-, 3-, 5-, 7-, 14-, and 28-days following injury. Histological and immunofluorescent analysis was used to evaluate thickness of the EP, LP area, proliferative (Ki67+) and basal cells (p63+) in the EP, and collagen III content in the LP.The depth of injury reached the superficial thyroarytenoid muscle on Day 1. The thickness of the EP of the injured VF was increased on Days 3 and 5, and the LP area was increased on Days 3, 5, and 7 as compared with the uninjured VF. Ki67+ and p63+ cells were increased on Day 3 and collagen III content was increased on Days 5 and 28 as compared with the uninjured VF.We successfully established an alternative method of creating unilateral VF injury in the mouse. This method will be useful for future research regarding VF surgical injury and wound healing.N/A Laryngoscope, 2024.

  View details for DOI 10.1002/lary.31732

  View details for PubMedID 39180435

• Effects of Short-term Electronic(e)-Cigarette Aerosol Exposure in the Mouse Larynx. The Laryngoscope Easwaran, M., Maria, C. S., Martinez, J. D., Hung, B., Yu, X., Soo, J., Kimura, A., Gross, E. R., Erickson-DiRenzo, E. 2023

  Abstract

  The effects of electronic cigarettes (e-cigarettes) on the larynx are relatively unknown. This study examined the short-term effects of e-cigarette inhalation on cellular and inflammatory responses within the mouse laryngeal glottic and subglottic regions after exposure to pod-based devices (JUUL).Male C57BL6/J mice (8-9 weeks) were assigned to control (n = 9), JUUL flavors Mint (JMi; n = 10) or Mango (JMa; n = 10). JUUL mice were exposed to 2 h/day for 1, 5, and 10 days using the inExpose inhalation system. Control mice were in room air. Vocal fold (VF) epithelial thickness, cell proliferation, subglandular area and composition, inflammatory cell infiltration, and surface topography were evaluated in the harvested larynges. Mouse body weight and urinary nicotine biomarkers were also measured. Chemical analysis of JUUL aerosols was conducted using selective ion flow tube mass spectrometry.JUUL-exposed mice had reduced body weight after day 5. Urinary nicotine biomarker levels indicated successful JUUL exposure and metabolism. Quantitative analysis of JUUL aerosol indicated that chemical constituents differ between JMi and JMa flavors. VF epithelial thickness, cellular proliferation, glandular area, and surface topography remained unchanged after JUUL exposures. Acidic mucus content increased after 1 day of JMi exposure. VF macrophage and T-cell levels slightly increased after 10 days of JMi exposures.Short-term e-cigarette exposures cause minimal flavor- and region-specific cellular and inflammatory changes in the mouse larynx. This work provides a foundation for long-term studies to determine if these responses are altered with multiple e-cigarette components and concentrations.N/A Laryngoscope, 2023.

  View details for DOI 10.1002/lary.31043

  View details for PubMedID 37698394

• End-to-end deep learning classification of vocal pathology using stacked vowels LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY Liu, G. S., Hodges, J. M., Yu, J., Sung, C., Erickson-DiRenzo, E., Doyle, P. C. 2023

  View details for DOI 10.1002/lio2.1144

  View details for Web of Science ID 001065156000001

• Method for Collecting Single Epithelial Cells from the Mouse Larynx. The Laryngoscope Khan, M. I., Easwaran, M., Martinez, J. D., Kimura, A., Erickson-DiRenzo, E. 2023

  Abstract

  The larynx is lined by specialized epithelial cell populations. Studying molecular changes occurring in individual epithelial cell types requires a reliable method for removing these cells from the larynx. Our objective was to develop a method to harvest individual epithelial cells from the mouse larynx while minimizing contamination from non-laryngeal sites and non-epithelial laryngeal cells.Mice were euthanized, and the larynx was carefully exposed and separated from non-laryngeal sites. A small dental brush was inserted into the laryngeal inlet and rotated to obtain epithelial cells. Cells were transferred to collection media, counted, and cytospin preparations stained for laryngeal epithelial (i.e., Pan-Keratin, EpCAM, NGFR, p63, K5, β-tubulin, MUC5AC) and non-epithelial (i.e., vimentin) cell markers. Histopathology was completed on brushed laryngeal tissue sections to evaluate the depth of cell collection. Preliminary Single-cell RNA sequencing (scRNA-seq) was performed to confirm this method can capture diverse laryngeal cell types.We collected 6000-8000 cells from a single larynx and 35000-40000 cells from combining brushings from three tissues. Histopathology demonstrated brushing removed the epithelial layer of the larynx and some underlying tissue. Immunofluorescence staining demonstrated the phenotype of harvested cells was primarily epithelial. Preliminary scRNA-seq was successfully conducted and displayed nine unique cell clusters.We developed a reliable method of harvesting individual epithelial cells from the mouse larynx. This method will be useful for collection of laryngeal cells for a variety of downstream cellular and molecular assays, including scRNA-seq, protein analyses, and cell-culture-based experiments, following laryngeal injury.N/A Laryngoscope, 2023.

  View details for DOI 10.1002/lary.30970

  View details for PubMedID 37602769

• Impact of Electronic Cigarettes on the Upper Aerodigestive Tract: A Comprehensive Review for Otolaryngology Providers OTO OPEN Soo, J., Easwaran, M., Erickson-DiRenzo, E. 2023; 7 (1)

  View details for DOI 10.1002/oto2.25

  View details for Web of Science ID 000937521100001

• Diagnosis and Management of Vocal Complications after Chondrolaryngoplasty. The Laryngoscope Nuyen, B., Qian, Z. J., Rakkar, M., Thomas, J. P., Erickson-DiRenzo, E., Sung, C. K. 2022

  Abstract

  OBJECTIVE: Transfeminine patients (transwomen/feminine nonbinary folks assigned male at birth) can undergo chondrolaryngoplasty ("tracheal shave") to feminize their neck appearance. While isolated cases of vocal complications have been reported following the procedure, aggregated outcomes have not been quantitatively studied. We present acoustic and stroboscopic data to describe a patient cohort with vocal complications after chondrolaryngoplasty and discuss reparative surgical technique.METHODS: Subjective and objective data, including videostroboscopy, were collected from patients with voice complaints after chondrolaryngoplasty. Dislocated anterior commissures were reconstructed with feminization laryngoplasty. Postoperative voice data were recorded and statistically compared to preoperative data using paired t-tests.RESULTS: On consecutive chart review, of the 94 transfeminine women with prior outside history of chondrolaryngoplasty, 27 (29%) reported chronic postoperative hoarseness, deepened pitch, or loss of upper register. On endoscopy, short, lax vocal folds with persistent anterior glottic gap and phase asymmetry were commonly noted; anterior commissure dislocation was confirmed in-office by using needle localization through absent thyroid cartilage. After open resuspension of the anterior commissure with feminization laryngoplasty, post-repair modal-speaking, minimum, and maximum fundamental frequencies (F0) increased on average by 7, 8, and 5 semitones, respectively (p<0.01), when compared to pre-repair values. On average, perioperative maximum phonation time did not change significantly (p=0.15). Average self-assessment of vocal femininity increased by 48% (p<0.01).CONCLUSION: Anterior commissure dislocation should be suspected with signs of vocal impairment after chondrolaryngoplasty. Following proper diagnosis, resuspension of the anterior commissure via feminization laryngoplasty approach can be an effective reparative technique.LEVEL OF EVIDENCE: This work represents a 2011 OCEBM Level 4 evidence as a case series Laryngoscope, 2022.

  View details for DOI 10.1002/lary.30518

  View details for PubMedID 36576093

• Social Perception of External Laryngeal Anatomy Related to Gender Expression in a Web-based Survey. The Laryngoscope Kiessling, P., Balakrishnan, K., Fauer, A., Sanan, A., McDonald, D., Thomas, J., Erickson-Direnzo, E., Sung, C. K., Nuyen, B. 2022

  Abstract

  To quantify the effect of laryngeal prominence size on socially perceived attributes relating to gender expression. Chondrolaryngoplasty ("tracheal shave") is a common procedure performed for transgender women to feminize neck appearance. The extent of thyroid cartilage resection needed to convey socially-perceived feminine gender expression without destabilizing the voice is incompletely understood.Cross-sectional evaluation of a randomized allocation of images of varying laryngeal prominence to a non-repeated, random sample from November 2021 to December 2021. Photos of laryngeal prominence were isolated against a constant neck baseline with lateral, oblique, and frontal views. The images were embedded into a web-based survey with visual analog scales to capture perceived scaled gender expression (masculinity, femininity) and social traits (e.g., attractiveness, friendliness, leadership). We performed bivariate and multivariate analyses relating the laryngeal prominence to perceived gender expression and social traits.The analytic sample included 1,026 respondents. Laryngeal grades similar to the demonstrated "grade M" in this study and smaller demonstrated similar perceptions of increased femininity and decreased masculinity. Grades larger than M demonstrate significantly increased perceived masculinity and significantly decreased perceived femininity. The lateral and oblique views of the neck appear to be the most gender-informative.This crowd-sourced analysis of external laryngeal anatomy by a large population of observers provides clear, reproducible insights into social perceptions of gender identity and specifically femininity. These data will meaningfully inform patient counseling and surgical planning for gender-affirming interventions by establishing normative data representing the general public's perceptions.N/A Laryngoscope, 2022.

  View details for DOI 10.1002/lary.30498

  View details for PubMedID 36453533

• Effects of Electronic (E)-cigarette Vapor and Cigarette Smoke in Cultured Vocal Fold Fibroblasts. The Laryngoscope Martinez, J. D., Easwaran, M., Ramirez, D., Erickson-DiRenzo, E. 2022

  Abstract

  OBJECTIVE: The public use of electronic-cigarettes (e-cigs) is rapidly growing. When heated, e-cigs produce a vapor that is inhaled. The vocal folds are among the first tissues exposed to this insult. However, the impact of e-cigs on vocal fold health is almost entirely unknown. Our objective was to evaluate the effects of e-cig vapor on cultured human vocal fold fibroblasts (hVFFs), the primary cell type of the lamina propria. We compared the cellular effects of e-cig vapor without and with nicotine and conventional cigarette smoke.STUDY DESIGN: In vitro.METHODS: E-cig vapor extract (EVE) and cigarette smoke extract (CSE) were created by bubbling vapor and smoke, respectively, into the cell culture medium. hVFFs were exposed to EVE without or with nicotine or CSE for 24hours. Untreated cells were used as a control group. Cells were harvested, and cytotoxicity, extracellular matrix and inflammatory gene expression, and DNA damage were assessed.RESULTS: Undiluted EVE without and with nicotine reduced the viability of hVFFs to a cytotoxic level. CSE reduced hVFFs viability to a greater extent than EVE and induced DNA damage as measured by DNA double-strand breaks. No changes in gene expression were observed following EVE or CSE exposure.CONCLUSION: EVE induces cytotoxicity in hVFFs. However, cellular responses were greater following exposure to CSE, suggesting cigarette smoke may induce more harm, at least in the short term. Findings from this investigation improve our understanding of responses of hVFFs to e-cigs and form the basis for an in vitro methodology to study the vocal fold responses to these products.LEVEL OF EVIDENCE: N/A Laryngoscope, 2022.

  View details for DOI 10.1002/lary.30073

  View details for PubMedID 35213064

• Feminization Laryngoplasty: 17-Year Review on Long-Term Outcomes, Safety, and Technique. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Nuyen, B. A., Qian, Z. J., Campbell, R. D., Erickson-DiRenzo, E., Thomas, J., Sung, C. K. 2021: 1945998211036870

  Abstract

  OBJECTIVES: Transfeminine patients can experience significant gender dysphoria in vocal communication. Feminization laryngoplasty (FL) is a gender-affirming surgery developed to elevate speaking vocal range, as well as alter vocal resonance and laryngeal cosmesis. The purpose here was to appraise FL's long-term voice outcomes across a 17-year review period.STUDY DESIGN: Level III, retrospective study and description of technique.SETTING: A single-institution transfeminine voice clinic.METHODS: Voice data (speaking fundamental frequency [F0], lowest F0, highest F0, F0 range in both Hertz and semitones, and maximum phonation time [MPT]) were collected and assessed. Self-assessment of voice femininity and complications were documented.RESULTS: The 162 patients, all transfeminine women, had a mean age of 40 years with 36-month mean follow-up. There were significant increases in mean speaking F0 (Delta = 50 ± 30 Hz, Delta = 6 ± 3 semitones; P < .001) and mean change in lowest F0 (Delta = 58 ± 31 Hz, Delta = 8 ± 4 semitones; P < .001). There was no significant difference in mean change in highest F0 or MPT. There was significant improvement (Delta = 60% ± 39%; P < .001) in perceptual self-assessment of vocal femininity. There was a 1.2% rate of major postoperative complications requiring inpatient admission or operative intervention. There were no differences in vocal outcomes between those patients who had less than 1-year follow-up and those who had 5-year follow-up.CONCLUSION: FL in this cohort was a safe and effective technique for increasing mean speaking F0, mean lowest F0, and voice gender perception over a prolonged follow-up period. These findings add to the possible treatments aimed at addressing the morbid dysphoria related to voice and communication for our transfeminine patients.

  View details for DOI 10.1177/01945998211036870

  View details for PubMedID 34399638

• The Impact of COVID-19 on Speech-Language Pathologists Engaged in Clinical Practices With Elevated Coronavirus Transmission Risk AMERICAN JOURNAL OF SPEECH-LANGUAGE PATHOLOGY Kearney, A., Searl, J., Erickson-DiRenzo, E., Doyle, P. C. 2021; 30 (4): 1673-1685

  Abstract

  Purpose This study assessed and described potential clinical practice changes secondary to COVID-19 that emerged as an early response to the pandemic for speech-language pathologists (SLPs) engaged in voice, alaryngeal, and swallowing activities that may increase the risk of virus transmission. Method SLPs from the United States and Canada (n = 665) who were engaged in clinical activities that might elevate the risk of COVID-19 exposure completed an online survey regarding their clinical practices. Topics assessed included potential clinical service modifications, COVID-19 testing and health, and potential financial impacts in the early time period of the pandemic. Results The percentage of SLPs completing the most endoscopic procedures prepandemic (≥ 10/week) was reduced from 39% of respondents to 3% due to the pandemic. Those who completed the most tracheoesophageal puncture voice prosthesis changes (≥ 5/week) reported a reduction in frequency from 24% to 6%. Twenty-five percent of SLPs reported that they were tested for COVID-19, and 6% reported a positive result. Descriptive statistics suggest that COVID-19 testing rates of SLPs, the percentage of SLPs experiencing a financial impact, and the percentage who were furloughed varied across SLP work setting. Conclusions These findings provide the first data characterizing the impact on COVID-19 on clinical practice for SLPs engaged in procedures such as endoscopy and laryngectomy care. The results indicate that, as frontline workers, SLPs were directly impacted in their practice patterns, personal health, safety, and financial security, and that these reported impacts occurred differently across SLP work settings.

  View details for DOI 10.1044/2021_AJSLP-20-00325

  View details for Web of Science ID 000683585400008

  View details for PubMedID 34161739

• Mainstream Cigarette Smoke Impacts the Mouse Vocal Fold Epithelium and Mucus Barrier. The Laryngoscope Erickson-DiRenzo, E., Easwaran, M., Martinez, J. D., Dewan, K., Sung, C. K. 2021

  Abstract

  OBJECTIVES/HYPOTHESIS: Cigarette smoke (CS) is a primary risk factor for the development of numerous benign and malignant laryngeal diseases. The epithelium and mucus lining the vocal folds (VF) are the first barriers against CS. The primary objective of this study was to investigate epithelial and mucus barrier changes in the mouse laryngeal mucosa upon exposure to subacute CS. The secondary objective was to compare mucus barrier changes in mice and human smokers and nonsmokers. Study Design Animal model.METHODS: Mice were exposed to CS for 4weeks for 4hours (N = 12, high dose [HD]) or 1hour (N = 12, low dose [LD]) per day. Air-exposed mice were used as a control group (N = 10). Larynges were harvested and VF epithelial barrier integrity was evaluated including cellular proliferation and expression of cell junctions. We also investigated mucus production by examining mucus cell area and mucin expression in mice and human smokers and nonsmokers.RESULTS: HD CS increased VF epithelial cellular proliferation but did not alter the expression of cell junctions. HD CS also induced hypertrophy of the mucus-producing submucosal glands. However, only LD CS increased MUC5AC gene expression. MUC5AC staining appeared elevated in laryngeal specimens from smokers, but this was not significant as compared to nonsmokers.CONCLUSIONS: These findings help us identify potential adaptive mechanisms to CS exposure as well as set the foundation for further study of key aspects of epithelial and mucus barrier integrity that may be implicated in laryngeal disease development following prolonged smoking.LEVEL OF EVIDENCE: NA Laryngoscope, 2021.

  View details for DOI 10.1002/lary.29572

  View details for PubMedID 33864646

• This Is the Voice (Book Review) SCIENCE Book Review Authored by: DiRenzo, E. 2021; 371 (6528): 471

  View details for DOI 10.1126/science.abf7191

  View details for Web of Science ID 000612983100026

• Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx. Toxicology reports Easwaran, M., Martinez, J. D., Ramirez, D. J., Gall, P. A., Erickson-DiRenzo, E. 2021; 8: 920-937

  Abstract

  The larynx is an essential organ in the respiratory tract and necessary for airway protection, respiration, and phonation. Cigarette smoking is a significant risk factor associated with benign and malignant laryngeal diseases. Despite this association, the underlying mechanisms by which cigarette smoke (CS) drives disease development are not well elucidated. In the current study, we developed a short-term murine whole body inhalation model to evaluate the first CS-induced cellular responses in the glottic [i.e. vocal fold (VF)] and subglottic regions of the larynx. Specifically, we investigated epithelial cell proliferation, cell death, surface topography, and mucus production, at various time points (1 day, 5 days, 10 days) after 2h exposure to 3R4F cigarettes (Delivered dose: 5.6968 mg/kg per cigarette) and following cessation for 5 days after a 5 day CS exposure (CSE). CSE elevated levels of BrdU labeled proliferative cells and p63 labeled epithelial basal cells on day 1 in the VF. CSE increased proliferative cells in the subglottis at days 5, 10 and following cessation in the subglottis. Cleaved caspase-3 apoptotic activity was absent in VF at all time points and increased at day 1 in the subglottis. Evaluation of the VF surface by scanning electron microscopy (SEM) revealed significant epithelial microprojection damage at day 10 and early signs of necrosis at days 5 and 10 post-CSE. SEM visualizations additionally indicated the presence of deformed cilia at days 5 and 10 after CSE and post-cessation in the respiratory epithelium lined subglottis. In terms of mucin content, the impact of short-term CSE was observed only at day 10, with decreasing acidic mucin levels and increasing neutral mucin levels. Overall, these findings reveal regional differences in murine laryngeal cellular responses following short-term CSE and provide insight into potential mechanisms underlying CS-induced laryngeal disease development.

  View details for DOI 10.1016/j.toxrep.2021.04.007

  View details for PubMedID 33996505

• Vocal Hygiene in Collegiate Singers-Does Formal Training Relate to Practices? Journal of voice : official journal of the Voice Foundation Santa Maria, C., Sung, C., Baird, B. J., Erickson-DiRenzo, E. 2020

  Abstract

  BACKGROUND: Vocal hygiene is vitally important for protecting vocal quality and promoting vocal longevity. It includes adequate hydration, avoidance of environmental irritants, and refraining from phonotraumatic behaviors such as screaming, excessive talking, and throat clearing. Formal singing training in addition to enhancing singing techniques, is also assumed to promote good vocal hygiene. Consequently, we investigated whether collegiate singers with formal training are more likely to practice good vocal hygiene habits than untrained collegiate singers.METHODS: We completed a prospective cohort study, where collegiate singers at Stanford University were voluntarily enrolled in an annual vocal health clinic. Full laryngeal exams were performed and demographic information, formal vocal training status, and information on vocal hygiene habits were obtained through questionnaires. The results were then analyzed by grouping singers as "untrained" if less than 1 year of formal training, and "trained" if greater than a year.RESULTS: A total of 82 singers were included for analysis, with 49 (59.8%) having greater than one year of formal training. Trained singers were more likely to employ a primary musical singing style of classical or operatic singing compared to untrained singers who were more likely to utilize "R&B" (P < 0.001). No significant differences were found between groups for hydration practices (P=0.20), caffeine consumption (P=0.73), warm up practices (P=0.08), and phonotraumatic behaviors. Alcohol consumption, smoking tobacco, marijuana, e-cigarette usage was similar between groups. Overall, 11% of our sample reported intermittent less than daily marijuana use, with one singer reporting daily consumption. None of the singers in this sample used e-cigarettes. These rates are noticeably lower than the agematched United States population. Perceptions of cigarettes, marijuana, electronic cigarettes, alcohol, and caffeine were also the same between groups, with the vast majority of singers perceiving these agents as harmful to the voice (64%-100% depending on the agent). No laryngeal pathology was identified during laryngeal examination of any singers.CONCLUSIONS: Vocal hygiene habits are similar between trained and untrained collegiate singers. This likely relates to a desire for vocal longevity irrespective of prior training. This may dispel the long-held assumption that formal training was necessary to develop good vocal habits. We do however, present a very homogenous, highly educated sample of collegiate singers from Stanford University, having significantly less at-risk behavior than their aged-matched counterparts in the general US population. A lack of laryngeal pathology despite extensive vocal demands may also be reflective of good vocal hygiene habits.

  View details for DOI 10.1016/j.jvoice.2020.03.014

  View details for PubMedID 32362576

• Intraoperative Evaluation of Essential Vocal Tremor in Deep Brain Stimulation Surgery. American journal of speech-language pathology Erickson-DiRenzo, E., Sung, C. K., Ho, A. L., Halpern, C. H. 2020: 1–13

  Abstract

  Purpose Essential vocal tremor (EVT) is a prevalent and difficult-to-manage voice disorder. There is evidence that deep brain stimulation (DBS) of the ventral intermediate nucleus (Vim) of the thalamus may be beneficial for treating EVT. The objective of this preliminary investigation was to conduct intraoperative voice assessments during Vim-DBS implantation in order to evaluate immediate voice outcomes in medication-refractory essential tremor patients with co-occurring EVT. Method Seven adult subjects diagnosed with EVT undergoing Vim-DBS surgery participated in this investigation. Voice samples of sustained vowels were collected by a speech-language pathologist preoperatively and intraoperatively, immediately following Vim-DBS electrode placement. Voice evaluation included objective acoustic assessment of the rate and extent of EVT fundamental frequency and intensity modulation and subjective perceptual ratings of EVT severity. Results The rate of intensity modulation, extent of fundamental frequency modulation, and perceptual rating of EVT severity were significantly reduced intraoperatively as compared to preoperatively. Moderate, positive correlations were appreciated between a subset of acoustic measures and perceptual severity ratings. Conclusions The results of this study demonstrate a speech-language pathologist can conduct intra-operative evaluation of EVT during DBS surgery. Using a noninvasive, simple acoustic recording method, we were able to supplement perceptual subjective observation with objective assessment and demonstrate immediate, intraoperative improvements in EVT. The findings of this analysis inform the added value of intraoperative voice evaluation in Vim-DBS patients and contribute to the growing body of literature seeking to evaluate the efficacy of DBS as a treatment for EVT.

  View details for DOI 10.1044/2019_AJSLP-19-00079

  View details for PubMedID 32073285

• Nasal Symptoms Following Laryngectomy: A Cross-sectional Analysis. American journal of rhinology & allergy Ayoub, N., Kearney, A., Sayyid, Z. N., Erickson-DiRenzo, E., Jeffrey, C., Hwang, P. H. 2020: 1945892420901631

  View details for DOI 10.1177/1945892420901631

  View details for PubMedID 31964149

• Multiparametric laryngeal assessment of the effect of thalamic deep brain stimulation on essential vocal tremor. Parkinsonism & related disorders Erickson-DiRenzo, E. n., Kuijper, F. M., Barbosa, D. A., Lim, E. A., Lin, P. T., Lising, M. A., Huang, Y. n., Sung, C. K., Halpern, C. H. 2020; 81: 106–12

  Abstract

  EVT is a refractory voice disorder that significantly affects quality of life. This work aims to conduct a multiparametric assessment of the effect of deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) on essential vocal tremor (EVT) and investigate the relation between DBS lead location and EVT outcomes.Nine participants underwent DBS for essential tremor and were diagnosed with co-occurring EVT in this prospective cohort study. Objective measurements including acoustic evaluation of vocal fundamental frequency (F0) and intensity modulation and subjective measurements including physiologic evaluation of the oscillatory movement of the laryngeal muscles and vocal tract and perceptual ratings of tremor severity were collected PRE and POST DBS. Finally, we investigated the relation between DBS lead location and EVT outcomes.Acoustic modulations of F0 and intensity were significantly improved POST DBS. Physiologic assessment showed a POST DBS reduction of oscillatory movement in the laryngeal muscles and vocal tract, but not significantly. Listener and participant perception, of EVT severity was also significantly reduced. Finally, our results indicate better EVT control with increased distance to midline of left VIM thalamic stimulation.By employing a battery of objective and subjective measures, our study supports the benefit of DBS for the treatment of EVT and specifies the acoustic and physiologic mechanisms that mediate its positive effect. We further provide preliminary results on the relation between lead location and EVT outcomes, laying the foundation for future studies to clarify the optimal DBS target for the treatment of EVT.

  View details for DOI 10.1016/j.parkreldis.2020.10.026

  View details for PubMedID 33120071

• Increased expression of estrogen receptor beta in idiopathic progressive subglottic stenosis. The Laryngoscope Damrose, E. J., Campbell, R. D., Darwish, S., Erickson-DiRenzo, E. 2019

  Abstract

  BACKGROUND/OBJECTIVES: Idiopathic progressive subglottic stenosis (IPSS) predominantly affects females in perimenopause. It has, therefore, been hypothesized that estrogen is involved in its pathogenesis. There are two main types of estrogen receptors: ER-alpha and ER-beta. Abnormal variants of ER-beta have previously been shown to be associated with poor wound healing. Estrogen receptors have recently been identified in subglottic tissue samples, with elevated levels of ER-alpha and progesterone receptors, and no expression of ER-beta, in stenotic specimens reported in one study. The objective of this study was to confirm the presence of estrogen receptors in the subglottis and investigate levels of expression and types of estrogen receptors in normal and stenotic subglottic tissue.METHODS: Subglottic tissue was obtained from three female and one male cadaver without laryngotracheal pathology to serve as controls. Subglottic tissue specimens from five female patients with IPSS were also analysed. Immunofluorescence stains for ER-alpha and ER-SS were performed on specimens. Staining patterns were compared qualitatively and semi-qualitatively between control and IPSS specimens.RESULTS: Immunofluorescence stains demonstrated the presence of both ER-alpha and ER-beta in subglottic tissue. IPSS specimens demonstrated significantly greater staining intensity of ER-alpha in the epithelium and ER-SS in glands and ducts compared to controls.CONCLUSIONS: This study confirms the presence of estrogen receptors in the subglottis. Increased expression of ER-alpha in the epithelium and ER-SS in glands and ducts in IPSS compared to controls may help to explain the predisposition to stenosis in these individuals.LEVEL OF EVIDENCE: 3b Laryngoscope, 2019.

  View details for DOI 10.1002/lary.28364

  View details for PubMedID 31643093

• Methodology for the establishment of primary porcine vocal fold epithelial cell cultures LARYNGOSCOPE Erickson-DiRenzo, E., Leydon, C., Thibeault, S. L. 2019; 129 (10): E355-E364

  Abstract

  A current lack of methods for epithelial cell culture significantly hinders our understanding of the role of the epithelial and mucus barriers in vocal fold health and disease. Our first objective was to establish reproducible techniques for the isolation and culture of primary porcine vocal fold epithelial cells. Our second objective was to evaluate the functional significance of cell cultures using an in vitro exposure to an inflammatory cytokine.Epithelial cells were isolated from porcine vocal folds and expanded in culture. Characterization of cultures was completed by immunostaining with markers for pan-cytokeratin (epithelial cells), vimentin (stromal cells), von Willebrand factor (endothelial cell), and MUC1 and MUC4 (mucin) glycoproteins. Established epithelial cell cultures were then exposed to the inflammatory cytokine tumor necrosis factor alpha (TNF-α) for 24-hours, and transcript expression of MUC1 and MUC4 was evaluated.Reproducible, porcine vocal fold epithelial cell cultures, demonstrating cobblestone appearance characteristic of the typical morphology of epithelial cell cultures were created. Cells showed positive staining for pan-cytokeratin with limited expression of vimentin and von Willebrand factor. Epithelial cells also expressed MUC1 and MUC4. TNF-α significantly increased transcript expression of MUC4.Here, we present the first report of successful culture of primary porcine vocal fold epithelial cells. Cultures will provide researchers with a valuable new in vitro tool to investigate vocal fold epithelium and mucus as well as the effects of common challenges, including inflammatory cytokines, on these barriers.NA Laryngoscope, 129:E355-E364, 2019.

  View details for DOI 10.1002/lary.27909

  View details for Web of Science ID 000488184200009

  View details for PubMedID 30848488

  View details for PubMedCentralID PMC6779414

• Endoscopic Management of Postradiation Dysphagia in Head and Neck Cancer Patients: A Systematic Review. The Annals of otology, rhinology, and laryngology Abu-Ghanem, S., Sung, C., Junlapan, A., Kearney, A., DiRenzo, E., Dewan, K., Damrose, E. J. 2019: 3489419837565

  Abstract

  OBJECTIVES:: To systematically review the success rate and safety profile of the available endoscopic surgical options for radiation-induced dysphagia in head and neck cancer patients following organ preservation treatment, including upper esophageal sphincter (UES) dilation, cricopharyngeus (CP) myotomy (CPM), and CP intramuscular botulinum toxin (Botox) injection.METHODS:: A search of MEDLINE, Scopus, Google Scholar, and Cochrane databases was done to identify articles published between January 1980 and December 2017. Pediatric series, foreign language articles, series with Zenker's diverticulum or following primary surgical treatment including laryngectomy, open UES/CP surgery, or samples with fewer than 5 patients were excluded.RESULTS:: An initial search identified 539 articles. All titles and abstracts were reviewed. One hundred and sixteen potentially relevant articles were inspected in more detail, and 14 retrospective studies met eligibility criteria. Dilation group included 10 studies on anterograde and/or retrograde dilation, with an overall 208 patients. Success rate ranged from 42% to 100%. The endoscopic CPM group included 3 studies with a total of 36 patients, and the success rate ranged from 27% to 90%. In the Botox group, 1 one study with 20 patients met our inclusion criteria, with an overall 65% success rate (13/20). Major complications were only reported in the dilation group, which included esophageal perforation and death.CONCLUSIONS:: The lack of consistency across trials indicates insufficient evidence for guiding clinical practice. This systematic review suggests the need for greater standardization of outcomes and instruments. Future prospective evaluation should use validated patient-rated and clinician-rated assessment tools to optimally measure postoperative swallowing outcomes of head and neck cancer dysphagic patients following organ preservation therapy.

  View details for PubMedID 30895823

• A Preliminary Study of Vocal Health Among Collegiate A Cappella Singers. Journal of voice : official journal of the Voice Foundation Baird, B. J., Mokhtari, T. E., Sung, C. K., Erickson-DiRenzo, E. 2018

  Abstract

  OBJECTIVE: Collegiate a cappella groups have grown significantly in popularity and prominence; however, there have been few studies that evaluate the vocal health of this subgroup of young singers. The objective of this preliminary study was to conduct a multiparametric evaluation of the vocal health characteristics of a sample of collegiate a cappella singers. We further tested whether differences in vocal health assessments exist between a cappella singers with and without vocal training and trained collegiate singers who do not participate in a cappella groups.STUDY DESIGN: Point prevalence study.METHODS: Forty-one collegiate singers participated in this study. Participants were divided into the following three groups: trained singers (TS), trained a cappella singers (ATS), and untrained a cappella singers (AUS). Participants were administered a set of surveys to assess self-perception of singing voice health and perceived access and attitudes toward voice-related health care. Acoustic and laryngoscopic assessments of participant's speaking and singing voice was performed and validated vocal health questionnaires administered as a means to objectively evaluate for the presence of voice problems.RESULTS: Overall, 87.5% of the ATS and 60% of the AUS groups reported experiencing problems with their singing voice. However, no vocal abnormalities were detected during laryngoscopic and acoustic assessments. Furthermore, minimal differences between any of the measured vocal health parameters were observed between the TS, ATS, and AUS groups.CONCLUSION: Collectively, a high percentage of collegiate a cappella singers with and without vocal training report singing voice problems. However, our sample of a cappella singers did not have increased singing voice problems as compared to vocally trained collegiate singers not in a cappella groups. We did find that a cappella singers may be more inclined to seek information about maintaining a healthy singing voice from their fellow musicians as opposed to singing teachers or other voice health professionals. Singing teachers, otolaryngologists, and speech-language pathologists may need to play a more active role in educating a cappella singers regarding maintaining good vocal health.

  View details for PubMedID 30442529

• Biocompatibility of injectable resilin-based hydrogels. Journal of biomedical materials research. Part A Li, L., Stiadle, J. M., Levendoski, E. E., Lau, H. K., Thibeault, S. L., Kiick, K. L. 2018; 106 (8): 2229-2242

  Abstract

  Vocal folds are connective tissues housed in the larynx, which can be subjected to various injuries and traumatic stimuli that lead to aberrant tissue structural alterations and fibrotic-induced biomechanical stiffening observed in patients with voice disorders. Much effort has been devoted to generate soft biomaterials that are injectable directly to sites of injury. To date, materials applied toward these applications have been largely focused on natural extracellular matrix-derived materials such as collagen, fibrin or hyaluronic acid; these approaches have suffered from the fact that materials are not sufficiently robust mechanically nor offer sufficient flexibility to modulate material properties for targeted injection. We have recently developed multiple resilin-inspired elastomeric hydrogels that possess similar mechanical properties as those reported for vocal fold tissues, and that also show promising in vitro cytocompatibility and in vivo biocompatibility. Here we report studies that test the delivery of resilin-based hydrogels through injection to the subcutaneous tissue in a wild-type mice model; histological and genetic expression outcomes were monitored. The rapid kinetics of crosslinking enabled facile injection and ensured the rapid transition of the viscous resilin precursor solution to a solid-like hydrogel in the subcutaneous space in vivo; the materials exhibited storage shear moduli in the range of 1000-2000 Pa when characterized through oscillatory rheology. Histological staining and gene expression profiles suggested minimal inflammatory profiles three weeks after injection, thereby demonstrating the potential suitability for site-specific in vivo injection of these elastomeric materials. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2229-2242, 2018.

  View details for DOI 10.1002/jbm.a.36418

  View details for PubMedID 29611890

  View details for PubMedCentralID PMC6030450

• Phonomicrosurgery simulation: A low-cost teaching model using easily accessible materials. Laryngoscope Zambricki, E. A., Bergeron, J. L., DiRenzo, E. E., Sung, C. K. 2016; 126 (11): 2528-2533

  Abstract

  To introduce the use of a new phonomicrosurgical trainer using easily accessible materials, and to establish the effectiveness of the model.The model uses a grape imbedded in gelatin, a microscope, and microlaryngeal instruments. The study was designed to test baseline differences in training levels, as well as improvement in performance after training with the simulation model.Thirty subjects enrolled in the Stanford University School of Medicine otolaryngology training program performed microlaryngeal surgery tasks on a grape. Tasks were designed to model both excision of a vocal fold lesion and vocal fold injection. Anonymized video recordings comparing presimulation and postsimulation training were collected and graded by an expert laryngologist. Both objective comparison of skills and subjective participant surveys were analyzed.Objectively, trainees in all groups made statistically significant improvements across all tested variables, including microscope positioning, creation of a linear incision, elevation of epithelial flaps, excision of a crescent of tissue, vocal fold injection, preservation of remaining tissue, and time to complete all tasks. Subjectively, 100% of participants felt that they had increased comfort with microlaryngeal instruments and decreased intimidation of microlaryngeal surgery after completing the simulation training. This appreciation of skills was most notable and statistically significant in the intern trainees.Microlaryngeal surgical simulation is a tool that can be used to train residents to prepare them for phonomicrosurgical procedures at all levels of training. Our low-cost model with accessible materials can be easily duplicated and used to introduce trainees to microlaryngeal surgery or improve skills of more senior trainees.1B. Laryngoscope, 2016.

  View details for DOI 10.1002/lary.25940

  View details for PubMedID 27107403

• Vocal Tremor: Novel Therapeutic Target for Deep Brain Stimulation. Brain sciences Ravikumar, V. K., Ho, A. L., Parker, J. J., Erickson-DiRenzo, E., Halpern, C. H. 2016; 6 (4)

  Abstract

  Tremulous voice is characteristically associated with essential tremor, and is referred to as essential vocal tremor (EVT). Current estimates suggest that up to 40% of individuals diagnosed with essential tremor also present with EVT, which is associated with an impaired quality of life. Traditional EVT treatments have demonstrated limited success in long-term management of symptoms. However, voice tremor has been noted to decrease in patients receiving deep brain stimulation (DBS) with the targeting of thalamic nuclei. In this study, we describe our multidisciplinary procedure for awake, frameless DBS with optimal stimulation targets as well as acoustic analysis and laryngoscopic assessment to quantify tremor reduction. Finally, we investigate the most recent clinical evidence regarding the procedure.

  View details for PubMedID 27735866

• Early Cellular Response to Radiation in Human Vocal Fold Fibroblasts. The Annals of otology, rhinology, and laryngology Erickson-DiRenzo, E., Enos, G., Thibeault, S. L. 2016; 125 (5): 425-432

  Abstract

  Radiation therapy is a common treatment strategy for laryngeal carcinoma. However, radiation is not without adverse side effects, especially toward healthy vocal fold tissue, which can lead to long-term impairments in vocal function. The objective of this preliminary study was to investigate early responses of healthy human vocal fold fibroblasts (VFF) to radiation.VFF were exposed to a single or fractionated dose radiation scheme. Nonradiated VFF served as controls. Morphology of radiated and control VFF was subjectively examined. Quantitative polymerase chain reaction was used to evaluate the effect of radiation on extracellular matrix and inflammatory-related genes. VFF viability was investigated using a LIVE/DEAD and clonogenic assay.Single or fractioned dose radiated VFF were morphologically indistinguishable from control VFF. No significant differences in gene expression were observed following either radiation scheme and as compared to controls. Clonogenic assay revealed reduced VFF viability following the fractionated but not single dose scheme. No changes in viability were detected using the LIVE/DEAD assay.We present one of the first investigations to evaluate early responses of healthy VFF to radiation. Findings will contribute to a growing body of literature seeking to elucidate the biological mechanisms underlying voice changes following radiation therapy for laryngeal carcinoma.

  View details for DOI 10.1177/0003489415615140

  View details for PubMedID 26553661

• Deep brain stimulation for vocal tremor: a comprehensive, multidisciplinary methodology NEUROSURGICAL FOCUS Ho, A. L., Erickson-DiRenzo, E., Pendharkar, A. V., Sung, C., Halpern, C. H. 2015; 38 (6)

  Abstract

  Tremulous voice is a characteristic feature of a multitude of movement disorders, but when it occurs in individuals diagnosed with essential tremor, it is referred to as essential vocal tremor (EVT). For individuals with EVT, their tremulous voice is associated with significant social embarrassment and in severe cases may result in the discontinuation of employment and hobbies. Management of EVT is extremely difficult, and current behavioral and medical interventions for vocal tremor result in suboptimal outcomes. Deep brain stimulation (DBS) has been proposed as a potential therapeutic avenue for EVT, but few studies can be identified that have systematically examined improvements in EVT following DBS. The authors describe a case of awake bilateral DBS targeting the ventral intermediate nucleus for a patient suffering from severe voice and arm tremor. They also present their comprehensive, multidisciplinary methodology for definitive treatment of EVT via DBS. To the authors' knowledge, this is the first time comprehensive intraoperative voice evaluation has been used to guide microelectrode/stimulator placement, as well as the first time that standard pre- and post-DBS assessments have been conducted, demonstrating the efficacy of this tailored DBS approach.

  View details for DOI 10.3171/2015.3.FOCUS1537

  View details for Web of Science ID 000355539900006

  View details for PubMedID 26030706

• Utility of cell viability assays for use with ex vivo vocal fold epithelial tissue. Laryngoscope Erickson-DiRenzo, E., Sivasankar, M. P., Thibeault, S. L. 2015; 125 (5): E180-5

  Abstract

  Ex vivo models are routinely used to investigate the barrier function of the vocal fold epithelium. However, there are limited reports on assays that can be used to investigate the effect of clinically relevant challenges on vocal fold epithelial tissue viability. Our objective was to determine the utility of two assays routinely used in cell culture-a cellular metabolic activity assay and a cell membrane integrity assay-to investigate the viability of ex vivo porcine vocal fold epithelium.Prospective, ex vivo animal study.Porcine vocal folds were exposed to acrolein, hydrochloric acid, or hydrogen peroxide challenge. An untreated, sham challenge was included as a control. Assays including metabolic activity, cell membrane integrity, and histology were used to determine whether challenges reduced epithelial viability as compared to sham.Cell membrane integrity and metabolic activity assays detected reductions in viability following hydrochloric acid and hydrogen peroxide challenges but not acrolein challenge as compared to sham. No challenge produced significant changes in epithelial appearance as evidenced by light microscopy.Metabolic activity and cell membrane integrity assays are valuable tools that can be used to evaluate the viability of ex vivo vocal fold epithelial tissue following clinically relevant challenges. As viability is reduced, the ability of epithelial tissue to maintain its barrier function is compromised. Accurate assessment of viability may provide us clues into understanding mechanisms underlying vocal fold epithelial injury and disease.NA Laryngoscope, 125:E180-E185, 2015.

  View details for DOI 10.1002/lary.25100

  View details for PubMedID 25511412

• Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report. Cureus Ho, A. L., Choudhri, O., Sung, C. K., DiRenzo, E. E., Halpern, C. H. 2015; 7 (3)

  Abstract

  Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS).

  View details for DOI 10.7759/cureus.256

  View details for PubMedID 26180680

• A preliminary investigation of potential biases in phonation threshold pressure analysis. Journal of voice Sundarrajan, A., Erickson-Levendoski, E., Sivasankar, M. P. 2015; 29 (1): 22-25

  Abstract

  Phonation threshold pressure (PTP) is a voice measure used in both research and clinic. PTP data analysis is susceptible to bias from investigator awareness of experimental hypothesis, and poor investigator training. The objective of this study was to systematically examine the role of these two biases on PTP data analysis.Prospective design.Two trained investigators analyzed PTP datasets. The datasets were identical, but uniquely labeled so that the investigators were not aware that the datasets contained the same data. Each investigator analyzed two datasets. For one dataset, investigators were "blinded" to the experimental hypothesis. For the other dataset, the investigators were "unblinded" and provided a fake experimental hypothesis. Intraclass correlations were used to examine intrarater and interrater reliability.For both investigators, intraclass correlations within the excellent range were obtained for intrarater reliability. In contrast, lower intraclass correlations were obtained for interrater reliability.The high intrarater reliability obtained in this preliminary study suggests that awareness of experimental hypothesis may not significantly bias PTP analysis. Conversely, lower interrater reliability is indicative of differences between investigators analyzing the same data. Our findings contribute to the growing body of literature that seeks to standardize the use of PTP in research and the clinic. Future investigations are needed to identify methods to improve interrater reliability and that quantify the effects of biases on PTP data collection.

  View details for DOI 10.1016/j.jvoice.2014.07.001

  View details for PubMedID 25484262

• Vocal fold epithelial barrier in health and injury: a research review. Journal of speech, language, and hearing research : JSLHR Levendoski, E. E., Leydon, C., Thibeault, S. L. 2014; 57 (5): 1679-91

  Abstract

  Vocal fold epithelium is composed of layers of individual epithelial cells joined by junctional complexes constituting a unique interface with the external environment. This barrier provides structural stability to the vocal folds and protects underlying connective tissue from injury while being nearly continuously exposed to potentially hazardous insults, including environmental or systemic-based irritants such as pollutants and reflux, surgical procedures, and vibratory trauma. Small disruptions in the epithelial barrier may have a large impact on susceptibility to injury and overall vocal health. The purpose of this article is to provide a broad-based review of current knowledge of the vocal fold epithelial barrier.A comprehensive review of the literature was conducted. Details of the structure of the vocal fold epithelial barrier are presented and evaluated in the context of function in injury and pathology. The importance of the epithelial-associated vocal fold mucus barrier is also introduced.Information presented in this review is valuable for clinicians and researchers as it highlights the importance of this understudied portion of the vocal folds to overall vocal health and disease. Prevention and treatment of injury to the epithelial barrier is a significant area awaiting further investigation.

  View details for DOI 10.1044/2014_JSLHR-S-13-0283

  View details for PubMedID 24686981

• Reducing the negative vocal effects of superficial laryngeal dehydration with humidification. The Annals of otology, rhinology, and laryngology Levendoski, E. E., Sundarrajan, A., Sivasankar, M. P. 2014; 123 (7): 475-81

  Abstract

  Environmental humidification is a simple, cost-effective method believed to reduce superficial laryngeal drying. This study sought to validate this belief by investigating whether humidification treatment would reduce the negative effects of superficial laryngeal dehydration on phonation threshold pressure (PTP). Phonation threshold pressure data analysis may be vulnerable to bias because of lack of investigator blinding. Consequently, this study investigated the extent of PTP analysis reliability between unblinded and blinded investigators.Healthy male and female adults were assigned to a vocal fatigue (n = 20) or control group (n = 20) based on their responses to a questionnaire. PTP was assessed after 2 hours of mouth breathing in low humidity (dehydration challenge), following a 5-minute break in ambient humidity, and after 2 hours of mouth breathing in high humidity (humidification).PTP significantly increased following the laryngeal dehydration challenge. After humidification, PTP returned toward baseline. These effects were observed in both subject groups. PTP measurements were highly correlated between the unblinded and blinded investigator.Humidification may be an effective approach to decrease the detrimental voice effects of superficial laryngeal dehydration. These data lay the foundation for future investigations aimed at preventing and treating the negative voice changes associated with chronic, surface laryngeal drying.

  View details for DOI 10.1177/0003489414527230

  View details for PubMedID 24690983

• Vocal Fold Ion Transport and Mucin Expression Following Acrolein Exposure JOURNAL OF MEMBRANE BIOLOGY Levendoski, E. E., Sivasankar, M. P. 2014; 247 (5): 441-450

  Abstract

  The vocal fold epithelium is exposed to inhaled particulates including pollutants during breathing in everyday environments. Yet, our understanding of the effects of pollutants on vocal fold epithelial function is extremely limited. The objective of this study was to investigate the effect of the pollutant acrolein on two vocal fold epithelial mechanisms: ion transport and mucin (MUC) synthesis. These mechanisms were chosen as each plays a critical role in vocal defense and in maintaining surface hydration which is necessary for optimal voice production. Healthy, native porcine vocal folds (N = 85) were excised and exposed to an acrolein or sham challenge. A 60-min acrolein, but not sham challenge significantly reduced ion transport and inhibited cyclic adenosine monophosphate-dependent, increases in ion transport. Decreases in ion transport were associated with reduced sodium absorption. Within the same timeline, no significant acrolein-induced changes in MUC gene or protein expression were observed. These results improve our understanding of the effects of acrolein on key vocal fold epithelial functions and inform the development of future investigations that seek to elucidate the impact of a wide range of pollutant exposures on vocal fold health.

  View details for DOI 10.1007/s00232-014-9651-2

  View details for Web of Science ID 000334426600008

  View details for PubMedID 24648011

• Influence of Obligatory Mouth Breathing, During Realistic Activities, on Voice Measures JOURNAL OF VOICE Sivasankar, M. P., Erickson-Levendoski, E. 2012; 26 (6)

  Abstract

  Low humidity environments and mouth breathing may contribute to superficial vocal fold dehydration. The purpose of this study was to investigate the effects of obligatory mouth breathing, during daily activities in low- and high-humidity environments, on voice measures. The activities included 15 minutes of obligatory mouth breathing alone, during loud reading and during exercise. The effects of mouth breathing and humidity were compared in subjects who either reported or did not report vocal worsening after heavy voice use.Prospective, between-group, repeated-measures design.Sixty-three healthy adults with normal respiratory function and perceptually normal voice participated in this study. Thirty-one subjects reported symptoms of voice worsening with heavy voice use. Thirty-two subjects who did not report these symptoms participated as controls. Phonation threshold pressure and perceived phonatory effort were measured at baseline and after each obligatory mouth breathing challenge. Ambient humidity was set to either low or high humidity.Obligatory mouth breathing in loud reading and exercise significantly increased phonation threshold pressure when compared with mouth breathing alone. This increase in phonation threshold pressure was observed at low and high humidity, in both subject groups. There were no significant effects for perceived phonatory effort.Obligatory mouth breathing during loud reading and exercise negatively impact phonation threshold pressure. Future investigations that include longer challenge durations, and subjects with voice disorders, are needed to elucidate the underlying mechanisms for increases in phonation threshold pressure.

  View details for DOI 10.1016/j.jvoice.2012.03.007

  View details for Web of Science ID 000311428300028

  View details for PubMedID 22921296

• Role for Ion Transport in Porcine Vocal Fold Epithelial Defense to Acid Challenge OTOLARYNGOLOGY-HEAD AND NECK SURGERY Erickson-Levendoski, E., Sivasankar, M. P. 2012; 146 (2): 272-278

  Abstract

  The vocal fold epithelium is routinely exposed to gastric contents, including acid and pepsin, during laryngopharyngeal reflux events. The epithelium may possess intrinsic defenses to reflux. The first objective of the current study was to examine whether vocal fold epithelial ion transport is one potential mechanism of defense to gastric contents. The second objective was to determine whether ion transport in response to gastric contents is associated with the secretion of bicarbonate.Prospective design in excised porcine larynges.Laboratory.Porcine vocal folds (N = 56) were exposed on the luminal surface to acid, pepsin, or sham challenges. Ion transport at baseline and following challenge exposure was measured using electrophysiological techniques. To examine specific ion transport mechanisms, vocal folds were pretreated with either a sodium channel blocker or bicarbonate channel blocker.Within 60 seconds of acid but not pepsin exposure, there was a significant increase in ion transport. This rapid increase in ion transport was transient and related to bicarbonate secretion.The current data suggest that porcine vocal folds immediately increase bicarbonate secretion following exposure to acid. Bicarbonate secretion may act to neutralize acid. These findings contribute to the identification of the mechanisms underlying vocal fold defense to reflux and offer implications for the development of treatments for reflux-induced vocal fold injury.

  View details for DOI 10.1177/0194599811428273

  View details for Web of Science ID 000303541300017

  View details for PubMedID 22086905

• Acute Stress to Excised Vocal Fold Epithelium From Reactive Oxygen Species Combined Otolaryngology Spring Meeting (COSM)/132nd Annual Meeting of the American-Laryngological-Association/Annual Meeting of the American-Otological-Society Alper, R., Fu, X., Erickson-Levendoski, E., Zheng, W., Sivasankar, M. WILEY-BLACKWELL. 2011: 2180–84

  Abstract

  Vocal fold epithelium is exposed to reactive oxygen species from the inhaled environment and from tissue inflammation. The objective of this study was to explore the functional and structural consequences of reactive oxygen species exposure on vocal fold epithelium.In vitro, prospective study design.Hydrogen peroxide (H(2)O(2)), a common reactive oxygen species, was utilized in this study. Freshly excised, viable porcine vocal fold epithelia (N = 32) were exposed to H(2) O(2) or sham challenge for 2 hours. Electrophysiology, western blotting, and light microscopy were used to quantify the functional and structural effects of reactive oxygen species on vocal fold epithelia.Exposure to reactive oxygen species did not significantly alter transepithelial resistance. There was a small, nonsignificant trend for decreased concentration of epithelial junctional complex protein with reactive oxygen species challenge. Minimal changes to the gross structural appearance of vocal fold epithelia were also noted.The stratified squamous epithelia of the vocal folds effectively defend against an acute reactive oxygen species challenge. The current study lays the groundwork for future investigations on the effects of reactive oxygen species on vocal fold epithelia that are compromised from phonotrauma.

  View details for DOI 10.1002/lary.22157

  View details for Web of Science ID 000295228800025

  View details for PubMedID 21898441

• Investigating the Effects of Caffeine on Phonation JOURNAL OF VOICE Erickson-Levendoski, E., Sivasankar, M. 2011; 25 (5): E215-E219

  Abstract

  A core component of vocal hygiene programs is the avoidance of agents that may dry the vocal folds. Clinicians commonly recommend that individuals reduce caffeine intake because of its presumed dehydrating effects on the voice. However, there is little evidence that ingestion of caffeine is detrimental to voice production. The first objective of this study was to evaluate whether caffeine adversely affects voice production. The second objective was to evaluate if caffeine exacerbates the adverse phonatory effects of vocal loading.Prospective, double-blinded, sham-controlled study.Sixteen healthy adults participated in two sessions where they consumed caffeine (caffeine concentration=480 mg) or sham (caffeine concentration=24 mg) beverages. Voice measures (phonation threshold pressure and perceived phonatory effort) were collected. Subjects then completed a vocal loading challenge and voice measures were obtained again.There were no significant differences in voice measures between the caffeine and sham conditions. Ingestion of caffeine did not adversely affect voice production (P>0.05) or exacerbate the detrimental phonatory effects of vocal loading (P>0.05).Our findings contribute to emerging knowledge on the effects of caffeine on voice production. Recommendations to completely eliminate caffeine from the diet, as a component of a vocal hygiene program, should be evaluated on an individual basis.

  View details for DOI 10.1016/j.jvoice.2011.02.009

  View details for Web of Science ID 000307778900002

  View details for PubMedID 21704493

• Simulated Reflux Decreases Vocal Fold Epithelial Barrier Resistance Annual Meeting of the American-Laryngological-Association Erickson, E., Sivasankar, M. WILEY-BLACKWELL. 2010: 1569–75

  Abstract

  The vocal fold epithelium provides a barrier to the entry of inhaled and systemic challenges. However, the location of the epithelium makes it vulnerable to damage. Past research suggests, but does not directly demonstrate, that exposure to gastric reflux adversely affects the function of the epithelial barrier. Understanding the nature of reflux-induced epithelial barrier dysfunction is necessary to better recognize the mechanisms for vocal fold susceptibility to this disease. Therefore, we examined the effects of physiologically relevant reflux challenges on vocal fold transepithelial resistance and gross epithelial and subepithelial appearance.Ex vivo, mixed design with between-group and repeated-measures analyses.Healthy, native porcine vocal folds (N = 52) were exposed to physiologically relevant acidic pepsin, acid-only, or pepsin-only challenges and examined with electrophysiology and light microscopy. For all challenges, vocal folds exposed to a neutral pH served as control.Acidic pepsin and acid-only challenges, but not pepsin-only or control challenges significantly reduced transepithelial resistance within 30 minutes. Reductions in transepithelial resistance were irreversible. Challenge exposure produced minimal gross changes in vocal fold epithelial or subepithelial appearance as evidenced by light microscopy.These findings demonstrate that acidic environments characteristic of gastric reflux compromise epithelial barrier function without gross structural changes. In healthy, native vocal folds, reductions in transepithelial resistance could reflect reflux-related epithelial disruption. These results might guide the development of pharmacologic and therapeutic recommendations for patients with reflux, such as continued acid-suppression therapy and patient antireflux behavioral education.

  View details for DOI 10.1002/lary.20983

  View details for Web of Science ID 000280695000014

  View details for PubMedID 20564752

• Evidence for Adverse Phonatory Change Following an Inhaled Combination Treatment JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH Erickson, E., Sivasankar, M. 2010; 53 (1): 75-83

  Abstract

  Voice problems are reported as a frequent side effect of inhaled combination (IC) treatments. The purpose of this experimental study was to investigate whether IC treatments are detrimental to phonation. We hypothesized that IC treatment would significantly increase phonation threshold pressure (PTP) and perceived phonatory effort (PPE), whereas sham treatment would not.Fourteen healthy adults participated in a repeated-measures design in which they received IC and sham treatments in counterbalanced order. PTP and PPE were measured prior to treatments, immediately following treatments, and at 1 and 2 hr following treatments.IC treatment increased PTP, but sham treatment did not. The increase in PTP was maintained for a 2 hr period following administration. PPE ratings were not significantly correlated with PTP.IC treatments can have acute, adverse effects on phonation. Detrimental phonatory effects were elicited in participants with no self-reported voice problems. IC treatments are being increasingly prescribed across the lifespan. The current data increase our understanding of the nature of phonatory deterioration associated with IC treatment and lay the groundwork for increased research effort to develop IC treatments that effectively control respiratory disease while minimizing an adverse effect on phonation.

  View details for DOI 10.1044/1092-4388(2009/09-0024)

  View details for Web of Science ID 000275168300006

  View details for PubMedID 19696437

• Hypertonic challenge to porcine vocal folds: Effects on epithelial barrier function OTOLARYNGOLOGY-HEAD AND NECK SURGERY Sivasankar, M., Erickson, E., Rosenblatt, M., Branski, R. C. 2010; 142 (1): 79-84

  Abstract

  Dehydration challenges can increase the chemical composition of surface fluid overlying vocal fold epithelia (hypertonic surface fluid). The vocal fold epithelium is posited to act as a barrier, shielding the lamina propria from perturbations in the airway lumen. However, the effects of hypertonic surface fluid on the barrier functions of vocal fold epithelia have not been quantified. We, therefore, sought to investigate whether hypertonic surface fluid compromises epithelial barrier function. We examined the effects of hypertonic surface fluid on vocal fold epithelial resistance, paracellular pathway morphology, and tight junction protein integrity.Ex vivo, between group design.Laboratory.Porcine vocal folds (n = 24) were exposed to hypertonic or isotonic challenge and examined by electrophysiology, transmission electron microscopy, and Western blot analyses.Hypertonic, but not isotonic, challenge significantly reduced transepithelial resistance. This decrease in resistance was observed immediately after the challenge and was consistent with the appearance of dilated paracellular pathway morphology. However, hypertonic challenge did not alter protein levels of occludin, zona occludens-1, E-cadherin, or beta-catenin.Hypertonic surface fluid alters epithelial barrier function in the vocal folds. Specifically, exposure to hypertonic challenges increases epithelial permeability. Given the important role of the vocal fold epithelium in shielding the underlying mucosa from inhaled pathogens and pollutants, our data provide the impetus for future studies on pharmacological treatments aimed at restoring the hydration level and chemical composition of vocal fold surface fluid.

  View details for DOI 10.1016/j.otohns.2009.09.011

  View details for Web of Science ID 000276574200014

  View details for PubMedID 20096227

• Short-Duration Accelerated Breathing Challenges Affect Phonation Annual Convention of the American-Speech-Language-Hearing-Association Sivasankar, M., Erickson, E. JOHN WILEY & SONS INC. 2009: 1658–63

  Abstract

  Inhaled air must be adequately humidified to prevent vocal fold drying, which is detrimental to phonation. The water content of inspired air is reduced by parameters, such as increased breathing rate and oral route. Accelerated oral breathing challenges induce airway dehydration and are posited to affect airway function. The primary objective of this study was to investigate whether accelerated oral breathing challenges are detrimental to phonation. The secondary objective of this study was to determine whether individuals at increased risk for developing voice problems (i.e., smokers) have greater adverse phonatory effects after accelerated breathing challenge than nonsmoking controls.Prospective study with between-subjects, repeated-measures design.Female smokers (n = 12) and nonsmoking controls (n = 12) participated in this experimental study over 2 days that differed in ambient humidity. Phonation threshold pressures (PTP) were collected prior to and following short-term accelerated and habitual breathing challenges. Respiratory measures were collected during the challenges.Short-term accelerated breathing challenges significantly increased PTP. This increase in PTP with accelerated breathing was transient and not significantly influenced by breathing route, ambient humidity, or smoking status. Likewise, respiratory measures were not affected by breathing route, ambient humidity, or smoking status.During daily activities, such as exercise, individuals may engage in accelerated breathing for prolonged durations. This study demonstrates that even extremely short durations of accelerated breathing may affect phonation.

  View details for DOI 10.1002/lary.20530

  View details for Web of Science ID 000268739500033

  View details for PubMedID 19522007

• Phonatory Effects of Airway Dehydration: Preliminary Evidence for Impaired Compensation to Oral Breathing in Individuals With a History of Vocal Fatigue JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH Sivasankar, M., Erickson, E., Schneider, S., Hawes, A. 2008; 51 (6): 1494-1506

  Abstract

  Airway drying is detrimental to phonation and is posited to exacerbate vocal fatigue. However, limited research has demonstrated the adverse phonatory effects of dehydration in speakers reporting vocal fatigue. We compared the negative phonatory consequences of short-term oral breathing at low, moderate, and high humidity in individuals reporting a history of vocal fatigue and control participants.Females reporting a history of vocal fatigue (N = 8) and matched controls (N = 8) participated in a repeated-measures design over 3 different days.Oral breathing at low and moderate humidity increased phonation threshold pressure (PTP) to a greater extent in individuals reporting a history of vocal fatigue as compared to controls. Conversely, PTP did not increase in either participant group after oral breathing in a humid environment. Perceived phonatory effort (PPE) ratings were poorly correlated with PTP.The emergence of between-group differences in PTP at low and moderate but not high ambient humidity demonstrates that drying challenges might be detrimental to voice production in individuals with a history of vocal fatigue. Based on the phonatory effects of dehydration, we suggest that individuals reporting vocal fatigue may demonstrate impaired compensation to airway drying induced by short-term oral breathing.

  View details for DOI 10.1044/1092-4388(2008/07-0181)

  View details for Web of Science ID 000261196100009

  View details for PubMedID 18664688