Mahalakshmi Sivasankar

Vocal fold surface hydration: a review.

Vocal fold surface liquid homeostasis contributes to optimal vocal physiology. In this paper we review emerging evidence that vocal fold surface liquid is maintained in part by salt and water fluxes across the epithelium. Based on recent immunolocalization and electrophysiological findings, we describe a transcellular pathway as one mechanism for regulating superficial vocal fold hydration. We propose that the pathway includes the sodium-potassium pump, sodium-potassium-chloride cotransporter, epithelial sodium channels, cystic fibrosis transmembrane regulator chloride channels, and aquaporin water channels. By integrating knowledge of the regulating mechanisms underlying ion and fluid transport with observations from hydration challenges and treatments using in vitro and in vivo studies, we provide a theoretical basis for understanding how environmental and behavioral challenges and clinical interventions may modify vocal fold surface liquid composition. We present converging evidence that clinical protocols directed at facilitating vocal fold epithelial ion and fluid transport may benefit healthy speakers, those with voice disorders, and those at risk for voice disorders.

Simulated reflux decreases vocal fold epithelial barrier resistance.

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.

The role of hydration in vocal fold physiology

Purpose of reviewIncreased vocal fold hydration is a popular target in the prevention and management of voice disorders. Current intervention strategies focus on enhancing both systemic (internal) and superficial (surface) hydration. We review relevant bench and human research on the role of hydration in vocal fold physiology. Recent findingsBench and human studies provide converging evidence that systemic and superficial dehydration are detrimental to vocal fold physiology. Dehydration challenges increase the viscous properties of excised vocal fold tissue. Systemic, superficial, and combined drying challenges increase aerodynamic and acoustic measures of voice production in speakers. Emerging theoretical and clinical data suggest that increasing both systemic and superficial hydration levels may benefit voice production; however, robust evidence for positive outcomes of hydration treatments is lacking. SummaryIncreased systemic and superficial vocal fold hydration as a component of vocal hygiene may improve overall health and efficiency of the vocal apparatus. However, continued exploration of biological mechanisms regulating vocal fold hydration is needed to optimize clinical hydration interventions. Specifically, the development of hydration treatments that maximize positive phonatory outcomes will necessitate understanding of the signaling pathways linking systemic and superficial hydration.

Hypertonic challenge to porcine vocal folds: effects on epithelial barrier function.

OBJECTIVE: 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. STUDY DESIGN: Ex vivo, between group design. SETTING: Laboratory. METHODS: Porcine vocal folds (n = 24) were exposed to hypertonic or isotonic challenge and examined by electrophysiology, transmission electron microscopy, and Western blot analyses. RESULTS: 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 β-catenin. CONCLUSION: 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.

Raised intensity phonation compromises vocal fold epithelial barrier integrity.

We investigated the hypothesis that 30 minutes of raised intensity phonation alters transcript levels of vocal fold intercellular tight junction proteins and disrupts the vocal fold epithelial barrier.

Investigating the Effects of Caffeine on Phonation

OBJECTIVE 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. STUDY DESIGN Prospective, double-blinded, sham-controlled study. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Short-Duration Accelerated Breathing Challenges Affect Phonation

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.

A Meta-Analysis of Outcomes of Hydration Intervention on Phonation Threshold Pressure

OBJECTIVES Vocal fold hydration is purported to promote optimal biomechanical characteristics of vocal fold mucosa, increase efficiency of vocal fold oscillation, and enhance voice quality. The purpose of this work was to determine the magnitude and consistency of the effect of vocal fold hydration on vocal fold function across published clinical studies. METHODS We completed a comprehensive meta-analysis of the effects of superficial and systemic vocal fold hydration on phonation threshold pressure (PTP), a measure of efficiency of voice production. RESULTS We identified 34 studies that examined the effects of hydration on vocal function. Of these studies, 14 examined the effects of hydration on PTP. Nine of these articles met the criteria for inclusion in this analysis. We observed an average effect size of 0.33, indicating that, overall, hydration treatment demonstrated a tendency to reduce PTP. However, this decrease in phonatory effort did not reach significance at the 95% confidence level. The effects of hydration intervention varied considerably across studies (-0.19 to 3.96). We considered that two factors, pitch level of the task and vocal health of participants, may have contributed to this variability in findings. However, our analysis found that these factors could not account for differences in effect size. CONCLUSION To understand the variability in outcomes across studies, the role of factors that may impact the effects of hydration, such as the amount, type, and duration of intervention, must be determined. Only then can we obtain data to guide best clinical practice for protecting and rehabilitating vocal function.

Glucocorticoids regulate extracellular matrix metabolism in human vocal fold fibroblasts

Given the recent emergence of encouraging efficacy data regarding the utility of intralesional glucocorticoid (GC) injection for a variety of vocal fold pathologies, we sought to describe the location and expression pattern of the GC receptors within the vocal folds and quantify the effects of GCs on vocal fold fibroblasts.

The effects of cigarette smoke condensate on vocal fold transepithelial resistance and inflammatory signaling in vocal fold fibroblasts.

In response to chronic cigarette smoke exposure, a subset of patients present with edematous vocal folds, characteristically referred to as Reinkes edema. This phenotype differs from the tissue changes associated with prolonged smoke exposure in the lower airway, and the mechanism underlying Reinkes edema remains poorly described. We hypothesize that the effects of smoke are diffuse and involve both the epithelium and mucosa.