Regulation of vocal fold transepithelial water fluxes.

Vocal fold hydration is critical to phonation. We hypothesized that the vocal fold generates bidirectional water fluxes, which are regulated by activity of the Na(+)-K(+)- ATPase. Western blots and immunohistochemistry demonstrated the presence of the alpha-subunit Na(+)-K(+)-ATPase in the canine vocal fold (n = 11). Luminal cells, basal and adjacent one to two layers of suprabasal cells within stratified squamous epithelium, were immunopositive, as well as basolateral membranes of submucosal seromucous glands underlying transitional epithelia. Canine (n = 6) and ovine (n = 14) vocal fold mucosae exhibited transepithelial potential differences of 8.1 +/- 2.8 and 9.3 +/- 1.3 mV (lumen negative), respectively. The potential difference and short-circuit current (ovine = 31 +/- 4 microA/cm(2); canine = 41 +/- 10 microA/cm(2)) were substantially reduced by luminal administration of 75 microM acetylstrophanthidin (P < 0.05). Ovine (n = 7) transepithelial water fluxes decreased from 5.1 +/- 0.3 to 4.3 +/- 0.3 microl x min(-1) x cm(-2) from the basal to luminal chamber and from 5.2 +/- 0.2 to 3.9 +/- 0.3 microl x min(-1) x cm(-2) from the luminal to basal chamber by luminal acetylstrophanthidin (P < 0.05). The presence of the Na(+)-K(+)-ATPase in the vocal fold epithelium and the electrolyte transport derived from its activity provide the intrinsic mechanisms to regulate cell volume as well as vocal fold hydration.

Phonatory effects of body fluid removal.

Adequate body and vocal fold hydration are believed to be critical to phonation. We hypothesized that body fluid reduction, without dehydration, would increase phonation threshold pressure (P(th)) and be associated with patient-perceived increases in phonatory effort and worsening voice quality. Using a single-subject, full-reversal design, a controlled volume of body fluid was repeatedly removed via ultrafiltration from adults with end stage renal disease (2 women, 4 men, ages 40-85 yrs). Two additional men (ages 81 and 68 yrs) served as placebo and healthy true controls, respectively. P(th), vocal effort and quality, blood pressure, and heart rate were assessed longitudinally. P(th) increased significantly with fluid volume reduction (3-4% of body weight from a hypervolemic to a grossly normovolemic body state) and reversed to baseline with fluid replacement in 4 of 6 treated subjects. Effects were observed with net ultrafiltration rates greater than or equal to 1.0 L/h; these effects were not observed in control subjects. Fluid loss accounted for 31.6% of variance in P(th) and 40.0% of variance in perceived vocal effort. Heart rate, systolic blood pressure, and/or diastolic blood pressure were significantly correlated with P(th) or fluid volume reduction in 6 subjects, including the placebo control (-.70 < or = r < or = -.44). Results indicate that substantial extracellular volume depletion without body dehydration causes voice symptoms, an effect possibly mediated by autonomic nervous control. We propose that mechanisms intrinsic to the vocal fold regulate its water flux and respond to hydration challenges.

Stroboscopic and acoustic measures of inspiratory phonation.

Inspiratory phonation (IP) is the production of voice as air is taken into the lungs. Although IP is promoted as a laryngeal assessment and voice treatment technique, it has been described quantitatively in very few speakers. This study quantified changes in laryngeal adduction, fundamental frequency, and intensity during IP relative to expiratory phonation (EP). We hypothesized that IP would increase laryngeal abduction and fundamental frequency. The experiment was a within-subjects, repeated measures design with each subject serving as her own control. Participants were 10 females (ages 19-50 years) who underwent simultaneous transoral videostrobolaryngoscopy and acoustic voice recording. We found that membranous vocal fold contact decreased significantly during IP relative to EP, while the trends for change of ventricular fold squeeze during IP varied across individuals. Vocal fundamental frequency increased significantly during IP relative to EP, but intensity did not vary consistently across conditions. Without teaching or coaching, changes that occurred during IP did not carry over to EP produced immediately following IP within the same respiratory cycle.

Electroglottographic tracking of phonatory response to Botox.

Botox injection into the thyroarytenoid muscle is thought to alter the glottal competence and laryngeal adduction of patients with adductor spasmodic dysphonia (ADSD). Hypofunctional responses to treatment have been rated subjectively and inferred from postinjection breathy voice, aphonia, midline glottal gap, or subclinical aspiration. Clinical experience suggests that temporary hypofunction varies in duration and severity among patients. This study used electroglottographic measures to examine changes over time in glottal competence during the relatively stable phonation produced by 5 patients with ADSD. Hierarchical linear modeling was used to test 3 hypotheses: (a) that reduced laryngeal adduction would occur during the first 3 weeks postinjection, followed by a reversal; (b) that patients' hypofunctional response curves would differ one from another; and (c) that changes in adduction, if present, would be related to changes in severity ratings of ADSD symptoms. For 3 participants, significant hypoadduction occurred after injection and reversed toward preinjection level over an 8-week period. Two participants demonstrated a flat or increasing vocal fold contact response curve during the early postinjection period. Observations were consistent with the previously reported differences and possibly complex relation between the resolution of breathy hypofunction and ultimate return of ADSD symptoms.

Does botulinum toxin alter laryngeal secretions and mucociliary transport?

Localized botulinum toxin injection disrupts cholinergic transmission and has potential to cause focal dysautonomia. Mucociliary transport and laryngeal secretions are thought to be mediated in part by autonomic, cholinergic transmission. We questioned whether patients who receive Botox injection for adductor spasmodic dysphonia (ADSD) report postinjection symptoms possibly related to altered mucociliary clearance or laryngeal secretions. Medical histories, audiotaped interviews, and symptom ratings were retrospectively examined for 29 patients with ADSD who were followed after one or more Botox injections. Patients had received bilateral, percutaneous Botox injections of 2.5 units using an EMG-guided approach. One or more weeks after injection, four patients reported either burning, tickling, or irritation of the larynx/throat, excessive thick secretions, or dryness. Symptoms recurred with subsequent injections in two patients and were not associated with swallowing difficulty. These symptoms are consistent with, but not diagnostic of, the known effects of botulinum toxin on cholinergic, autonomic transmission.

Estimating phonation threshold pressure.

Phonation threshold pressure (PTP) is the minimum subglottal pressure required to initiate vocal fold oscillation. Although potentially useful clinically, PTP is difficult to estimate noninvasively because of limitations to vocal motor control near the threshold of soft phonation. Previous investigators observed, for example, that trained subjects were unable to produce flat, consistent oral pressure peaks during/pae/syllable strings when they attempted to phonate as softly as possible (Verdolini-Marston, Titze, & Druker, 1990). The present study aimed to determine if nasal airflow or vowel context affected phonation threshold pressure as estimated from oral pressure (Smitheran & Hixon, 1981) in 5 untrained female speakers with normal velopharyngeal and voice function. Nasal airflow during /p/occlusion was observed for 3 of 5 participants when they attempted to phonate near threshold pressure. When the nose was occluded, nasal airflow was reduced or eliminated during /p/;however, individuals then evidenced compensatory changes in glottal adduction and/or respiratory effort that may be expected to alter PTP estimates. Results demonstrate the importance of monitoring nasal flow (or the flow zero point in undivided masks) when obtaining PTP measurements noninvasively. Results also highlight the need to pursue improved methods for noninvasive estimation of PTP.

Longitudinal phonatory characteristics after botulinum toxin type A injection.

Following Botulinum Toxin Type A injection, glottal competency of an adductor spasmodic dysphonia patient is thought to vary over a wide range. This study quantifies variability in laryngeal adduction for one such patient over a 10-week period. Analyses of kinematic and aerodynamic measures were used to track the voice weekly. The measures included the electroglottographic waveform width (EGGW50), nondimensional electroglottographic slope quotient (SLQ), glottal flow open quotient (FOQ), dc glottal flow, and nondimensional glottal flow peak quotient (FPQ). The results suggested that change in degree of glottal adduction over time can be observed even when vocal instability is present within each recording session. Perceptual ratings of vocal quality (breathy to pressed) were related to the laryngeal measures. The coefficient of variation for EGGW50 and the percentage of dichrotic phonations reached minima during sessions with predominantly breathy and hypoadducted phonation. The methods used in this study show potential to aid decisions about dose level and sources of perceptual adductor spasmodic dysphonia symptoms for a given patient.