Faculty Bibliography

SUMMARY: The basic science of wound healing is largely omitted from the curriculum of many voice clinicians. This fact is relatively disheartening as most therapeutic manipulation in the realm of laryngology and voice disorders deals with injured tissue. Therefore, the selection of therapeutic tasks for persons with vocal injury should ideally be informed by basic science in wound healing. Recently, several investigators have initiated lines of research to determine the course of vocal fold wound healing and the potential role of therapeutic agents, including behavioral agents. The current review seeks to provide a foundation of basic wound healing science and present the most current data regarding the wound healing process in the vocal folds

The application of topical anesthesia to the oropharynx is a common clinical practice during oral and nasal laryngoscopy. Clinically, questions have been raised about whether topical anesthesia alters laryngeal secretions, which distorts clinical impressions. A double-blind, placebo controlled design was employed to address this issue. Ten premenopausal women with healthy vocal folds and 10 premenopausal women with phonotraumatic lesions underwent oral videolaryngoscopic examinations on subsequent days under both anesthesia and placebo conditions, in counterbalanced order. Video segments were rated by three judges. Dependent variables were balling and pooling of secretions, as previously described in the literature. Statistical analyses failed to reveal any clear effect of topical anesthesia on either secretion balling or pooling for the collapsed data set, but one cannot exclude changes in individual cases. Moreover, there was no evidence that secretions were differentially affected by anesthesia across subject groups. Null results in this data set replicate and extend previously reported findings by other authors. An incidental but potentially interesting finding was that the order of treatment condition (anesthesia versus placebo first) seemed relevant for secretions: Subjects who received the anesthesia condition first tended to show more secretion balling in general, as compared with subjects who received the placebo condition first. Speculation is entertained regarding possible physiological pathways for these incidental findings, which could be relevant for some clinical practice

The current study retrospectively reviewed the cases of 68 patients who had undergone total laryngectomy and tracheoesophageal puncture (TEP) over a 16-year period. Fifty-one patients underwent primary TEP and 17 underwent secondary TEP. Nearly 80% of patients who received TEP at the time of laryngectomy achieved excellent voice quality perceptually. In contrast, only 50% of secondary TEP patients achieved excellent voice ratings. This difference was statistically robust (p = 0.03). Although both surgical and prosthesis-related complications occurred more frequently following primary TEP, statistically significant differences were not achieved. Neither pre- nor postoperative radiotherapy had any effect on voice restoration or complication rates. Based on these data, primary TEP may be preferable for several reasons, including a greater likelihood of successful voice restoration, a shorter duration of postoperative aphonia, and the elimination of the need for a second operation and interim tube feedings

This study seeks to determine the ability of enzyme-linked immunosorbent assays (ELISAs) of vocal fold secretions to detect and describe the acute tissue response to injury in a rabbit vocal fold model. Vocal fold secretions were collected before the induction of a unilateral surgical injury to the vocal fold and at 6 timepoints after injury (1, 5, 7, 10, 14, and 21 days). Secretions were then subjected to ELISAs to assess concentrations of interleukin-1 beta (IL-1beta) and prostaglandin-E2 (PGE-2). The results indicate that ELISAs may be useful in documenting fluctuations in these markers associated with the wound healing process in the rabbit model. The temporal expression of both IL-1beta and PGE-2 was consistent with their proposed roles in the wound healing cascade in other systems, pointing to the potential that surface secretions may be at least partial indicators of wound healing events within the tissue

OBJECTIVES: To build on work in laryngology and oral biology that suggests utility in the assay of secretions collected from wound sites as a predictive instrument to determine which infants will likely develop subglottic stenosis following endotracheal intubation and to document and describe the wound-healing process. DESIGN: Prospective, randomized design. INTERVENTION: Laser-induced subglottic injury was established in 3 rabbits. Secretions were collected from the subglottic region at 6 time points from days 4 to 21 following injury and from 4 uninjured control airways. The secretions were then subjected to enzyme-linked immunoassays for interleukin 1 beta and prostaglandin E2. SUBJECTS: Three adult New Zealand white rabbits. MAIN OUTCOME MEASURES: Interleukin 1 beta and prostaglandin E2 levels. RESULTS: Measurable amounts of both mediators were obtained. Furthermore, different temporal patterns of expression were observed with interleukin 1 beta, showing increased levels on days 4 to 18, and with prostaglandin E2, showing increased levels on days 7 to 18. These results concur with emerging data regarding the role of each mediator in the wound-healing process. CONCLUSION: Although in its infancy, the analysis of secretions collected from the site of injury in the subglottis may have utility in the management of patients following intubation-related trauma

Several authors have eloquently described the characteristics of vocal fold scar, a long-term consequence of vocal fold injury. However, events in the acute stage of mucosal injury, which lead up to fibrosis, have been largely overlooked. The current study describes acute events with regard to mucosal re-formation in a rabbit model. Vocal fold injury was induced surgically. A fibrinous clot was present 1 day after injury. Massive cellular infiltration was noted on day 3, and complete epithelial coverage was achieved by day 5. Also, neo-matrix deposition was noted as early as 5 days after injury, and more mature collagen was seen by day 7. The general timetable described in the current study can contribute to the experimental foundation for the development of regenerative models of healing in the vocal folds. Most notably, the proliferation phase of wound healing appears to occur approximately 3 days after injury, indicating a critical time for intervention. Manipulation and/or alteration of naturally occurring neo-matrix deposition and organization may yield improved biophysical function of the injured vocal fold

This study seeks to determine the ability of enzyme-linked immunosorbent assays of vocal fold secretions to detect and describe the inflammatory response in the vocal folds. Vocal fold and palatal secretions were collected during operation from patients with a range of vocal fold disorders and from control patients. The secretions were subjected to assays for interleukin-1beta, prostaglandin E2, and transforming growth factor beta. The results indicate a differential expression of mediators associated with the wound healing cascade in the vocal folds. The prostaglandin E2 levels clearly differentiated vocal fold secretions associated with laryngeal disease versus control sites. Furthermore, the interleukin-1beta concentrations were significantly elevated in subjects with epithelial lesions of the vocal folds as opposed to lesions of the lamina propria. Although still in its infancy, such analysis may ultimately hold scientific and clinical utility in the study and management of patients with vocal fold disease

The current study sought to determine whether shifts in key components of the inflammatory process could be detected from laryngeal secretions sampled before and after vocal loading. A healthy 44-year-old woman served as the subject. The vocal folds were swabbed to collect baseline secretions. Ten and 20 minutes after nearly constant loud phonation for 1 hour, the vocal folds were swabbed again. The findings indicated strong shifts in several key inflammatory mediators: interleukin-1beta, tumor necrosis factor alpha, and matrix metalloproteinase 8. The concentrations of those mediators continued to increase from the 10- to 20-minute postloading time-points. Transforming growth factor beta and prostaglandin E2 did not demonstrate clear shifts. In summary, mediators reflecting the acute inflammatory process could be detected from laryngeal secretions in an awake human. The upward slope of the curves at the 20-minute time interval indicates the need for longer follow-up sampling to determine the full biological response of the vocal folds to acute phonotrauma

Acoustic analysis of a reading passage was used to identify the abnormal phonatory events associated with adductor spasmodic dysphonia (ADSD) pre- and postinjection of Botulinum Toxin A (Botox). Thirty-one patients (age 22 to 74 years) diagnosed with ADSD were included for study. All patients were new recipients of Botox, and the examination of their voice occurred before and after their initial injection of Botox. Acoustic events were identified from reading samples of the Rainbow Passage produced by each of the patients. These events were examined from sentences containing primarily voiced sound segments. Dependent variables included the number of phonatory breaks, frequency shifts, and aperiodic segments--all variables previously defined by the investigators. Additionally, calculated variables were made of the percentage of time these events occurred relative to the duration of the cumulative voiced segments. A sex- and age-matched control group (+/-2 years) was included for statistical comparison. Results indicated that those with ADSD produced more aberrant acoustic events than the controls. Aperiodicity was the predominant acoustic event produced during the reading, followed by frequency shifts and phonatory breaks. Within the ADSD group, the number of atypical acoustic events decreased following Botox injection. It is important that the occurrence of specific abnormal acoustic events was sufficient to differentiate the disordered speakers from the controls following as well as preceding initial Botox injection, as indicated by discriminant function analysis. This paper complements our previous work using this acoustic analysis method for defining the abnormal events present in the voice of those with ADSD and further suggests that these measures can be used in conjunction with perceptual impressions to differentiate speakers on the basis of initial severity

OBJECTIVE: To determine the reliability of the assessment of laryngoscopic findings potentially associated with laryngopharyngeal reflux disease (LPRD). STUDY DESIGN: Prospective randomized blinded study. METHODS: One hundred twenty video segments of rigid fiberoptic laryngeal examinations were prospectively analyzed by five otolaryngologists blinded to patient information and were scored according to several variables potentially associated with LPRD. Separate assessments of the degree of erythema and degree of edema were scored on a five-point scale for the anterior commissure, membranous vocal fold, and interarytenoid region. Similarly, interarytenoid pachydermia, likelihood of LPRD involvement, and severity of LPRD findings were assessed. For each of these scored physical findings, inter-rater and intrarater reliabilities were determined. RESULTS: The inter-rater reliabilities of the laryngoscopic findings associated with LPRD were poor. Intraclass correlation coefficients were 0.161 and 0.461 for edema of the arytenoids and membranous vocal folds, respectively (P <.001). Intraclass correlation coefficients were 0.181 and 0.369 for erythema of the arytenoids and membranous vocal folds, respectively (P <.001). Raters demonstrated poor agreement as to the severity of LPRD findings (intraclass correlation coefficient, 0.265) and the likelihood of an LPRD component for dysphonia (intraclass correlation coefficient, 0.248). Similarly, intrarater reliability was extremely variable for the various physical findings, with Kendall correlation coefficients ranging from -0.121 to 0.837. CONCLUSIONS: Accurate clinical assessment of laryngeal involvement with LPRD is likely to be difficult because laryngeal physical findings cannot be reliably determined from clinician to clinician. Such variability makes the precise laryngoscopic diagnosis of LPRD highly subjective