Faculty Bibliography

OBJECTIVE: To investigate the hypothesis that prophylactic triamcinolone modulates acute vocal fold inflammatory and profibrotic signaling during acute phonotrauma. STUDY DESIGN: In vivo rabbit phonation model. SETTING: Academic medical center. SUBJECTS AND METHODS: Forty New Zealand white breeder rabbits were randomly assigned to 1 of 4 groups: control (no intervention), no treatment (30 minutes of raised intensity phonation), sham treatment (bilateral intralaryngeal triamcinolone acetonide injection at 0 microg/25 microL followed by 30 minutes of raised intensity phonation), or steroid treatment (bilateral intralaryngeal triamcinolone acetonide injection at 400 microg/25 microL followed by 30 minutes of raised intensity phonation). Quantitative polymerase chain reaction (qPCR) was used to investigate gene expression levels of cyclooxygenase-2 (COX-2), interleukin (IL)-1beta, and transforming growth factor (TGF)-beta1. RESULTS: Results revealed a significant main effect for COX-2 (P = .002). Post hoc testing revealed that rabbits receiving no treatment (15.10) had higher COX-2 gene expression than control (5.90; P < .001). There were no significant differences in COX-2 expression between treatment groups. Results revealed a significant main effect for IL-1beta (P < .001). Post hoc testing revealed that rabbits receiving no treatment (14.70) had higher IL-1beta gene expression than control (6.30) (P = .001). There were no significant differences in IL-1beta gene expression between treatment groups. There were no significant differences in TGF-beta1 gene expression (P = .525) between treatment and control groups. CONCLUSION: Given conflicting evidence, further studies are necessary to investigate vocal fold steroid injections prior to and following the induction of phonotrauma. Prophylactic administration of triamcinolone immediately prior to acute phonotrauma resulted in no significant changes in COX-2, IL-1beta, and TGF-beta1 gene transcript levels.

Objective: Glucocorticoids are commonly used treatments in otolaryngology, but guidelines about their use are vague and irregular. We sought to assess clinical practices with regard to glucocorticoid use for patients with laryngeal disease and to ascertain factors driving clinician drug choice. Method: A web-based survey was distributed to otolaryngologists via email using the Ear, Nose, and Throat (ENT) Journal database. This survey was composed of 20 questions and collected the following data from respondents: 1) indications for the use of glucocorticoids in their practice, 2) decision-making process influencing the choice of glucocorticoid, 3) background and demographics. Results: Two hundred eight otolaryngologists completed the survey, with 99% (n = 196) reporting that glucocorticoids were valuable to their practice. "Previous experience/results," "familiarity," and "use in practice" (n = 144, 114, and 79, respectively) were commonly cited reasons for choosing a particular glucocorticoid, whereas pharmacokinetic profile and "academic literature" were infrequently cited concerns. Only 54.4% (n = 106) of respondents said that they were more likely to prescribe glucocorticoids for vocal performers as compared to other patients. Additionally, most respondents said side effects only "occasionally" prevented them from prescribing glucocorticoids to patients. Conclusion: These results suggest that glucocorticoid prescription practices vary greatly between otolaryngologists, and drug choice is driven primarily by clinician preference rather than more objective factors. These findings indicate a need for further research about this powerful class of drugs, and the importance of establishing clear, appropriate guidelines regarding their use.

OBJECTIVES/HYPOTHESIS: In this article we describe a methodology for obtaining high-quality dynamic magnetic resonance imaging (MRI) sequences of the swallow sequence in healthy volunteers. The study includes comparison to previous work done in our lab using a 1.5 Tesla (T) magnet. STUDY DESIGN: Case series. METHODS: Three healthy volunteers underwent turbo-fast low angle shot MRI at 3T while swallowing liquid boluses delivered via intravenous tubing to the oral cavity. Imaging was performed in the sagittal and axial planes. RESULTS: Imaging provided by this sequence provided high temporal resolution, with the ability to depict deglutition in the axial and sagittal planes. Comparison with imaging at 1.5T demonstrated benefits in temporal resolution and signal-to-noise. Anatomic information provided differed from comparative videofluoroscopy. CONCLUSIONS: MRI of swallowing using the described technique is reliable and provides a unique evaluation of the swallowing sequence. Laryngoscope, 2012.

OBJECTIVES: We sought to better characterize pathologic changes that occur in the human vocal fold after radiotherapy for head and neck cancer. METHODS: In a blinded, controlled study of archived tissue, we evaluated postirradiation salvage laryngectomy vocal fold tissue without evidence of malignant disease. Clinical and demographic patient data were collected. In a blinded fashion, irradiated tissue was compared to nonirradiated, benign control tissue. Histomorphometric analysis was used to assess muscle and collagen organization, superficial lamina propria (SLP) and vocal ligament thickness, vocalis muscle fiber area, collagen content, and hyaluronic acid content. Immunohistochemical analysis was used to assess the content of type I collagen, type IV collagen, vimentin, fibronectin, alpha-smooth muscle actin, matrix metalloproteinase 9, and laminin. RESULTS: Twenty irradiated vocal folds were evaluated and compared to control specimens. Collagen and muscle disorganization was noted in the irradiated specimens. The SLP and vocal ligament thicknesses and the mean muscle fiber diameters did not differ significantly. The SLP fibronectin and the vocalis muscle and SLP collagen content were significantly increased in the irradiated vocal folds, and the SLP collagen content increased significantly with time between irradiation and resection. The laminin content of irradiated vocalis muscles was significantly decreased. CONCLUSIONS: Radiotherapy results in significant vocal fold tissue changes. Having more precisely defined these changes, we plan continued investigation seeking targeted preventive and therapeutic interventions for improved vocal quality following radiotherapy.

OBJECTIVES/HYPOTHESIS: 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. STUDY DESIGN: In vitro, in vivo. METHODS: Immunolocalization of the GC receptor was performed on normal rat vocal fold tissue. Receptor expression was also assayed in our human vocal fold fibroblast cell line. These cells were then treated with exogenous dexamethasone (DM) to quantify the effects of GCs on receptor expression, proliferation, transforming growth factor (TGF)-beta-induced collagen secretion, and matrix protease synthesis. RESULTS: Positive immunostaining for the GC receptor was found throughout the vocal fold with particularly strong staining in the epithelium and capillaries. Human vocal fold fibroblasts constitutively express the GC receptor, but this expression decreased in response to exogenous DM. DM also decreased fibroblast proliferation and TGF-beta-induced collagen synthesis. DM also abrogated TGF-beta-mediated effects on enzymes related extracellular matrix turnover. CONCLUSIONS: Our data are the first to provide mechanistic insight regarding the recently published favorable data regarding the utility of GCs in patients with vocal fold scar. Although further investigation is warranted, both the accessibility of this class of agents and the amenability to office-based procedures are likely to direct patient care models

OBJECTIVES/HYPOTHESIS.: Prostaglandin (PG)E(2) has been implicated in a variety of disease processes. It has been described as antifibrotic in the lower airway, yet scar-inducing in the skin. We seek to describe the effects of PGE(2) on vocal fold fibroblasts and its interactions with transforming growth factor (TGF)-beta1. In addition, we describe a novel organotypic model, a critical step in the development of therapeutic trials. STUDY DESIGN.: In vitro, ex vivo. METHODS: Collagen secretion by human vocal fold fibroblasts (HVFF) was assayed in response to TGF-beta1, PGE(2) , and specific EP receptor agonists. Basal HVFF migratory rate was also quantified in response to PGE(2) . TGF-beta1 induced COX-2 mRNA expression/PGE(2) secretion was assayed. Excised vocal folds were subjected to exogenous IL-1beta; PGE(2) secretion into the supernatant was then assayed. RESULTS: TGF-beta1-induced collagen secretion was blunted in a dose-dependent manner in response to PGE(2) . This effect appears to be mediated primarily through the EP1 and EP2 receptors. TGF-beta1 induced COX-2 mRNA expression and PGE(2) secretion. In our organ culture model, IL-1beta stimulated PGE(2) secretion in a dose-dependent manner. CONCLUSIONS: PGE(2) is antifibrotic; this finding suggests that the upper airway response to this inflammatory mediator differs significantly from the lower airway. These data have important clinical implications for a variety of pathological processes. Furthermore, exogenous TGF-beta1 elicits induction of COX-2, suggesting inherent complexity regarding these processes and PGE(2) signaling, specifically. In addition, our organ culture model may prove useful as a means to quantify biological phenomena in the vocal folds

Although Reinke's space, or layer, is a critical laryngeal structure, and the eponym is in current use in both clinical and research milieus, little is known about the life of the eponymist, German anatomist Friedrich Berthold Reinke. Extensive investigation of the archives at the University of Rostock and other sources, as well as multinational collaboration, has yielded unique insight into the personal and professional life of this pioneer who, among other things, identified and characterized the subepithelial space of the vocal fold and structures in the Leydig cells of the testicles and ovaries. This breadth of investigation reflects Reinke's intellectual curiosity and broad-ranging interest as well as his scientific environment. Without question, Reinke's observations of the human vocal fold are substantive contributions, without which modern laryngology could not have evolved. In 2009, at the 90th anniversary of Reinke's death, we summarize his achievements to express our appreciation for his singular brilliance and fundamental contribution to laryngology.

Perception of the impact of voice disorders may differ across different cultural backgrounds. This study investigated the difference in the perception of the impact of voice disorders between the American (Pittsburgh) and Chinese (Hong Kong) cultures. Study Design and Setting: Sixty dysphonic subjects from Hong Kong, China, and 60 dysphonic subjects from Pittsburgh, USA, were recruited to complete the Chinese and English versions of the Voice Activity and Participation Profile (VAPP), respectively. Data analyses using independent t tests were conducted on (1) the total profile scores; (b) total activity limitation score (ALS) and total participation restriction score (PRS); (c) section scores of job, daily communication, and social communication; and (d) section ALS and section PRS. Results: Hong Kong subjects showed significantly higher scores than the Pittsburgh subjects in total profile and other subsections except in the job PRS. Conclusion: Results support the possible influence of individualist and collectivist cultures on the perceived impact of voice disorders on the activity and participation.

OBJECTIVES/HYPOTHESIS: In response to chronic cigarette smoke exposure, a subset of patients present with edematous vocal folds, characteristically referred to as Reinke's edema. This phenotype differs from the tissue changes associated with prolonged smoke exposure in the lower airway, and the mechanism underlying Reinke's edema remains poorly described. We hypothesize that the effects of smoke are diffuse and involve both the epithelium and mucosa. STUDY DESIGN: In vitro, ex vivo experiment. METHODS: Transepithelial resistance (R(T) ) was quantified in an ex vivo, viable, porcine vocal fold model. Excised tissue was exposed to cigarette smoke condensate (CSC) and R(T) was computed at baseline and 1 and 4 hours after exposure. In vitro, human vocal fold fibroblasts were exposed to CSC. Cyclooxygenase 2 (COX-2), microsomal prostaglandin E synthase-1, and 15-hydroxyprostaglandin dehydrogenase mRNA expression were assessed at 4 hours. Prostaglandin E2 (PGE2) synthesis was quantified via immunoassay following 24 hours of CSC exposure. RESULTS: CSC had no effect on R(T) . CSC did, however, induce COX-2 mRNA expression as well as its downstream lipid mediator PGE2. PGE2 metabolism appears to be regulated via both synthetic and degradative enzymes in response to cigarette smoke. CONCLUSIONS: In vitro, CSC initiates an inflammatory response in vocal fold fibroblasts. However, in isolation, the epithelial resistance is not altered by CSC, at least acutely. These data may suggest a role for the interaction between the inflammatory response in the mucosa and compromised epithelial barrier function, as has been shown in other tissues. Laryngoscope, 2011