255 results on '"Susan L. Thibeault"'
Search Results
2. Single-cell view into the role of microbiota shaping host immunity in the larynx
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Ran An, Zijian Ni, Elliott Xie, Federico E. Rey, Christina Kendziorski, and Susan L. Thibeault
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Immunity ,Microbiome ,Transcriptomics ,Science - Abstract
Summary: Microbiota play a critical role in the development and training of host innate and adaptive immunity. We present the cellular landscape of the upper airway, specifically the larynx, by establishing a reference single-cell atlas, while dissecting the role of microbiota in cell development and function at single-cell resolution. We highlight the larynx’s cellular heterogeneity with the identification of 16 cell types and 34 distinct subclusters. Our data demonstrate that commensal microbiota have extensive impact on the laryngeal immune system by regulating cell differentiation, increasing the expression of genes associated with host defense, and altering gene regulatory networks. We uncover macrophages, innate lymphoid cells, and multiple secretory epithelial cells, whose cell proportions and expressions vary with microbial exposure. These cell types play pivotal roles in maintaining laryngeal and upper airway health and provide specific guidance into understanding the mechanism of immune system regulation by microbiota in laryngeal health and disease.
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- 2024
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3. Patient perceptions of the impact of inducible laryngeal obstruction on quality of life
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Katherine M. McConville and Susan L. Thibeault
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Medicine ,Science - Published
- 2024
4. Age and sex-related variations in murine laryngeal microbiota
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Ran An, Anumitha Venkatraman, John Binns, Callie Saric, Federico E. Rey, and Susan L. Thibeault
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Medicine ,Science - Published
- 2024
5. Localization of TRPV3/4 and PIEZO1/2 sensory receptors in murine and human larynges
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Alexander G. Foote, Julianna Tibbetts, Stephanie M. Bartley, and Susan L. Thibeault
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development ,larynx ,sensory receptors ,somatosensation ,vocal fold ,Otorhinolaryngology ,RF1-547 ,Surgery ,RD1-811 - Abstract
Abstract Objective The primary aim of this study was to identify expression of TRPV3 and TRPV4 chemoreceptors across perinatal and adult stages using a murine model with direct comparisons to human laryngeal mucosa. Our secondary aim was to establish novel cell expression patterns of mechanoreceptors PIEZO1 and PIEZO2 in human tissue samples. Study design In vivo. Methods We harvested murine laryngeal tissue to localize and describe TRPV3/4 endogenous protein expression patterns via immunofluorescence analyses across two developmental (E16.5, P0) and adult (6 weeks) timepoints. Additionally, we obtained a 60‐year‐old female larynx including the proximal trachea and esophagus to investigate TRPV3/4 and PIEZO1/2 protein expression patterns via immunofluorescence analyses for comparison to murine adult tissue. Results Murine TRPV3/4 expression was noted at E16.5 with epithelial cell colocalization to supraglottic regions of the arytenoids, aryepiglottic folds and epiglottis through to birth (P0), extending to the adult timepoint. Human TRPV3/4 protein expression was most evident to epithelium of the arytenoid region, with additional expression of TRPV3 and TRPV4 to proximal esophageal and tracheal epithelium, respectively. Human PIEZO1 expression was selective to differentiated, stratified squamous epithelia of the true vocal fold and esophagus, while PIEZO2 expression exhibited selectivity for intermediate and respiratory epithelia of the false vocal fold, ventricles, subglottis, arytenoid, and trachea. Conclusion Results exhibited expression of TRPV3/4 chemoreceptors in utero, suggesting their importance during fetal/neonatal stages. TRPV3/4 and PIEZO1/2 were noted to adult murine and human laryngeal epithelium. Data indicates conservation of chemosensory receptors across species given similar regional expression in both the murine and human larynx.
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- 2022
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6. Vocal fold mucus layer: Comparison of histological protocols for visualization in mice
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Ran An, Daniel Robbins, Federico E. Rey, and Susan L. Thibeault
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histology ,mouse ,mucin ,mucus layer ,vocal fold ,Otorhinolaryngology ,RF1-547 ,Surgery ,RD1-811 - Abstract
Abstract Objectives The epithelial associated mucus layer of vocal fold (VF) mucosa, plays an essential role in protecting and lubricating the tissue, as well as promoting normal voice quality. Serving as a habitat for laryngeal microbiota involved in the regulation of host immunity, VF mucus contributes to laryngeal health and disease. However, its unstable structure renders its' investigation challenging. We aim to establish a reproducible histological protocol to recover the natural appearance of the VF mucus layer for investigation. Methods Using a murine model, we compared the suitability of multiple fixation methods—methacarn, formalin, and cryopreservation followed by post‐fixation with formalin, paraformaldehyde (PFA), acetone, and two staining methods—Alcian Blue (pH 2.5)/Periodic Acid Schiff (AB/PAS) or PAS. Fixation and staining outcomes were evaluated based on the preservation of tissue morphology and mucus layer integrity. Mucin proteins, Muc1 and Muc4, were stained to validate the presence of mucus layer overlaying the VF mucosa. Results Methacarn fixation followed by PAS staining was capable of preserving and displaying the smooth and continuous mucus layer, ensuring the determination of mucus thickness and mucin staining. Conclusions Our study if the first to establish a histological protocol for the visualization of the in situ VF mucus layer whereby facilitating the study of VF mucus biology including VF surface hydration, ion/nutrients transports, biomechanical properties that maintains normal voice quality as well as VF pathophysiology and host‐microbe interactions in the larynx. Level of Evidence N/A.
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- 2022
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7. Exposure to e-cigarette vapor extract induces vocal fold epithelial injury and triggers intense mucosal remodeling
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Vlasta Lungova, Kristy Wendt, and Susan L. Thibeault
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electronic cigarettes ,vaping ,chemical injury ,human vocal fold mucosa ,remodeling ,Medicine ,Pathology ,RB1-214 - Abstract
Vaping has been reported to cause acute epiglottitis, a life-threatening airway obstruction induced by direct epithelial injury and subsequent inflammatory reaction. Here, we show that we were able to recapitulate this phenomenon in vitro. Exposure of human engineered vocal fold (VF) mucosae to 0.5% and 5% electronic cigarette (e-cigarette) vapor extract (ECVE) for 1 week induced cellular damage of luminal cells, disrupting homeostasis and innate immune responses. Epithelial erosion was likely caused by accumulation of solvents and lipid particles in the cytosol and intercellular spaces, which altered lipid metabolism and plasma membrane properties. Next, we investigated how the mucosal cells responded to the epithelial damage. We withdrew the ECVE from the experimental system and allowed VF mucosae to regenerate for 1, 3 and 7 days, which triggered intense epithelial remodeling. The epithelial changes included expansion of P63 (TP63)-positive basal cells and cytokeratin 14 (KRT14) and laminin subunit α-5 (LAMA5) deposition, which might lead to local basal cell hyperplasia, hyperkeratinization and basement membrane thickening. In summary, vaping presents a threat to VF mucosal health and airway protection, thereby raising further concerns over the safety of e-cigarette use. This article has an associated First Person interview with the first author of the paper.
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- 2022
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8. Transcriptome Dynamics in the Developing Larynx, Trachea, and Esophagus
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Kristy D. Wendt, Jared Brown, Vlasta Lungova, Vidisha Mohad, Christina Kendziorski, and Susan L. Thibeault
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RNAseq ,development ,larynx ,morphogenesis ,esophagus ,trachea ,Biology (General) ,QH301-705.5 - Abstract
The larynx, trachea, and esophagus share origin and proximity during embryonic development. Clinical and experimental evidence support the existence of neurophysiological, structural, and functional interdependencies before birth. This investigation provides the first comprehensive transcriptional profile of all three organs during embryonic organogenesis, where differential gene expression gradually assembles the identity and complexity of these proximal organs from a shared origin in the anterior foregut. By applying bulk RNA sequencing and gene network analysis of differentially expressed genes (DEGs) within and across developing embryonic mouse larynx, esophagus, and trachea, we identified co-expressed modules of genes enriched for key biological processes. Organ-specific temporal patterns of gene activity corresponding to gene modules within and across shared tissues during embryonic development (E10.5-E18.5) are described, and the laryngeal transcriptome during vocal fold development and maturation from birth to adulthood is characterized in the context of laryngeal organogenesis. The findings of this study provide new insights into interrelated gene sets governing the organogenesis of this tripartite organ system within the aerodigestive tract. They are relevant to multiple families of disorders defined by cardiocraniofacial syndromes.
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- 2022
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9. Human induced pluripotent stem cell-derived vocal fold mucosa mimics development and responses to smoke exposure
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Vlasta Lungova, Xia Chen, Ziyue Wang, Christina Kendziorski, and Susan L. Thibeault
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Science - Abstract
There is a lack of human models to study vocal fold epithelia making it difficult to provide therapies for vocal fold disease. Here, the authors generate a human-based model of vocal fold mucosa that mimics in utero development and shows inflammation on exposure to cigarette smoke abstract.
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- 2019
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10. Tissue specific human fibroblast differential expression based on RNAsequencing analysis
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Alexander G. Foote, Ziyue Wang, Christina Kendziorski, and Susan L. Thibeault
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Vocal fold biology ,RNA-seq ,Human vocal fold fibroblast ,Functional gene expression ,Transcriptome profiling ,Mechanobiology ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Physical forces, such as mechanical stress, are essential for tissue homeostasis and influence gene expression of cells. In particular, the fibroblast has demonstrated sensitivity to extracellular matrices with assumed adaptation upon various mechanical loads. The purpose of this study was to compare the vocal fold fibroblast genotype, known for its unique mechanically stressful tissue environment, with cellular counterparts at various other anatomic locales to identify differences in functional gene expression profiles. Results By using RNA-seq technology, we identified differentially expressed gene programs (DEseq2) among seven normal human fibroblast primary cell lines from healthy cadavers, which included: vocal fold, trachea, lung, abdomen, scalp, upper gingiva, and soft palate. Unsupervised gene expression analysis yielded 6216 genes differentially expressed across all anatomic sites. Hierarchical cluster analysis revealed grouping based on anatomic site origin rather than donor, suggesting global fibroblast phenotype heterogeneity. Sex and age-related effects were negligible. Functional enrichment analyses based on separate post-hoc 2-group comparisons revealed several functional themes within the vocal fold fibroblast related to transcription factors for signaling pathways regulating pluripotency of stem cells and extracellular matrix components such as cell signaling, migration, proliferation, and differentiation potential. Conclusions Human fibroblasts display a phenomenon of global topographic differentiation, which is maintained in isolation via in vitro assays. Epigenetic mechanical influences on vocal fold tissue may play a role in uniquely modelling and maintaining the local environmental cellular niche during homeostasis with vocal fold fibroblasts distinctly specialized related to their anatomic positional and developmental origins established during embryogenesis.
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- 2019
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11. A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus
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Renee E. King, Andrea Bilger, Josef Rademacher, Ella T. Ward-Shaw, Rong Hu, Paul F. Lambert, and Susan L. Thibeault
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mouse ,papillomavirus ,larynx ,vocal folds ,recurrent respiratory papillomatosis ,RRP ,Microbiology ,QR1-502 - Abstract
Recurrent respiratory papillomatosis (RRP), caused by laryngeal infection with low-risk human papillomaviruses, has devastating effects on vocal communication and quality of life. Factors in RRP onset, other than viral presence in the airway, are poorly understood. RRP research has been stalled by limited preclinical models. The only known papillomavirus able to infect laboratory mice, Mus musculus papillomavirus (MmuPV1), induces disease in a variety of tissues. We hypothesized that MmuPV1 could infect the larynx as a foundation for a preclinical model of RRP. We further hypothesized that epithelial injury would enhance the ability of MmuPV1 to cause laryngeal disease, because injury is a potential factor in RRP and promotes MmuPV1 infection in other tissues. In this report, we infected larynges of NOD scid gamma mice with MmuPV1 with and without vocal fold abrasion and measured infection and disease pathogenesis over 12 weeks. Laryngeal disease incidence and severity increased earlier in mice that underwent injury in addition to infection. However, laryngeal disease emerged in all infected mice by week 12, with or without injury. Secondary laryngeal infections and disease arose in nude mice after MmuPV1 skin infections, confirming that experimentally induced injury is dispensable for laryngeal MmuPV1 infection and disease in immunocompromised mice. Unlike RRP, lesions were relatively flat dysplasias and they could progress to cancer. Similar to RRP, MmuPV1 transcript was detected in all laryngeal disease and in clinically normal larynges. MmuPV1 capsid protein was largely absent from the larynx, but productive infection arose in a case of squamous metaplasia at the level of the cricoid cartilage. Similar to RRP, disease spread beyond the larynx to the trachea and bronchi. This first report of laryngeal MmuPV1 infection provides a foundation for a preclinical model of RRP.
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- 2022
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12. Expanded Basal Compartment and Disrupted Barrier in Vocal Fold Epithelium Infected with Mouse Papillomavirus MmuPV1
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Renee E. King, Ella T. Ward-Shaw, Rong Hu, Paul F. Lambert, and Susan L. Thibeault
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mouse ,papillomavirus ,larynx ,vocal folds ,epithelium ,recurrent respiratory papillomatosis ,Microbiology ,QR1-502 - Abstract
Laryngeal infection with low-risk human papillomaviruses can cause recurrent respiratory papillomatosis (RRP), a disease with severe effects on vocal fold epithelium resulting in impaired voice function and communication. RRP research has been stymied by limited preclinical models. We recently reported a murine model of laryngeal MmuPV1 infection and disease in immunodeficient mice. In the current study, we compare quantitative and qualitative measures of epithelial proliferation, apoptosis, differentiation, and barrier between mice with MmuPV1-induced disease of the larynx and surrounding tissues and equal numbers of uninfected controls. Findings supported our hypothesis that laryngeal MmuPV1 infection recapitulates many features of RRP. Like RRP, MmuPV1 increased proliferation in infected vocal fold epithelium, expanded the basal compartment of cells, decreased differentiated cells, and altered cell–cell junctions and basement membrane. Effects of MmuPV1 on apoptosis were equivocal, as with RRP. Barrier markers resembled human neoplastic disease in severe MmuPV1-induced disease. We conclude that MmuPV1 infection of the mouse larynx provides a useful, if imperfect, preclinical model for RRP that will facilitate further study and treatment development for this intractable and devastating disease.
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- 2022
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13. Selective Bacterial Colonization of the Murine Larynx in a Gnotobiotic Model
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Ran An, Madhu Gowda, Federico E. Rey, and Susan L. Thibeault
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gnotobiotic ,laryngeal mucosa ,microbiota ,upper airway ,colonization ,Microbiology ,QR1-502 - Abstract
The larynx is a mucosal organ situated between the respiratory and gastrointestinal tracts. Little is known about microbial contributions to laryngeal epithelial health and pathogenesis. Developing a gnotobiotic laryngeal model will introduce new avenues for targeted explorations of microbes in laryngeal mucosal biology, allowing for enhanced understanding of host–microbe interaction in the upper airway. In this study, we first assessed the potential of using gut microbiota as a source to establish laryngeal microbiota in germ-free mice. Results demonstrated the selective nature of the upper airway and provided evidence that gut bacteria can assemble into communities that resemble the commensal resident bacteria occurring in the larynx of conventionally-raised animals phylogenetically and functionally. Then, we confirmed the reproducibility of laryngeal colonization through comparison of laryngeal microbiota in the larynx along with neighboring regions (base of tongue, esophagus, and trachea) between conventionally-raised and germ-free mice that conventionalized with cecal microbiota. Despite taxonomic differences, the established laryngeal microbiota from cecal content exhibited similarity to commensal resident microbiota in diversity within/between communities and predicted metagenomic functions. Our data also suggests little difference in bacterial distribution across the larynx and its surrounding regions and that cell motility and the ability to degrade xenobiotics is critical for bacteria colonizing upper airway. Successful colonization of laryngeal and oropharyngeal regions with gut microbiota in our study will greatly facilitate the investigation of potential localized inflammatory responses within host tissues that contribute to the disorders of essential laryngeal functions. Utilizing said gnotobiotic model to conduct future studies will allow for novel insights into direct microbial contributions to laryngeal epithelial health and pathogenesis.
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- 2020
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14. Laryngotracheal Microbiota in Adult Laryngotracheal Stenosis
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Alexander T. Hillel, Sharon S. Tang, Camila Carlos, Joseph H. Skarlupka, Madhu Gowda, Linda X. Yin, Kevin Motz, Cameron R. Currie, Garret Suen, and Susan L. Thibeault
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Acinetobacter ,Moraxella ,fibrosis ,laryngotracheal stenosis ,subglottic stenosis ,upper airway microbiota ,Microbiology ,QR1-502 - Abstract
ABSTRACT Laryngotracheal stenosis is an obstructive respiratory disease that leads to voicing difficulties and dyspnea with potential life-threatening consequences. The majority of incidences are due to iatrogenic etiology from endotracheal tube intubation; however, airway scarring also has idiopathic causes. While recent evidence suggests a microbial contribution to mucosal inflammation, the microbiota associated with different types of stenosis has not been characterized. High-throughput sequencing of the V4 region of the16S rRNA gene was performed to characterize the microbial communities of 61 swab samples from 17 iatrogenic and 10 adult idiopathic stenosis patients. Nonscar swabs from stenosis patients were internal controls, and eight swabs from four patients without stenosis represented external controls. Significant differences in diversity were observed between scar and nonscar samples and among sample sites, with decreased diversity detected in scar samples and the glottis region. Permutational analysis of variance (PERMANOVA) results revealed significant differences in community composition for scar versus nonscar samples, etiology type, sample site, groups (iatrogenic, idiopathic, and internal and external controls), and individual patients. Pairwise Spearman’s correlation revealed a strong inverse correlation between Prevotella and Streptococcus among all samples. Finally, bacteria in the family Moraxellaceae were found to be distinctly associated with idiopathic stenosis samples in comparison with external controls. Our findings suggest that specific microbiota and community shifts are present with laryngotracheal stenosis in adults, with members of the family Moraxellaceae, including the known pathogens Moraxella and Acinetobacter, identified in idiopathic scar. Further work is warranted to elucidate the contributing role of bacteria on the pathogenesis of laryngotracheal stenosis. IMPORTANCE The laryngotracheal region resides at the intersection between the heavily studied nasal cavity and lungs; however, examination of the microbiome in chronic inflammatory conditions of the subglottis and trachea remains scarce. To date, studies have focused on the microbiota of the vocal folds, or the glottis, for laryngeal carcinoma, as well as healthy larynges, benign vocal fold lesions, and larynges exposed to smoking and refluxate. In this study, we seek to examine the structure and composition of the microbial community in adult laryngotracheal stenosis of various etiologies. Due to the heterogeneity among the underlying pathogenesis mechanisms and clinical outcomes seen in laryngotracheal stenosis disease, we hypothesized that different microbial profiles will be detected among various stenosis etiology types. Understanding differences in the microbiota for subglottic stenosis subtypes may shed light upon etiology-specific biomarker identification and offer novel insights into management approaches for this debilitating disease.
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- 2019
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15. A Mouse Model of Oropharyngeal Papillomavirus-Induced Neoplasia Using Novel Tools for Infection and Nasal Anesthesia
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Andrea Bilger, Renee E. King, Josh P. Schroeder, Jared T. Piette, Louis A. Hinshaw, Andrew D. Kurth, Ronnie W. AlRamahi, Matthew V. Barthel, Ella T. Ward-Shaw, Darya Buehler, Kristyn S. Masters, Susan L. Thibeault, and Paul F. Lambert
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mouse ,papillomavirus ,throat ,head-and-neck ,OPSCC ,oropharynx ,Microbiology ,QR1-502 - Abstract
Human head and neck cancers that develop from the squamous cells of the oropharynx (Oropharyngeal Squamous Cell Carcinomas or OPSCC) are commonly associated with the papillomavirus infection. A papillomavirus infection-based mouse model of oropharyngeal tumorigenesis would be valuable for studying the development and treatment of these tumors. We have developed an efficient system using the mouse papillomavirus (MmuPV1) to generate dysplastic oropharyngeal lesions, including tumors, in the soft palate and the base of the tongue of two immune-deficient strains of mice. To maximize efficiency and safety during infection and endoscopy, we have designed a nose cone for isoflurane-induced anesthesia that takes advantage of a mouse’s need to breathe nasally and has a large window for oral manipulations. To reach and infect the oropharynx efficiently, we have repurposed the Greer Pick allergy testing device as a virus delivery tool. We show that the Pick can be used to infect the epithelium of the soft palate and the base of the tongue of mice directly, without prior scarification. The ability to induce and track oropharyngeal papillomavirus-induced tumors in the mouse, easily and robustly, will facilitate the study of oropharyngeal tumorigenesis and potential treatments.
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- 2020
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16. Microarray-based characterization of differential gene expression during vocal fold wound healing in rats
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Nathan V. Welham, Changying Ling, John A. Dawson, Christina Kendziorski, Susan L. Thibeault, and Masaru Yamashita
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Fibrosis ,Larynx ,Scar formation ,Tissue repair ,Transcriptome ,Medicine ,Pathology ,RB1-214 - Abstract
The vocal fold (VF) mucosa confers elegant biomechanical function for voice production but is susceptible to scar formation following injury. Current understanding of VF wound healing is hindered by a paucity of data and is therefore often generalized from research conducted in skin and other mucosal systems. Here, using a previously validated rat injury model, expression microarray technology and an empirical Bayes analysis approach, we generated a VF-specific transcriptome dataset to better capture the system-level complexity of wound healing in this specialized tissue. We measured differential gene expression at 3, 14 and 60 days post-injury compared to experimentally naïve controls, pursued functional enrichment analyses to refine and add greater biological definition to the previously proposed temporal phases of VF wound healing, and validated the expression and localization of a subset of previously unidentified repair- and regeneration-related genes at the protein level. Our microarray dataset is a resource for the wider research community and has the potential to stimulate new hypotheses and avenues of investigation, improve biological and mechanistic insight, and accelerate the identification of novel therapeutic targets.
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- 2015
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17. Therapy Outcomes for Teenage Athletes With Exercise-Induced Laryngeal Obstruction
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Robert Brinton Fujiki, Bryn Olson-Greb, Maia Braden, and Susan L. Thibeault
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Speech and Hearing ,Linguistics and Language ,Otorhinolaryngology ,Developmental and Educational Psychology - Abstract
Purpose: This study examined treatment outcomes of speech-language pathology intervention addressing exercise-induced laryngeal obstruction (EILO) symptoms in teenage athletes. Method: A prospective cohort design was utilized; teenagers diagnosed with EILO completed questionnaires during initial EILO evaluations, posttherapy, 3-month posttherapy, and 6-month posttherapy. Questionnaires examined the frequency of breathing problems, the use of the techniques taught in therapy, and the use of inhaler. Patients completed the Pediatric Quality of Life (PedsQL) inventory at all time points. Results: Fifty-nine patients completed baseline questionnaires. Of these, 38 were surveyed posttherapy, 32 at 3-month posttherapy, and 27 at 6-month posttherapy. Patients reported more frequent and complete activity participation immediately posttherapy ( p = .017) as well as reduced inhaler use ( p = .036). Patients also reported a significant reduction in the frequency of breathing problems 6-month posttherapy ( p = .015). Baseline PedsQL physical and psychosocial scores were below normative range and were not impacted by therapy. Baseline physical PedsQL score significantly predicted frequency of breathing difficulty 6-month posttherapy ( p = .04), as better baseline scores were associated with fewer residual symptoms. Conclusions: Therapy with a speech-language pathologist for EILO allowed for more frequent physical activity following therapy completion and decreased dyspnea symptoms 6-month posttherapy. Therapy was associated with a decrease in inhaler use. PedsQL scores indicated mildly poor health-related quality of life even after EILO symptoms improved. Findings support therapy as an effective treatment for EILO in teenage athletes and suggest that dyspnea symptoms may continue to improve following discharge as patients continue using therapy techniques.
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- 2023
18. Videostroboscopy Versus High-Speed Videoendoscopy: Factors Influencing Ratings of Laryngeal Oscillation
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Robert Brinton Fujiki, Caitlin K. Croegaert-Koch, and Susan L. Thibeault
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Speech and Hearing ,Linguistics and Language ,Language and Linguistics - Abstract
Purpose: The purpose of this study was to determine whether patient voice-related diagnosis, severity of dysphonia, and rater's experience influence the relationship between laryngeal oscillation ratings made from videostroboscopic and high-speed videoendoscopic (HSV) exams. Method: Stroboscopy and HSV exams from 15 patients with adductor spasmodic dysphonia (ADSD) and 15 with benign vocal fold lesions were rated for laryngeal oscillation and closure by 10 licensed speech-language pathologists (SLPs). Raters were divided into low- (< 5 years) and high-experience (> 5 years) groups. Ratings of vocal fold amplitude, mucosal wave, periodicity, phase symmetry, nonvibrating portion of the vocal fold, and glottal closure were examined using an online form adapted from the Voice Vibratory Assessment of Laryngeal Imaging (VALI). Results: Stroboscopy and HSV ratings were more strongly positively correlated for patients with benign vocal fold lesions ( r between .43 and .75) than for those with ADSD ( r between .40 and .68). Differences between stroboscopy and HSV exams were significantly greater for ratings of amplitude, mucosal wave, and periodicity in patients with ADSD than for patients with benign vocal fold lesions. Raters with < 5 years of experience showed significantly greater differences between stroboscopy and HSV ratings of amplitude and nonvibrating portion of the vocal fold for patients with ADSD only. Significantly greater differences between ratings of periodicity and phase symmetry were observed in patients with more severe dysphonia. Conclusions: Differences in laryngeal ratings made between HSV and stroboscopy exams may be influenced by patient diagnosis, severity of dysphonia, and rater experience. Future study is warranted to determine how the differences observed influence clinical diagnosis and outcomes.
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- 2023
19. Examining Relationships Between GRBAS Ratings and Acoustic, Aerodynamic and Patient-Reported Voice Measures in Adults With Voice Disorders
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Susan L. Thibeault and Robert Brinton Fujiki
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medicine.medical_specialty ,Range (music) ,GRBAS scale ,Audiology ,LPN and LVN ,Article ,Articulatory phonetics ,Laryngeal airway ,Speech and Hearing ,Otorhinolaryngology ,Quality of life ,Multiple objective ,otorhinolaryngologic diseases ,medicine ,Phonation ,Psychology ,Breathy voice - Abstract
SUMMARY Objective To determine if auditory-perceptual voice ratings performed using the GRBAS scale correlate with acoustic and aerodynamic measures of voice. A secondary aim was to examine the relationship between GRBAS ratings and patient-reported quality of life scales. Methods GRBAS ratings, acoustic, aerodynamic and patient-reported quality of life ratings were collected from the University of Wisconsin Madison Voice and Swallow Outcomes Database for 508 adults with voice disorders. Acoustic measures included noise to harmonic ratio, jitter%, shimmer%, highest fundamental frequency (F0) of vocal range, lowest F0 of vocal range, maximum phonation time and dysphonia severity index. Aerodynamic measures included phonation threshold pressure, subglottal pressure, mean transglottal airflow and laryngeal airway resistance. Patient-reported quality of life measures included the Vocal Handicap Index (VHI) and Glottal Function Index (GFI). Results GRBAS ratings were significantly correlated with several acoustic and aerodynamic measures, VHI and GFI. The strongest significant correlations for acoustic measures were observed between GRBAS ratings of overall voice quality and perturbation measures (jitter% r = 0.58, shimmer% r = 0.45, noise to harmonic ratio r = 0.36, Dysphonia Severity Index r = -0.56). The strongest significant correlation for aerodynamic voice measures was observed between GRBAS ratings of breathiness and transglottal airflow (r = 0.23), subglottal pressure (r = 0.49), and phonation threshold pressure (r = 0.26). GRBAS ratings were also significantly correlated with both VHI and the GFI scales. R values were higher for the VHI, but remained largely in low range for both scales. Conclusions Although GRBAS ratings were significantly correlated with multiple objective voice and patient related quality of life ratings, r values were low. These findings support the need for multiple voice measures when performing voice evaluations as no single voice measure was highly correlated with voice quality as measured by the GRBAS scale.
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- 2023
20. Pediatric Voice Therapy: How Many Sessions to Discharge?
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Robert Brinton Fujiki and Susan L. Thibeault
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Speech and Hearing ,Linguistics and Language ,Phonation ,Otorhinolaryngology ,Voice Quality ,Developmental and Educational Psychology ,Humans ,Vocal Cords ,Child ,Dysphonia ,Research Articles ,Patient Discharge - Abstract
Purpose: Voice therapy is the primary treatment for children presenting with benign morphological vocal fold changes. This study examined the number of voice therapy sessions required to meet treatment goals and identified factors that predicted treatment length for pediatric voice patients. Method: An observational cohort design was employed. Data were extracted from the University of Wisconsin–Madison Voice and Swallow Outcome Database. This study examined 62 children who completed a course of voice therapy with a speech-language pathologist (SLP) addressing dysphonia caused by benign vocal fold lesions. Extracted data included patient demographics, auditory-perceptual assessments, acoustic and aerodynamic voice measures, videostroboscopy ratings, and medical comorbidities. Linear regression was used to identify predictors of number of therapy sessions. Results: Patients received an average of 7.5 sessions of voice therapy prior to discharge. Baseline auditory-perceptual assessment of dysphonia ( p = .032), phonation threshold pressure (PTP, p = .005), Glottal Function Index (GFI) score ( p = .006), and glottic closure pattern ( p = .023) were significant predictors of number of voice therapy sessions. These measures, as well as hourglass glottic closure, predicted longer intervention duration. The regression model had an overall r 2 of .62. Conclusions: Pediatric voice therapy addressing benign vocal fold lesions and/or laryngeal edema required an average of 7.54 sessions before voice outcomes were sufficiently improved for discharge. More severe overall SLP ratings of dysphonia, GFI scores, PTP, or hourglass glottic closure pattern significantly predicted increased number of therapy sessions prior to discharge. Future work should determine what other factors affect treatment duration and how the efficiency of pediatric voice therapy can be maximized.
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- 2022
21. Localization of <scp>TRPV3</scp> /4 and <scp>PIEZO1</scp> /2 sensory receptors in murine and human larynges
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Alexander G. Foote, Julianna Tibbetts, Stephanie M. Bartley, and Susan L. Thibeault
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General Medicine - Abstract
The primary aim of this study was to identify expression of TRPV3 and TRPV4 chemoreceptors across perinatal and adult stages using a murine model with direct comparisons to human laryngeal mucosa. Our secondary aim was to establish novel cell expression patterns of mechanoreceptors PIEZO1 and PIEZO2 in human tissue samples.In vivoWe harvested murine laryngeal tissue to localize and describe TRPV3/4 endogenous protein expression patterns via immunofluorescence analyses across two developmental (E16.5, P0) and adult (6 weeks) timepoints. Additionally, we obtained a 60-year-old female larynx including the proximal trachea and esophagus to investigate TRPV3/4 and PIEZO1/2 protein expression patterns via immunofluorescence analyses for comparison to murine adult tissue.Murine TRPV3/4 expression was noted at E16.5 with epithelial cell colocalization to supraglottic regions of the arytenoids, aryepiglottic folds and epiglottis through to birth (P0), extending to the adult timepoint. Human TRPV3/4 protein expression was most evident to epithelium of the arytenoid region, with additional expression of TRPV3 and TRPV4 to proximal esophageal and tracheal epithelium, respectively. Human PIEZO1 expression was selective to differentiated, stratified squamous epithelia of the true vocal fold and esophagus, while PIEZO2 expression exhibited selectivity for intermediate and respiratory epithelia of the false vocal fold, ventricles, subglottis, arytenoid, and trachea.Results exhibited expression of TRPV3/4 chemoreceptors in utero, suggesting their importance during fetal/neonatal stages. TRPV3/4 and PIEZO1/2 were noted to adult murine and human laryngeal epithelium. Data indicates conservation of chemosensory receptors across species given similar regional expression in both the murine and human larynx.
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- 2022
22. Risk Factors for Dysphagia in Patients Hospitalized with COVID-19
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Anna Holdiman, Nicole Rogus-Pulia, Michael S. Pulia, Lily Stalter, and Susan L. Thibeault
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Speech and Hearing ,Otorhinolaryngology ,Gastroenterology - Abstract
Patients hospitalized with COVID-19 may be at risk for dysphagia and vulnerable to associated consequences. We investigated predictors for dysphagia and its severity in a cohort of patients hospitalized with COVID-19 at a single hospital center. A large level I trauma center database was queried for all patients hospitalized with COVID-19. Demographics, medical information associated with COVID-19, specific to dysphagia, and interventions were collected. 947 patients with confirmed COVID-19 met the criteria. 118 (12%) were seen for a swallow evaluation. Individuals referred for evaluation were significantly older, had a lower BMI, more severe COVID-19, and higher rates of intubation, pneumonia, mechanical ventilation, tracheostomy placements, prone positioning, and ARDS. Pneumonia (OR 3.57, p = 0.004), ARDS (OR 3.57, p = 0.029), prone positioning (OR 3.99, p = 0.036), ventilation (OR 4.01, p = 0.006), and intubation (OR 4.75, p = 0.007) were significant risk factors for dysphagia. Older patients were more likely to have more severe dysphagia such that for every 1-year increase in age, the odds of severe dysphagia were 1.04 times greater (OR 1.04, p = 0.028). Patients hospitalized with COVID-19 are at risk for dysphagia. We show predictive variables that should be considered when referring COVID-19 patients for dysphagia services to reduce time to intervention/evaluation.
- Published
- 2022
23. Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review
- Author
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Renee E. King, Andrea Bilger, Josef Rademacher, Paul F. Lambert, and Susan L. Thibeault
- Subjects
Otorhinolaryngology - Published
- 2023
24. Predictors of Voice Therapy Initiation: A Cross-Sectional Cohort Study
- Author
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Susan L. Thibeault, Jennylee Diaz, and Kevin Pasternak
- Subjects
Occupational voice ,education.field_of_study ,medicine.medical_specialty ,Voice Quality ,business.industry ,Voice therapy ,Population ,Attendance ,Dysphonia ,LPN and LVN ,Severity of Illness Index ,Voice Disorder ,Cohort Studies ,Speech and Hearing ,Cross-Sectional Studies ,Otorhinolaryngology ,Voice handicap index score ,Physical therapy ,Humans ,Medicine ,Child ,business ,education ,Breathy voice ,Cohort study - Abstract
Summary Objectives/Hypothesis To determine predictors of voice therapy initiation. Study Design Cross-sectional cohort study. Methods All patients were evaluated in an interdisciplinary model at the University of Wisconsin Voice and Swallow Clinics between June 2016 and October 2017. Patients were eligible if they were diagnosed with a voice disorder and recommended for voice therapy as the only treatment. The dependent variable was attendance in at least once voice therapy session. Independent variables included therapeutic alliance, measured using the Session Rating Scale, and patient- and disease-related factors. These factors included gender, age, distance to the clinic, education level, household composition, occupational voice demand, Voice Handicap Index score, auditory-perceptual dysphonia severity (Grade, Roughness, Breathiness, Asthenia, Strain), and medical voice diagnosis. Results Ninety-five patients were enrolled in the study. Voice therapy initiation rate was 70%. Having fewer school-aged children (5-18 years) in the household was significantly different between the group that initiated voice therapy and the group that did not (P = 0.048). There was no difference between groups for all other factors. Conclusions This investigation suggests that household composition, specifically having fewer school-aged children in the household, may predict initiation of voice therapy. This study confirms in a prospective fashion the absence of relationship between voice therapy initiation and most patient- and disease-related factors. Therapeutic alliance should be further investigated for its ability to predict voice therapy initiation using a measure that is validated for the population of patients with dysphonia.
- Published
- 2022
25. Setting Up for Success: Strategies to Foster Surgeons’ Pursuit of Basic Science Research
- Author
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Esra Alagoz, Susan L. Thibeault, Angela Gibson, Keon Young Park, and Devon Livingston-Rosanoff
- Subjects
Surgeons ,Medical education ,Biomedical Research ,Mentors ,education ,Psychological intervention ,Achievement ,Surgeon scientist ,Article ,Leadership ,Science research ,Work (electrical) ,Content analysis ,Humans ,Surgery ,Psychology ,Active support - Abstract
Background Surgeons make important contributions to basic science research and are in a unique position to innovate scientifically. The number of surgeons pursuing basic science research has been declining over the past two decades. We sought to describe perceived barriers to surgeons’ pursuit of basic science research and identify interventions that mitigate these obstacles. Materials & Methods An online survey was sent to chairs of academic surgery departments and practicing surgeons involved in basic science research. A subset of these participants were interviewed about their experiences. Interviews were audio-recorded, transcribed, and uploaded to NVivo. Two coders developed a codebook using inductive content analysis to identify relevant themes. Results 97 people responded to the survey, 27 (29%) were department chairs. Major barriers to basic science research for all respondents were lack of funding, clinical duties and lack of dedicated time for research. Nine surgeons and three departmental chairs were subsequently interviewed. The importance of having clear research goals and timetables with specific plans for attaining funding were mentioned by all. Chairs described the usefulness of embedding early surgeon scientists in their scientific mentors’ labs in a post-doctoral model. Additionally, departmental leaders must actively work to protect surgeon scientists from encroaching clinical and administrative demands. Conclusions While barriers to surgeons’ pursuit of basic science research exist, the surgeon scientist is a phenotype that can be fostered with the dedication and commitment of surgeons to continue to pursue science research and active support of departmental leadership.
- Published
- 2021
26. Voice Therapy According to the Rehabilitation Treatment Specification System: Expert Consensus Ingredients and Targets
- Author
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Shirley Gherson, John Whyte, Joseph R. Duffy, Nelson Roy, Joseph C. Stemple, Jarrad H. Van Stan, Julie Barkmeier-Kraemer, Carol Jorgensen Tolejano, Brian Petty, Lisa Kelchner, Susan L. Thibeault, Jason Muise, and Patricia Doyle
- Subjects
Linguistics and Language ,medicine.medical_specialty ,Consensus ,Rehabilitation ,Delphi Technique ,Voice therapy ,business.industry ,medicine.medical_treatment ,Expert consensus ,Voice Treatment ,Clinical trial ,Speech and Hearing ,Physical medicine and rehabilitation ,Otorhinolaryngology ,Research Design ,Developmental and Educational Psychology ,medicine ,Humans ,Speech ,business ,Research Articles - Abstract
Purpose Clinical trials have demonstrated that standardized voice treatment programs are effective for some patients, but identifying the unique individual treatment ingredients specifically responsible for observed improvements remains elusive. To address this problem, the authors used a taxonomy of voice therapy, the Rehabilitation Treatment Specification System (RTSS), and a Delphi process to develop the RTSS-Voice (expert consensus categories of measurable and unique voice treatment ingredients and targets). Method Initial targets and ingredients were derived from a taxonomy of voice therapy. Through six Delphi Rounds, 10 vocal rehabilitation experts rated the measurability and uniqueness of individual treatment targets and ingredients. After each round, revisions (guided by the experts' feedback) were finalized among a primary reader (a voice therapy expert) and two external readers (rehabilitation experts outside the field of voice). Consensus was established when the label and definition of an ingredient or target reached a supramajority threshold (≥ 8 of 10 expert agreement). Results Thirty-five target and 19 ingredient categories were agreed to be measurable, unique, and accurate reflections of the rules and terminology of the RTSS. Operational definitions for each category included differences in the way ingredients are delivered and the way individual targets are modified by those ingredients. Conclusions The consensus labels and operationalized ingredients and targets making up the RTSS-Voice have potential to improve voice therapy research, practice, and education/training. The methods used to develop these lists may be useful for other speech, language, and hearing treatment specifications. Supplemental Material https://doi.org/10.23641/asha.15243357
- Published
- 2021
27. Economic Burden Associated With Management of Paradoxical Vocal Fold Motion Disorder
- Author
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David O. Francis, Susan L. Thibeault, and Tadeas Lunga
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Speech therapy ,Indirect costs ,Cost of Illness ,Interquartile range ,Health care ,medicine ,Paradoxical Vocal Fold Motion Disorder ,Humans ,health care economics and organizations ,Retrospective Studies ,Asthma ,business.industry ,Health Care Costs ,Evidence-based medicine ,Middle Aged ,medicine.disease ,Dyspnea ,Treatment Outcome ,Vocal Cord Dysfunction ,Otorhinolaryngology ,Female ,business ,Time to diagnosis - Abstract
OBJECTIVES Paradoxical vocal fold movement (PVFM) is often misdiagnosed as asthma and tends to have a prolonged time to diagnosis. Study aims were to estimate the time from dyspnea onset to PVFM diagnosis, to estimate associated pre- and postdiagnosis direct and indirect healthcare cost, and to compare the cost of postdiagnosis care among patients who did and did not undergo standard-of-care speech therapy. METHODS Patients diagnosed with PVFM were identified retrospectively. Time from dyspnea symptom onset to diagnosis was measured. Direct costs consisting of office visits, procedures, and prescribed pharmaceuticals before and after diagnosis were calculated. Indirect costs associated with lost wages related to healthcare were also estimated. Costs for patients who initiated versus did not initiate speech therapy and who had successful versus unsuccessful therapy were compared. RESULTS Among 110 patients, median time from dyspnea onset to PVFM diagnosis was 33 months (interquartile range [IQR] 5-60). Direct and indirect prediagnosis median costs were $8,625 (IQR $1,687-$35,812) and $736 (IQR $421-$1,579) while first year following dyspnea symptom onset median direct and indirect costs were $1,706 (IQR $427-$7,118) and $315 (IQR $131-$631). Median direct and indirect costs of care in the postdiagnosis year were $2,062 (IQR $760-$11,496) and $841 (IQR $631-$1,261). Pharmaceuticals were predominant cost drivers in all time periods. Of those who completed speech therapy, 85% had breathing symptom improvement while incurring significant cost savings compared to those whose symptoms persisted. CONCLUSION Costs of care leading to diagnosis of PVFM are substantial. More efficient methods of identifying patients with PVFM are essential to reduce prolonged time to diagnosis and associated costs. LEVEL OF EVIDENCE N/A Laryngoscope, 2021.
- Published
- 2021
28. Inactivation of Lats1 and Lats2 highlights the role of hippo pathway effector YAP in larynx and vocal fold epithelium morphogenesis
- Author
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Vlasta Lungova, Susan L. Thibeault, Vidisha Mohad, and Jamie M. Verheyden
- Subjects
Male ,Morphogenesis ,Cell Cycle Proteins ,Vocal Cords ,Basement membrane organization ,Protein Serine-Threonine Kinases ,Biology ,Epithelium ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Animals ,Hippo Signaling Pathway ,Cell adhesion ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,Hippo signaling pathway ,Kinase ,Tumor Suppressor Proteins ,Embryogenesis ,Cell Differentiation ,Epithelial Cells ,YAP-Signaling Proteins ,Cell Biology ,Cell biology ,Mice, Inbred C57BL ,Hippo signaling ,Laryngeal Muscle ,Female ,Larynx ,030217 neurology & neurosurgery ,Signal Transduction ,Transcription Factors ,Developmental Biology - Abstract
Proliferation and differentiation of vocal fold epithelial cells during embryonic development is poorly understood. We examined the role of Hippo signaling, a vital pathway known for regulating organ size, in murine laryngeal development. Conditional inactivation of the Hippo kinase genes Lats1 and Lats2, specifically in vocal fold epithelial cells, resulted in severe morphogenetic defects. Deletion of Lats1 and Lats2 caused abnormalities in epithelial differentiation, epithelial lamina separation, cellular adhesion, basement membrane organization with secondary failed cartilage, and laryngeal muscle development. Further, Lats1 and Lats2 inactivation led to failure in differentiation of p63+ basal progenitors. Our results reveal novel roles of Hippo-Lats-YAP signaling in proper regulation of VF epithelial fate and larynx morphogenesis.
- Published
- 2021
29. Piezo1-expressing vocal fold epithelia modulate remodeling via effects on self-renewal and cytokeratin differentiation
- Author
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Alexander G. Foote, Vlasta Lungova, and Susan L. Thibeault
- Subjects
Pharmacology ,Cellular and Molecular Neuroscience ,Molecular Medicine ,Keratins ,Hedgehog Proteins ,Epithelial Cells ,Cell Biology ,Vocal Cords ,Molecular Biology ,Epithelium - Abstract
Mechanoreceptors are implicated as functional afferents within mucosa of the airways and the recent discovery of mechanosensitive channels Piezo1 and Piezo2 has proved essential for cells of various mechanically sensitive tissues. However, the role for Piezo1/2 in vocal fold (VF) mucosal epithelia, a cell that withstands excessive biomechanical insult, remains unknown. The purpose of this study was to test the hypothesis that Piezo1 is required for VF mucosal repair pathways of epithelial cell injury. Utilizing a sonic hedgehog (shh) Cre line for epithelial-specific ablation of Piezo1/2 mechanoreceptors, we investigated 6wk adult VF mucosa following naphthalene exposure for repair strategies at 1, 3, 7 and 14 days post-injury (dpi). PIEZO1 localized to differentiated apical epithelia and was paramount for epithelial remodeling events. Injury to wildtype epithelium was most appreciated at 3 dpi. Shhcre/+; Piezo1loxP/loxP, Piezo2 loxP/+ mutant epithelium exhibited severe cell/nuclear defects compared to injured controls. Conditional ablation of Piezo1 and/or Piezo2 to uninjured VF epithelium did not result in abnormal phenotypes across P0, P15 and 6wk postnatal stages compared to heterozygote and control tissue. Results demonstrate a role for Piezo1-expressing VF epithelia in regulating self-renewal via effects on p63 transcription and YAP subcellular translocation—altering cytokeratin differentiation.
- Published
- 2022
30. Voice Therapy Improves Acoustic and Auditory-Perceptual Outcomes in Children
- Author
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Robert Brinton Fujiki, Maia Braden, and Susan L. Thibeault
- Subjects
Otorhinolaryngology - Abstract
This study employed acoustic measures as well as auditory-perceptual assessments to examine the effects of voice therapy in children presenting with benign vocal fold lesions.A retrospective, observational cohort design was employed. Sustained vowels produced by 129 children diagnosed with benign vocal fold lesions were analyzed, as well as connected speech samples produced by 47 children. Treatment outcome measures included Consensus of Auditory-Perceptual Evaluation of Voice (CAPE-V), jitter, shimmer, Noise-to-Harmonic Ratio (NHR), cepstral peak prominence (CPP), and Low-to-High Ratio (LHR) on sustained vowels, and CPP and LHR on connected speech.Following voice therapy, significant improvements in CAPE-V ratings (p 0.001) were observed. Additionally, jitter (p = 0.041), NHR (p = 0.019), and CPP (p 0.01) on sustained vowels, and CPP (p = 0.002), and LHR (p = 0.008) on connected speech significantly improved following voice therapy. CPP increased with age in males but did not change in females. CAPE-V ratings and perturbation measures indicated that dysphonia was more severe in younger children pre and post-therapy.Auditory-perceptual and acoustic measures demonstrated improved voice quality following voice therapy in children with dysphonia. CPP effectively quantified voice therapy gains and allowed for analysis of connected speech, in addition to sustained vowels. These findings demonstrate the value of CPP as a tool in assessing therapy outcomes and support the efficacy of voice therapy for children presenting with vocal fold lesions.4 Laryngoscope, 2022.
- Published
- 2022
31. Patient-Reported Qualitative Analysis of Chronic Refractory Cough
- Author
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Miranda L. Wright, Robert Brinton Fujiki, Tadeas Lunga, and Susan L. Thibeault
- Subjects
Male ,Linguistics and Language ,Middle Aged ,Speech and Hearing ,Otorhinolaryngology ,Cough ,Chronic Disease ,Developmental and Educational Psychology ,Quality of Life ,Humans ,Female ,Patient Reported Outcome Measures ,Prospective Studies ,Qualitative Research - Abstract
Purpose: Chronic cough has been shown to be associated with adverse effects on quality of life. There is a paucity of research characterizing quality-of-life factors associated with chronic refractory cough (CRC), a cough persisting > 8 weeks despite evaluation and treatment of possible etiologies. The purpose of this study was to elucidate the features of CRC from the patient's perspective, including presenting symptoms, past treatment methods, and quality-of-life factors. Method: Prospective semistructured interviews were conducted, recorded, and transcribed for 20 patients diagnosed with CRC. Exclusion criteria included lung disease, smoking history, laryngeal cancer, and neurological disease. Grounded theory analysis was completed on transcribed interviews. Results: Eighteen participants were women. Mean participant age was 53.5 years ( SD = 1.41), and average cough duration was 52 months ( SD = 71.6 months). Responses to 30 open-ended questions revealed four dominant themes with 24 subthemes. Conclusions: CRC affects patient quality of life. Understanding patient perspective on CRC diagnosis and treatment helps providers better understand the physical and emotional toll CRC takes on patients. Findings suggest that providers should spend more time counseling patients regarding their treatment and diagnosis, as patients with CRC do not always fully understand their diagnosis and resort to self-blame.
- Published
- 2022
32. Sensory Innervation of the Larynx and the Search for Mucosal Mechanoreceptors
- Author
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Alexander G. Foote and Susan L. Thibeault
- Subjects
0301 basic medicine ,Larynx ,Linguistics and Language ,Sensory system ,Somatosensory system ,Mechanotransduction, Cellular ,Language and Linguistics ,03 medical and health sciences ,Speech and Hearing ,Superior laryngeal nerve ,0302 clinical medicine ,medicine ,Persistent cough ,Animals ,Humans ,Speech ,Mechanotransduction ,030223 otorhinolaryngology ,Mucous Membrane ,business.industry ,Laryngeal Nerves ,Mechanoreceptor ,030104 developmental biology ,medicine.anatomical_structure ,Reflex ,business ,Mechanoreceptors ,Neuroscience - Abstract
Purpose The larynx is a uniquely situated organ, juxtaposed between the gastrointestinal and respiratory tracts, and endures considerable immunological challenges while providing reflexogenic responses via putative mucosal mechanoreceptor afferents. Laryngeal afferents mediate precise monitoring of sensory events by relay to the internal branch of the superior laryngeal nerve (iSLN). Exposure to a variety of stimuli (e.g., mechanical, chemical, thermal) at the mucosa–airway interface has likely evolved a diverse array of specialized sensory afferents for rapid laryngeal control. Accordingly, mucosal mechanoreceptors in demarcated laryngeal territories have been hypothesized as primary sources of sensory input. The purpose of this article is to provide a tutorial on current evidence for laryngeal afferent receptors in mucosa, the role of mechano-gated ion channels within airway epithelia and mechanisms for mechanoreceptors implicated in laryngeal health and disease. Method An overview was conducted on the distribution and identity of iSLN-mediated afferent receptors in the larynx, with specific focus on mechanoreceptors and their functional roles in airway mucosa. Results/Conclusions Laryngeal somatosensation at the cell and molecular level is still largely unexplored. This tutorial consolidates various animal and human researches, with translational emphasis provided for the importance of mucosal mechanoreceptors to normal and abnormal laryngeal function. Information presented in this tutorial has relevance to both clinical and research arenas. Improved understanding of iSLN innervation and corresponding mechanotransduction events will help shed light upon a variety of pathological reflex responses, including persistent cough, dysphonia, and laryngospasm.
- Published
- 2021
33. Relationship Between Auditory-Perceptual and Objective Measures of Resonance in Children with Cleft Palate: Effects of Intelligibility and Dysphonia
- Author
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Robert Brinton Fujiki, George Kostas, and Susan L. Thibeault
- Subjects
Otorhinolaryngology ,Oral Surgery - Abstract
To investigate the relationship between auditory-perceptual ratings of resonance and nasometry scores in children with cleft palate. Factors which may impact this relationship were examined including articulation, intelligibility, dysphonia, sex, and cleft-related diagnosis. Retrospective, observational cohort study Outpatient pediatric cranio-facial anomalies clinic Four hundred patients Relationship between auditory-perceptual ratings of resonance and nasometry scores Pearson's correlations indicated that auditory-perceptual resonance ratings and nasometry scores were significantly correlated across oral-sound stimuli on the picture-cued portion of the MacKay-Kummer SNAP-R Test (r values .69 to.72) and the zoo reading passage (r = .72). Linear regression indicated that intelligibility ( p ≤ .001) and dysphonia ( p = .009) significantly impacted the relationship between perceptual and objective assessments of resonance on the Zoo passage. Moderation analyses indicated that the relationship between auditory-perceptual and nasometry values weakened as severity of speech intelligibility increased ( P Speech intelligibility and dysphonia alter the relationship between auditory-perceptual and nasometry assessments of hypernasality in children with cleft palate. SLPs should be aware of potential sources of auditory-perceptual bias and shortcomings of the Nasometer when following patients with limited intelligibility or moderate dysphonia. Future study may identify the mechanisms by which intelligibility and dysphonia affect auditory-perceptual and nasometry evaluations.
- Published
- 2023
34. The Relationship Between Auditory-Perceptual Rating Scales and Objective Voice Measures in Children With Voice Disorders
- Author
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Robert Brinton Fujiki and Susan L. Thibeault
- Subjects
Linguistics and Language ,medicine.medical_specialty ,Voice Quality ,media_common.quotation_subject ,Concurrent validity ,Audiology ,Speech Acoustics ,030507 speech-language pathology & audiology ,03 medical and health sciences ,Speech and Hearing ,0302 clinical medicine ,Rating scale ,Perception ,Developmental and Educational Psychology ,medicine ,Humans ,Child ,030223 otorhinolaryngology ,Breathy voice ,media_common ,Observer Variation ,Voice Disorders ,Reproducibility of Results ,Acoustics ,Dysphonia ,Otorhinolaryngology ,0305 other medical science ,Psychology - Abstract
Purpose The purpose of this study was to determine concurrent validity of the Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) and Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) auditory-perceptual scales in children with voice disorders. A secondary purpose was to determine correlation between the GRBAS, CAPE-V, and objective voice measures. Method GRBAS and CAPE-V ratings and acoustic and aerodynamic measures were collected from the University of Wisconsin–Madison Voice and Swallow Outcomes Database. Correlations between CAPE-V and GRBAS ratings were calculated for overall severity of dysphonia, roughness, breathiness, and strain. Correlations between auditory-perceptual voice ratings and objective voice measures were also examined. Results One hundred thirty GRBAS and CAPE-V auditory-perceptual ratings were significantly correlated for overall severity, roughness, breathiness, and strain. r 2 values were highest for overall severity of dysphonia ( r 2 = .75) and lowest for strain ( r 2 = .54). CAPE-V and GRBAS ratings were largely associated with similar acoustic and aerodynamic measures. The highest correlations were observed for auditory-perceptual ratings of breathiness and jitter% (CAPE-V r 2 = .44, GRBAS r 2 = .44), shimmer% (CAPE-V r 2 = .45, GRBAS r 2 = .45), noise-to-harmonic ratio (CAPE-V r 2 = .42, GRBAS r 2 = .40), fundamental frequency (CAPE-V r 2 = .47, GRBAS r 2 = .44), and maximum phonation time (CAPE-V r 2 = .56, GRBAS r 2 = .51). Akaike information criterion values indicated that CAPE-V ratings were more strongly correlated with objective voice measures than GRBAS ratings. Conclusions CAPE-V and GRBAS scales have concurrent validity in children with voice disorders. CAPE-V ratings are more strongly correlated with acoustic and aerodynamic voice measures.
- Published
- 2021
35. Correlation Between EAT-10 and Aspiration Risk Differs by Dysphagia Etiology
- Author
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Mary K. Kenz, Rebecca S. Bartlett, Susan L. Thibeault, and Heidi A. Wayment
- Subjects
medicine.medical_specialty ,business.industry ,digestive, oral, and skin physiology ,Head and neck cancer ,Gastroenterology ,Disease ,medicine.disease ,Dysphagia ,Speech and Hearing ,Otorhinolaryngology ,Swallowing ,Internal medicine ,Etiology ,medicine ,medicine.symptom ,business ,Stroke ,Oropharyngeal dysphagia - Abstract
Agreement between self-reported dysphagic symptoms and actual swallowing physiology can vary widely across individuals. The Eating Assessment Tool-10 (EAT-10) is a self-report questionnaire commonly used to identify individuals with oropharyngeal dysphagia, but its interpretation for highly prevalent populations is poorly defined. Our primary objective was to determine if correlation strength between EAT-10 and Penetration-Aspiration Scale (PAS) scores differed by dysphagia etiology. Our secondary objective was to identify clinical factors that were associated with a mismatch between EAT-10 scores and videofluoroscopic findings. Outpatients with Parkinson disease (PD), stroke, and/or head and neck cancer (HNC) who completed EAT-10 and underwent videofluoroscopy were included (n = 203). EAT-10/PAS correlations were calculated by dysphagia etiology. We found that across the sample, higher EAT-10 scores were significantly correlated to higher PAS scores (rs = 0.31, p < 0.001). EAT-10 and PAS were moderately correlated in the HNC group (rs = 0.41, p < 0.001, n = 87), but correlations were modest in the PD (rs = 0.18, n = 41) and stroke groups (rs = 0.12, n = 59). Clinical characteristics of individuals with a "matched" profile (normal EAT-10 score and normal swallow physiology) and a "mismatched" profile (normal EAT-10 score and abnormal swallow physiology) were also compared. Individuals with a "mismatched" EAT-10/PAS profile appeared to be significantly older and had a worse Charlson Comorbidity Index than individuals with a "matched" profile. Within the HNC subgroup, EAT-10/PAS correlations for specific tumor sites, treatment types, and time since treatment are reported. Clinicians may consider these aspiration risk profiles when making recommendations for instrumented swallowing assessment.
- Published
- 2021
36. Vocal fold mucus layer: Comparison of histological protocols for visualization in mice
- Author
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Ran An, Daniel Robbins, Federico E. Rey, and Susan L. Thibeault
- Subjects
General Medicine - Abstract
The epithelial associated mucus layer of vocal fold (VF) mucosa, plays an essential role in protecting and lubricating the tissue, as well as promoting normal voice quality. Serving as a habitat for laryngeal microbiota involved in the regulation of host immunity, VF mucus contributes to laryngeal health and disease. However, its unstable structure renders its' investigation challenging. We aim to establish a reproducible histological protocol to recover the natural appearance of the VF mucus layer for investigation.Using a murine model, we compared the suitability of multiple fixation methods-methacarn, formalin, and cryopreservation followed by post-fixation with formalin, paraformaldehyde (PFA), acetone, and two staining methods-Alcian Blue (pH 2.5)/Periodic Acid Schiff (AB/PAS) or PAS. Fixation and staining outcomes were evaluated based on the preservation of tissue morphology and mucus layer integrity. Mucin proteins, Muc1 and Muc4, were stained to validate the presence of mucus layer overlaying the VF mucosa.Methacarn fixation followed by PAS staining was capable of preserving and displaying the smooth and continuous mucus layer, ensuring the determination of mucus thickness and mucin staining.Our study if the first to establish a histological protocol for the visualization of the in situ VF mucus layer whereby facilitating the study of VF mucus biology including VF surface hydration, ion/nutrients transports, biomechanical properties that maintains normal voice quality as well as VF pathophysiology and host-microbe interactions in the larynx.N/A.
- Published
- 2021
37. Are Children with Cleft Palate at Increased Risk for Laryngeal Pathology?
- Author
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Robert Brinton Fujiki and Susan L. Thibeault
- Subjects
Otorhinolaryngology ,Oral Surgery - Abstract
To determine the prevalence of laryngeal pathology in children presenting with cleft palate with or without cleft lip (CP ± L) who underwent nasoendoscopy to assess palatal function. A secondary aim was to determine the relationship between patient demographics, resonance, articulation, and prevalence of laryngeal pathology in this population. Retrospective, observational cohort study Outpatient pediatric cranio-facial anomalies clinic Children ≤18 years of age presenting with CP ± L (N = 215) who underwent nasoendoscopy, speech language pathology, plastic surgery, and otolaryngological evaluations between 2009 and 2020. Laryngeal diagnosis by pediatric otolaryngologists. 21.9% of children presented with laryngeal pathology. Diagnoses included benign vocal fold lesions and laryngeal edema sufficiently severe to alter vocal fold edge contour. Likelihood of laryngeal pathology increased by approximately 12% with every increase of 1 year in age ( P = .001, OR = 1.12). Children with laryngeal pathology were 50% more likely to have undergone palatal repair ( P This population is at increased risk for laryngeal pathologies as determined by nasoendoscopy. This finding underscores the importance of careful laryngeal imaging in assessing these children. Additional research is warranted to identify the mechanisms underlying the increased risk for morphological vocal fold changes.
- Published
- 2022
38. Tissue specific human fibroblast differential expression based on RNAsequencing analysis
- Author
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Christina Kendziorski, Alexander G. Foote, Ziyue Wang, and Susan L. Thibeault
- Subjects
0106 biological sciences ,Adult ,Male ,Human vocal fold fibroblast ,Cell signaling ,lcsh:QH426-470 ,lcsh:Biotechnology ,Biology ,01 natural sciences ,Extracellular matrix ,Mechanobiology ,03 medical and health sciences ,lcsh:TP248.13-248.65 ,Gene expression ,Genetics ,medicine ,Humans ,Epigenetics ,Fibroblast ,Vocal fold biology ,Tissue homeostasis ,030304 developmental biology ,Transcriptome profiling ,0303 health sciences ,Sequence Analysis, RNA ,Gene Expression Profiling ,Fibroblasts ,Phenotype ,Cell biology ,lcsh:Genetics ,medicine.anatomical_structure ,Functional gene expression ,Mechanical force ,Organ Specificity ,Female ,Signal transduction ,RNA-seq ,010606 plant biology & botany ,Biotechnology ,Research Article - Abstract
Background Physical forces, such as mechanical stress, are essential for tissue homeostasis and influence gene expression of cells. In particular, the fibroblast has demonstrated sensitivity to extracellular matrices with assumed adaptation upon various mechanical loads. The purpose of this study was to compare the vocal fold fibroblast genotype, known for its unique mechanically stressful tissue environment, with cellular counterparts at various other anatomic locales to identify differences in functional gene expression profiles. Results By using RNA-seq technology, we identified differentially expressed gene programs (DEseq2) among seven normal human fibroblast primary cell lines from healthy cadavers, which included: vocal fold, trachea, lung, abdomen, scalp, upper gingiva, and soft palate. Unsupervised gene expression analysis yielded 6216 genes differentially expressed across all anatomic sites. Hierarchical cluster analysis revealed grouping based on anatomic site origin rather than donor, suggesting global fibroblast phenotype heterogeneity. Sex and age-related effects were negligible. Functional enrichment analyses based on separate post-hoc 2-group comparisons revealed several functional themes within the vocal fold fibroblast related to transcription factors for signaling pathways regulating pluripotency of stem cells and extracellular matrix components such as cell signaling, migration, proliferation, and differentiation potential. Conclusions Human fibroblasts display a phenomenon of global topographic differentiation, which is maintained in isolation via in vitro assays. Epigenetic mechanical influences on vocal fold tissue may play a role in uniquely modelling and maintaining the local environmental cellular niche during homeostasis with vocal fold fibroblasts distinctly specialized related to their anatomic positional and developmental origins established during embryogenesis. Electronic supplementary material The online version of this article (10.1186/s12864-019-5682-5) contains supplementary material, which is available to authorized users.
- Published
- 2019
39. Safety and Tolerability of Pharyngeal High-Resolution Manometry
- Author
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Stevie Marvin, Susan L. Thibeault, and Molly A. Knigge
- Subjects
Male ,Linguistics and Language ,medicine.medical_specialty ,Manometry ,Severity of Illness Index ,Catheterization ,Gagging ,030507 speech-language pathology & audiology ,03 medical and health sciences ,Speech and Hearing ,0302 clinical medicine ,Developmental and Educational Psychology ,medicine ,Humans ,Prospective Studies ,030223 otorhinolaryngology ,High resolution manometry ,Device Removal ,Aged ,Aged, 80 and over ,business.industry ,Swallowing Disorders ,Pharyngitis ,Middle Aged ,Deglutition ,Catheter ,Upper aerodigestive tract ,Cough ,Otorhinolaryngology ,Tolerability ,Pharynx ,Female ,Radiology ,Nasal Cavity ,Deglutition Disorders ,0305 other medical science ,business - Abstract
Purpose Pharyngeal high-resolution manometry is an emerging practice for diagnosis of swallowing disorders in the upper aerodigestive tract. Advancement of a catheter through the upper esophageal sphincter may introduce safety considerations. There are no published studies of catheter placement complications, side effects, or tolerability. This study examines patient-reported side effects and tolerability of pharyngeal high-resolution manometry. Method Data were collected prospectively from 133 adult patients who underwent pharyngeal high-resolution manometry for the 1st time. Patients rated tolerability specific to “nose” and “throat” using a visual analog scale for 4 procedure time points: catheter passage, during the procedure, catheter removal, and after the procedure. Complications during catheter passage and removal were recorded. A telephone call was placed to the patient within 6 days to survey side effects experienced after the procedure. Results The patient sample was composed of 91 males and 42 females with a mean age of 66 years ( SD = 14.4). Tolerability scores for catheter passage showed no significant difference ( p = .7288) in the nose versus throat. Tolerability for females was significantly less ( p = .0144) than that for males. Participants with the shortest procedure duration showed greatest discomfort in the nose ( p = .0592) and throat ( p = .0286). Complications included gag response (14%), emesis (2%), and epistaxis (< 1%). Side effects included sore throat (16%), nose discomfort (16%), coughing (11 %), nosebleed (4%), and nausea/vomiting (4%). Conclusions High-resolution manometry appears to have high patient tolerability with low incidence of side effects. Rates of complications and side effects are similar to those reported for other transnasal procedures.
- Published
- 2019
40. Prospective Investigation of Incidence and Co-Occurrence of Dysphagia, Dysarthria, and Aphasia Following Ischemic Stroke
- Author
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Kaila L. Stipancic, James C. Borders, Danielle Brates, and Susan L. Thibeault
- Subjects
Male ,Linguistics and Language ,Pediatrics ,medicine.medical_specialty ,Comorbidity ,030507 speech-language pathology & audiology ,03 medical and health sciences ,Speech and Hearing ,Dysarthria ,Wisconsin ,0302 clinical medicine ,Swallowing ,Aphasia ,Developmental and Educational Psychology ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Stroke ,Aged ,Aged, 80 and over ,business.industry ,Incidence ,Incidence (epidemiology) ,Middle Aged ,medicine.disease ,Dysphagia ,Otorhinolaryngology ,Female ,medicine.symptom ,Deglutition Disorders ,0305 other medical science ,business ,030217 neurology & neurosurgery - Abstract
Purpose The high incidence of swallowing and communication disorders following stroke is well documented. However, many of these studies have used retrospective chart reviews to make estimates of incidence and co-occurrence. The current study prospectively examined the incidence and co-occurrence of dysphagia, dysarthria, and aphasia following a 1st occurrence of ischemic stroke at an academic medical center hospital. Method One hundred patients who experienced their 1st ischemic stroke were recruited for participation in this study. All participants received a clinical swallowing evaluation to assess for dysphagia, administration of the Frenchay Dysarthria Assessment–Second Edition ( Enderby & Palmer, 2008 ) and Western Aphasia Battery–Revised ( Kertesz, 2006 ) to screen for the presence of dysarthria and aphasia, respectively. Results Incidence rates of dysphagia, dysarthria, and aphasia were 32%, 26%, and 16%, respectively. Forty-seven percent of participants had at least 1 of these disorders, 28% had 2 of these disorders, and 4% had all 3. Although the incidence rates in this study were smaller in magnitude than incidence rates in previous research, the pattern of results is broadly similar (i.e., dysphagia had the highest incidence rate, followed by dysarthria and, lastly, aphasia). Conclusions This prospective study yielded slightly lower incidence rates than have been previously obtained from retrospective chart reviews. The high incidence and co-occurrence of devastating swallowing and communication disorders post–ischemic stroke provides clear motivation for speech-language pathology involvement in the early phase of stroke rehabilitation.
- Published
- 2019
41. Mechanotransduction of vocal fold fibroblasts and mesenchymal stromal cells in the context of the vocal fold mechanome
- Author
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Susan L. Thibeault, Joel Gaston, Shuyun Ye, Christina Kendziorski, and Rebecca S. Bartlett
- Subjects
Cell type ,0206 medical engineering ,Biomedical Engineering ,Biophysics ,Context (language use) ,Vocal Cords ,02 engineering and technology ,Biology ,Mechanotransduction, Cellular ,Vibration ,Article ,Focal adhesion ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Tissue engineering ,medicine ,Humans ,Orthopedics and Sports Medicine ,Mechanotransduction ,Tissue Engineering ,Rehabilitation ,Mesenchymal stem cell ,Bayes Theorem ,Mesenchymal Stem Cells ,Fibroblasts ,020601 biomedical engineering ,Extracellular Matrix ,Cell biology ,medicine.anatomical_structure ,Vocal folds ,Stress, Mechanical ,030217 neurology & neurosurgery - Abstract
The design of cell-based therapies for vocal fold tissue engineering requires an understanding of how cells adapt to the dynamic mechanical forces found in the larynx. Our objective was to compare mechanotransductive processes in therapeutic cell candidates (mesenchymal stromal cells from adipose tissue and bone marrow, AT-MSC and BM-MSC) to native cells (vocal fold fibroblasts-VFF) in the context of vibratory strain. A bioreactor was used to expose VFF, AT-MSC, and BM-MSC to axial tensile strain and vibration at human physiological levels. Microarray, an empirical Bayes statistical approach, and geneset enrichment analysis were used to identify significant mechanotransductive pathways associated with the three cell types and three mechanical conditions. Two databases (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes) were used for enrichment analyses. VFF shared more mechanotransductive pathways with BM-MSC than with AT-MSC. Gene expression that appeared to distinguish the vibratory strain condition from polystyrene condition for these two cells types related to integrin activation, focal adhesions, and lamellipodia activity, suggesting that vibratory strain may be associated with cytoarchitectural rearrangement, cell reorientation, and extracellular matrix remodeling. In response to vibration and tensile stress, BM-MSC better mimicked VFF mechanotransduction than AT-MSC, providing support for the consideration of BM-MSC as a cell therapy for vocal fold tissue engineering. Future research is needed to better understand the sorts of physical adaptations that are afforded to vocal fold tissue as a result of focal adhesions, integrins, and lamellipodia, and how these adaptations could be exploited for tissue engineering.
- Published
- 2019
42. Derivation of Three-Dimensional Human Induced Pluripotent Stem Cell-Derived Vocal Fold Mucosa for Clinical and Pharmacological Applications
- Author
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Susan L. Thibeault and Vlasta Lungova
- Subjects
Cell type ,Induced Pluripotent Stem Cells ,Cell Differentiation ,Epithelial Cells ,Stratified squamous epithelium ,Inflammation ,Vocal Cords ,respiratory system ,Biology ,Article ,Epithelium ,Cell biology ,medicine.anatomical_structure ,Tissue engineering ,Laryngeal Mucosa ,otorhinolaryngologic diseases ,medicine ,Humans ,medicine.symptom ,Progenitor cell ,Stem cell ,Induced pluripotent stem cell - Abstract
Healthy vocal fold mucosa is composed of two major cell types, non-keratinized stratified squamous epithelium and vocal fold fibroblasts. Although dysfunction of the epithelium may play a significant pathogenic role in vocal fold diseases, studies at the genetic and molecular level using primary epithelial cells or models of human vocal fold mucosa have been significantly limited by the availability of relevant tissue types, poor growth, and heterogeneity of primary vocal fold epithelial cells. Here, we describe in vitro developmental differentiation of human induced pluripotent stem cells into vocal fold basal epithelial progenitors that were reseeded on collagen-fibroblast constructs to induce stratification and generate a three-dimensional model of human vocal fold mucosa. The engineered vocal fold mucosa represents physiologically relevant and clinically useful model that can be used as a tool for disease modeling and testing of therapeutic approaches for the treatment of laryngeal and VF inflammation.
- Published
- 2021
43. Characterization of intrauterine growth, proliferation and biomechanical properties of the murine larynx
- Author
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Hailey M Pedersen, Vlasta Lungova, Susan L. Thibeault, Kate V. Griffin, and Kari Stauss
- Subjects
0301 basic medicine ,Vocal Cords ,Stiffness ,Extracellular matrix ,Mice ,0302 clinical medicine ,Tissue engineering ,Animal Cells ,Medicine and Health Sciences ,Morphogenesis ,Biomechanics ,030223 otorhinolaryngology ,Musculoskeletal System ,Multidisciplinary ,Stem Cells ,Muscles ,Cell Differentiation ,Muscle Differentiation ,Cell biology ,Extracellular Matrix ,Connective Tissue ,Physical Sciences ,Medicine ,Anatomy ,Larynx ,Cellular Types ,Research Article ,Science ,Materials Science ,Material Properties ,Embryonic Development ,Biology ,Throat ,03 medical and health sciences ,Mechanical Properties ,Animals ,Progenitor cell ,Process (anatomy) ,Cell Proliferation ,Cell growth ,Regeneration (biology) ,Embryogenesis ,Biology and Life Sciences ,Cell Biology ,Embryo, Mammalian ,030104 developmental biology ,Biological Tissue ,Cartilage ,Skeletal Muscles ,Developmental biology ,Neck ,Developmental Biology - Abstract
Current research approaches employ traditional tissue engineering strategies to promote vocal fold (VF) tissue regeneration, whereas recent novel advances seek to use principles of developmental biology to guide tissue generation by mimicking native developmental cues, causing tissue or allogenic/autologous progenitor cells to undergo the regeneration process. To address the paucity of data to direct VF differentiation and subsequent new tissue formation, we characterize structure-proliferation relationships and tissue elastic moduli over embryonic development using a murine model. Growth, cell proliferation, and tissue biomechanics were taken at E13.5, E15.5, E16.5, E18.5, P0, and adult time points. Quadratic growth patterns were found in larynx length, maximum transverse diameter, outer dorsoventral diameter, and VF thickness; internal VF length was found to mature linearly. Cell proliferation measured with EdU in the coronal and transverse planes of the VFs was found to decrease with increasing age. Exploiting atomic force microscopy, we measured significant differences in tissue stiffness across all time points except between E13.5 and E15.5. Taken together, our results indicate that as the VF mature and develop quadratically, there is a concomitant tissue stiffness increase. Greater gains in biomechanical stiffness at later prenatal stages, correlated with reduced cell proliferation, suggest that extracellular matrix deposition may be responsible for VF thickening and increased biomechanical function, and that the onset of biomechanical loading (breathing) may also contribute to increased stiffness. These data provide a profile of VF biomechanical and growth properties that can guide the development of biomechanically-relevant scaffolds and progenitor cell differentiation for VF tissue regeneration.
- Published
- 2021
44. Perioperative Voice Therapy
- Author
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Alexandra Mechler-Hickson and Susan L. Thibeault
- Subjects
medicine.medical_specialty ,Presbyphonia ,business.industry ,Physical therapy ,Medicine ,Treatment options ,Laryngeal tremor ,Perioperative ,Phonation ,Vocal fold paralysis ,business ,Voice therapy (transgender) ,Patient education - Abstract
Voice therapy should be a component of treatment for any dysphonic patient. Indirect therapy centered around voice hygiene and patient education, as well as direct therapy that intervenes on the physiology of phonation, are both important to include as treatment options. Voice therapy has been studied in the treatment of a variety of conditions that may also include vocal fold injection as part of their treatment, including benign vocal fold lesions, vocal fold paralysis, presbyphonia, and laryngeal tremor. There is evidence of patient benefit with even one session of preoperative voice therapy, and a variety of studies to support the use of postoperative therapy as well. Content, timing, and duration of voice therapy has not been standardized, and in the absence of this should be decided between the individual patient and their speech-language pathologist.
- Published
- 2021
45. Novel immortalized human vocal fold epithelial cell line: In vitro tool for mucosal biology
- Author
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Xia Chen, Chitrasen Mohanty, Christina Kendziorski, Vlasta Lungova, Susan L. Thibeault, and Haiyan Zhang
- Subjects
Male ,0301 basic medicine ,Telomerase ,Primary Cell Culture ,Vocal Cords ,Biology ,immortalization ,telomerase ,Biochemistry ,Cell Line ,03 medical and health sciences ,Cytokeratin ,0302 clinical medicine ,three‐dimensional VF mucosal model ,Genetics ,medicine ,Humans ,Telomerase reverse transcriptase ,Molecular Biology ,Cells, Cultured ,Research Articles ,Aged ,Cell Proliferation ,Epithelial Cells ,Karyotype ,Transfection ,Epithelium ,In vitro ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Cell Line Authentication ,Laryngeal Mucosa ,Cell culture ,Keratins ,Female ,030217 neurology & neurosurgery ,Biotechnology ,Research Article ,human vocal fold epithelial cells - Abstract
Study of vocal fold (VF) mucosal biology requires essential human vocal fold epithelial cell (hVFE) lines for use in appropriate model systems. We steadily transfected a retroviral construct containing human telomerase reverse transcriptase (hTERT) into primary normal hVFE to establish a continuously replicating hVFE cell line. Immortalized hVFE across passages have cobblestone morphology, express epithelial markers cytokeratin 4, 13 and 14, induced hTERT gene and protein expression, have similar RNAseq profiling, and can continuously grow for more than 8 months. DNA fingerprinting and karyotype analysis demonstrated that immortalized hVFE were consistent with the presence of a single cell line. Validation of the hVFE, in a three‐dimensional in vitro VF mucosal construct revealed a multilayered epithelial structure with VF epithelial cell markers. Wound scratch assay revealed higher migration capability of the immortalized hVFE on the surface of collagen‐fibronectin and collagen gel containing human vocal fold fibroblasts (hVFF). Collectively, our report demonstrates the first immortalized hVFE from true VFs providing a novel and invaluable tool for the study of epithelial cell‐fibroblast interactions that dictate disease and health of this specialized tissue.
- Published
- 2021
46. Selective Bacterial Colonization of the Murine Larynx in a Gnotobiotic Model
- Author
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Madhu Gowda, Ran An, Susan L. Thibeault, and Federico E. Rey
- Subjects
Microbiology (medical) ,Larynx ,lcsh:QR1-502 ,gnotobiotic ,Gut flora ,Microbiology ,lcsh:Microbiology ,Pathogenesis ,03 medical and health sciences ,Bacterial colonization ,medicine ,microbiota ,Colonization ,Respiratory system ,030304 developmental biology ,Original Research ,0303 health sciences ,biology ,030306 microbiology ,laryngeal mucosa ,biology.organism_classification ,colonization ,upper airway ,medicine.anatomical_structure ,Metagenomics ,Bacteria - Abstract
The larynx is a mucosal organ situated between the respiratory and gastrointestinal tracts. Little is known about microbial contributions to laryngeal epithelial health and pathogenesis. Developing a gnotobiotic laryngeal model will introduce new avenues for targeted explorations of microbes in laryngeal mucosal biology, allowing for enhanced understanding of host–microbe interaction in the upper airway. In this study, we first assessed the potential of using gut microbiota as a source to establish laryngeal microbiota in germ-free mice. Results demonstrated the selective nature of the upper airway and provided evidence that gut bacteria can assemble into communities that resemble the commensal resident bacteria occurring in the larynx of conventionally-raised animals phylogenetically and functionally. Then, we confirmed the reproducibility of laryngeal colonization through comparison of laryngeal microbiota in the larynx along with neighboring regions (base of tongue, esophagus, and trachea) between conventionally-raised and germ-free mice that conventionalized with cecal microbiota. Despite taxonomic differences, the established laryngeal microbiota from cecal content exhibited similarity to commensal resident microbiota in diversity within/between communities and predicted metagenomic functions. Our data also suggests little difference in bacterial distribution across the larynx and its surrounding regions and that cell motility and the ability to degrade xenobiotics is critical for bacteria colonizing upper airway. Successful colonization of laryngeal and oropharyngeal regions with gut microbiota in our study will greatly facilitate the investigation of potential localized inflammatory responses within host tissues that contribute to the disorders of essential laryngeal functions. Utilizing said gnotobiotic model to conduct future studies will allow for novel insights into direct microbial contributions to laryngeal epithelial health and pathogenesis.
- Published
- 2020
47. Electronic cigarette vaping triggers lipid mediated vocal fold mucosal injury
- Author
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Vlasta Lungova and Susan L. Thibeault
- Subjects
Innate immune system ,medicine.diagnostic_test ,business.industry ,Lipid metabolism ,Airway obstruction ,Pharmacology ,medicine.disease ,In vitro ,Cytosol ,Biopsy ,Medicine ,business ,Airway ,Intracellular - Abstract
Electronic cigarettes (e-cigs) are nicotine delivery systems that have been touted as safer alternatives to smoking. A recently reported case of epiglottitis revealed a connection between vaping and swollen laryngeal and vocal fold (VF) structures that can lead to acute life-threatening airway obstruction. The clinical course and biopsy revealed direct epithelial injury and subsequent inflammatory reaction. Here we show that we were able to recapitulate this phenomenon in in vitro conditions. Exposure of engineered VF mucosae to 5% e-cig vapor extract for one week induced cellular damage in VF luminal epithelial cells, disrupting mucosal homeostasis and mucosal innate immune responses. Epithelial erosion was likely caused by the accumulation of solvents and lipid particles, most likely medium chain fatty acids, in the cytosol and intercellular spaces, which altered lipid metabolism and plasma membrane properties. In summary, vaping represents a threat to the VF mucosa health and airway protection.
- Published
- 2020
48. Correlation Between EAT-10 and Aspiration Risk Differs by Dysphagia Etiology
- Author
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Rebecca S, Bartlett, Mary K, Kenz, Heidi A, Wayment, and Susan L, Thibeault
- Subjects
Head and Neck Neoplasms ,Surveys and Questionnaires ,Humans ,Deglutition Disorders ,Deglutition - Abstract
Agreement between self-reported dysphagic symptoms and actual swallowing physiology can vary widely across individuals. The Eating Assessment Tool-10 (EAT-10) is a self-report questionnaire commonly used to identify individuals with oropharyngeal dysphagia, but its interpretation for highly prevalent populations is poorly defined. Our primary objective was to determine if correlation strength between EAT-10 and Penetration-Aspiration Scale (PAS) scores differed by dysphagia etiology. Our secondary objective was to identify clinical factors that were associated with a mismatch between EAT-10 scores and videofluoroscopic findings. Outpatients with Parkinson disease (PD), stroke, and/or head and neck cancer (HNC) who completed EAT-10 and underwent videofluoroscopy were included (n = 203). EAT-10/PAS correlations were calculated by dysphagia etiology. We found that across the sample, higher EAT-10 scores were significantly correlated to higher PAS scores (r
- Published
- 2020
49. Rehabilitation Treatment Specification System: Methodology to Identify and Describe Unique Targets and Ingredients
- Author
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Jason Muise, Joseph R. Duffy, Patricia Doyle, John Whyte, Joseph C. Stemple, Shirley Gherson, Jarrad H. Van Stan, Carol Jorgensen Tolejano, Brian Petty, Nelson Roy, Lisa Kelchner, Susan L. Thibeault, and Julie Barkmeier-Kraemer
- Subjects
Occupational therapy ,030506 rehabilitation ,medicine.medical_specialty ,Delphi Technique ,Computer science ,medicine.medical_treatment ,Clinical Decision-Making ,Physical Therapy, Sports Therapy and Rehabilitation ,Patient Care Planning ,Article ,Domain (software engineering) ,03 medical and health sciences ,0302 clinical medicine ,Clinical Protocols ,Health care ,Outcome Assessment, Health Care ,medicine ,Content validity ,Humans ,Operationalization ,Rehabilitation ,business.industry ,Reproducibility of Results ,Cognition ,Data science ,System methodology ,0305 other medical science ,business ,030217 neurology & neurosurgery - Abstract
Although significant advances have been made in measuring the outcomes of rehabilitation interventions, comparably less progress has been made in measuring the treatment processes that lead to improved outcomes. A recently developed framework called the Rehabilitation Treatment Specification System (RTSS) has potential to identify which clinician actions (ie, ingredients) actively improve specific patient functions (ie, targets). However, the RTSS does not provide methodology for standardly identifying specific unique targets or ingredients. Without a method to evaluate the uniqueness of an individual target or ingredient, it is difficult to know whether variations in treatment descriptions are synonymous (ie, different words describing the same treatment) or meaningfully different (eg, different words describing different treatments or variations of the same treatment). A recent project used vocal rehabilitation ingredients and targets to create RTSS-based lists of unique overarching target and ingredient categories with underlying dimensions describing how individual ingredients and targets vary within those categories. The primary purpose of this article is to describe the challenges encountered during the project and the methodology developed to address those challenges. Because the methodology was based on the RTSS's broadly applicable framework, it can be used across all areas of rehabilitation regardless of the discipline (speech-language pathology, physical therapy, occupational therapy, psychology, etc) or impairment domain (language, cognition, ambulation, upper extremity training, etc). The resulting standard operationalized lists of targets and ingredients have high face and content validity. The lists may also facilitate implementation of the RTSS in research, education, interdisciplinary communication, and everyday treatment.
- Published
- 2020
50. Voice-Gender Incongruence and Voice Health Information-Seeking Behaviors in the Transgender Community
- Author
-
Susan L. Thibeault and Evan Kennedy
- Subjects
Male ,Linguistics and Language ,Health information seeking ,Information Seeking Behavior ,MEDLINE ,Transgender Persons ,Likert scale ,03 medical and health sciences ,Speech and Hearing ,0302 clinical medicine ,Transgender ,Developmental and Educational Psychology ,Complaint ,Humans ,Voice Handicap Index ,030223 otorhinolaryngology ,030505 public health ,Perspective (graphical) ,Gender Identity ,Otorhinolaryngology ,Scale (social sciences) ,Voice ,Female ,0305 other medical science ,Psychology ,Transsexualism ,Clinical psychology - Abstract
Purpose Voice–gender incongruence has predominantly been investigated in the past through the perspective of feminine-identifying individuals seeking feminine-sounding voices. The purpose of this study was to determine the prevalence of self-reported voice–gender incongruence in the transgender, nonbinary, and gender-nonconforming (TNG) community and to describe health information–seeking behaviors exhibited when individuals attempt to address their voice and communication challenges. Method An online survey was designed with questions targeting the self-reported prevalence of voice–gender incongruence, characteristics of this complaint, and health information–seeking behaviors. Valid standardized measures, including the Voice Handicap Index and the Barriers to Help-Seeking Scale, were also included. Results Four hundred five participants were sorted into three groups based on gender identity (feminine, masculine, gender-neutral) to facilitate comparative analysis. Ninety-six percent of participants reported the experience of voice–gender incongruence in the past, and 88% reported that they currently experience voice–gender incongruence. There were no significant differences in reported voice–gender incongruence between groups. Voice Handicap Index scores were significantly higher for those who currently experience voice–gender incongruence ( p < .0001) and reflected differences in how much this concern bothers participants, as rated on a Likert scale, ranging from no problem to a very big problem ( p < .0001). Barriers to Help-Seeking Scale scores indicated that the masculine group perceived greater barriers to seeking help as compared to the feminine group. Discussion We present foundational evidence for the prevalence of voice–gender incongruence within the TNG community and barriers encountered when individuals attempt to access care. Future work should investigate the specific needs of subgroups within the TNG community and whether those who desire feminine-, masculine-, and/or androgynous-sounding voices experience voice–gender incongruence and access to services differently. Supplemental Material https://doi.org/10.23641/asha.12462422
- Published
- 2020
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