Faculty Bibliography

This study employs validated cough assessment tools to prospectively determine the impact of tramadol on cough severity and quality of life in subjects with neurogenic cough. The study was a prospective case series with planned data collection at a tertiary care academic medical center laryngology practice. Sixteen consecutive collected subjects with neurogenic cough prospectively completed pre- and posttreatment validated cough assessment tools, the cough severity index (CSI) and Leicester Cough Questionnaire (LCQ). All subjects in the study reported at least some improvement in their cough symptoms. In a Wilcoxon signed rank test that compared paired results, CSI scores improved from 23 to 14 and LCQ scores improved from 74 to 103 ( P = .003 and P = .005, respectively). This small preliminary assessment suggests that tramadol warrants additional evaluation as a treatment for neurogenic cough.

Importance/UNASSIGNED:Human papillomavirus (HPV) vaccination is recommended for children and younger adults but not older adults or those with prior HPV exposure, leaving a large portion of the population at risk for HPV-mediated disease. Emerging data suggest a possible role for vaccination as an adjuvant treatment for individuals with HPV-related clinical disease. Objective/UNASSIGNED:To systematically review the literature regarding HPV vaccination for secondary disease prevention after treatment of active clinical disease across disease sites to serve as a platform for the management of HPV-related disease of the head and neck. Evidence Review/UNASSIGNED:A systematic search from August 3 to 21, 2015, of the PubMed, MEDLINE, EMBASE, CINAHL, Cochrane Library, Web of Science, Biosis Citation Index, Current Contents Connect, Scientific Library Online, and Global Health databases used PRISMA guidelines to identify 326 relevant articles related to adjuvant use of HPV vaccination. Primary search terms were (HPV vaccine OR human papillomavirus vaccine OR papillomarvirus vaccines OR alphapapillomavirus vaccine) AND (HPV OR human papillomavirus OR alphapapillomavirus OR papillomaviridae OR virus warts OR wart virus) AND (recurrence OR relapse OR reoccurrence OR recurrences OR relapses OR relapsing). Forty-five full texts in English were reviewed, with 19 articles included in the final review. In some studies, subpopulations of individuals with HPV DNA positivity and/or seropositivity were extracted for inclusion. Included studies were assessed for bias and separated based on the presence of active clinical disease or HPV DNA positivity or seropositivity. Findings/UNASSIGNED:Nineteen studies with 22 474 unique patients were included in the review. When HPV vaccination was used as an adjuvant treatment for active clinical disease, 9 of 12 studies reported decreased disease recurrence, decreased disease burden, or increased intersurgical interval. In contrast, none of the 7 studies of vaccination in individuals with HPV DNA positivity and/or seropositivity without clinical disease reported improved outcomes. Conclusions and Relevance/UNASSIGNED:Differences between adjuvant vaccination in HPV-mediated clinical disease and vaccination in HPV DNA-positive and/or HPV-seropositive populations posit underlying differences in disease and immune processes. These data suggest that additional evaluation of adjuvant HPV vaccination in individuals with active clinical disease is warranted.

OBJECTIVE: Morbidity associated with suspension laryngoscopy has been well documented. However, standard of care with regard to postoperative analgesia has not been described, and anecdotal evidence suggests wide variability with regard to postoperative narcotic and non-narcotic recommendations. We sought to quantify the postoperative course following suspension microlaryngoscopy by relating patient-based and intraoperative measures with analgesic use. METHODS: Body mass index (BMI), Friedman tongue position (FTP), and Mallampati scores as well as laryngoscope type, number of attempts required for optimal visualization, and suspension time were documented in 50 consecutive patients undergoing routine suspension microlaryngoscopy. Postoperative symptoms and analgesic use was queried on postoperative days 1, 3, and 10. RESULTS: In this cohort, 62.5% employed postoperative analgesia. However, only 20% required narcotics. No difference in suspension time was identified in those taking analgesics (33.0 vs 37.3 minutes, P = .44). In addition, no relationship between procedure type and the need for analgesia was noted. The majority of patients (76%) described sore throat persisting for 3 postoperative days; 36% reported sore throat persisting beyond postoperative day 3. CONCLUSIONS: The majority of patients undergoing microlaryngoscopy reported discomfort, but symptoms were largely ameliorated with over-the-counter analgesics. Routine prescription of narcotics following routine suspension laryngoscopy may be unnecessary.

Objective Given the recalcitrant nature of recurrent respiratory papillomatosis, targeted therapies to reduce disease burden are fundamental to improved patient care paradigms. We seek to demonstrate the safety of imiquimod injection into vocal fold mucosa by evaluating the degree of laryngeal edema, histopathologic changes to vocal fold structure, and serologic interferon alpha (IFNalpha) levels following injection. Study Design Preclinical. Setting Academic institution. Subjects and Methods Six New Zealand White rabbits underwent unilateral injection of 100 microg of sterile imiquimod (1 microg/microL), with 100 microL of normal saline injected into the contralateral vocal fold. Direct laryngoscopy was performed on days 3, 7, and 30 following injection. Larynges from 3 rabbits were harvested on postinjection day 7 for histologic analysis. The remaining 3 rabbit larynges were harvested on day 30. Serial serum samples were drawn for IFNalpha quantification via immunoassay. Results No signs of respiratory distress were observed at any point. Vocal fold appearance was not clinically divergent between imiquimod and control conditions via serial direct laryngoscopic evaluation. No inflammatory lesions or scarring were identified following injection. Histology showed no signs of acute inflammatory processes or changes in the control or imiquimod injection groups. Serum IFNalpha increased at days 3 and 7 following imiquimod injection ( P < .0001 and P = .0368, respectively), before returning to baseline by day 14. Conclusions Vocal fold imiquimod injection did not result in notable morbidity in this preclinical model. However, serum IFNalpha concentrations increased transiently. These data are critical to advance the therapeutic utility of this compound, particularly in the setting of recurrent respiratory papillomatosis.

OBJECTIVE: Conflicting data exist regarding false vocal fold (FVF) anatomy; it is unclear if this structure is an extension of the thyroarytenoid muscle or an independent muscle system. This confusion is amplified by diverse clinical findings in the setting of unilateral recurrent laryngeal neuropathy and presbylarynges. We sought to characterize FVF behavior in these contexts. METHODS: Laryngoscopic/stroboscopic examinations from 11 patients with unilateral recurrent laryngeal nerve paresis and 12 patients with presbylarynges were reviewed by 4 laryngologists, blinded to the goal of the study but informed of diagnosis. Variables related to FVF structure and function at rest and during phonation were rated. RESULTS: In recurrent laryngeal neuropathy, no significant association between atrophic/paretic vocal fold (VF) and FVF size was observed at rest (P = .69). During phonation, FVF compression was noted bilaterally; contralateral FVF hypertrophy was more common (P = .002). In presbylarynges, neither FVF size at rest (P = .86) nor compression during phonation (P = .37) was associated with the more atrophic VF; FVF compression/hypertrophy was common. CONCLUSIONS: Consistent with clinical dogma, FVF compression was more common contralateral to VF neuropathy. This finding, however, was inconsistent and may suggest individual variability in FVF innervation and/or morphology. Intra- and interrater reliability of these clinical findings was poor.

OBJECTIVES/HYPOTHESIS: Inhalation injury significantly increases morbidity and mortality in burn patients. Approximately one in five burn patients have acute injury to the larynx, trachea, and/or lungs-and as many as 70% have long-term laryngeal abnormalities. Although inhalation injury to the lung has been studied extensively, no models exist to study these insults to the larynx. As such, we developed an in vivo rabbit model to create precise and reproducible laryngeal burn with resultant tissue damage as a foundation for interventional studies. METHODS: Following tubeless tracheotomy, a custom temperature-control device was employed to apply heated air (70 degrees C-80 degrees C, 150 degrees C-160 degrees C, or 310 degrees C-320 degrees C) +/- smoke derived from unbleached cotton to the larynx, endoscopically, minimizing adjacent tissue damage in six rabbits. Pain, nutrition, and level of activity were monitored. Direct laryngoscopy and histological examination were performed 24 hours following insult. RESULTS: All animals survived injury with appropriate pain control; oral intake was initiated and all were adequately ventilating via tracheostomy. Burn sequelae were noted under direct visualization 24 hours after injury, and graded levels of edema and tissue damage were observed as a function of temperature. Edema obstructed true vocal fold visualization at increased temperatures. These injury patterns correlated with graded tissue damage on histology. CONCLUSION: We created an in vivo model of laryngeal burn injury employing a custom burn device resulting in graded tissue injury. This model is critical for investigation of the mechanisms underlying burn injury, and ultimately, the development and evaluation of therapies for this challenging population. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2016.

The vocal folds (VFs) are exposed to a number of injurious stimuli that frequently lead to aberrant structural alterations and altered biomechanical properties that clinically manifest as voice disorders. Therapies to restore both structure and function of this delicate tissue are ideal. However, such methods have not been adequately developed. Our group and others hypothesize that tissue engineering and regenerative medicine approaches, previously described for other tissue systems, hold significant promise for the VFs. In the current review, we explore the concept of tissue engineering as it relates to the VFs as well as recent studies employing both naturally- and synthetically-derived biomaterials, including those from laryngeal and non-laryngeal sources, in combination with stem cells for a tissue-engineered approach to VF repair.

OBJECTIVE: To determine the prevalence and also accuracy of the laryngopharyngeal reflux (LPR) referring diagnosis and to determine the most useful clinical tool in arriving at the final diagnosis in a tertiary laryngology practice. STUDY DESIGN: Case series with planned data collection. SETTING: Six tertiary academic laryngology practices. SUBJECTS AND METHODS: We collected referring diagnosis and demographic information, including age, sex, ethnicity, referring physician, and whether or not patients had prior flexible laryngoscopy for 1077 patients presenting with laryngologic complaints from January 2010 and June 2013. Final diagnosis after the referred laryngologist's examination and the key diagnostic test used was then recorded. RESULTS: Of 1077 patients, 132 had a singular referring diagnosis of LPR. Only 47 of 132 patients (35.6%) had LPR confirmed on final primary diagnosis. Transnasal flexible laryngoscopy confirmed this in 27 of 47 (57.4%) patients. Eighty-five of 132 (64.4%) had a different final diagnosis than LPR. Sixty-five of 85 (76.5%) of these alternative pathologies were diagnosed with the aid of laryngeal stroboscopy. CONCLUSIONS: LPR appears to be an overused diagnosis for laryngologic complaints. For patients who have already had transnasal flexible laryngoscopic exams prior to their referral, laryngeal stroboscopy is the key diagnostic tool in arriving at the correct diagnosis.

The human vocal folds are complex structures made up of distinct layers that vary in cellular and extracellular composition. The mechanical properties of vocal fold tissue are fundamental to the study of both the acoustics and biomechanics of voice production. To date, quantitative methods have been applied to characterize the vocal fold tissue in both normal and pathologic conditions. This review describes, summarizes, and discusses the most commonly employed methods for vocal fold biomechanical testing. Force-elongation, torsional parallel plate rheometry, simple-shear parallel plate rheometry, linear skin rheometry, and indentation are the most frequently employed biomechanical tests for vocal fold tissues and each provide material properties data that can be used to compare native tissue to diseased or treated tissue. Force-elongation testing is clinically useful, as it allows for functional unit testing, while rheometry provides physiologically relevant shear data, and nanoindentation permits micrometer scale testing across different areas of the vocal fold as well as whole organ testing. Thoughtful selection of the testing technique during experimental design to evaluate a hypothesis is critical to optimize biomechanical testing of vocal fold tissues.