Faculty Bibliography

Importance/UNASSIGNED:Compromised cough effectiveness is correlated with dysphagia and aspiration. Glottic insufficiency likely yields decreased cough strength and effectiveness. Although vocal fold augmentation favorably affects voice and likely improves cough strength, few data exist to support this hypothesis. Objective/UNASSIGNED:To assess whether vocal fold augmentation improves peak airflow measurements during maximal-effort cough following augmentation. Design, Setting, and Participants/UNASSIGNED:This case series study was conducted in a tertiary, academic laryngology clinic. Participants included 14 consecutive individuals with glottic insufficiency due to vocal fold paralysis, which was diagnosed via videostrobolaryngoscopy as a component of routine clinical examination. All participants who chose to proceed with augmentation were considered for the study whether office-based or operative augmentation was planned. Postaugmentation data were collected only at the first follow-up visit, which was targeted for 14 days after augmentation but varied on the basis of participant availability. Data were collected from June 5, 2014, to October 1, 2015. Data analysis took place between October 2, 2015, and March 3, 2017. Main Outcomes and Measures/UNASSIGNED:Peak airflow during maximal volitional cough was quantified before and after vocal fold augmentation. Participants performed maximal coughs, and peak expiratory flow during the maximal cough was captured according to American Thoracic Society guidelines. Results/UNASSIGNED:Among the 14 participants (7 men and 7 women), the mean (SD) age was 62 (18) years. Three types of injectable material were used for vocal fold augmentation: carboxymethylcellulose in 5 patients, hyaluronic acid in 5, and calcium hydroxylapatite in 4. Following augmentation, cough strength increased in 11 participants and decreased cough strength was observed in 3. Peak airflow measurements during maximal cough varied from a decrease of 40 L/min to an increase of 150 L/min following augmentation. When preaugmentation and postaugmentation peak airflow measurements were compared, the median improvement was 50 L/min (95% CI, 10-75 L/min; P = .01). Immediate peak airflow measurements during cough collected within 30 minutes of augmentation varied when compared with measurements collected at follow-up (103-380 vs 160-390 L/min). Conclusions and Relevance/UNASSIGNED:Peak airflow during maximal cough may improve with vocal fold augmentation. Additional assessment and measurements are needed to further delineate which patients will benefit most regarding their cough from vocal fold augmentation.

OBJECTIVE: Recent reports highlight the efficacy of small interfering RNA (siRNA) targeting SMAD3 to regulate transforming growth factor beta (TGF-beta)-mediated fibroplasia in vocal fold fibroblasts. The current study sought to investigate SMAD3 expression during wound healing in vivo and quantify the downstream transcriptional events associated with SMAD3 knockdown in vitro. STUDY DESIGN: In vivo and in vitro. METHODS: Unilateral vocal fold injury was created in a rabbit model. SMAD3 and SMAD7 mRNA expression was quantified at 1 hour and 1, 3, 7, 14, 30, 60, and 90 days following injury. In vitro, multi-gene analysis technology was employed in our immortalized human vocal-fold fibroblast cell line following TGF-beta1 stimulation +/- SMAD3 knockdown across time points. RESULTS: SMAD3 mRNA expression increased following injury; upregulation was significant at 3 and 7 days compared to control (both P < 0.001). SMAD7 mRNA was also upregulated at 3, 7, and 14 days (P = 0.02, P < 0.001, and P < 0.001, respectively). In vitro, SMAD3 knockdown reduced the expression of multiple profibrotic, TGF-beta signaling, and extracellular matrix metabolism genes at 6 and 24 hours following TGF-beta1 stimulation. CONCLUSION: Cumulatively, these data support SMAD3 as a potential master regulator of TGF-beta-mediated fibrosis. SMAD3 transcription peaked 7 days following injury. Multi-gene analysis indicated that the therapeutic effectiveness of SMAD3 knockdown may be related to regulation of downstream mediators of fibroplasia and altered TGF-beta signaling. LEVEL OF EVIDENCE: NA. Laryngoscope, 2017.

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.

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.

OBJECTIVES: This study aims (1) to present a case of asystole during direct laryngoscopy in an otherwise healthy patient at an outpatient surgery center and (2) to review literature on cardiac complications, specifically asystole and bradycardia, during direct laryngoscopy. METHODS: A 67-year-old woman with no prior cardiac history underwent induction with succinylcholine and remifentanil for direct laryngoscopy and vocal fold augmentation. During suspension laryngoscopy, the patient became asystolic, and advanced care life support measures were started. The patient regained a cardiac rhythm after chest compressions and epinephrine and was transferred to a tertiary care hospital for further treatment. She remained intubated overnight, requiring pressors, and regained normal cardiac function over the next few days. RESULTS: A structured literature review uncovered few reports of asystole during suspension laryngoscopy. Although bradycardia is common during suspension laryngoscopy, likely secondary to stimulation of afferent visceral sensory parasympathetic fibers of the vagus nerve, asystole is rare. CONCLUSIONS: Cardiac complications are possible in otolaryngologic surgery, especially with activation of the oculocardiac or trigeminocardiac reflexes. Asystole during direct laryngoscopy, although rare, is not always predictable from medicine or cardiac risk indices. Awareness, rapid recognition, and early implementation of advanced care life support are crucial to avoid further complications.

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.

Therapeutic monocolonal antibodies (MAbs) are a new, rapidly growing class of medications that frequently have poorly characterized side-effect profiles. We present a patient who developed inflammatory lesions of the vocal folds in temporal relation to the initiation of alirocumab. Lesions of the vocal folds represent a previously unreported adverse effect of alirocumab therapy, making it the second MAb documented with such a side effect. The potential laryngeal effects of alirocumab specifically, and of MAbs more broadly, warrant investigation. Laryngoscope, 2016.

OBJECTIVES/HYPOTHESIS: Quantification of clinical outcomes after vocal fold (VF) interventions is challenging with current technology. High-speed digital imaging and optical coherence tomography (OCT) of excised larynges assess intact laryngeal function, but do not provide critical biomechanical information. We developed a protocol to quantify tissue properties in intact, excised VFs using dynamic nanomechanical analysis (nano-DMA) to obtain precise biomechanical properties in the micrometer scale. STUDY DESIGN: Experimental animal study. METHODS: Three pig larynges were bisected in the sagittal plane, maintaining an intact anterior commissure, and subjected to nano-DMA at nine locations with a 250-mum flat-tip punch and frequency sweep load profile (10-105 Hz, 1,000 muN peak force) across the free edge of the VF and inferiorly along the conus elasticus. RESULTS: Storage, loss, and complex moduli increased inferiorly from the free edge. Storage moduli increased from a mean of 32.3 kPa (range, 6.5-55.38 kPa) at the free edge to 46.3kPa (range, 7.4-71.6) 5 mm below the free edge, and 71.4 kPa (range, 33.7-112 kPa) 1 cm below the free edge. Comparable values were 11.6 kPa (range, 5.0-20.0 kPa), 16.7 kPa (range, 5.7-26.8 kPa), and 22.6 kPa (range, 9.7-38.0 kPa) for loss modulus, and 35.7 kPa (range, 14.4-56.4 kPa), 50.1 kPa (range, 18.7-72.8 kPa), and 75.4 kPa (range, 42.0-116.0 kPa) for complex modulus. Another larynx repeatedly frozen and thawed during technique development had similarly increased storage, loss, and complex modulus trends across locations. CONCLUSIONS: Nano-DMA of the intact hemilarynx provides a platform for quantification of biomechanical responses to a myriad of therapeutic interventions to complement data from high-speed imaging and OCT. LEVEL OF EVIDENCE: NA Laryngoscope, 2016.

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.