Effects of vocal fold lesions on particle deposition in a mouth-throat model: A numerical study.

OBJECTIVE: Dysphonia is very common worldwide and aerosol drug inhalation is an important treatment for patients with dysphonia. This study aimed to explore the effects of vocal fold (VF) lesions on the particle deposition pattern using computational modeling. METHODS: A realistic mouth-throat (MT) model of a healthy adult was constructed based on computed tomography images. Small and large vocal fold lesions were incorporated in the original model. A steady inhalation flowrate of 15 and 30 liter per minute (LPM) was used as the velocity inlet and monodisperse particles with diameters of 5 to 10 µm were simulated. RESULTS: Particles of larger size are more likely to be deposited in MT models, most of them distributed in oral cavity, oropharynx and supraglottis. The ideal sizes at 30 LPM ranged over 7-10 µm for healthy VFs and 6-8 µm for VF lesions. The best sizes at 15 LPM ranged over 6-8 µm for healthy VFs and 8-9 µm for VF lesions. CONCLUSION: Based on this study, VF lesions influence the deposition pattern in the glottis obviously. The ideal sizes differ at the flow rates of 15 and 30 LPM.

Effects of vocal fold adduction on the particle deposition in the glottis: A numerical analysis and in vitro assessment.

BACKGROUND: The efficacy of inhalation therapy depends on the drug deposition in the human respiratory tract. This study investigates the effects of vocal fold adduction on the particle deposition in the glottis. METHODS: A realistic mouth-throat (MT) geometry was built based on CT images of a healthy adult (MT-A). Mild (MT-B) and great (MT-C) vocal fold (VF) adduction were incorporated in the original model. Monodisperse particles range in size from 3 to 12 µm were simulated at inspiration flow rates of 15, 30 and 45 L per minute (LPM). The regional deposition of drug aerosols was performed in 3D-printed models and quantified using high-performance liquid chromatography. RESULTS: Both the numerical analysis and in vitro experiments show that most particles are deposited in the mouth, pharynx and supraglottis, while few are deposited in the glottis and subglottis. For most cases in MT-A, the particle quantity in glottis is lower than 0.02 N/mm2 at 15 and 30 LPM while they increase dramatically at 45 LPM. It peaked at 0.347 N/mm2 for 5-µm particles at 45 LPM in MT-B and 2.324 N/mm2 for 6-µm particles at 30 LPM in MT-C. The lowest drug mass faction in the glottis in vitro were found at 15 LPM for MT-A and MT-C, and at 30 LPM for MT-B, whereas it peaked at 45 LPM for all MT models, 0.71% in MT-A, 1.16% in MT-B, and 2.53% in MT-C, respectively. CONCLUSION: Based on the results of this study, larger particles are more likely to be deposited in the oral cavity, oropharynx, and supraglottis than in the glottis. However, particle deposition in the glottis generally increases with VF adduction and greater inspiratory flow rates.

The Effects of Photobiomodulation on Vocal Fold Wound Healing: In Vivo and In Vitro Studies.

Background: Photobiomodulation (PBM) is increasingly used in dermatology and dentistry due to its benefit of promoting wound healing and relieving pain; however, there is no corresponding research report on the application of PBM to vocal fold wound healing. Objective: To assess the potential wound-healing effects of PBM on the vocal folds via in vivo and in vitro experiments. Materials and methods: In in vitro study, vocal fold fibroblasts (VFFs) were irradiated under a diode laser with wavelength of 635 nm at energy density of 8 J/cm2. The Cell Counting Kit-8 (CCK-8) assay was used to study the viability of VFFs, and the gene expressions of COL1A2, COL3A1, IL-6, HAS2, and COX-2 were investigated by real-time polymerase chain reaction (RT-PCR). In in vivo study, 15 rabbits were used. Lamina propria of the left vocal folds of 12 rabbits was unilaterally stripped, and 6 of them were treated with PBM. The remaining three rabbits served as normal controls. After 3 months, all animals were sacrificed to obtain histological results. We used laryngoscope to record images of the healing phase. Results: Irradiation with energy density of 8 J/cm2 resulted in a 2.8% increase in cell proliferation (p < 0.05). However, the difference between the experimental and the control group became larger after 48 and 72 h of subsequent irradiation. RT-PCR results showed that the expression of COL1A2, COL3A1, and HAS2 was higher, and the expression of IL-6 and COX-2 was lower. Histological examination showed that, compared with the injury group, hyaluronic acid (HA) increased significantly, collagen deposition decreased, and the configuration of collagen was more organized after PBM treatment. Conclusions: PBM can inhibit inflammatory reaction and promote the secretion of HA to decrease the deposition of collagen and regenerate vocal fold tissue without scar.

Radiologic and histologic characterization of silk fibroin as scaffold coating for rabbit tracheal defect repair.

OBJECTIVES: To explore the feasibility of silk fibroin as a biomaterial coating used in tracheal defect reconstruction. METHODS: Silk fibroin was subcutaneously embedded in three rabbits and as an artificial implant material coating to reconstruct 12 rabbits' tracheal defects. The postoperative radiologic and histologic characterization was summarized. RESULTS: The thickness of the fibroblasts layer covering the porus and nonporus silk fibroin film was 240.4 +/- 9.9 and 302.3 +/- 10.5 microm, respectively, and there was no statistical difference (P > 0.05) within each group. There was no foreign-body granuloma or macrophagocyte infiltration around the silk film. The tracheal reconstruction study showed a normal mucous membrane with normal cilial growth on the artificial implant and no visible granulation tissue in the reconstructed tracheal cavity. CONCLUSIONS: Silk fibroin is a potential new biomaterial coating for tracheal defect reconstruction. The mechanism of silk fibroin appears to promote tracheal mucous membrane, which may be related to its molecular structure and biology.

Experimental study on repair of the facial nerve with Schwann cells transfected with GDNF genes and PLGA conduits.

CONCLUSIONS: Schwann cells transfected by GDNF genes + PLGA were superior to Schwann cells + PLGA and direct anastomesis. This is a new and effective strategy for repair of facial nerve defects. OBJECTIVE: To evaluate the effect of bioactive artificial nerve conduits in the repair of facial nerve defects in Sprague-Dawley rats. MATERIALS AND METHODS: Schwann cells were harvested and transfected with PcDNA3.1 (+)/GDNF. After injection with Schwann cells, the conduits were cultured in the culture medium for 2 weeks. Thirty female Sprague-Dawley rats were selected and randomly divided into three groups (A, B, and C), which were treated as follows: A, direct anastomesis; B, Schwann cells + PLGA conduits; C, Schwann cells transfected by GDNF genes + PLGA conduits. General observation, electrophysiological study, histological study, and image analysis were performed 2 weeks, 1 month, 2 months, and 3 months postoperatively. RESULTS: The recovery of nerve regeneration and electrophysiological results in group C were superior to those in groups A and B; the difference was statistically significant (p < 0.01).

Effects of Straw Phonation Through Tubes of Varied Lengths on Sustained Vowels in Normal-Voiced Participants.

OBJECTIVE: To examine the immediate effects of straw phonation exercises in normal subjects while altering the effective length of the vocal tract. STUDY DESIGN: A nonrandomized comparison of semi-occluded vocal tract length during straw phonation exercises was carried out. METHODS: Oral pressure, mean airflow, aerodynamic resistance, and contact quotient were measured in 20 healthy subjects immediately before and after straw phonation exercises. A short- and long-duration phonatory task was used to examine the voice parameters during semi-occluded vocal tract exercises. These tasks involved repeating a vocalization of the vowel /a/ through a tube. Each subject underwent the protocol using tubes of three different lengths (7.5 cm, 15 cm, and 30 cm) to allow for the effect of moving the outlet of the vocal tract distal to the mouth to be monitored. RESULTS: Oral pressure and aerodynamic resistance decreased significantly, contact quotient showed a decreasing trend, and airflow increased significantly in pre- and postmeasurements 15 minutes after a long-duration phonatory task. Short-duration tasks were found to have no effect on voice parameters. CONCLUSION: The results present and validate a method to isolate the effect that the length of a semi-occluded vocal tract has during straw phonation exercises.

The Measurement of Airflow Using Singing Helmet That Allows Free Movement of the Jaw.

OBJECTIVES: Airflow measurement is a useful method of evaluating laryngeal physiology. We introduce a noninvasive device that measures airflow without restricting jaw movement or requiring phonation into a mouthpiece, thus facilitating measurement during singing and connected speech. STUDY DESIGN: Validation and human subject trials were conducted. Airflow measurements were obtained from 16 male and 16 female subjects during singing, speech, and constant vowel production tasks. METHODS: A similar helmet was designed by Stevens and Mead in 1968. The new device validity was evaluated by comparing the measured volume of air to a known volume of administered air using a calibration syringe. Subjects were asked to voice sustained vowels at low, medium, and high vocal intensity, read two sentences at a conversational volume, and perform different singing exercises while airflow was recorded. RESULTS: The device accurately and reliably measured airflow with mean airflow values falling within previously published ranges. There was an experimentally determined response time of 0.173 ± 0.014 seconds. Subjects were able to comfortably perform speech and singing exercises. Male subjects had higher airflow for all sustained vowels (P < 0.05). Airflow was higher for abduction rather than adduction sentences (P < 0.05). CONCLUSIONS: No other portable device has been shown to measure airflow during singing and speech while allowing for free movement of the jaw. This device provides a more natural environment to measure airflow that could be used to help evaluate laryngeal function and aid in singing training.

A pilot study of macrophage responses to silk fibroin particles.

Silk fibroin (SF) shows promise for tissue engineering and other biomedical applications due to its excellent biocompatibility, unique biomechanical properties, and controllable biodegradability. The particulate form of SF materials may have many potential uses, including the use as a filler for tissue defects or as a controlled-release agent for drug delivery. However, many past in vivo and in vitro studies evaluating the biocompatibility and biodegradability of SF have involved bulk implants. It is essential to evaluate the inflammatory effects of SF particles before further use. In this study, two different sizes of SF particles were evaluated to assess their impact on the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, in comparison with lipopolysaccharide positive control stimulation. The inflammatory processes were characterized using real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and light microscopy evaluations. The results indicated that small silk fibroin particles and large silk fibroin particles, in culture with RAW 264.7 murine macrophage cells for 24 h, caused up-regulation of mRNA coding for TNF-α, which indicated that both size of particles have potential inflammatory effects. There was a statistically significant increase in this up-regulation under small silk fibroin stimulation. However, the immunosorbent assay suggested that there was virtually no observed release of IL-1ß, IL-6, or TNF-α, relative to the control group. The results suggest that SF particles of the chosen dimensions may have good biocompatibility in culture with RAW 264.7 murine macrophages.

Noninvasive monitoring of vocal fold vertical vibration using the acoustic Doppler effect.

OBJECTIVES/HYPOTHESIS: To validate a proposed method of noninvasively monitoring vocal fold vertical vibration through utilization of the acoustic Doppler effect and the waveguide property of the vocal tract. STUDY DESIGN: Validation case-control study. METHODS: In this device, an ultrasound beam is generated and directed into the mouth. The vocal tract, acting as a natural waveguide, guides the ultrasound beam toward the vibrating vocal folds. The vertical velocity of vocal fold vibration is then recovered from the Doppler frequency of the reflected ultrasound. One subject (age 32, male) was studied and measurements were taken under three modes of vocal fold vibration: breathing (no vibration), whispering (irregular vibration), and normal phonation (regular vibration). RESULTS: The peak-to-peak amplitude of the measured velocity of vocal fold vertical vibration was about 0.16 m/s, and the fundamental frequency was 172 Hz; the extracted velocity information showed a reasonable waveform and value in comparison with the previous studies. In all three modes of phonation, the Doppler frequencies derived from the reflected ultrasound corresponded with the vertical velocity of vocal fold vibration as expected. CONCLUSIONS: The proposed method can accurately represent the characteristics of different phonation modes such as no phonation, whisper and normal phonation. The proposed device could be used in daily monitoring and assessment of vocal function and vocal fold vibration.

Preliminary investigation of adjustable balloon implant for type I thyroplasty.

OBJECTIVE: We present the adjustable balloon implant (ABI), a novel implant to be used in type I thyroplasty for the treatment of vocal fold paralysis. The ABI offers the same medialization provided by other implants, but can easily be catered to individual patient anatomy as well as modified postoperatively without the need for a revision thyroplasty. STUDY DESIGN: Repeated measures with each larynx serving as its own control. METHODS: Medialization thyroplasty (MT) with the ABI was performed on five excised canine larynges. Mucosal wave, aerodynamic, and acoustic parameters were measured for three conditions: normal; right vocal fold paralysis; and paralysis with the ABI. RESULTS: Insertion of the ABI resulted in significant decreases in both phonation threshold pressure and phonation threshold flow. Perturbation parameters of percent jitter and percent shimmer were also significantly decreased and restored to normal levels. Signal-to-noise ratio was significantly increased to the normal level as well. The mucosal wave was preserved after implant insertion. CONCLUSIONS: This preliminary experiment showing significant improvements in aerodynamic and acoustic parameters demonstrates the potential of the ABI as a thyroplasty implant. Effective medialization and preservation of the mucosal wave combined with postoperative adjustability makes it a potentially valuable clinical device.

Prospective multi-arm evaluation of surgical treatments for vocal fold scar and pathologic sulcus vocalis.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to compare the clinical effectiveness of type I thyroplasty, injection laryngoplasty, and graft implantation for the treatment of vocal fold scar and pathologic sulcus vocalis. STUDY DESIGN: Prospective, multi-arm, quasi-experimental research design. METHODS: Twenty-eight patients with newly diagnosed vocal fold scar and/or pathologic sulcus vocalis were assigned to one of three treatment modalities: type I thyroplasty (n = 9), injection laryngoplasty (n = 9), and graft implantation (n = 10). Psychosocial, auditory-perceptual, acoustic, aerodynamic, and videostroboscopic data were collected pretreatment and at 1, 6, 12, and 18 months posttreatment. RESULTS: Type I thyroplasty and graft implantation both resulted in reduced voice handicap with no concomitant improvement in auditory-perceptual, acoustic, aerodynamic, or vocal fold physiologic performance. Injection laryngoplasty resulted in no improvement on any vocal function index. Patients who underwent graft implantation exhibited the slowest improvement trajectory across the 18-month follow-up period. CONCLUSIONS: A persistent challenge in this area is that no single treatment modality is successful for the majority of patients, and there is no evidence-based decision algorithm for matching a given treatment to a given patient. Progress therefore requires the identification and categorization of predictive clinical features that can drive evidence-based treatment assignment.