Anxiety, Depression, and Posttraumatic Stress Disorder in Patients With Induced Laryngeal Obstruction.

Importance: Patients with induced laryngeal obstruction (ILO) present with a variety of behavioral health profiles. Identifying these profiles is crucial in that behavioral health conditions may affect treatment duration and outcomes. Objective: To characterize the prevalence of anxiety, depression, posttraumatic stress disorder (PTSD), and physical somatic symptoms in adult and pediatric patients with ILO and determine the factors associated with anxiety, depression, PTSD, and physical somatic symptoms in patients with ILO? Design, Setting, and Participants: This cross-sectional study included a nonprobability sample of 83 adult and 81 pediatric patients diagnosed with ILO at outpatient adult and pediatric otolaryngology clinics between 2021 and 2023. Exclusion criteria included a comorbid respiratory diagnosis other than asthma, head or neck cancer, or neurological impairments. Recruitment took place between September 2021 and March 2023. The analyses were run in January 2024. Main Outcome Measures: Patients were prospectively screened for anxiety, depression, PTSD, and somatic physical symptoms. In addition, any past behavioral health diagnoses were extracted from the medical record. Comorbidities, ILO symptoms triggers, and onset details were gathered from ILO evaluations. Adult patients completed the Screen for Adult Anxiety Related Disorders (SCAARED), depression (Patient Health Questionnaire [PHQ]-9), and somatic physical symptoms portions of the Patient Health Questionnaires (PHQ-15), and the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5). Pediatric patients completed the Screen for Child Anxiety Related Disorders (SCARED), depression (PHQ-9A) and somatic physical symptoms portions of the Patient Health Questionnaires for Adolescents (PHQ-15A), and the UCLA PTSD Reaction Index brief screeners. Results: Eighty-three adult patients participated in this study (mean [SD] age, 45.8 [14.3] years; 64 female, 19 male). Eighty-one pediatric patients participated (mean [SD] age, 13.83 [2.55] years; 67 female, 14 male). Adult and pediatric patients with ILO screened positive for elevated rates of anxiety (53 adults [63%]; 49 children [60%]), depression (27 adults [32%]; 25 children [30%]), and PTSD (29 adults [34%]; 13 children [16%]). Most of the patients with anxiety and depression symptoms were formally diagnosed prior to ILO evaluation, with rates of previously diagnosed anxiety, depression, and PTSD also above published norms. Adults were twice as likely as children to present with PTSD (odds ratio, 2.1; 95% CI, 0.05-4.48). Elevated rates of physical somatic symptoms were also evident, with 38 adults (45%) and 32 children (39%) scoring in the moderate to severe range. Conclusions and Relevance: This study found high rates of adult and pediatric patients with ILO screened positive for anxiety, depression, and PTSD symptoms. Future work should investigate how behavioral health and ILO treatments can best be coordinated to maximize treatment outcomes.

Economic Burden of Induced Laryngeal Obstruction in Adolescents and Children.

PURPOSE: Diagnosing pediatric induced laryngeal obstruction (ILO) requires equipment typically available in specialist settings, and patients often see multiple providers before a diagnosis is determined. This study examined the financial burden associated with the diagnosis and treatment of ILO in pediatric patients with reference to socioeconomic disadvantage. METHODS: Adolescents and children (<18 years of age) diagnosed with ILO were identified through the University of Madison Voice and Swallow Outcomes Database. Procedures, office visits, and prescribed medications were collected from the electronic medical record. Expenditures were calculated for two time periods (1) pre-diagnosis (first dyspnea-related visit to diagnosis), and (2) the first year following diagnosis. The Area Deprivation Index (ADI) was used to estimate patient socioeconomic status to determine if costs differed with neighborhood-level disadvantage. RESULTS: A total of 113 patients met inclusion criteria (13.9 years, 79% female). Total pre-diagnosis costs of ILO averaged $6486.93 (SD = $6604.14, median = $3845.66) and post-diagnosis costs averaged $2067.69 (SD = $2322.78; median = $1384.12). Patients underwent a mean of 3.01 (SD = 1.9; median = 2) procedures and 5.8 (SD = 4.7; median = 5) office visits prior to diagnosis. Pharmaceutical, procedure/office visit, and indirect costs significantly decreased following diagnosis. Patients living in neighborhoods with greater socioeconomic disadvantage underwent fewer procedures and were prescribed more medication than those from more affluent areas. However, total expenditures did not differ based on ADI. CONCLUSIONS: Pediatric ILO is associated with considerable financial costs. The source of these costs, however, differed according to socioeconomic advantage. Future work should determine how ILO diagnosis and management can be more efficient and equitable across all patients. Laryngoscope, 2024.

Clinical Profiles of Children and Adolescents With Induced Laryngeal Obstruction (ILO) and Exercise Induced Laryngeal Obstruction (EILO).

PURPOSE: To compare clinical profiles of pediatric patients with Induced Laryngeal Obstruction (ILO), Exercise Induced Laryngeal Obstruction (EILO), and EILO with non-exertion related secondary triggers (EILO+). METHODS: A retrospective observational cohort design was employed. Four-hundred and twenty-three patients <18 years of age were identified from the electronic medical record of a large children's hospital. All patients underwent evaluations with a laryngologist and speech-language pathologist and were diagnosed with EILO/ILO. Patients were divided into 3 groups based on dyspnea triggers reported in initial evaluations. Groups consisted of patients with EILO (N = 281), ILO (N = 30), and EILO+ (N = 112). Patient demographics, EILO/ILO symptoms, endoscopy findings, medical comorbidities, medical history, and EILO/ILO treatment information were extracted and compared across EILO/ILO subtypes. RESULTS: Patients with EILO experienced higher rates of hyperventilation (P < .001), sore throat (P = .023), and chest pain (P = .003). Patients with ILO were significantly younger in age (P = .017) and presented with increased rates of nighttime symptoms (P < .001), globus sensation (P = .008), self-reported reflux symptoms (P = .023), and history of gastrointestinal conditions (P = .034). Patients with EILO+ were more likely to be female (P = .037) and presented with higher prevalence of anxiety (P = .003), ADHD (P = .004), chest tightness (P = .030), and cough (P < .001). CONCLUSIONS: Patients with EILO, ILO, and EILO+ present with overlapping but unique clinical profiles. A prospective study is warranted to determine the etiology of these differences and clarify how the efficacy of EILO, ILO, and EILO+ treatment can be maximized. LEVEL OF EVIDENCE: 4.

Examining therapy duration in adults with induced laryngeal obstruction (ILO).

OBJECTIVE: This study examined the number of therapy sessions required to sufficiently improve (exercise) induced laryngeal obstruction (EILO/ILO) symptoms for discharge. Factors predicting therapy duration were examined as was the likelihood of patients returning for additional therapy sessions following initial discharge. METHODS: Retrospective observational cohort design. Data for 350 patients were gathered from the University of Wisconsin-Madison Voice and Swallow Clinics Outcome Database. Patients (>18 years of age) diagnosed with EILO/ILO received therapy from a Speech-Language Pathologist (SLP) and were successfully discharged. EILO/ILO treatment details, symptoms, triggers, medical comorbidities, and patient demographics were collected from initial evaluations and subsequent course of therapy. RESULTS: Patients required an average of 3.59 (SD = 3.7) therapy sessions prior to discharge. A comorbid behavioral health diagnosis (p = .026), higher Vocal Handicap Index Score (p = .009) and reduced physical activity due to EILO/ILO symptoms (p = .032) were associated with increased therapy duration. Patients with ILO or EILO with secondary environmental triggers required significantly more sessions than those with exercise-induced symptoms (p < .01). Eight percent of patients returned for additional sessions following discharge. Patients returning for additional sessions all came from affluent neighborhoods as measured by the Area Deprivation Index (ADI). CONCLUSIONS: Patients with EILO/ILO required an average of 3.59 therapy sessions prior to discharge. As such, 4 sessions is a reasonable estimate for clinicians to provide patients. Six sessions may be a more conservative estimate for patients who present with a behavioral health diagnosis, a voice complaint, or reduced physical activity from EILO/ILO symptoms.

The Larynx is Protected from Secondary and Vertical Papillomavirus Infection in Immunocompetent Mice.

OBJECTIVE: Mouse papillomavirus MmuPV1 causes both primary and secondary infections of the larynx in immunocompromised mice. Understanding lateral and vertical transmission of papillomavirus to the larynx would benefit patients with recurrent respiratory papillomatosis (RRP). To test the hypothesis that the larynx is uniquely vulnerable to papillomavirus infection, and to further develop a mouse model of RRP, we assessed whether immunocompetent mice were vulnerable to secondary or vertical laryngeal infection with MmuPV1. METHODS: Larynges were collected from 405 immunocompetent adult mice that were infected with MmuPV1 in the oropharynx, oral cavity, or anus, and 31 mouse pups born to immunocompetent females infected in the cervicovaginal tract. Larynges were analyzed via polymerase chain reaction (PCR) of lavage fluid or whole tissues for viral DNA, histopathology, and/or in situ hybridization for MmuPV1 transcripts. RESULTS: Despite some positive laryngeal lavage PCR screens, all laryngeal tissue PCR and histopathology results were negative for MmuPV1 DNA, transcripts, and disease. There was no evidence for lateral spread of MmuPV1 to the larynges of immunocompetent mice that were infected in the oral cavity, oropharynx, or anus. Pups born to infected mothers were negative for laryngeal MmuPV1 infection from birth through weaning age. CONCLUSION: Secondary and vertical laryngeal MmuPV1 infections were not found in immunocompetent mice. Further work is necessary to explore immunologic control of laryngeal papillomavirus infection in a mouse model and to improve preclinical models of RRP. LEVEL OF EVIDENCE: N/a Laryngoscope, 2023.

Factors influencing behavioral cough suppression therapy in children with nonspecific chronic cough.

BACKGROUND: Behavioral cough suppression therapy (BCST) with a speech-language pathologist is a common treatment for chronic nonspecific cough (a.k.a., tic cough) in children. Yet, the outcomes and duration of pediatric BCST have eluded formal investigation. This study examined whether BCST improves cough in children with nonspecific cough and factors that predict the course of treatment. Additionally, the cough characteristics and comorbidities associated with the condition were examined. METHODS: A retrospective, observational cohort design was utilized. Cough characteristics, medical history, and BCST treatment details and outcomes for 151 children were extracted from the electronic medical record of a large outpatient pediatric otolaryngology clinic. RESULTS: Cough was dry and onset unaccompanied by illness in most cases. Roughly half of patients reported gradual onset and cough proceeded by tickle. On average, patients experienced symptoms for 19 months (SD = 20.09) before diagnosis. Rates of comorbid General Anxiety Disorder were elevated compared to pediatric norms. Additionally, high rates of asthma (22.1%), reflux (62.3%), and disordered sleep breathing (19.2%) were observed. Common findings on laryngoscopy included interarytenoid edema and erythema. Vocal fold changes were observed in 22.9% of children. BCST reduced cough in 92.5% of patients following an average of 1.7 sessions. Comorbid behavioral health diagnoses (p = 0.013) or induced laryngeal obstruction symptoms (p = 0.025) were significant predictors of increased therapy sessions. Cough proceeded by tickle significantly predicted fewer sessions in therapy (p = 0.011). INTERPRETATION: Although randomized clinical trials are needed, these data suggest that BCST is a low-risk, effective treatment for children with nonspecific cough.

Examining Therapy Duration in Adults With Voice Disorders.

PURPOSE: This study examined the number of voice therapy sessions and the number of weeks in treatment to achieve desired voice outcomes in adults with voice disorders. Factors that may predict therapy duration were examined, as was the percentage of patients returning to the clinic for additional voice therapy after initial discharge. METHOD: An observational cohort design was utilized. Data from 558 patients were extracted from the University of Wisconsin-Madison Voice and Swallow Outcomes Database. Patients diagnosed with muscle tension dysphonia, vocal fold paralysis, benign vocal fold lesions, laryngospasm/irritable larynx, and presbyphonia were examined. Patient demographics, auditory-perceptual assessments, acoustics, aerodynamics, videostroboscopy ratings, self-reported scales, and medical comorbidities were collected. RESULTS: Patients required an average of 5.32 (SD = 3.43) sessions of voice therapy before voice outcomes were sufficiently improved for discharge. Average number of sessions ranged from 4.3 for presbyphonia to 6.7 for benign vocal fold lesions. Baseline overall Grade Roughness Breathiness Asthenia and Strain rating (p < .001), Dysphonia Severity Index (p < .001), Voice Handicap Index score (p < .01), age (p = .006), and occupational voice user status (p < .001) significantly predicted the number of therapy sessions required. Overall, 14.5% of patients returned for additional voice therapy following an initial discharge from treatment. CONCLUSIONS: Findings inform our understanding of how many sessions patients with voice disorders require to achieve desired voice outcomes. Additional research is needed to optimize the efficacy of voice treatment and determine how recurrence of dysphonia might best be prevented.

Preclinical Models of Laryngeal Papillomavirus Infection: A Scoping Review.

OBJECTIVE: Laryngeal human papillomavirus (HPV) infection causes recurrent respiratory papillomatosis (RRP) and accounts for up to 25% of laryngeal cancers. Lack of satisfactory preclinical models is one reason that treatments for these diseases are limited. We sought to assess the literature describing preclinical models of laryngeal papillomavirus infection. DATA SOURCES: PubMed, Web of Science, and Scopus were searched from the inception of database through October 2022. REVIEW METHODS: Studies searched were screened by two investigators. Eligible studies were peer-reviewed, published in English, presented original data, and described attempted models of laryngeal papillomavirus infection. Data examined included type of papillomavirus, infection model, and results including success rate, disease phenotype, and viral retention. RESULTS: After screening 440 citations and 138 full-text studies, 77 studies published between 1923 and 2022 were included. Models used low-risk HPV or RRP (n = 51 studies), high-risk HPV or laryngeal cancer (n = 16), both low- and high-risk HPV (n = 1), and animal papillomaviruses (n = 9). For RRP, 2D and 3D cell culture models and xenografts retained disease phenotypes and HPV DNA in the short term. Two laryngeal cancer cell lines were consistently HPV-positive in multiple studies. Animal laryngeal infections with animal papillomaviruses resulted in disease and long-term retention of viral DNA. CONCLUSIONS: Laryngeal papillomavirus infection models have been researched for 100 years and primarily involve low-risk HPV. Most models lose viral DNA after a short duration. Future work is needed to model persistent and recurrent diseases, consistent with RRP and HPV-positive laryngeal cancer. LEVEL OF EVIDENCE: NA Laryngoscope, 133:3256-3268, 2023.

Therapy Outcomes for Teenage Athletes With Exercise-Induced Laryngeal Obstruction.

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.

Videostroboscopy Versus High-Speed Videoendoscopy: Factors Influencing Ratings of Laryngeal Oscillation.

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.

Relationship Between Auditory-Perceptual and Objective Measures of Resonance in Children with Cleft Palate: Effects of Intelligibility and Dysphonia.

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 <18 years of age identified with CP ± L, seen for auditory-perceptual and nasometry evaluations of hypernasality as well as assessments of articulation and voice.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 < .001) and when children presented with moderate dysphonia (p ≤ .001). No significant impact of articulation testing or sex were observed.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.

Risk Factors for Dysphagia in Patients Hospitalized with COVID-19.

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.

Examining Relationships Between GRBAS Ratings and Acoustic, Aerodynamic and Patient-Reported Voice Measures in Adults With Voice Disorders.

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.

Are Children with Cleft Palate at Increased Risk for Laryngeal Pathology?

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 < .001, OR = 1.50). In addition, children with severely hypernasal resonance were 78% less likely to present with laryngeal pathology (P =.046, OR = 0.22).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.

Voice Therapy Improves Acoustic and Auditory-Perceptual Outcomes in Children.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:977-983, 2023.

Localization of TRPV3/4 and PIEZO1/2 sensory receptors in murine and human larynges.

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.

Piezo1-expressing vocal fold epithelia modulate remodeling via effects on self-renewal and cytokeratin differentiation.

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.

Pediatric Voice Therapy: How Many Sessions to Discharge?

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.

Transcriptome Dynamics in the Developing Larynx, Trachea, and Esophagus.

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.

Exposure to e-cigarette vapor extract induces vocal fold epithelial injury and triggers intense mucosal remodeling.

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.