Vocal cord dysfunction/inducible laryngeal obstruction: novel diagnostics and therapeutics.

INTRODUCTION: Vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO) is an important medical condition but understanding of the condition is imperfect. It occurs in healthy people but often co-exists with asthma. Models of VCD/ILO pathophysiology highlight predisposing factors rather than specific mechanisms and disease expression varies between people, which is seldom appreciated. Diagnosis is often delayed, and the treatment is not evidence based. AREAS COVERED: A unified pathophysiological model and disease phenotypes have been proposed. Diagnosis is conventionally made by laryngoscopy during inspiration with vocal cord narrowing >50% Recently, dynamic CT larynx was shown to have high specificity (>80%) with potential as a noninvasive, swift, and quantifiable diagnostic modality. Treatment entails laryngeal retraining with speech pathology intervention and experimental therapies such as botulinum toxin injection. Multidisciplinary team (MDT) clinics are a novel innovation with demonstrated benefits including accurate diagnosis, selection of appropriate treatment, and reductions in oral corticosteroid exposure. EXPERT OPINION: Delayed diagnosis of VCD/ILO is pervasive, often leading to detrimental treatments. Phenotypes require validation and CT larynx can reduce the necessity for laryngoscopy, thereby fast-tracking diagnosis. MDT clinics can optimize management. Randomized controlled trials are essential to validate speech pathology intervention and other treatment modalities and to establish international standards of care.

Office-Based Photodynamic Therapy Using Locally Applied 5-aminolevulinic Acid and 635 nm Laser for Laryngeal Leukoplakia.

OBJECTIVE: Photodynamic therapy (PDT) is a minimally invasive method with strong tissue selectivity and nonthermal effects. We aim to investigate the efficacy of an in-office method utilizing PDT with local application of 5-aminolevulinic acid (ALA) and 635 nm diode laser for treating laryngeal leukoplakia. STUDY DESIGN: Retrospective cohort study. SETTING: Outpatient clinic-tertiary medical center. METHODS: This study reviewed 32 patients with laryngeal leukoplakia, including 11 recurrent cases after surgery. All the procedures were performed in an office setting under topical anesthesia. Fifteen percent ALA solution was locally applied to the lesion through a flexible laryngoscope. Light illumination was performed using a 635 nm diode laser through a 400 µm optic fiber. The power density was 165 mW/cm2 to reach 100 J/cm2 . Results of laryngostroboscopy and voice evaluation during follow-up were collected. RESULTS: The mean follow-up was 7.91 ± 4.83 (3-18) months. Thirty-nine procedures were performed, including 1 session for 27 patients, 2 sessions for 3 patients, and 3 sessions for 2 patients. The total response rate was 96.875% (31/32), including complete responses in 26 (81.25%) patients, partial responses in 5 patients (15.625%), and no response in 1 patient (3.125%). It appeared that PDT selectively eliminated the leukoplakia without affecting lamina propria and the surrounding normal mucosa remained unharmed. Scores of Voice Handicap Index-10, jitter, shimmer, and harmonic-to-noise ratio were significantly improved after PDT. CONCLUSION: Office-based PDT is an effective, repeatable, and practical method for treating laryngeal leukoplakia. Local application of ALA is sufficient to achieve photodynamic reactions. PDT could eliminate laryngeal leukoplakia selectively while protecting the normal laryngeal structure.

Vocal Fold Steroid Injection for Benign Vocal Lesions in Professional Voice Users.

OBJECTIVES: Current treatments for benign vocal lesions consist mainly voice therapy and phonomicrosurgery. However, these options are not always suitable for professional voice users because of their tight performance schedule and limited time for voice rest. This study investigated vocal fold steroid injection (VFSI) as an alternative treatment. STUDY DESIGN: Matched case series. METHODS: We retrospectively enrolled 28 professional voice users (i.e., singers, actors and news anchors) who received VFSI for vocal nodules and polyps in an office setting of a tertiary teaching hospital. Outcomes were evaluated using videolaryngostroboscopy (VLS), the 10-item Voice Handicap Index (VHI-10), maximum phonation time, and acoustic and perceptual analyses before and 1 month after VFSI. Study results were compared with 56 patients of nonprofessional voice users (i.e., routine or high occupational vocal demands), matched in a 1:2 ratio by age, sex, and treatment date. RESULTS: After VFSI, VLS revealed substantial lesion resolution in 82% professional voice users. One professional voice user developed a self-limited vocal fold hematoma after VFSI. VHI-10 scores in the professional group decreased from 21 to 14 points, compared with 23 to 16 points in the non-professional group, demonstrating a significant within-group effect (P < 0.01, GEE) and a nonsignificant between-group effect (P = 0.86). Other outcomes also improved significantly after VFSI (P < 0.05), without significant differences between the two groups. CONCLUSION: VFSI can be an effective and safe alternative treatment for professional voice users with benign vocal lesions.

Practice Patterns and Barriers in Botulinum Toxin Injection for the Treatment of Voice Disorders.

Laryngeal botulinum toxin injection is an important treatment modality for spasmodic dysphonia and other laryngeal disorders. We sought to compare usage patterns of laryngeal botulinum toxin injections for voice disorders and to identify and quantify inefficiencies and barriers in providing this treatment. A 26 item survey was written and approved for distribution by the American Academy of Otolaryngology-Head and Neck Surgery and the National Spasmodic Dysphonia Association. It was distributed to Otolaryngologists who perform laryngeal botulinum toxin injections via the e-mail lists of the National Spasmodic Dysphonia Association provider database, American Academy of Otolaryngology-Head and Neck Surgery Voice Committee and the American Laryngological Association Neurolaryngology Study Group. There were 81 survey participants who collectively reported performing >1700 laryngeal botulinum toxin injections for voice disorders monthly (Mean = 21.5 pts/month). Regarding botulinum toxin A (BtxA) vial use, 54% of participants reported using multiple doses per vial for different patients during a single clinic day, while 14% reported using pharmacy predrawn single use aliquots. A combination of usage practices was reported by 7% of participants. Using an individual vial per patient and discarding the unused remainder was reported by 26% of participants with an associated annual cost in wasted BtxA of $84,300 per physician. There is wide variation in injection practices regarding management of BtxA vials and adherence to an individual vial per patient policy is associated with significant waste of health care resources. Alternative approaches to BtxA vial use could positively impact health care resource utilization.

Quistes subglóticos adquiridos: Reporte de tres casos y revisión de la literatura / Acquired subglottic cysts: Report of three cases and review of the literature

Los quistes subglóticos adquiridos son una causa rara de estridor en la infancia, cuyo reporte ha ido en aumento en las últimas décadas. Su aparición se relaciona con la prematurez y la intubación en el periodo neonatal. Histológicamente, se observa una obstrucción de las glándulas mucosas de la subglotis debido una metaplasia escamosa del epitelio respiratorio. Esta es una condición que usualmente requiere de un alto índice de sospecha para llegar al diagnóstico, ya que pueden confundirse con otras patologías como laringitis aguda (croup), laringomalacia o asma. La nasofibroscopía permite sospechar su presencia, pero el gold standard diagnóstico lo constituye la laringo-tra-queo-broncoscopía directa en pabellón. Existen diversas técnicas para su manejo, siendo las más frecuentemente utilizadas la marsupialización con instrumental frío y láser. La recurrencia es frecuente, por lo que algunos autores han utilizado mitomicina C y la terapia antirreflujo para intentar disminuirla. Sin embargo, hasta la fecha falta evidencia de calidad que permita llegar a un consenso respecto al manejo ideal de esta patología. En este trabajo, presentamos tres casos clínico de pacientes con antecedentes de prematurez que fueron diagnosticados con quistes subglóticos adquiridos y manejados en un hospital pediátrico de alta complejidad.

Acquired subglottic cysts are an infrequent cause of stridor in infants, which has been increasingly reported in the last decades. Its appearance is related to prematurity and intubation in the neonatal period. Histologically, findings are characterized by an obstruction of the mucosal glands, due to squamous metaplasia of the respiratory epithelium. This condition usually requires a high index of suspicion to be diagnosed, as it can be misdiagnosed as croup, laryngomalacia or asthma. Flexible nasendoscopy allows an initial exploration of the larynx, but direct laryngo-tracheo-bronchoscopy in the operating room is the diagnostic gold standard. There are several techniques for its management, but the most frequently used are cold-steel marsupialization and laser. Recurrence is common, and some authors have used mitomycin C and antireflux therapy to try to decrease it. However, up to date, there is a lack of high-quality evidence, regarding the ideal management of this pathology, which prevents reaching a consensus. In this article, we present three clinical cases of premature patients who were diagnosed with subglottic cysts, treated in a tertiary pediatric hospital.

Comparison of therapeutic effects of steroid injection by benign vocal fold lesion type.

BACKGROUND: Benign vocal fold lesions (BVFLs) can cause voice changes, including reduced loudness and pitch range. In recent times, with progression in endoscopic technology, office-based vocal fold steroid injection (VFSI) has been used as an alternative therapy for BVFLs. AIMS/OBJECTIVES: In this study, we analyzed the efficacy and safety of VFSI to investigate the mechanism underlying its therapeutic effects and determine the conditions in which VFSI will be most effective. MATERIALS AND METHODS: In this retrospective cohort study, we included 40 condition-matched patients (8 patients per lesion) with chorditis, vocal nodules, vocal polyps, Reinke's edema (RE), or vocal scars who received similar regimens of steroid injection using a commercial preparation of triamcinolone acetonide. Their phonological outcomes were evaluated 2 or 3 months after the injection. RESULTS: Significant improvements were observed in Voice Handicap Index scores, results of laboratory voice evaluation, and voice quality measured using the Grade, Roughness, Breathiness, Asthenia, Strain scale in all participants. In subgroup analysis, VFSI was highly effective against chorditis and vocal nodules, but less effective against RE and vocal scars. CONCLUSIONS: Single-dose VFSI is valuable as an alternative to voice rehabilitation and laryngo-microsurgery, but higher concentrations or repeated injections are required for intractable lesions.

Long-time remission of laryngeal Rosai-Dorfman disease with thalidomide: a report of three cases.

OBJECTIVE AND IMPORTANCE: Rosai-Dorfman disease (RDD) is a benign and rare non-Langerhans cell histiocytic proliferative disorder. Laryngeal involvement is an unusual site of extranodal involvement of RDD. Laryngeal RDD can cause life-threatening airway obstruction that requires effective control of the disease. In this study, we report three cases of laryngeal RDD with excellent and durable responses to thalidomide. CLINICAL PRESENTATION: Patient 1 was a 39-year-old male who presented with a two-year history of nasal obstruction. Patient 2 was a 26-year-old woman who presented complaining of a hoarse voice for one year. Patient 3 was a 24-year-old man who presented with complaints of a hoarse voice and progressing dyspnea for five months. Electronic laryngoscopy revealed submucous nodular lesions in the nasal cavity, nasopharynx, and larynx of the three patients. Biopsy of the lesions showed large histiocytes with abundant pale cytoplasm which were S-100 and CD68 positive consistent with RDD. INTERVENTION: Before thalidomide treatment, patient 1 received chemotherapy and six times surgical excision due to the recurrence of laryngeal lesions. Patient 2 failed steroid treatment. Patient 3 underwent an emergency tracheostomy due to airway obstruction. All three patients then received thalidomide 100 mg/d treatment and achieved satisfactory and durable responses with the longest follow-up of 45 months. CONCLUSION: Thalidomide may induce long-term remission in laryngeal RDD.

Cytomegalovirus-associated supraglottic mass in a patient on immunosuppressive therapy.

A 33-year-old woman on chronic immunosuppressive treatment for rheumatoid arthritis with a history of inhaled methamphetamine use presented with respiratory failure requiring mechanical ventilation for a prolonged period. After being given plasma exchange, pulses of methylprednisolone and a dose of cyclosporine for suspected ANCA (anti-neutrophilic cytoplasmic autoantibodies) vasculitis, she developed an obstructive supraglottic laryngeal mass that required a tracheostomy to bypass. Biopsy findings revealed the mass to be an inflammatory pseudomass secondary to cytomegalovirus (CMV). The mass resolved after several weeks of intravenous ganciclovir therapy. This is an extremely unusual presentation of localised CMV disease, with only two or three similar cases having been reported worldwide.

Sarcoidosis of the ear, nose and throat: A review of the literature.

OBJECTIVES: Sarcoidosis is a multisystemic inflammatory disease with extrathoracic manifestations, most commonly affecting the young and middle-aged, female and Black populations. Diagnosis usually requires evidence of non-caseating granulomata and, when treated, prognosis is usually favourable. We aim to establish the incidence, clinical features and optimal treatment of ENT manifestations of this disease. DESIGN: We performed a PubMed literature review to determine the evidence base supporting this. RESULTS: ENT manifestations are present in 5%-15% of patients with sarcoidosis, often as a presenting feature, and require vigilance for swift recognition and coordinated additional treatment specific to the organ. Laryngeal sarcoidosis presents with difficulty in breathing, dysphonia and cough, and may be treated by speech and language therapy (SLT) or intralesional injection, dilatation or tissue reduction. Nasal disease presents with crusting, rhinitis, nasal obstruction and anosmia, usually without sinus involvement. It is treated by topical nasal or intralesional treatments but may also require endoscopic sinus surgery, laser treatment or even nasal reconstruction. Otological disease is uncommon but includes audiovestibular symptoms, both sensorineural and conductive hearing loss, and skin lesions. CONCLUSIONS: The consequences of ENT manifestations of sarcoidosis can be uncomfortable, disabling and even life-threatening. Effective management strategies require good diagnostic skills and use of specific therapies combined with established treatments such as corticosteroids. Comparisons of treatment outcomes are needed to establish best practice in this area.

Atypical presentation of immunoglobulin G4-related disease as subglottic stenosis: a case-based review.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory pathology that has been reported to affect principally the retroperitoneum, hepatobiliary system, salivary glands, orbital structures or lymph nodes. However, IgG4-RD with laryngeal involvement is a very rare entity. Our aims were to describe a case of subglottic stenosis as first and only manifestation of IgG4-RD and review the literature. A patient with IgG4-RD affecting the larynx that presented as subglottic stenosis is described. A MEDLINE database search of IgG4-RD cases with laryngopharyngeal manifestations was also conducted. A 30-year-old Caucasian woman was referred to a tertiary care hospital for dyspnea on exertion, which had been increasing for the last 4 months. Medical and surgical procedures revealed a subglottic stenosis, with a histological finding of IgG4 positive plasma cell infiltration. There was no evidence of other organ involvement. She was successfully treated with oral glucocorticoids and rituximab infusions. Glucocorticoids were rapidly tapered and the rituximab regimen was optimized, with no evidence of relapses. In the literature review, we found a total of 12 reported cases with laryngopharyngeal involvement, two of them with subglottic stenosis. IgG4-RD of the larynx is rare but should be considered after excluding more common disorders.

Office-Based Intralesional Steroid Injection for Treatment of Laryngeal Sarcoidosis.

OBJECTIVES: To report preliminary outcomes of a case series of in-office intralesional steroid injections for treatment of laryngeal sarcoidosis. METHODS: After diagnosis of laryngeal sarcoidosis, 3 patients were offered in-office steroid injections for primary or adjunctive treatment. Triamcinolone 40 was injected into supraglottic sarcoidosis lesions in the office using a channel laryngoscope. Response to treatment and need for further injections was determined based on patient symptoms and repeat flexible laryngoscopy. RESULTS: In-office intralesional steroid injections provided rapid symptom relief within days that lasted for months, thus decreasing the frequency of operative interventions. For one of the patients in this series, these injections even eliminated the need for tracheostomy. No complications were observed. CONCLUSIONS: In-office intralesional steroid injection is an emerging adjunctive treatment for laryngeal sarcoidosis. Prospective studies are required to determine efficacy and long-term risk profiles in relation to the current standard of operative management and systemic treatments.

Laryngeal Candidiasis Mimicking Supraglottic Carcinoma by Prolonged Inhaled Steroid Therapy: A Case Report and Review of the Literature.

Candidiasis is a rare entity reported as an isolated and primary laryngeal disease. In this condition, inhaled steroids were the single most common predisposing factor. Also mycotic infections of larynx are frequently seen in patients with immune insufficiency, although they have also been reported in individual with normal immune status. We report a case of isolated laryngeal Candidiasis in an immunocompetent individual, with an unusual presentation with exophytic lesion, edema, ulceration, white plaque, and pseudomembranous formation mimicking supraglottic carcinoma, to highlight the clinical of this condition and provide a review of the literature.

The Effect of Antioxidant Agents on Cisplatin-Induced Laryngeal Histological Alterations in Rats.

The larynx-related adverse effects that depend on cisplatin decrease patient comfort and many antioxidants have been used to eliminate these side effects. We aimed to identify the laryngeal mucosal changes imposed by cisplatin and investigated whether antioxidants, and their healing effects on these changes, may help reduce laryngeal complications in patients resulting from adverse effects in the larynx. A rat model was designed to evaluate the effects of cisplatin on the larynx and the protective role of antioxidants. Single-dose cisplatin was given both intraperitoneally alone and additionally administered with p-coumaric acid, melatonin, resveratrol, vitamin D, and oleic acid over 5 days. Whole larynges were dissected and evaluated histologically, histochemically, and immunohistochemically. Varying degrees of mucosal changes cisplatin group, but neither erosion nor an ulcer was observed. Numerous variable histological effects of antioxidants were observed on cisplatin exposed laryngeal mucosa. The most obvious effects of cisplatin were edema. The results of the study showed that resveratrol was the most preventive antioxidant agent against cisplatin-dependent mucosal changes. The highest increase in the Ki67 index was in the oleic acid group. Vitamin D increased stromal cyclooxygenase-2 expression that may have an effect on increasing mucosal damage.

The Role of Cytokines in Modulating Vocal Fold Fibrosis: A Contemporary Review.

OBJECTIVES: Vocal fold (VF) scarring and laryngeal stenosis are a significant clinical challenge. Excessive scar formation causes low voice quality or even life-threatening obstructions. Cytokines are thought to modulate multiple steps of the establishment of VF fibrosis, but there is no systematic report regarding their role in modulating VF fibrosis. This review aims to investigate the role of cytokines in modulating vocal fold fibrosis. STUDY DESIGN: Literature review. METHODS: This review searched for all relevant peer publications in English for the period 2009 to 2019 in the PubMed database using search terms: "laryngeal stenosis," "vocal fold scarring," and "cytokines." A thorough investigation of the methods and results of the reviewed studies was performed. RESULTS: Comprehensive research in various studies, including analyses of prostaglandin E2 (PGE2), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), transforming growth factor-ß3 (TGF-ß3), and interleukin-10 (IL-10), supports cytokine therapy for VF scarring and laryngeal stenosis to some extent. A few clinical studies on this topic support the conclusion that HGF and bFGF can be selected as effective drugs, and no serious side effects were found. CONCLUSIONS: This review describes the potential of cytokines for modulating the process of VF fibrogenesis, although cytokines are still an unproven treatment method. As no ideal drugs exist, cytokines may be considered the candidate treatment for preventing VF fibrogenesis. Laryngoscope, 131:139-145, 2021.

Alternating Unilateral Versus Bilateral Injections of Botulinum Toxin for the Treatment of Adductor Spasmodic Dysphonia.

OBJECTIVE: This study aimed to compare the long-term efficacy, durability, and dose and interval stability between alternating unilateral and bilateral injections of botulinum neurotoxin type A for the treatment of adductor spasmodic dysphonia. STUDY DESIGN: Retrospective cohort study. SETTING: Academic tertiary medical center. METHODS: A total of 137 patients (105 alternating unilateral and 32 bilateral injections) who were administered ≥5 injections of botulinum neurotoxin type A were included in this study. The mean dosage change, dose adjustment ratio (number of dose increases/total number of injections), and stability of treatment responses were compared between the alternating unilateral and bilateral injection groups. RESULTS: Long-term changes in the mean dosages for alternating unilateral (mean ± SD, -0.010 ± 0.048 IU) and bilateral (-0.042 ± 0.142 IU) injections did not differ between groups (P = .225), suggesting that both methods follow a decreasing dosing trend over time. The dose adjustment ratio also did not differ between groups (P = .077), although a longer average treatment interval (P < .001) and duration of hoarse voice (P = .045) were found in the bilateral injection group. The proportion of stable patients who did not increase injection dose and had regular follow-up did not differ between the groups. CONCLUSION: Both alternating unilateral and bilateral injection methods showed a long-term decreasing dosing trend, with comparable levels of efficacy, durability, and stability for treating adductor spasmodic dysphonia. Our findings indicate that alternating unilateral injections can be routinely performed with fewer side effects, albeit at shorter treatment intervals, than bilateral injections.

A case of vocal polyps improved with herbal medicine: A case report.

Vocal polyps are benign vocal cord lesions, which mainly manifest as a hoarse voice. Laryngeal microsurgery is the most common treatment. However, because of anxiety regarding invasive treatment, it is necessary to have a non-invasive treatment option. A 43 year old female patient who is a teacher visited a Korean medical hospital for persistent hoarseness with a vocal polyp. After taking herbal medicine for hoarseness (Kyung-Hee-cheong-um-whan) and pharyngitis (cheong-in-li-gyok-tang and cheong-in-ryu-que-whan) for almost 10 weeks, the vocal polyp was reduced and symptoms improved. Herbal prescription for pharyngitis and hoarseness can be applied to vocal polyps as non-invasive treatment.

Pseudomonas laryngeal perichondritis: unexpected diagnosis.

A 57-year-old male chronic smoker with underlying diabetes mellitus presented with dysphonia associated with cough, dysphagia and reduced effort tolerance of 3 months' duration. Videoendoscope finding revealed bilateral polypoidal and erythematous true and false vocal fold with small glottic airway. The patient was initially treated as having tuberculous laryngitis and started on antituberculous drug. However, no improvement was observed. CT of the neck showed erosion of thyroid cartilage, which points to laryngeal carcinoma as a differential diagnosis. However, the erosion was more diffuse and appeared systemic in origin. The diagnosis of laryngeal perichondritis was made when the histopathological examination revealed features of inflammation, and the tracheal aspirate isolated Pseudomonas aeruginosa The patient made a good recovery following treatment with oral ciprofloxacin.

What is the truth about proton pump inhibitors?

PURPOSE OF REVIEW: This review explores the recent evidence and established scientific literature surrounding proton pump inhibitors in the context of laryngology. RECENT FINDINGS: Proton pump inhibitors are often associated with gastroenterology; however, they also have a place in laryngology. Several laryngopharyngeal disorders are treated with proton pump inhibitors, though limited evidence regarding effectiveness, dosing and length of treatment exists. With the recent influx of articles reporting possible adverse effects of proton pump inhibitors, the appropriate prescribing of them has come under scrutiny. These reported risks include cancer, stroke, myocardial infarction, kidney disease and cognitive decline. It should be noted though that many of these studies by nature, are fraught with potential confounding. Regardless, clinicians ought to be aware of any risks associated with treatment regimens and prescribe the optimal dosage and duration. SUMMARY: Proton pump inhibitor treatment should be dose-appropriate and for a limited duration. Concerning potential adverse effects, the limitations of retrospective cohort studies must be taken into consideration when reviewing the evidence.