Pathophysiology of Fibrosis in the Vocal Fold: Current Research, Future Treatment Strategies, and Obstacles to Restoring Vocal Fold Pliability

Kumai, Yoshihiko

doi:10.3390/ijms20102551

Cited by 53 publications

(45 citation statements)

References 150 publications

(214 reference statements)

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“…Regarding their voice impairment, patients with laryngeal or hypopharyngeal carcinomas reported significantly higher values than patients with cancer of the oral cavity/oropharynx or other localizations from t1 to t3, independent of their treatment regimen (multimodal vs. monomodal). This seems comprehensible because the tumor- and treatment-related side effects directly influence the voice through modified function of the vocal fold through scarring and fibrosis [ 29 ]. Additionally, the presence of tracheotomy and feeding tubes showed negative associations but a diminishing impairment over time.…”

Section: Discussionmentioning

confidence: 99%

Course of Self-Reported Dysphagia, Voice Impairment and Pain in Head and Neck Cancer Survivors

Zebralla

Wiegand

Dietz

et al. 2021

Biology

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Background: Head and neck cancer (HNC)-specific symptoms have a substantial impact on health-related quality of life. The aim of this study was to determine whether self-reported dysphagia, voice problems and pain of HNC patients changed over time and whether specific clinical or sociodemographic variables were associated with these symptoms. Methods: HNC patients (n = 299) in an outpatient setting answered questionnaires (Eating Assessment Tool-10; questions from the EORTC QLQ-C30 and EORTC H&N35) on dysphagia, voice problems and pain, collected with the software “OncoFunction” at three different timepoints (t1–t3) after diagnosis. The mean score changes from t1 to t3 were expressed in terms of effect sizes d. The impact of sociodemographic and clinical factors on the course of the variables was tested with multivariate analyses of variance. Results: Dysphagia, voice impairment and pain in HNC survivors significantly improved over a period of approximately 14 months after diagnosis. Tumor site, stage, treatment modality, occupational state and ECOG state were significantly correlated with self-reported functional outcome. The pain level of the HNC patients was rather low. Conclusions: Patients suffer from functional impairments after HNC treatment, but an improvement in self-reported symptoms could be demonstrated within this time period.

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Section: Discussionmentioning

confidence: 99%

Course of Self-Reported Dysphagia, Voice Impairment and Pain in Head and Neck Cancer Survivors

Zebralla

Wiegand

Dietz

et al. 2021

Biology

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“…Although these fibroblasts were derived from the vocal folds and not the lungs, this pathway may indicate enrichment of pro-fibrotic pathways. Vocal-fold fibrosis/scarring is one of the most common causes of voice-related disability [ 25 ] and these data may suggest that interactions between mycoplasma and glucocorticoids may impact the therapeutic efficacy of GCs for vocal-fold fibrosis. Conversely, in mycoplasma-negative cells treated with DM, the transforming growth factor (TGF)-β receptor signalling pathway was significantly enriched.…”

Section: Discussionmentioning

confidence: 99%

Mycoplasma affects baseline gene expression and the response to glucocorticoids in vocal fold fibroblasts

Doyle

Nakamura

Bing

et al. 2021

Journal of Medical Microbiology

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Introduction. In vitro experimentation is intentionally contrived to isolate specific phenomena in the context of profound biological complexity. Mycoplasmas in the upper airway likely contribute to this complexity and play a largely unknown role in both health and disease. Similarly, the presence and role of mycoplasma in in vitro investigation are largely unknown. Hypothesis. We hypothesize mycoplasma in human vocal fold fibroblasts (VFF) will affect both basal gene-expression patterns as well as the cell response to exogenous stimuli. Aim. We sought to determine mycoplasma presence across vocal fold fibroblast cultures, basal transcriptional changes as a function of mycoplasma, and responsiveness to exogenous glucocorticoids in mycoplasma-positive and -negative VFF. Methodology. PCR-based mycoplasma detection was performed in an immortalized human VFF line as well as rat and rabbit primary VFF cultures and extracted rat laryngeal tissue. RNA sequencing was performed in mycoplasma-positive and -negative human cells at baseline and in response to dexamethasone. Results. Mycoplasma was identified in the human cell line as well as primary culture from rabbits. Mycoplasma was not detected in tissue or primary culture from rat vocal folds. Basal mRNA expression in human VFF differed significantly following mycoplasma treatment. In addition, differential responses to dexamethasone were observed across multiple pathways as a function of mycoplasma presence in these cells. Pathways including apoptosis, DNA damage repair, and G1 to S cell cycle signalling were significantly enriched in mycoplasma-positive cells. Conclusion. Variability of mycoplasma presence across culture conditions and differential responses to exogenous stimuli as a function of mycoplasma presence are potentially problematic for the translation of in vitro experimentation in the upper aerodigestive tract. It remains unclear if these findings represent contamination or the baseline state of this specialized tissue.

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“…The vocal fold consists of fibroblasts which have been proven to be closely associated with inflammatory response [ 67 ]. Inflammation in vocal fold is one of the pathological factors leading to vocal fold scarring [ 68 ]. As biomaterials are injected into the biological system, immune cells such as leukocytes detect them as foreign particles.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of Biomaterials for Vocal Fold Injection: A Systematic Review

Baki

Lokanathan

et al. 2021

Polymers

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Vocal fold injection is a preferred treatment in glottic insufficiency because it is relatively quick and cost-saving. However, researchers have yet to discover the ideal biomaterial with properties suitable for human vocal fold application. The current systematic review employing PRISMA guidelines summarizes and discusses the available evidence related to outcome measures used to characterize novel biomaterials in the development phase. The literature search of related articles published within January 2010 to March 2021 was conducted using Scopus, Web of Science (WoS), Google Scholar and PubMed databases. The search identified 6240 potentially relevant records, which were screened and appraised to include 15 relevant articles based on the inclusion and exclusion criteria. The current study highlights that the characterization methods were inconsistent throughout the different studies. While rheologic outcome measures (viscosity, elasticity and shear) were most widely utilized, there appear to be no target or reference values. Outcome measures such as cellular response and biodegradation should be prioritized as they could mitigate the clinical drawbacks of currently available biomaterials. The review suggests future studies to prioritize characterization of the viscoelasticity (to improve voice outcomes), inflammatory response (to reduce side effects) and biodegradation (to improve longevity) profiles of newly developed biomaterials.

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Pathophysiology of Fibrosis in the Vocal Fold: Current Research, Future Treatment Strategies, and Obstacles to Restoring Vocal Fold Pliability

Cited by 53 publications

References 150 publications

Course of Self-Reported Dysphagia, Voice Impairment and Pain in Head and Neck Cancer Survivors

Course of Self-Reported Dysphagia, Voice Impairment and Pain in Head and Neck Cancer Survivors

Mycoplasma affects baseline gene expression and the response to glucocorticoids in vocal fold fibroblasts

In Vitro Evaluation of Biomaterials for Vocal Fold Injection: A Systematic Review

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