Exploring the Pathophysiology of Reinke's Edema: The Cellular Impact of Cigarette Smoke and Vibration

Abstract

Objectives To explore the isolated or combined effects of cigarette smoke extract (CSE) and vibration on human vocal fold fibroblasts (hVFF) in an in vitro setting in order to elucidate their influence in the pathophysiology of Reinke's edema (RE). Study design Immortalized hVFF were exposed to CSE or control medium under static or vibrational conditions. A phonomimetic bioreactor was used to deliver vibrational patterns to hVFF over a period of 5 days. Methods Cytotoxicity was quantified using a lactate dehydrogenase assay. We employed reverse transcription–quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, and Magnetic Luminex(R) assays (R&D Systems, Minneapolis, MN) to assess the influence on extracellular matrix production, fibrogenesis, inflammation, and angiogenesis. Results We observed significant changes induced by CSE alone (hyaluronic acid, matrix metalloproteinase 1, Interleukin‐8, cyclooxygenase [COX]1, COX2, vascular endothelial growth factor [VEGF]D), as well as settings in which only the combination of CSE and vibration led to significant changes (transforming growth factor beta 1, VEGFA, VEGFC). Also, CSE‐induced levels of COX2 were only significantly reduced when vibration was applied. Conclusion We were able to explore the cellular effects of CSE and vibration on hVFF by employing a phonomimetic bioreactor. Whereas cigarette smoke is generally accepted as a risk factor for RE, the role of vibration remained unclear as it is difficult to study in humans. Our data showed that some genes and proteins in the pathophysiological context of RE were only affected when CSE in combination with vibration was applied. Level of Evidence NA Laryngoscope, 131:E547–E554, 2021

In vitro mechanical vibration down-regulates pro-inflammatory and pro-fibrotic signaling in human vocal fold fibroblasts

“…Mechanical stimulation was performed using a phonomimetic bioreactor developed and established by our group. In short, the flexible bottomed 6-well plates were oscillated by aerodynamic pressure fluctuation induced by a loudspeaker beneath the plate [29,49].…”

Acute Variceal Hemorrhage and Airway Obstruction in a Patient With Reinke’s Edema

“…3 Additionally, an in-vitro study found that specific genes, when associated with the combination of cigarette smoke and vocal cord vibration, had greater effects on the pathophysiology of Reinke’s edema. 4 We believe that this patient’s edema did not occur as a direct result of the type of endotracheal tube used but due to her persistent smoking before the procedure, which led to hemorrhage and inflammation of the vocal cords during intubation. Thus, to prevent the exacerbation of Reinke’s edema, we recommend that the patient remain on voice rest for 7 to 10 days and stops smoking 6 weeks before the procedure.…”

Molekulare Laryngologie

“…Eine Stimulation mit nur einem der beiden führte zu keiner signifikanten Veränderung. Gleichzeitig wurden durch Zigarettenrauch getriggerte hohe COX-2-Spiegel durch zusätzliche Vibration herunterreguliert [ 34 ].…”

“…Weltweit gibt es etwa 6 verschiedene Prototypen für derartige „Bioreaktoren“, wobei keiner davon kommerziell erhältlich ist. Die Gruppe der Autor(inn)en hat in den letzten Jahren einen derartigen „phonomimetischen“ Bioreaktor entwickelt und führt damit bereits Experimente zu verschiedenen Fragstellungen durch [ 28 , 34 , 41 ]. Der Vorteil des Prototypen der Autor(inn)en besteht darin, dass er aus kommerziell erhältlichen Einzelteilen besteht und deswegen relativ leicht von anderen Gruppen nachgebaut werden kann.…”