Akari Kimura

All Publications

• Wildfire Smoke and the Human Larynx: Preliminary Evidence of Functional and Molecular Change. Journal of voice : official journal of the Voice Foundation Erickson-DiRenzo, E., Clark, C., Seidman, A., Kimura, A., Ramos, J. M., Rameau, A. 2026

  Abstract

  Air pollution is a major public health burden. Wildfires are a known source of air pollution in their production of smoke, containing fine particulate matter (PM2.5). PM2.5 is known to induce respiratory inflammation, but its effects on the human larynx remain poorly understood. This case report provides a preliminary investigation into the impact of wildfire-related air pollution on vocal function and laryngeal tissue biology in an adult participant exposed to elevated PM2.5 during a wildfire event.Comprehensive voice and laryngeal assessments were conducted during a period of wildfire smoke exposure (PM2.5 > 100 µg/m³) and a subsequent period of normal air quality (PM2.5 < 10 µg/m³). Voice evaluation included acoustic and aerodynamic measures as well as laryngeal endoscopy with stroboscopy. Ventricular fold biopsies were also collected at each time point for gene expression analysis using quantitative PCR (qPCR) targeting extracellular matrix (ECM) remodeling and inflammatory markers.During record breaking air pollution with PM2.5 levels up to 117 μg m-3 related to massive regional wildfires, the participant exhibited a reduction in speaking fundamental frequency compared to baseline under normal air quality conditions. Laryngeal endoscopy revealed visibly increased laryngeal mucus. qPCR analysis demonstrated approximately a twofold increase in MMP-1 expression, consistent with heightened ECM turnover. Other ECM and inflammatory genes showed variable expression patterns without consistent upregulation.These preliminary findings suggest that acute exposure to wildfire-associated PM2.5 may alter vocal function and induce early molecular changes in the laryngeal tissue consistent with matrix remodeling. Further studies with larger cohorts are warranted to define the mechanisms by which wildfire smoke impacts the human larynx and voice.

  View details for DOI 10.1016/j.jvoice.2026.07.048

  View details for PubMedID 42603772

• Establishing an air-liquid interface system for exposure of mouse laryngeal epithelial cells to cigarette smoke. Inhalation toxicology Kimura, A., Golchin, A., Easwaran, M., Kiessling, P. T., Khan, M. I., Martinez, J. D., Erickson-DiRenzo, E. 2026: 1-18

  Abstract

  The laryngeal epithelium is one of the first lines of defense against inhaled insults, including cigarette smoke (CS). However, a lack of suitable in vitro models has limited mechanistic studies of laryngeal epithelial injury and disease pathogenesis in response to CS. The purpose of this investigation was to establish an air-liquid interface (ALI) system for modeling airborne CS exposure in laryngeal epithelial cells.Primary mouse laryngeal epithelial cells were harvested, cultured, and transitioned from submerged to ALI conditions to induce epithelial differentiation. ALI cultures were characterized by electrophysiological evaluation of transepithelial resistance (TEER), histology, and immunofluorescent staining and quantification for epithelial markers and compared with native laryngeal tissue. ALI cultures were exposed to increasing doses of CS during differentiation, and epithelial barrier integrity was assessed by evaluating cytotoxicity, TEER, and structure.Submerged laryngeal epithelial cultures were primarily proliferating basal cells. Differentiated ALI cultures demonstrated progressive epithelial maturation, with formation of a multilayered structure and high TEER, indicative of robust barrier integrity. Epithelial marker localization in ALI cultures closely resembled that of native mouse vocal fold epithelium. CS exposure disrupted epithelial barrier integrity in a dose-dependent manner, including increased cytotoxicity and reductions in TEER. Moderate exposure permitted some recovery of function and structure, underscoring the intrinsic resilience of laryngeal epithelial cells.This investigation establishes a physiologically relevant in vitro model system that recapitulates key features of native laryngeal epithelium and provides a robust platform for investigating the cellular and molecular pathways governing CS-induced epithelial injury and repair.

  View details for DOI 10.1080/08958378.2026.2657360

  View details for PubMedID 42021631

• Laryngeal Basal Cell Response to Cigarette Smoke and E-Cigarette Aerosol Exposures. The Laryngoscope Easwaran, M., Kimura, A., Liao, H. Y., Khan, M. I., Golchin, A., Kiessling, P., Erickson-DiRenzo, E. 2025

  Abstract

  The laryngeal epithelium contains a basal cell (BC) layer. The BC layer is a reservoir of progenitor cells necessary for the formation and regeneration of the epithelium. The epithelium is susceptible to the deposition of inhaled irritants such as cigarette smoke (CS) and electronic cigarette (E-Cig) aerosol. The objective of this study was to quantify BC, proliferating cells, and epithelial histologic architecture in the larynx following a 6-week exposure to CS or E-Cig aerosol.Mice (N = 12) were assigned to a room-air control, CS-exposed, or an E-Cig-exposed group. Exposures were conducted for 2 h per day, 5 days a week for a total of 6 weeks. Mice were then euthanized and the larynx was evaluated using immunofluorescence and histology. We assessed p63-positive BCs, Ki67-positive proliferating cells, p63 and Ki67 colocalized cells, overall cellularity, and epithelial thickness across the supraglottic, vocal fold, and subglottic regions of the larynx.Following E-Cig exposure, there was a significant reduction in p63-positive BC in the vocal folds as compared to the CS-exposed and control group and epithelial thickness compared to the CS-exposed group. No significant changes were observed in the numbers of BCs, proliferating cells, colocalized cells, or overall cellularity in any of the other laryngeal regions examined.An E-Cig-induced reduction in BCs within the vocal fold epithelium may have implications for decreased regenerative capacity. Overall, our findings highlight distinct epithelial responses to CS and E-Cig exposures and underscore the regional heterogeneity of the laryngeal response to these common inhaled challenges.

  View details for DOI 10.1002/lary.70092

  View details for PubMedID 40888519

• Establishing a Mouse Model of Surgical Vocal Fold Injury. The Laryngoscope Kimura, A., Khan, M. I., Easwaran, M., Soo, J., Golchin, A., Erickson-DiRenzo, E. 2024

  Abstract

  Animal models of vocal fold (VF) surgical injury and scar formation provide insight into the wound healing process. The purpose of this study was to establish an alternative model of surgical injury to the mouse VF using materials commonly available in most research laboratories or for purchase and to investigate wound healing of the epithelium (EP) and lamina propria (LP).Mice were anesthetized by isoflurane gas delivery and positioned on a platform so that the larynx could be observed using a laryngoscope and dissection microscope. Unilateral VF injury was created using a wire brush. Mice were euthanized and the larynx evaluated 1-, 3-, 5-, 7-, 14-, and 28-days following injury. Histological and immunofluorescent analysis was used to evaluate thickness of the EP, LP area, proliferative (Ki67+) and basal cells (p63+) in the EP, and collagen III content in the LP.The depth of injury reached the superficial thyroarytenoid muscle on Day 1. The thickness of the EP of the injured VF was increased on Days 3 and 5, and the LP area was increased on Days 3, 5, and 7 as compared with the uninjured VF. Ki67+ and p63+ cells were increased on Day 3 and collagen III content was increased on Days 5 and 28 as compared with the uninjured VF.We successfully established an alternative method of creating unilateral VF injury in the mouse. This method will be useful for future research regarding VF surgical injury and wound healing.N/A Laryngoscope, 2024.

  View details for DOI 10.1002/lary.31732

  View details for PubMedID 39180435

• Effects of Short-term Electronic(e)-Cigarette Aerosol Exposure in the Mouse Larynx. The Laryngoscope Easwaran, M., Maria, C. S., Martinez, J. D., Hung, B., Yu, X., Soo, J., Kimura, A., Gross, E. R., Erickson-DiRenzo, E. 2023

  Abstract

  The effects of electronic cigarettes (e-cigarettes) on the larynx are relatively unknown. This study examined the short-term effects of e-cigarette inhalation on cellular and inflammatory responses within the mouse laryngeal glottic and subglottic regions after exposure to pod-based devices (JUUL).Male C57BL6/J mice (8-9 weeks) were assigned to control (n = 9), JUUL flavors Mint (JMi; n = 10) or Mango (JMa; n = 10). JUUL mice were exposed to 2 h/day for 1, 5, and 10 days using the inExpose inhalation system. Control mice were in room air. Vocal fold (VF) epithelial thickness, cell proliferation, subglandular area and composition, inflammatory cell infiltration, and surface topography were evaluated in the harvested larynges. Mouse body weight and urinary nicotine biomarkers were also measured. Chemical analysis of JUUL aerosols was conducted using selective ion flow tube mass spectrometry.JUUL-exposed mice had reduced body weight after day 5. Urinary nicotine biomarker levels indicated successful JUUL exposure and metabolism. Quantitative analysis of JUUL aerosol indicated that chemical constituents differ between JMi and JMa flavors. VF epithelial thickness, cellular proliferation, glandular area, and surface topography remained unchanged after JUUL exposures. Acidic mucus content increased after 1 day of JMi exposure. VF macrophage and T-cell levels slightly increased after 10 days of JMi exposures.Short-term e-cigarette exposures cause minimal flavor- and region-specific cellular and inflammatory changes in the mouse larynx. This work provides a foundation for long-term studies to determine if these responses are altered with multiple e-cigarette components and concentrations.N/A Laryngoscope, 2023.

  View details for DOI 10.1002/lary.31043

  View details for PubMedID 37698394

• Method for Collecting Single Epithelial Cells from the Mouse Larynx. The Laryngoscope Khan, M. I., Easwaran, M., Martinez, J. D., Kimura, A., Erickson-DiRenzo, E. 2023

  Abstract

  The larynx is lined by specialized epithelial cell populations. Studying molecular changes occurring in individual epithelial cell types requires a reliable method for removing these cells from the larynx. Our objective was to develop a method to harvest individual epithelial cells from the mouse larynx while minimizing contamination from non-laryngeal sites and non-epithelial laryngeal cells.Mice were euthanized, and the larynx was carefully exposed and separated from non-laryngeal sites. A small dental brush was inserted into the laryngeal inlet and rotated to obtain epithelial cells. Cells were transferred to collection media, counted, and cytospin preparations stained for laryngeal epithelial (i.e., Pan-Keratin, EpCAM, NGFR, p63, K5, β-tubulin, MUC5AC) and non-epithelial (i.e., vimentin) cell markers. Histopathology was completed on brushed laryngeal tissue sections to evaluate the depth of cell collection. Preliminary Single-cell RNA sequencing (scRNA-seq) was performed to confirm this method can capture diverse laryngeal cell types.We collected 6000-8000 cells from a single larynx and 35000-40000 cells from combining brushings from three tissues. Histopathology demonstrated brushing removed the epithelial layer of the larynx and some underlying tissue. Immunofluorescence staining demonstrated the phenotype of harvested cells was primarily epithelial. Preliminary scRNA-seq was successfully conducted and displayed nine unique cell clusters.We developed a reliable method of harvesting individual epithelial cells from the mouse larynx. This method will be useful for collection of laryngeal cells for a variety of downstream cellular and molecular assays, including scRNA-seq, protein analyses, and cell-culture-based experiments, following laryngeal injury.N/A Laryngoscope, 2023.

  View details for DOI 10.1002/lary.30970

  View details for PubMedID 37602769

• Inhibition of extracellular signal-regulated kinase pathway suppresses tracheal stenosis in a novel mouse model PLOS ONE Kimura, A., Araki, K., Satoh, Y., Mogi, S., Fujitani, K., Kurioka, T., Endo, S., Shiotani, A., Yamashita, T. 2021; 16 (9): e0256127

  Abstract

  Tracheal stenosis is a refractory and recurrent disease induced by excessive cell proliferation within the restricted tracheal space. We investigated the role of extracellular signal-regulated kinase (ERK), which mediates a broad range of intracellular signal transduction processes in tracheal stenosis and the therapeutic effect of the MEK inhibitor which is the upstream kinase of ERK. We histologically analyzed cauterized tracheas to evaluate stenosis using a tracheal stenosis mouse model. Using Western blot, we analyzed the phosphorylation rate of ERK1/2 after cauterization with or without MEK inhibitor. MEK inhibitor was intraperitoneally injected 30 min prior to cauterization (single treatment) or 30 min prior to and 24, 48, 72, and 96 hours after cauterization (daily treatment). We compared the stenosis of non-inhibitor treatment, single treatment, and daily treatment group. We successfully established a novel mouse model of tracheal stenosis. The cauterized trachea increased the rate of stenosis compared with the normal control trachea. The phosphorylation rate of ERK1 and ERK2 was significantly increased at 5 min after the cauterization compared with the normal controls. After 5 min, the rates decreased over time. The daily treatment group had suppressed stenosis compared with the non-inhibitor treatment group. p-ERK1/2 activation after cauterization could play an important role in the tracheal wound healing process. Consecutive inhibition of ERK phosphorylation is a potentially useful therapeutic strategy for tracheal stenosis.

  View details for DOI 10.1371/journal.pone.0256127

  View details for Web of Science ID 000707052600010

  View details for PubMedID 34587174

  View details for PubMedCentralID PMC8480895

• Transoral endoscopic surgical approach to venous malformation of the parapharyngeal space SAGE OPEN MEDICAL CASE REPORTS Kimura, A., Seino, Y., Yamashita, T. 2020; 8: 2050313X20938248

  Abstract

  We encountered a rare case of venous malformation located in the parapharyngeal space. The 65-year-old female patient did not have any symptoms, and the malformation was discovered incidentally during a clinical survey. Examination of the oral cavity revealed a mass in the left soft palate. Magnetic resonance imaging showed a well-defined mass in the left parapharyngeal space. Fine needle aspiration cytology suggested no malignancy. Four years after the first visit, she underwent surgery for diagnosis and treatment. We safely removed the mass with a rigid videoendoscope trans-orally. No postoperative complications arose, and she was discharged 7 days after the operation. Histopathological examination identified cavernous hemangioma. Venous malformation (cavernous hemangioma) of the parapharyngeal space is very rare, and few cases of removal under a transoral approach using a rigid endoscope with a flexible tip have been reported. This approach is safe and can be recommended for selected tumors of the parapharyngeal space.

  View details for DOI 10.1177/2050313X20938248

  View details for Web of Science ID 000548830100001

  View details for PubMedID 32670582

  View details for PubMedCentralID PMC7339072

• Clinical predictors of descending necrotizing mediastinitis after deep neck infections LARYNGOSCOPE Kimura, A., Miyamoto, S., Yamashita, T. 2020; 130 (11): E567-E572

  Abstract

  To identify the clinical predictors of descending necrotizing mediastinitis (DNM) secondary to deep neck infections (DNIs) before treatment.Retrospective case series.We reviewed 73 patients with DNIs who had been treated with external drainage at our institute between April 2009 and March 2019. We divided these patients into either a DNI group without mediastinitis (n = 55) or a DNM group secondary to DNI (n = 18). We collected clinical data and compared them between the groups, conducting univariate and multiple logistic regression analysis to identify the predictors of DNM.We identified age, C-reactive protein (CRP), neutrophil percentage, lymphocyte percentage, neutrophil to lymphocyte ratio (NLR), presence of comorbidities, presence of gas, and abscess extension below the hyoid bone as statistically significant by univariate analysis. Moreover, multiple logistic regression analysis showed that age ≥55 years, NLR ≥13, and CRP ≥30 mg/dL were statistically significant.We identified age ≥55, NLR ≥13, and CRP ≥30 before DNI treatment as clinical predictors of a DNM complication.4 Laryngoscope, 130:E567-E572, 2020.

  View details for DOI 10.1002/lary.28406

  View details for Web of Science ID 000497258700001

  View details for PubMedID 31747058

• A Case of Gastric Meningeal Carcinomatosis Involving Bilateral Hearing Loss: The Difference between Clinical Images and Autopsy Findings JOURNAL OF INTERNATIONAL ADVANCED OTOLOGY Kimura, A., Takahashi, Y., Mizutari, K., Tsujimoto, H., Nakanishi, K., Shiotani, A. 2019; 15 (2): 333-336

  Abstract

  We describe a rare case of meningeal carcinomatosis (MC) in a 66-year-old man who presented with bilateral deafness and vertigo, initially presumed to be neurofibromatosis type-2. Brain magnetic resonance imaging (MRI) of the patient revealed bilateral gadolinium enhanced masses at the cerebellopontine angle. However, multiple central nervous system symptoms, including loss of consciousness, gradually appeared. He had a history of gastric cancer; therefore, a lumbar puncture was performed. Cytological examination of the cerebrospinal fluid confirmed the presence of adenocarcinoma cells. The general condition of this patient worsened, and he died 46 days after the first onset of hearing loss. An autopsy was performed, and multiple infiltrations of adenocarcinoma cells in the brain were confirmed, though undetected by MRI. The prognosis of MC is extremely poor; therefore, rapid diagnosis is important to prevent mortality. Retrospectively, a lumbar puncture could have been conducted earlier to identify MC, especially in consideration of the clinical history of this patient.

  View details for DOI 10.5152/iao.2019.6080

  View details for Web of Science ID 000483026300028

  View details for PubMedID 31257192

  View details for PubMedCentralID PMC6750794