Therapeutic Effects of Intranasal Tofacitinib on Chronic Rhinosinusitis with Nasal Polyps in Mice.

OBJECTIVES: The Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway play a key role in immune modulation, especially in the polarization of T helper cells. JAK inhibitors reduce inflammation by inhibiting the phosphorylation of STAT. We investigated whether a JAK inhibitor, tofacitinib, can reduce inflammation in a mouse model of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: An eosinophilic CRSwNP model was induced using 4-week-old BALB/c mice. The therapeutic effects of topical tofacitinib were compared with the effects of triamcinolone acetonide (TAC). Polyp formation and eosinophilic infiltration were assessed by histology. Levels of phosphorylated STAT (pSTAT), eosinophil cationic protein, and eotaxin were measured by immunohistochemistry. Gene expression levels of GATA-3 was measured using quantitative PCR. The production of cytokines in sinonasal tissues, including interleukin IL-4, IL-5, IL-12, and interferon-γ, were measured using enzyme-linked immunosorbent assays (ELISA). RESULTS: Topical tofacitinib administration significantly reduced the number of polyp-like lesions and the degree of eosinophilic infiltration, with an efficacy comparable with that of systemic TAC administration. Similarly, the levels of pSTAT6, eosinophil cationic protein, and eotaxin decreased with tofacitinib treatment. Tofacitinib decreased the gene expression level of GATA-3. Lastly, tofacitinib significantly decreased IL-4 and IL-5 production to a similar extent as that by systemic or topical TAC administration. Tofacitinib, but not TAC, significantly increased the production of interferon-γ. CONCLUSION: Topical tofacitinib administration may be an effective treatment for eosinophilic CRSwNP by inhibiting phosphorylation of STATs. LEVEL OF EVIDENCE: N/A. Laryngoscope, 131:E1400-E1407, 2021.

Triangular excision and submucosal rejoining to correct horizontally folded caudal nasal septum.

BACKGROUND: Surgical correction of severe caudal deviation of nasal septum using an endonasal approach is challenging for surgeons. Among cases of severe caudal septal deflection, fracture lines along the horizontal direction are occasionally encountered during the surgery. We devised a simple and efficient technique called "triangular excision and submucosal rejoining" to address this kind of deformity. METHODS: A total of 9 patients with severe caudal septal deflection underwent "triangular excision and submucosal rejoining." After the removal of the deformed posteroinferior portion of the quadrangular cartilage, 2 incision lines were made on the remaining caudal septum, starting from a point at the most anterior portion of the fracture line and diverging posteriorly above and below the fracture line. After removing a triangular cartilaginous piece, the upper and lower remaining cartilage segments were approximated using a single or 2 simple interrupted sutures. Sutures exiting the mucosa were re-entered from the exit point so that all the sutures were buried underneath the mucosa while the mucosal flap was elevated only unilaterally. RESULTS: This technique was effective in all cases. Septal batten grafts were applied in 3 patients, in whom the remaining quadrangular cartilage was weak and thin. One patient showed a mildly recurred septal deviation, but the nasal cavities remained patent with no symptoms. Serious complications such as dorsal saddling or tip ptosis did not occur in any cases. CONCLUSION: "Triangular excision and submucosal rejoining" may be a safe and efficient septoplasty technique to correct a horizontally folded caudal septum.

Establishment and verification of a mouse model of nasal wound healing.

OBJECTIVES: Poor wound healing as reflected by the development of synechia and osteitis after endoscopic sinus surgery may trigger disease recurrence. Animal models provide insights into the pathogenesis of poor wound healing and may aid in the development of new therapeutics. Here, we established a mouse model of nasal wound healing and confirmed its utility. STUDY DESIGN: Animal study. METHODS: Unilateral intranasal wounds were induced using a small interdental brush in 6-week-old C57BL/6 mice. Forty-five mice were divided into three groups (each n = 15): one control and two experimental groups (intranasal vs. intraperitoneal dexamethasone). Mice were sacrificed on days 2, 14, and 28 after injury (each n = 5). Serial changes in nasal wound histopathology were described, and intergroup differences were analyzed. RESULTS: On day 2, mucosal detachment, hemorrhage, and exudate were observed. On day 14, synechiae featuring neo-osteogenesis (bone lacunae, osteoblasts, and multinucleated osteoclasts) between the septum and the maxilloturbinate were prominent, followed by wound maturation on day 28: fewer lacunae and smaller osteoblasts. Macrophages were evident only on day 2, and lymphocytes were predominant on day 28. The amount of exudate on day 2 and the synechial area on day 28 were significantly reduced in mice that received dexamethasone systemically compared with control mice, with similar trends in those treated intranasally. CONCLUSION: Our mouse model of nasal wound healing was characterized by the development of bony synechia and neo-osteogenesis, not soft-tissue synechia. The model may be useful in the assessment of novel therapeutics to prevent those wounds. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E266-E271, 2019.

Influence of a medialized middle turbinate on olfactory function: a prospective randomized double-blind study.

BACKGROUND: Medialization of the middle turbinate (MT) is an effective technique to prevent recurrent rhinosinusitis but could, in theory, reduce olfactory function by interfering the odorants to reach the olfactory mucosae. We performed a prospective randomized double-blind trial under the hypothesis that olfactory functions would be affected by the status of olfactory mucosae, not by MT medialization. METHODS: In randomly selected sides, the unilateral MT was medialized in 80 patients undergoing bilateral endoscopic sinus surgery for chronic rhinosinusitis. The status of the bilateral olfactory cleft (OC) was photodocumented intraoperatively and categorized into patent (normal or mucosal swelling with discharge) and congested (hypertrophied mucosae or nasal polyps) groups. The butanol threshold test (BTT) was conducted in each nostril before and 6 months after the surgery. Correlation between the BTT scores and MT medialization or the OC status was assessed. No smell identification test was conducted side by side, which might limit clinical implications. RESULTS: In total, 46 of 80 patients completed the trial. MT medialization was performed on the left and right side of the nose in 19 and 27 cases, respectively. The intraoperative OC status did not differ between the 2 sides. Perioperative changes in the BTT scores were similar between the medialized and intact MT sides, whereas the preoperative and postoperative BTT scores were higher in the patent OC group than in the congested OC group, regardless of side. CONCLUSION: MT medialization does not impair olfactory function, and OC status is closely related to olfactory function.

Idiopathic benign paroxysmal positional vertigo in the elderly: a long-term follow-up study.

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral-type vertigo in the elderly. While some studies have investigated BPPV among the elderly, no study has focused on the isolated idiopathic BPPV (iBPPV) in the elderly. AIMS: To investigate the clinical features and recurrence rate in elderly patients diagnosed with iBPPV. METHODS: The authors prospectively reviewed the medical records of 627 patients diagnosed with BPPV, and a total of 370 patients fulfilled the inclusion criteria. The subjects were divided into two groups by age (experimental group ≥65 years and control group 17-64 years), and the gender, numbers of canalith reposition maneuver (CRM) for successful treatment, time elapsed from onset of symptoms to clinic visit, the affected semicircular canal, and the 1- and 5-year recurrence proportion were analyzed. RESULTS: The gender, numbers of CRM for successful treatment, affected semicircular canal, and the 1- and 5-year recurrence proportion showed no statistically significant difference between two groups (p > 0.05). The only exception was the experimental group which took a longer duration from manifestation of symptoms to hospital visit than control group (student's t test, p = 0.021). DISCUSSION: Several previous studies report that the elderly with iBPPV shows more protracted clinical course and much higher recurrence rate than younger adult. Unlike those reports, our study showed no significant differences about the clinical features and recurrence rate between age groups. CONCLUSION: The elderly with iBPPV could be treated as effective as general population.

Anti-inflammatory effects of intranasal cyclosporine for allergic rhinitis in a mouse model.

BACKGROUND: Although topical corticosteroids are considered a safe and effective drug for allergic rhinitis (AR), some AR patients do not show sufficient symptomatic improvement by use of topical corticosteroids. Topical cyclosporine is a safe and effective drug for patients with allergic conjunctivitis, particularly for those with steroid-resistant allergic conjunctivitis. We investigated the anti-inflammatory effects of intranasal cyclosporine for AR using a mouse model. METHODS: After establishment of allergic inflammation in 5-week-old BALB/c mice, cyclosporine was administered intranasally 3 times per week for 2 weeks. To confirm its anti-inflammatory effects, triamcinolone acetonide (TAC) was utilized as a control drug. Histopathologic changes were evaluated using Sirius red and Giemsa staining for eosinophilic and mast cell infiltration, respectively. The levels of cytokines in sinonasal tissues, including tumor necrosis factor (TNF), interleukin (IL)-4, IL-5, and IL-13, were assessed based on a cytometric bead array. RESULTS: The degree of eosinophilic infiltration was significantly decreased by instillation of cyclosporine, the potency being similar to TAC. However, the number of mast cells was not decreased by cyclosporine or TAC. The levels of TNF, IL-4, IL-5, and IL-13 were significantly decreased after treatment with cyclosporine. CONCLUSION: The anti-inflammatory effects of topical cyclosporine for AR were equivalent to those of topical corticosteroids. Topical cyclosporine may be useful for the treatment of AR, although human studies are required.

Interleukin-4 enzyme-linked immunospot assay may be useful for diagnosing sensitization to house dust mite.

BACKGROUND: The skin prick test (SPT) is considered a standard test for identification of allergens, but it has some limitations in clinical practice. The multiple allergen simultaneous test (MAST), which measures allergen-specific immunoglobulin E in patients' serum, is a widely used alternative test, but is limited by its relatively low sensitivity and specificity. As a novel diagnostic test to identify allergens, we investigated the sensitivity and specificity of an interleukin-4 (IL-4) enzyme-linked immunospot (ELISpot) assay for Dermatophagoides farinae (Der f) and Dermatophagoides pteronyssinus (Der p). METHODS: Based on the symptoms and SPT results, 43 house dust mite (HDM) allergic rhinitis (AR) patients and 41 control subjects were included. Peripheral blood was drawn from each subject for IL-4 ELISpot assay and MAST. The receiver operating characteristic (ROC) curve analysis was conducted to determine the cutoff values. Sensitivity, specificity, and positive and neg predictive values were compared between the 2 tests. RESULTS: The sensitivity, specificity, and areas under the ROC curve (AUCs) of the IL-4 ELISpot assay were 88.4%, 97.6%, and 0.939 for Der f, and 95.3%, 97.5%, and 0.971 for Der p, respectively. However, the sensitivity, specificity, and AUC of MAST were 76.7%, 73.2%, and 0.777 for Der f, and 69.8%, 75.6%, and 0.788 for Der p, respectively. CONCLUSION: The IL-4 ELISpot assay showed higher sensitivity, specificity, and AUC than MAST, which indicates its clinical feasibility for diagnosing allergy for HDM. A further study is needed to determine the accuracy of the IL-4 ELISpot assay for other common allergens.

Chronic anosmia induces depressive behavior and reduced anxiety via dysregulation of glucocorticoid receptor and corticotropin-releasing hormone in a mouse model.

BACKGROUND: Olfactory loss is highly prevalent, and comorbid mood disorders are common. Considering olfactory input is highly interconnected with the limbic system, and that the limbic system manages mood, it is predictable that impairments in the sense of smell may result in mood changes. METHODOLOGY: Chronic olfactory deficits were induced by repeated intranasal irrigation of ZnSO4 for 12 weeks in BALB/c mice. H&E staining, OMP staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression, as well as open field, elevated plus maze tests were applied to assess anxiety. The mRNA levels of glucocorticoid receptor (GR) and corticotropin releasing hormone (CRH) were measured by real-time PCR to confirm relevant molecular changes. RESULTS: Disruption of the olfactory epithelium and olfactory loss was confirmed in histological studies and potato chip finding test. Behavioral tests show that the chronic anosmic state caused increased depression and reduced anxiety. PCR data showed that mRNA levels of GR in the hypothalamus and CRH in the amygdala were significantly decreased. CONCLUSIONS: These results propose that ZnSO4-induced chronic anosmia can cause a depressive and anxiolytic state via decreased hypothalamic GR and amygdalar CRH.

Age-related differences in human palatine tonsillar B cell subsets and immunoglobulin isotypes.

The tonsils provide defense of the upper aerodigestive tract against pathogens. Although long known to undergo functional changes with age, the precise changes occurring within tonsillar B cell populations remain undefined. In the present study, we investigated age-related changes in palatine tonsillar B cell subsets and immunoglobulin (Ig) isotypes. Palatine tonsils were obtained from forty-two tonsillectomy patients without tonsillitis who were divided into three groups: young children (4-9 years), adolescents (10-19 years), and adults (20-60 years). Tonsillar B cells were then analyzed by flow cytometry. Using expression of CD38 and IgD to define B cell subsets, we found that the frequency of germinal center (GC) B cells in the tonsils was significantly higher, and the frequency of memory B cells lower, in young children as compared to adolescents and adults. Within the GC B cell subsets, adults had a higher frequency of IgA(+) cells and a lower frequency of IgM(+) cells as compared to individuals in the younger age groups. Moreover, young children had a higher frequency of IgG(+) cells in the GC B cell subsets than did individuals in the older age groups. We also observed an abundance of IgM(+) cells among memory B cells and plasmablasts in young children and IgA(+) cells in adults. In summary, the proportion of GC B cells in palatine tonsillar B cells decreases with age, while the proportion of memory B cells increases with age. In addition, Ig isotypes in tonsils preferentially switch from IgM to IgA as individuals age.

Posterosuperior extension of caudal septal incision for endoscopic septoplasty.

BACKGROUND: Endoscopic septoplasty provides several advantages over traditional headlight septoplasty in terms of better visualization. However, surgeons may experience frequent soiling of the endoscope lens by blood from the incision site and awkwardness in finding adequate space for the endoscope and dissectors in narrow septal mucosal tunnels. Here, we propose a simple and safe modification for endoscopic septoplasty. METHODS: A total of 21 patients underwent endoscopic septoplasty using a new modification. Briefly, a posterosuperior extension incision was made along the dorsal septum at the superior end of the caudal septal incision, and a posteroinferior-based septal mucosal flap was developed and placed laterally over the inferior turbinate during surgery. RESULTS: The new modification reported here provided clear endoscopic visualization and a comfortable working space from making the incision to closing the wound. In addition, no significant complications related to this modification, such as increased operation time, intraoperative or postoperative bleeding, delayed wound healing, synechia, nasal septal perforation, and reduced olfaction, were observed. CONCLUSION: Adding a posterosuperior extension incision to the caudal septal incision might be a safe and efficient modification for endoscopic septoplasty.

Therapeutic effects of intranasal cyclosporine for eosinophilic rhinosinusitis with nasal polyps in a mouse model.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a principally type 2 T helper cell (Th2)-mediated inflammatory disease. Systemic corticosteroids currently represent the most effective treatment for CRSwNP, but their long-term use is constrained due to their detrimental side effects. Long-term use of topical steroids is safe, but their efficacy is often limited. Topical cyclosporine has proven to be safe and effective for Th2-mediated diseases such as allergic conjunctivitis. OBJECTIVE: It was hypothesized that topical cyclosporine would be an effective novel drug for the treatment of CRSwNP; its therapeutic efficacy was assessed using a previously established mouse model. METHODS: After induction of eosinophilic CRSwNP in four-week-old BALB/c mice according to previous protocols, the therapeutic effects of intranasal cyclosporine were evaluated and compared with those of triamcinolone acetonide (TAC). Histopathologic changes were evaluated using hematoxylin and eosin for polyp formation and Sirius red staining for eosinophilic infiltration. The production of cytokines in sinonasal tissues, including tumor necrosis factor (TNF), interleukin (IL)-2, interferon (IFN)-γ, IL-4, IL-5, IL-13, and IL-17A, was measured using a cytometric bead array. RESULTS: The number of polyp-like lesions was reduced significantly only by systemic TAC, but the degree of eosinophilic infiltration was decreased significantly by topical cyclosporine, the potency of which was similar to that of topical or systemic TAC. Except for IFN-γ, the majority of measured cytokines were reduced significantly by topical cyclosporine, although their effects on IL-2 and IL-13 were less potent than those of systemic TAC. CONCLUSION: Topical cyclosporine might be an effective drug for the management of CRSwNP.

Palatal sensory threshold reflects nocturnal hypoxemia and airway occlusion in snorers and obstructive sleep apnea patients.

STUDY OBJECTIVES: Upper airway sensory deficit has been reported to be associated with snoring or obstructive sleep apnea. There are limited data on the correlation between disease severity and upper airway sensation. In this study, we investigated the relationship between clinical parameters and standardized palatal sensory threshold (SPST) using Semmes Weinstein monofilaments. METHODS: We recruited 40 snorers and 19 control subjects. Palatal sensory threshold was measured in all study subjects, using Semmes Weinstein monofilaments. Standardized palatal sensory threshold was determined by subtraction of hard palate sensation from uvular sensation. All subjects with snoring underwent a modified Muller maneuver during wakefulness before polysomnography. RESULTS: SPST was higher in snorers than in control subjects, but did not differ according to the severity of obstructive sleep apnea. Patients with higher SPST (≥ 0.45 g/mm(2)) were older and had more severe hypoxemia indices: lower nadir oxyhemoglobin saturation (SpO2) and higher percentage of sleep time at < 90% SpO2. Adjusted for age, sex, neck circumference, and body mass index, SPST was correlated with the apnea-hypopnea index and hypoxemia indices. With a cutoff value ≥ 0.45 g/mm(2), the sensitivity of SPST for nocturnal hypoxemia (nadir SpO2, < 80%) was 81.3%. Patients with higher SPST (≥ 0.45 g/mm(2)) showed more airway occlusion in modified Muller maneuver, than those with lower values. CONCLUSIONS: The SPST measured using Semmes Weinstein monofilaments reflects nocturnal hypoxemia and airway occlusion. This test provides a potential tissue marker of the severity of hypoxemia in patients who snore.

Postoperative olfactory results in chronic rhinosinusitis with nasal polyposis according to wound healing status.

OBJECTIVES: Postoperative wound healing status has not been considered in earlier studies on olfactory changes after surgery. This may be a factor accounting for the equivocal postoperative olfactory results. The aim of this study was to investigate postoperative olfactory results according to wound healing status. METHODS: Fifty patients who underwent endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps with smelling disturbance were examined preoperatively, and at 6 months after surgery. Patients were divided into two groups according to postoperative Lund-Kennedy score: favorable and unfavorable wound healing. Preoperative ostiomeatal unit computed tomography (CT), such as Lund-Mackay score and olfactory cleft opacification score, clinical characteristics and olfactory function tests such as the butanol threshold test and cross-cultural smell identification test, and questionnaire responses were compared between the two groups. RESULTS: There were no differences in preoperative clinical characteristics between the favorable and unfavorable wound healing groups. The favorable wound healing group displayed greater improvement of olfactory results after surgery than the unfavorable wound healing group. Postoperative olfactory improvement patterns showed a hierarchy from subjective to objective improvement and from threshold to identification improvement. Patients who had postoperative favorable wound healing but showed no success of olfaction were characterized by more severe preoperative subjective symptoms and higher olfactory cleft opacification, especially in the upper part of olfactory cleft on preoperative CT scan. CONCLUSION: Wound healing status is an apparent risk factor for postoperative olfactory improvement. Moreover, preoperative opacification in the olfactory cleft may predict bad olfactory results after surgery, even in patients with favorable wound healing.

Ethmoidal mucocele presenting as oculomotor nerve paralysis.

A 56-year-old male was admitted with an acute headache and sudden ptosis on the right side. No ophthalmological or neurological etiologies were apparent. A mucocele of the right posterior ethmoid sinus was observed with radiology. After the marsupialization of the mucocele via a transnasal endoscopic approach, the patient's symptoms (oculomotor nerve paralysis and headache) resolved in 4 weeks. Oculomotor paralysis is a rare symptom of an ethmoidal mucocele. In this article, we report this rare case along with a literature review.

Clinical and histologic studies of olfactory outcomes after nasoseptal flap harvesting.

OBJECTIVES/HYPOTHESIS: Since the introduction of an endonasal endoscopic approach in transsphenoidal pituitary surgery, reports of perioperative olfactory changes have presented conflicting results. We examined the incidence of olfactory loss in cases of endoscopic transsphenoidal pituitary surgery with skull base repair using the nasoseptal flap (NSF) and the effects of monopolar electrocautery commonly used in designing the NSF. STUDY DESIGN: Case-control study. METHODS: Fifteen patients who underwent endoscopic transsphenoidal pituitary surgery with skull base reconstruction using the NSF were divided into cold knife (n = 8) and electrocautery (n = 7) groups according to the device used in the superior incision of the NSF. Patients were followed regularly to monitor the need for dressing or adhesiolysis around the olfactory cleft. All subjects received olfactory tests before and 6 months after surgery. Septal mucosa specimens obtained during posterior septectomy were incised with different devices, and the degree of mucosal damage was evaluated. RESULTS: One patient in the electrocautery group demonstrated olfactory dysfunction postoperatively, but the other 14 patients showed no decrease in olfaction. In histologic analyses, 55.8% and 76.9% of the mucosal surface showed total epithelial loss when the mucosa was cut with cutting- and coagulation-mode electrocautery, respectively. In contrast, only 20% of the mucosal surface exhibited total epithelial loss when the mucosa was cut with a cold knife (P < .01). CONCLUSIONS: Olfactory impairment is not common after use of the NSF. Use of the cold knife in making superior incision may reduce tissue damage with better olfactory outcomes.

Versatility of the pedicled nasoseptal flap in the complicated basal skull fractures.

With the advancement of transnasal endoscopic technique, endoscopic repair of basal skull fractures has considerably substituted former external approaches. The endoscopically feasible pedicled flap, named nasoseptal flap has been extending its range of application, since it was introduced for the reconstruction of the defect after resection of skull base tumors. We introduce two patients with complicated basal skull fractures at different sites who were successfully treated by the transnasal endoscopic approach using nasoseptal flap.

Periostin may play a protective role in the development of eosinophilic chronic rhinosinusitis with nasal polyps in a mouse model.

OBJECTIVES/HYPOTHESIS: Several genes have been reported to be upregulated in human nasal polyps in previous genetic analyses. Among these genes, periostin is known to be overexpressed in nasal polyps obtained from aspirin-sensitive patients. Using periostin-null mice, we investigated the role of periostin in a murine model of eosinophilic rhinosinusitis with nasal polyps. STUDY DESIGN: Animal study. METHODS: Eosinophilic rhinosinusitis was induced in both periostin-null and wild-type mice according to previously established protocols. In brief, ovalbumin (OVA) was used for sensitization and prolonged intranasal stimulation. Staphylococcus aureus enterotoxin B was applied intranasally to develop polyplike lesions. To examine the inflammation and mucosal lesions, hematoxylin and eosin, Sirius red, and Giemsa staining were performed. RESULTS: There was no definite difference in the maximal mucosal thickness between periostin-null and wild-type mice. In contrast, some parameters of inflammation, including the number of polyplike lesions and mast cells, were aggravated in the periostin-null mice compared to wild type. Eosinophilic infiltration was aggravated in the OVA-stimulated periostin-null mice, compared to OVA-stimulated wild-type mice, whereas there was no apparent difference between wild-type and periostin-null mice challenged with additional S aureus enterotoxin B. CONCLUSIONS: The loss of periostin appears to enhance polyplike lesion formation and mast cell infiltration in a mouse model of eosinophilic rhinosinusitis with nasal polyps.

Advantages of glove finger-coated polyvinyl acetate pack in endoscopic sinus surgery.

BACKGROUND: This study investigated the efficacy of glove finger-coated polyvinyl acetate (PA) pack on hemostasis, pain levels, and wound healing after endoscopic sinus surgery (ESS). METHODS: A prospective, randomized, double-blinded controlled study was performed in 30 patients who underwent bilateral ESS for chronic rhinosinusitis. Fifteen patients (control group) had both nasal cavities packed with PA pack (Merocel; Medtronic Xomed, Jacksonville, FL) and another 15 subjects (experimental group) had their nasal cavities packed with PA in a glove finger. Pain levels were assessed by patients on a visual analog scale 12 hours after surgery and at the time of packing removal. The amount of bleeding on removal were quantified by weighing it after removal. Lund-Kennedy score and synechiae formation were assessed at 4, 8, and 12 weeks after surgery. The use of analgesics and oral steroid was compared between the two groups. RESULTS: The experimental group showed lower levels of pain and lessened bleeding during packing removal than the control group. There were no differences in pain levels at 12 hours after surgery, use of analgesics and oral steroid between the two groups. One (6%) of each group had postoperative bleeding and required additional packing for hemostasis. Lower Lund-Kennedy score at postoperative 4 weeks was documented in the experimental group. In addition, two (13%) control subjects developed a synechiae between the middle turbinate and the lateral wall. CONCLUSION: PA packing in a glove finger is advantageous in terms of pain, bleeding on packing removal, and postoperative wound healing, compared with PA pack only.

Clinical characteristics and natural course of recurrent vestibulopathy: a long-term follow-up study.

OBJECTIVES/HYPOTHESIS: To investigate the clinical characteristics and the natural course of recurrent vestibulopathy (RV). STUDY DESIGN: Retrospective study. METHODS: During the period April 2002 to February 2008, we reviewed the clinical records of 98 patients diagnosed with RV. All patients were approached by telephone and using a questionnaire. The analysis included age, sex distribution, natural history, pure-tone audiometry, caloric response, age at onset, and the characteristics of vertigo. RESULTS: Median follow-up was 63.1 months (range, 24-103 months). Patients had a mean age at onset of 39 years and a mean duration of 4.2 years. An obvious female predilection was found, and unilateral caloric paresis (≥ 25%) was seen in 35%. Of the 98 patients, symptoms resolved in 82% but were unchanged in 12%. RV developed to Ménière's disease in four patients and to migraine in two. No patient with RV developed a central nervous system disease or benign paroxysmal positional vertigo during follow-up. CONCLUSIONS: The study suggests that in the majority of cases, vertigo spontaneously resolves and that the risks of development to Ménière's disease or migraine are low.

Hypoxia-inducible factor 1 mediates nasal polypogenesis by inducing epithelial-to-mesenchymal transition.

RATIONALE: Nasal polyposis implies a refractory clinical course in case of chronic rhinosinusitis (CRS). Although hypoxia is believed to be associated with nasal polyposis, little is known about the mechanism underlying polypogenesis. OBJECTIVES: To determine if hypoxia drives nasal polyposis by epithelial-to-mesenchymal transition (EMT). METHODS: Immunoblotting, immunofluorescence, flow cytometry, and real-time polymerase chain reaction were performed to evaluate EMT and hypoxic markers in human nasal epithelial cells (hNECs) and in sinonasal tissues from patients with CRS with or without polyps. In addition, the effects of hypoxia-inducible factor (HIF)-1α inhibitors on nasal polypogenesis were investigated in a murine model. MEASUREMENTS AND MAIN RESULTS: E-cadherin and α-smooth muscle actin (α-SMA) were down-regulated and up-regulated, respectively, in patients with polyps as compared with patients without polyps. Under hypoxia, hNECs transformed to a mesenchymal shape, and demonstrated representative changes in EMT markers; that is, mesenchymal markers (α-SMA, vimentin, and twist) increased but epithelial markers (E-cadherin and ß-catenin) decreased. Mechanistically, E-cadherin level was recovered in hypoxia by silencing HIF-1α and decreased in normoxia by expressing HIF-1α. Furthermore, hypoxia was found to down-regulate PP2Ac phosphatase and up-regulate pSmad3, which led to α-SMA induction. In CRS sinonasal specimens, HIF-1α expression was found to correlate with E-cadherin loss and α-SMA expression. Finally, HIF-1α inhibitors suppressed nasal polypogenesis in a murine model. CONCLUSIONS: hNECs undergo EMT during hypoxia and this process is critically mediated by HIF-1α and pSmad3. This study shows that hypoxia-induced EMT is likely to contribute to nasal polyposis in CRS, and suggests that HIF-1α be viewed as a therapeutic target for nasal polyposis.