Shintaro Baba

Expression of IL‐33 and its receptor ST2 in chronic rhinosinusitis with nasal polyps

Interleukin (IL)−33 is a novel member of the IL‐1 cytokine family and a ligand for the orphan IL‐1 family receptor ST2. IL‐33 induces T helper 2‐type inflammatory responses and is considered to play a crucial role in allergic inflammatory reactions such as asthma and atopic dermatitis. However, the role of IL‐33 and its receptor ST2 in chronic rhinosinusitis remains unclear.

Noninvasive system for evaluating allergen-induced nasal hypersensitivity in murine allergic rhinitis

Until now there has been no method for physiologically evaluating nasal hypersensitivity in mice. Enhanced pause (Penh) has been used as an indicator that reflects changes in the lower airway. Recently, however, there is disagreement regarding the significance of the Penh system; this is because Penh is not essentially a physiological parameter, and it might not necessarily represent a change in the lower respiratory tract. The purpose of the present study is to investigate whether Penh could be applicable for analyzing nasal hypersensitivity in mice. BALB/c mice were sensitized with ovalbumin (OVA) through a combination of intraperitoneal injection and daily intranasal challenge in an awake condition. Penh was measured at each time point during sensitization, or a serial change in Penh value was followed after the final nasal challenge and the effect of treatment was assessed. Following sensitization and nasal challenge, the Penh value gradually increased and showed a significant difference on day 14. Changes in IgE, eosinophil infiltration into nasal mucosa, and OVA-induced symptoms all strongly correlated with the increase in Penh. On day 19, after OVA nasal provocation, Penh gradually increased and reached maximal values 25 min after the challenge. Pretreatment with dexamethasone or a histamine H1 blocker significantly suppressed this increase in Penh. We confirmed that intranasal OVA challenge did not induce bronchoconstriction by measuring airway resistance and bronchoalveolar lavage fluid, and through histological examination. These results clearly demonstrate that Penh could be a useful noninvasive indicator for studying nasal hypersensitivity.

Local increase in IgE and class switch recombination to IgE in nasal polyps in chronic rhinosinusitis

Chronic rhinosinusitis with nasal polyps is generally characterized by local Th2 inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis (similar to chronic rhinosinusitis with nasal polyps in western countries) and non‐eosinophilic chronic rhinosinusitis (characterized by Th1‐dominant inflammation).

T-cell phenotypes in chronic rhinosinusitis with nasal polyps in Japanese patients.

AbstractBackgroundChronic rhinosinusitis with nasal polyps is characterized by local inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis, and non-eosinophilic chronic rhinosinusitis. The objective of this study was to investigate the expression of key transcription factors for Treg and Th1/Th2/Th17 cells, in relation to the mRNA expression of representative cytokines in these two subtypes of chronic rhinosinusitis with nasal polyps.MethodsThe expression of forkhead box P3 (FOXP3), T-box transcription factor (T-bet), GATA3, retinoid acid-related orphan receptor C (RORc), the suppressive cytokines TGF-β1 and IL-10, and Th1/Th2/Th17 cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-17) were analyzed by means of RT-PCR in eosinophilic polyps. Eosinophilic polyps were defined as having an eosinophil count of more than 50 per microscopic field (×400 magnification) using five fields located in the subepithelial area of the polyps, while the non-eosinophilic polyps and controls did not fulfill this criteria. The numbers of T cells, CD4+ T cells, CD8+ T cells and Treg were histologically counted using sections that were immunostained for CD3, CD4, CD8, and FOXP3, respectively.ResultsIn eosinophilic polyps, we observed significantly fewer CD4+ T cells and CD8+ T cells, and lower GATA3, RORc and IL-10 mRNA expression, but a significantly higher IL-5, and IL-13 mRNA expression compared with controls, whereas FOXP3 and T-bet mRNA expression were not significantly different compared with controls. In non-eosinophilic polyps, FOXP3, IL-10, IL-17A, TGFβ1 and IFNγ mRNA expression was significantly higher compared with controls, whereas IL-4, 5 and 13 expression was not significantly different from controls.ConclusionWe showed a reduction of GATA3 and RORc mRNA, low Treg-related cytokines and elevated Th2 cytokine levels in eosinophilic chronic rhinosinusitis, whereas we demonstrated the upregulation of Treg cells and increases of Th1 and Th17 cytokines in non-eosinophilic chronic rhinosinusitis in the Japanese population. The different mRNA expression profiles of Treg and Th1/Th2/Th17 signature transcription factors and cytokines between eosinophilic chronic rhinosinusitis and non-eosinophilic chronic rhinosinusitis suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Leptin enhances ICAM-1 expression, induces migration and cytokine synthesis, and prolongs survival of human airway epithelial cells.

There is rising interest in how obesity affects respiratory diseases, since epidemiological findings indicate a strong relationship between the two conditions. Leptin is a potent adipokine produced mainly by adipocytes. It regulates energy storage and expenditure and also induces inflammation. Previous studies have shown that leptin is able to activate inflammatory cells such as lymphocytes and granulocytes, but little is known about its effect on lung structural cells. The present study investigated the effects of leptin on human airway epithelial cells by using human primary airway epithelial cells and a human airway epithelial cell line, BEAS-2B. Flow cytometry showed enhanced ICAM-1 expression by both of those cells in response to leptin, and that effect was abrogated by dexamethasone or NF-κB inhibitor. Flow cytometry and quantitative PCR showed that airway epithelial cells expressed leptin receptor (Ob-R), whose expression level was downregulated by leptin itself. Multiplex cytokine analysis demonstrated enhanced production of CCL11, G-CSF, VEGF, and IL-6 by BEAS-2B cells stimulated with leptin. Furthermore, transfection of Ob-R small interference RNA decreased the effect of leptin on CCL11 production as assessed by quantitative PCR. Finally, leptin induced migration of primary airway epithelial cells toward leptin, suppressed BEAS-2B apoptosis induced with TNF-α and IFN-γ, and enhanced proliferation of primary airway epithelial cells. In summary, leptin was able to directly activate human airway epithelial cells by binding to Ob-R and by NF-κB activation, resulting in upregulation of ICAM-1 expression, induction of CCL11, VEGF, G-CSF, and IL-6 synthesis, induction of migration, inhibition of apoptosis, and enhancement of proliferation.

Bell's palsy in children: relationship between electroneurography findings and prognosis in comparison with adults.

Objectives To investigate the correlation between electroneurography (ENoG) findings and the prognosis of Bell’s palsy in children compared with adults. Methods Twenty-two children and 92 adults with Bell’s palsy who underwent ENoG between 8 days and 4 weeks from the onset of symptoms were retrospectively enrolled. The time to maximal recovery and rate of favorable recovery (House-Brackmann grade I or II) was assessed. Children (C) and adults (A) were further subdivided into low (<10%) or high (≧10%) subgroups according to their ENoG values (affected versus unaffected side) at initial evaluation. The numbers in each subgroup were as follows: C-low (n = 8), A-low (n = 21), C-high (n = 14), and A-high (n = 71). Results Of the 22 children assessed, 2 of the 4 patients who showed a total loss of evoked potentials on the affected side (0% ENoG value) exhibited an unfavorable recovery. The remaining 20 patients achieved a favorable recovery eventually. Patients in group C-low reached a maximal recovery of facial movement significantly later than those in group C-high (p < 0.001). Time to maximal recovery of facial movement in group A-low was later than that in group C-low, although the difference was not statistically significant (p = 0.15). The patients in group A-high reached a maximal recovery significantly later than those in group C-high (p < 0.05). Conclusion Bell’s palsy seems to recover earlier in children than adults when matched for severity. The presence of an identifiable response in ENoG, irrespective of its amplitude, may indicate a favorable recovery of facial movement in children.

Correlation of basophil infiltration in nasal polyps with the severity of chronic rhinosinusitis

Chronic rhinosinusitis (CRS) represents a heterogeneous disease group characterized by local inflammation of the sinonasal tissues.1 It has been defined as symptomatic inflammation of the sinonasal mucosa that lasts more than 12 weeks as confirmed by computed tomography (CT) and nasal endoscopy.2 Generally, CRS is divided into 2 subsets based on endoscopic findings: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP).3 In Europe and the United States, eosinophilia is evident in nasal polyps (NPs) from patients with CRSwNP.4 In contrast, heterogeneity of CRSwNP has been reported in East Asian countries, such as Japan, Korea, and China, where the presence and extent of eosinophilia are variable and a significant proportion of NPs do not manifest local eosinophilia.5 Although the pathogenesis of CRS remains controversial, eosinophilic inflammation is considered at least partly responsible. Eosinophilic NPs contain an environment enriched for TH2 cytokines, including interleukin (IL) 4, IL-5, and IL-13.6 TH2 cytokines are believed to contribute to the pathogenesis of eosinophilic CRSwNP, with IL-5 and IL-13 inducing eosinophil recruitment and promoting their activation and IL-4 promoting the switching of the immunoglobulin to the IgE isotype.7 Basophils are reportedly increased in the bronchial submucosa of asthmatic patients and the nasal submucosa of patients with allergic rhinitis.8,9 Research is increasingly addressing the role of basophils in inducing TH2-type responses.10 Although CRSwNP is a highly TH2-biased disease, making the involvement of basophils likely, there are few reports of the involvement of basophils in CRS.11

Electrophysiological Evaluation of the Facial Muscles in Congenital Unilateral Lower Lip Palsy

OBJECTIVES Congenital unilateral lower lip palsy (CULLP) is a congenital facial asymmetry in which one corner of the mouth does not dip downward symmetrically (Kobayashi, 1979). We analyzed the electrophysiological findings in cases of CULLP to understand the facial nerve mechanisms underlying this pathological condition. METHODS The electrophysiological findings in 20 patients with CULLP including an electroneuronography (ENoG) of the orbicularis oris muscle, nerve excitability test (NET) results, and the blink reflex (BR) were analyzed. RESULTS Of 21 patients with CULLP, 20 underwent ENoG, 12 underwent a NET, and 14 underwent a BR examination. Nine of 19 patients with CULLP showed higher ENoG amplitude in the affected side than in the unaffected side. In four patients, the ENoG amplitude in the affected side was similar to that in the unaffected side whereas six patients had higher ENoG amplitude in the unaffected side. All patients showed a normal BR response and only one patient had a left-right difference in the NET response in the marginal mandibular branch. NET also demonstrated that the muscular twitch appeared on the lower lip of the affected side. CONCLUSION These results suggested that in CULLP, each of the facial nerve branches including the marginal mandibular branch appeared to function within normal parameters. The marginal mandibular branch of the facial nerve, which usually innervates the depressor anguli oris and depressor labii inferioris muscles, may innervate adjacent muscles as well, such as the orbicularis oris muscle, during prenatal development.

Infraorbital Nerve Located Medially to Postoperative Maxillary Cysts: A Risk of Endonasal Surgery

Background/Aims: This study aimed to examine variations in the location of the infraorbital nerve relative to postoperative maxillary cysts to assess the potential risk of nerve injury during endonasal marsupialization. Methods: Coronal computed tomography images of 130 patients (162 sides) with postoperative maxillary cysts who visited our clinic between 2003 and 2014 were reviewed from the viewpoint of the anatomical relationship between the infraorbital nerves and cysts. Results: The proportions of the six locations were as follows: upside 45.1% (n = 73), separate 13.0% (n = 21), medial 5.6% (n = 9), lateral 14.2% (n = 23), in-between 7.4% (n = 12), and unevaluable 14.8% (n = 24). The proportion of the cases with a potential risk of infraorbital nerve damage during endoscopic marsupialization, including medial, in-between, and unevaluable locations, was 27.8%. Retrospective chart review revealed that 2 patients with a postoperative maxillary cyst that were unevaluable complained of persistent postoperative hypoesthesia of the cheek. Conclusion: The anatomical relationship between the infraorbital nerve and postoperative maxillary cysts varied among patients, with approximately one-fourth of the patients being at risk of infraorbital nerve injury even during endoscopic procedures.

Amblyopia Associated with Congenital Facial Nerve Paralysis

The association between congenital facial paralysis and visual development has not been thoroughly studied. Of 27 pediatric cases of congenital facial paralysis, we identified 3 patients who developed amblyopia, a visual acuity decrease caused by abnormal visual development, as comorbidity. These 3 patients had facial paralysis in the periocular region and developed amblyopia on the paralyzed side. They started treatment by wearing an eye patch immediately after diagnosis and before the critical visual developmental period; all patients responded to the treatment. Our findings suggest that the incidence of amblyopia in the cases of congenital facial paralysis, particularly the paralysis in the periocular region, is higher than that in the general pediatric population. Interestingly, 2 of the 3 patients developed anisometropic amblyopia due to the hyperopia of the affected eye, implying that the periocular facial paralysis may have affected the refraction of the eye through yet unspecified mechanisms. Therefore, the physicians who manage facial paralysis should keep this pathology in mind, and when they see pediatric patients with congenital facial paralysis involving the periocular region, they should consult an ophthalmologist as soon as possible.