Association of upper and lower airway eosinophilic inflammation with response to omalizumab in patients with severe asthma.

Background: The anti-immunoglobulin E monoclonal antibody, omalizumab, is used to treat severe asthma and has the potential to ameliorate airway inflammation. However, the effect of omalizumab in ameliorating upper airway inflammation has not been fully elucidated. Objective: We investigated the association of upper and lower airway inflammation with the response to omalizumab treatment. Methods: We used the Global Evaluation of Treatment Effectiveness to assess the efficacy of omalizumab in treating 16 patients with severe asthma. We also investigated the symptom score, short-acting ß-agonist inhaler use, pulmonary function, biomarkers, computed tomography scans, and nasal mucosa pathology at omalizumab initiation and after four months of treatment. Results: When the fraction of exhaled nitric oxide (FeNO) and the percentage of sputum eosinophil were used as indicators of lower airway inflammation, positive correlations were found between CD20 B-cell, mast cell, and eosinophil counts in the nasal mucosa. Improved asthma symptoms were observed in 12 of the 16 severe asthma cases. The FeNO and eosinophil levels in the nasal tissue, prior to the administration of omalizumab were predictors of the response to asthma treatment. Conclusions: These findings suggest heterogeneity among people with severe asthma. In addition, the phenotype associated with response to omalizumab, leading to improvement in asthma symptoms, comprises upper airway eosinophilia and high FeNO levels.

Effects of unilateral sinonasal surgery on sleep-disordered breathing.

Aims/objectives: To examine the effects of surgery for unilateral sinonasal lesions on sleep-disordered breathing (SDB). Material and methods: Oxygen desaturation index (3%ODI) as a marker of SDB and bilateral/unilateral nasal resistance were measured before and after surgery for 18 patients with unilateral sinonasal lesions. Various parameters were compared between those who achieved 60% or less decrease of 3%ODI and those who did not. Results: Bilateral nasal resistance as well as that of the surgical side five days after surgery was significantly lower than those of pre-operative value. Preoperative 3%ODI (times/hour) was 10.08 ± 7.32, which significantly decreased to 7.67 ± 5.79 five days after surgery. Even in unilateral patients, sinonasal surgery could reduce the bilateral nasal resistance, resulting in a decrease in 3%ODI. Age was younger and postoperative nasal resistance of the surgical side was significantly lower in the group who achieved 60% or less decrease in 3%ODI than those who did not. Conclusions and significance: SDB is influenced by even unilateral nasal obstruction. Surgery for unilateral lesion can improve the respiration during sleep as well as bilateral nasal resistance. Favorable outcome by surgery could be brought about in younger patients and those for whom sufficient improvement of nasal resistance was expected by surgery.

A Survey of the Otorhinolaryngological Screening of Children in Niigata Prefecture: Kindergarten to High School.

We conducted the first survey of otorhinolaryngological (ORL) screening at educational institutions, from kindergarten to high school, in Niigata Prefecture. The survey results showed that ORL screening is not performed in 62.1% of kindergartens and nursery schools, and that screening was conducted by non-ENT doctors in 23.9% of them. At elementary school entry health check-ups, ORL screening was performed by otorhinolaryngologists in only 4.2% of children overall. ORL screening was conducted in students in all grades by 51.7% of all elementary schools and 31.6% of all junior high schools. Audiometry was performed in students in all grades by over 80% of elementary schools and junior high schools. With regard to high schools, ORL screening was performed in students in all grades at only three schools among 105 high school; ORL screening and audiometry were conducted primarily in the first-year students. In addition to the above results, the survey revealed that no ORL screening whatsoever was performed during a period of 9 years at an elementary school and a junior high school in a certain municipality; as a result of discussion with the relevant municipality, it was decided that screening will be conducted starting at 2016. From the viewpoint of reinforcing the structure of conducting ORL screening in infants in whom ORL findings are identified at a high frequency, we requested that Niigata City conduct ORL screening at private kindergartens in Niigata City where the ORL screening rate is low. We consider this survey to have been productive, as it identified meaningful new facts and measures that could be devised to address the relevant issues. It is our aim to become more proactively than ever involved in school health including health check-ups.

[A Case of the Relapsing Polychondritis Limited to the Trachea].

A 62-year-old woman, who had dysesthesia in the throat, and polyposia the previous year, was admitted in a coma because of respiratory failure. Computed tomography scans demonstrated dilatation of the esophagus and stenosis of the trachea. After emergency intubation, extubation was not possible due to a collapsed trachea, so we performed a tracheostomy. The tracheoscopy from the stoma showed an esophagus-like trachea due to disappearance of the tracheal cartilage and the straight pattern on the membranous portion, and the lumen deformed with coughing. With the continuous dyspnea episode, the patient was diagnosed as having tracheomalacia. Anti-type II collagen antibody and pathological findings of the trachea led us to the diagnosis of Relapsing Polychondritis.

[MRI-CT fusion image navigation during surgery for inverted papilloma].

We report two cases of intraoperative computer-aided surgery using magnetic resonance imaging (MRI)/computed tomography (CT) fusion imaging for inverted papilloma (IP). Case 1: IP had spread to the frontal recess/sinus so we chose a combined endoscopic sinus surgery (ESS) and external approach. Case 2: For a maxillary sinus tumor, we combined ESS and the adjuvant external (Caldwell-Luc) procedure. This is helpful to surgeons when, shifting fusion imaging when opening the frontal sinus bone to obtain CT data, and shifting to MRI to detect the tumor pedicle, then approaching the bone defect using MRI-CT fusion imaging (50-50%).

Knockdown of synapse-associated protein Dlg1 reduces syncytium formation induced by human T-cell leukemia virus type 1.

Human T-cell leukemia virus type 1 (HTLV-1) spreads through cell-to-cell contact by forming a virological synapse. Based on the finding that HTLV-1 envelope glycoprotein (Env) binds to a PDZ domain containing scaffold protein Dlg1, whose function has been implicated in the organization of neuronal and immunological synapses, we examined the role of Dlg1 in the cell-cell infection by HTLV-1. The coculture of an HTLV-1-infected T-cell line MT-2 with an uninfected MOLT-4 induced syncytium, a marker of cell-cell HTLV-1 infection, but an RNA interference-mediated knockdown of Dlg1 in both cells cooperatively reduced the syncytium formation. In HTLV-1-uninfected 293T cells, Dlg1 induced the clustering of GLUT1, a cellular receptor for HTLV-1, but such clustering was abrogated by a deletion of the PDZ domain binding motif of GLUT1 (GLUT1DeltaC). GLUT1 expression in MDBK cells induced HTLV-1-mediated syncytium formation, and the activity was much greater than that of GLUT1DeltaC. These results suggest that Dlg1, through the interaction with GLUT1 as well as Env, plays a positive role in the syncytium formation induced by HTLV-1.

Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line induced by human T-cell leukemia virus type 1 Tax protein.

BACKGROUND: The interaction of human T-cell leukemia virus type 1 (HTLV-1) Tax1 protein with the tumor suppressor Dlg1 is correlated with cellular transformation. RESULTS: Here, we show that Dlg1 knockdown by RNA interference increases the ability of Tax1 to transform a mouse T-cell line (CTLL-2), as measured interleukin (IL)-2-independent growth. A Tax1 mutant defective for the Dlg1 interaction showed reduced transformation of CTLL-2 compared to wild type Tax1, but the transformation was minimally affected by Dlg1 reduction. The few Tax1DeltaC-transduced CTLL-2 cells that became transformed expressed less Dlg1 than parental cells, suggesting that Dlg1-low cells were selectively transformed by Tax1DeltaC. Moreover, all human T-cell lines immortalized by HTLV-1, including the recombinant HTLV-1-containing Tax1DeltaC, expressed less Dlg1 than control T-cell lines. CONCLUSION: These results suggest that inactivation of Dlg1 augments Tax1-mediated transformation of CTLL-2, and PDZ protein(s) other than Dlg1 are critically involved in the transformation.