Hiromi Nagashima

Multiple Scedosporium apiospermum abscesses in a woman survivor of a tsunami in northeastern Japan: a case report

IntroductionScedosporium apiospermum is increasingly recognized as a cause of localized and disseminated mycotic infections in near-drowning victims.Case presentationWe report the case of a 59-year-old Japanese woman who was a survivor of a tsunami in northeastern Japan and who had lung and brain abscesses caused by S. apiospermum. Initially, an aspergillus infection was suspected, so she was treated with micafungin. However, computed tomography scans of her chest revealed lung abscesses, and magnetic resonance images demonstrated multiple abscesses in her brain. S. apiospermum was cultured from her bronchoalveolar lavage fluid, and antimycotic therapy with voriconazole was initiated. Since she developed an increase in the frequency of premature ventricular contractions, an adverse drug reaction to the voriconazole was suspected. She was started on a treatment of a combination of low-dose voriconazole and liposomal amphotericin B. After combination therapy, further computed tomography scans of the chest and magnetic resonance images of her brain showed a demarcation of abscesses.ConclusionsVoriconazole appeared to have a successful record in treating scedosporiosis after a near drowning but, owing to several adverse effects, may possibly not be recommended. Thus, a combination treatment of low-dose voriconazole and liposomal amphotericin B may be a safe and effective treatment for an S. apiospermum infection. Even though a diagnosis of scedosporiosis may be difficult, a fast and correct etiological diagnosis could improve the patients chance of recovery in any case.

Scedosporium aurantiacum brain abscess after near-drowning in a survivor of a tsunami in Japan

Many victims of the tsunami that occurred following the Great East Japan Earthquake on March 11, 2011 developed systemic disorders owing to aspiration pneumonia. Herein, we report a case of tsunami lung wherein Scedosporium aurantiacum was detected in the respiratory tract. A magnetic resonance image of the patients head confirmed multiple brain abscesses and lateral right ventricle enlargement. In this case report, we describe a potential refractory multidrug-resistant infection following a tsunami disaster.

Periostin in the bronchial lavage fluid of asthma patients

Serum periostin has recently emerged as a novel and useful biomarker for bronchial asthma.1 Serum periostin is a surrogate biomarker reflecting type 2 immune responses because periostin is a downstreammolecule of interleukin-4 (IL-4) or IL-13, the signature cytokines of type 2 immune responses. This characteristic of periostin can potentially be applied to predict the efficacy of antagonists such as anti-IL-13 or anti-IgE antibodies against type 2 immune responses. Furthermore, we have recently found that since periostin reflects tissue remodeling or fibrosis in bronchial asthma, it can predict hypo-responsiveness to inhaled corticosteroids in asthma patients, particularly in thosewho are late-onset and eosinophil-dominant.2,3 In spite of the usefulness of periostin as a biomarker for bronchial asthma, serum periostin can be affected by periostin produced in sites other than lung tissues, particularly bones. Therefore, it would be of great benefit in caring for and treating asthma patients if periostin in lung tissues could be specifically detected. However, it remains obscure how periostin is secreted from the cells and circulated in asthma patients. No study has yet been performed to investigate whether periostin is secreted in the bronchial lumens of asthma patients. Bronchial resident cellsdepithelial cells, fibroblasts, and endothelial cellsdare assumed to be sources of periostin in lung tissues.4e6 It has been demonstrated in vitro that periostin can be secreted from the basal side, but not from the apical side, in bronchial epithelial cells.4 These results negate the notion that periostin is secreted in the bronchial lumens in asthma patients. In contrast, it has been reported that periostin is highly detected in nasal lavage fluid in chronic rhinosinusitis patients, which may nevertheless support this notion.7 Therefore, in this study, we examined periostin in the bronchial lavage fluid (BLF) of asthma patients to explore whether it can be a more specific biomarker for bronchial asthma. Ten asthma patients and ten healthy donors were recruited from the Iwate Medical University Hospital. Bronchial asthma was diagnosed according to the criteria by Global Initiative for Asthma, Global Strategy for Asthma Management and Prevention, updated 2010. Spirometry was performed and airway methacholine responsiveness was measured using an Astograph (Jupiter 21, CHEST, Tokyo, Japan). The asthma patients had no other

Effect of genetic variation of IL-13 on airway remodeling in bronchial asthma.

BACKGROUND IL-13 is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation, and common single-nucleotide polymorphisms in IL13 are associated with allergic phenotypes in several ethnically diverse populations. In particular, IL13Q110 is the non-conservative replacement of a positively charged arginine (R) with a neutral glutamine (Q) at position 110 of IL-13, and as we already know, individuals homozygous for glutamine (Q110/Q110) are strongly associated with asthma and IgE. IL13Q110 has been demonstrated to show that increased allergic inflammation depended on the enhanced IL-13-mediated Th2 effector function. Therefore, we investigated whether Q110/Q110 accelerated the decline in pulmonary function and development of airway remodeling of asthmatic patients in the general population. METHODS A total 336 asthmatic subjects living in Japan were recruited, genotyped, and had a pulmonary function test performed on them. To analyze airway inflammation and remodeling, bronchial lavage fluid (BLF) and endobronchial biopsy specimens were examined. RESULTS Forced expiratory volume in one second (FEV1), %predicted, forced expiratory volume/forced vital capacity ratio, and forced expiratory flow 25-75%, % predicted were significantly decreased in Q110/Q110 compared to R110/R110, and the decline in FEV1 was increased significantly in Q110/Q110 compared to R110/R110. The concentration of IL-13, IL-23, IL-11, GM-CSF, hyaluronic acid, and CCL8 in BLF were increased in Q110/Q110 compared to R110/R110 and the thickness of the subepithelial layer was thicker. CONCLUSIONS Our study demonstrates that Q110/Q110 increases, at least in part, allergic inflammation and the propensity for airway remodeling, thus resulting in low lung function.

Effects of imatinib mesylate on pulmonary allergic vasculitis in a murine model

Imatinib mesylate (IM) is a potent and specific tyrosine inhibitor and has been reported to inhibit mesenchymal cell proliferation in pulmonary fibrosis. In the present study, we examine the effects of IM on vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration.

Association of IL-13 gene polymorphisms with airway hyperresponsiveness in a Japanese adult asthmatic population

BACKGROUND A single nucleotide polymorphism (SNP; rs20541) in the IL-13 gene has been recognized as a risk factor for asthma. This SNP causes Arg to Gln (Q) substitution at position 110 in the mature IL-13 protein. We have recently showed that FEV1 in asthmatics with the Q110 variant of IL-13 declined faster, and progressive airway remodeling was observed in these subjects (Wynn, 2003 [1]). However, the effects of the IL-13 variant on airway hyperresponsiveness (AHR) remain to be elucidated. We analyzed the relationship between SNP rs20541 in IL-13 and AHR in asthmatics. METHODS We recruited 182 asthmatics who visited the asthma outpatient clinic at Iwate Medical University Hospital from 2006 to 2011. Subjects were genotyped for rs20541. Asthma severity, atopic status, age of asthma onset, serum IgE concentration, AHR, and pulmonary function were studied in these subjects. AHR was measured using the continuous methacholine inhalation method (Astograph; Chest; Tokyo, Japan). RESULTS Genotyping of rs20541 revealed 26 A/A, 77 A/G, and 79 G/G patient genotypes. The D min (U) of the 3 genotypes was 1.17±0.300 in A/A, 1.99±0.35 in A/G, and 2.85±0.39 in G/G. The D min in the 3 genotypes was significantly different. Spirometric data revealed that % FEV1 and % FEF75 were significantly different among the 3 groups of IL-13 genotypes, whereas no significant differences were observed in therapeutic steps, atopic status, house dust mite sensitization, or serum IgE concentration. CONCLUSION The SNP rs20541 in IL-13 was associated with AHR in Japanese adult asthmatics.

Novel ribbon-type nuclear factor of activated T cells decoy oligodeoxynucleotides preclude airways hyperreactivity and Th2 cytokine expression in experimental asthma.

Background: Nuclear factor of activated T cells (NFAT) is required for the differentiation of Th2 responses, so we examined its role in mouse experimental asthma and tested the hypothesis that an NFAT blockade with a decoy against NFAT can prevent asthma progression. Objective: To determine the effects of the NFAT decoy oligodeoxynucleotides (ODNs) on the development of airway inflammation, we designed a novel ribbon-type ODN containing two binding sites for NFAT in a single decoy molecule without an open end, which is more stable than a conventional decoy, and largely preserved its structural integrity in the presence of nucleases. Methods: Ribbon-type NFAT decoy ODNs were transfected into ovalbumin (OVA)-sensitized CD3+ T cells in vitro. OVA-immunized mice received these cells by intraperitoneal injection. Airway hyperreactivity (AHR) was measured and the transfected CD3+ T cells’ responses to the airways were characterized. Results: Development of AHR after OVA challenge was effectively abolished after adoptive transfer of ribbon-type NFAT decoy ODN transfected CD3+ T cells. Transfer of ribbon-type decoy significantly reduced the number of inflammatory cells and the concentrations of IL-4, IL-5 and IL-13, but not IFN-γ, in the bronchoalveolar lavage of the recipient mice. Conclusion: These results suggest the inhibitory effect of ribbon-type decoy ODNs against NFAT on the induction of bronchial asthma. Adoptively transferred CD3+ T cells, which are transfected with NFAT decoy, may be an effective strategy for the treatment of asthma.

Impact of the genetic variants of GLCCI1 on clinical features of asthmatic patients

Several gene variants are associated with a response to an inhaled corticosteroids (ICSs) treatment in patients with bronchial asthma. A variant of the glucocorticoid‐induced transcript 1 (GLCCI1) genes has previously been associated with decreased lung function improvement upon treatment with ICSs in patients with bronchial asthma. Another report has also demonstrated that this genetic biomarker did not influence the change in flow volume in 1 second. However, no studies have considered the treatment content and the GLCCI1 variants. We were able to determine the relationship between the pulmonary function and clinical features and the variant of the GLCCI1 in Japanese asthmatic patients receiving long‐term ICS treatment.

Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin

BACKGROUND Statin use in individuals with chronic obstructive pulmonary disease (COPD) with coexisting cardiovascular disease is associated with a reduced risk of exacerbations. The mechanisms by which statin plays a role in the pathophysiology of COPD have not been defined. To explore the mechanisms involved, we investigated the effect of statin on endothelial cell function, especially endothelial cell tight junctions. METHOD We primarily assessed whether pitavastatin could help mitigate the development of emphysema induced by continuous cigarette smoking (CS) exposure. We also investigated the activation of liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signaling, which plays a role in maintaining endothelial functions, important tight junction proteins, zonula occludens (ZO)-1 and claudin-5 expression, and lung microvascular endothelial cell permeability. RESULTS We found that pitavastatin prevented the CS-induced decrease in angiomotin-like protein 1 (AmotL1)-positive vessels via the activation of LKB1/AMPK signaling and IFN-γ-induced hyperpermeability of cultured human lung microvascular endothelial cells by maintaining the levels of AmotL1, ZO-1, and claudin-5 expression at the tight junctions. CONCLUSION Our results indicate that the maintenance of lung microvascular endothelial cells by pitavastatin prevents tight junction protein dysfunctions induced by CS. These findings may ultimately lead to new and novel therapeutic targets for patients with COPD.

Changes in pulmonary function of residents in Sanriku Seacoast following the tsunami disaster from the Great East Japan Earthquake

BACKGROUND Residents in the district struck by the Great East Japan Earthquake Tsunami (GEJET) suffered from adverse living conditions and various pulmonary diseases. OBJECTIVES To evaluate the influence of GEJET, we performed serial assessment of pulmonary function of approximately 10,000 residents in the district struck by GEJET. METHODS Using a spirometer, we assessed the pulmonary function of approximately 10,000 residents older than 18 years in the Sanriku seacoast, which was struck by the tsunami. Measurements were performed in 2011 and 2012. RESULTS We compared FVC (forced vital capacity) % pred. and FEV1 (forced expiratory volume in 1second) % pred. of subjects between 2011 and 2012, by serial spirometry. Of the 7053 subjects studied, including 2611 men and 4442 women, FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011. Physical indices including height, body weight and the body mass index (BMI) did not change significantly during this period. Smoking prevalence changed significantly between 2010, 2011, and 2012. Both FVC% pred. and FEV1% pred. of subjects who had quit smoking increased significantly on spirometry carried out in 2012, compared with those in 2011. CONCLUSIONS The pulmonary function expressed as FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011 among the subjects studied. The changes in the smoking status may be one of the reasons for the increase in values observed. However, other undetermined factors during recovery from a disaster might have resulted in improved pulmonary function.