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Artikel ; Online: Natural Autoantibodies in Chronic Pulmonary Diseases

Kiyoharu Fukushima / Kazuyuki Tsujino / Shinji Futami / Hiroshi Kida

International Journal of Molecular Sciences, Vol 21, Iss 3, p

2020 Band 1138

Abstract: In autoantibody-mediated autoimmune diseases, pathogenic autoantibodies generated by a failure of central or peripheral tolerance, have different effects mediated by a variety of mechanisms. Interestingly, even non-autoimmune chronic diseases have a set ... ...

Abstract	In autoantibody-mediated autoimmune diseases, pathogenic autoantibodies generated by a failure of central or peripheral tolerance, have different effects mediated by a variety of mechanisms. Interestingly, even non-autoimmune chronic diseases have a set of disease-specific natural autoantibodies that are maintained for a long time. Because most of these natural autoantibodies target intracellular proteins or long non-coding RNAs, they are speculated to be non-pathological and have some important as yet unrecognized physiological functions such as debris clearance. Recently, we revealed a set of disease-specific natural autoantibodies of chronic pulmonary diseases with unknown etiology by protein arrays that enable detection of specific autoantibodies against >8000 targets. Surprisingly, some of the targeted antigens of disease-specific autoantibodies were subsequently reported by other laboratories as strongly associated with the disease, suggesting that these antigens reflect the pathology of each disease. Furthermore, some of these autoantibodies that target extracellular antigens might modify the original course of each disease. Here, we review the disease-specific natural autoantibodies of chronic pulmonary diseases, including chronic fibrosing idiopathic interstitial pneumonias, sarcoidosis, and autoimmune pulmonary alveolar proteinosis, and discuss their utility and effects.
Schlagwörter	autoantibody ; protein array ; idiopathic interstitial pneumonias ; sarcoidosis ; autoimmune pulmonary alveolar proteinosis ; mx1 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Thema/Rubrik (Code)	610
Sprache	Englisch
Erscheinungsdatum	2020-02-01T00:00:00Z
Verlag	MDPI AG
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: First line treatment selection modifies disease course and long-term clinical outcomes in Mycobacterium avium complex pulmonary disease

Kiyoharu Fukushima / Seigo Kitada / Sho Komukai / Tomoki Kuge / Takanori Matsuki / Hiroyuki Kagawa / Kazuyuki Tsujino / Mari Miki / Keisuke Miki / Hiroshi Kida

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Band 10

Abstract: Abstract The combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by ... ...

Abstract	Abstract The combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by current guidelines have been reported. We undertook a single-centred retrospective cohort study to evaluate the long-term outcomes in 295 patients with MAC-PD following first line treatment with standard (RFP, EB, clarithromycin [CAM]) or alternative (EB and CAM with or without fluoroquinolones (FQs) or RFP, CAM, and FQs) regimens. In this cohort, 80.7% were treated with standard regimens and 19.3% were treated with alternative regimens. After heterogeneity was statistically corrected using propensity scores, outcomes were superior in patients treated with standard regimens. Furthermore, alternative regimens were significantly and independently associated with sputum non-conversion, treatment failure and emergence of CAM resistance. Multivariate cox regression analysis revealed that older age, male, old tuberculosis, diabetes mellitus, higher C-reactive protein, and cavity were positively associated with mortality, while higher body mass index and M. avium infection were negatively associated with mortality. These data suggest that, although different combination regimens are not associated with mortality, first line administration of a standard RFP + EB + macrolide regimen offers the best chance of preventing disease progression in MAC-PD patients.
Schlagwörter	Medicine ; R ; Science ; Q
Thema/Rubrik (Code)	616
Sprache	Englisch
Erscheinungsdatum	2021-01-01T00:00:00Z
Verlag	Nature Portfolio
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Managing COPD with expiratory or inspiratory pressure load training based on a prolonged expiration pattern

Keisuke Miki / Kazuyuki Tsujino / Mari Miki / Kenji Yoshimura / Hiroyuki Kagawa / Yohei Oshitani / Kiyoharu Fukushima / Takanori Matsuki / Yuji Yamamoto / Hiroshi Kida

ERJ Open Research, Vol 6, Iss

2020 Band 3

Abstract: Background Exertional prolonged expiration should be identified as a therapeutic target in COPD. The efficacy of expiratory or inspiratory pressure load training (EPT/IPT) based on the degree of prolonged expiration was investigated. Methods A total of ... ...

Abstract	Background Exertional prolonged expiration should be identified as a therapeutic target in COPD. The efficacy of expiratory or inspiratory pressure load training (EPT/IPT) based on the degree of prolonged expiration was investigated. Methods A total of 21 patients with COPD were divided into two groups according to the exertional change in the inspiratory duty cycle (TI/Ttot). For 12 weeks, patients whose exertional TI/Ttot decreased received EPT (EPT group, n=11, mean percentage forced expiratory volume in 1 s (V1), 32.8%) and those whose exertional TI/Ttot increased received IPT (IPT group, n=10, mean V1, 45.1%). Results The therapeutic responses were as follows. In both groups, endurance time (EPT, +5.7 min, p<0.0001; IPT, +6.1 min, p=0.0004) on the constant work rate exercise test (WRET) and peak oxygen uptake increased (EPT, p=0.0028; IPT, p=0.0072). In the EPT group the following occurred: 1) soon after commencement of exercise with the constant WRET, the expiratory tidal volume (VTex) increased, reducing dyspnoea; 2) VTex and mean expiratory flow increased and then prolonged expiration (p=0.0001) improved at peak exercise with the incremental exercise test (ET); and 3) St. George's Respiratory Questionnaire total, activity and impact scores were improved. In the IPT group, on both the constant WRET and incremental ET, breathing frequency increased, which led to greater exercise performance with effort dyspnoea. Conclusions This study showed the benefits of EPT/IPT on exercise performance. If the choice of managing COPD with EPT/IPT is appropriate, inexpensive EPT/IPT may become widespread as home-based training.
Schlagwörter	Medicine ; R
Thema/Rubrik (Code)	796
Sprache	Englisch
Erscheinungsdatum	2020-08-01T00:00:00Z
Verlag	European Respiratory Society
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Pleuroparenchymal fibroelastosis in Mycobacterium avium complex pulmonary disease

Yuji Yamamoto / Kazuyuki Tsujino / Tomoki Kuge / Fukuko Okabe / Takahiro Kawasaki / Takanori Matsuki / Hiroyuki Kagawa / Mari Miki / Keisuke Miki / Masahide Mori / Hiroshi Kida

ERJ Open Research, Vol 7, Iss

clinical characteristics and prognostic impact

2021 Band 1

Abstract: The association between Mycobacterium avium complex pulmonary disease (MAC-PD) and pleuroparenchymal fibroelastosis (PPFE) has been reported previously, and interstitial pneumonia as a comorbidity is associated with a worse prognosis. However, no study ... ...

Abstract	The association between Mycobacterium avium complex pulmonary disease (MAC-PD) and pleuroparenchymal fibroelastosis (PPFE) has been reported previously, and interstitial pneumonia as a comorbidity is associated with a worse prognosis. However, no study has thoroughly reported on PPFE associated with MAC-PD. The present study investigated the prevalence, clinical characteristics, and prognostic impact of PPFE in patients with MAC-PD. A total of 224 patients, newly diagnosed with MAC-PD, were retrospectively reviewed. At the time of diagnosis, chest high-resolution computed tomography (HRCT), sputum examination, and clinical characteristics were collected. The extent of PPFE and MAC-PD was evaluated semi-quantitatively using HRCT scores. Risk factor analysis for clinical or radiological deterioration necessitating multidrug antimicrobial treatment within 3 years, and all-cause mortality within 5 years, from the initial diagnosis was performed based on the PPFE score. PPFE was observed in 59 out of 224 patients (26.3%). A higher PPFE score was a risk factor for dyspnoea, fatigue, and lower body mass index (BMI) (p<0.05). Although PPFE score did not correlate with clinical or radiological deterioration within 3 years (p=0.576), a higher PPFE score (adjusted OR 1.66, 95% CI 1.06–2.60, p=0.028) and lower BMI (adjusted OR 0.61, 95% CI 0.39–0.94, p=0.028) increased the risk of 5-year mortality. PPFE is a relatively common complication and an independent poor prognostic factor of MAC-PD. This study highlights the need for further studies investigating whether the presence of PPFE can be a clinical indicator for initiating treatment of MAC-PD.
Schlagwörter	Medicine ; R
Thema/Rubrik (Code)	610
Sprache	Englisch
Erscheinungsdatum	2021-02-01T00:00:00Z
Verlag	European Respiratory Society
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Evaluation of disease severity in bronchiectasis using impulse oscillometry

Yuji Yamamoto / Keisuke Miki / Kazuyuki Tsujino / Tomoki Kuge / Takanori Matsuki / Kiyoharu Fukushima / Yohei Oshitani / Hiroyuki Kagawa / Kenji Yoshimura / Mari Miki / Hiroshi Kida

ERJ Open Research, Vol 6, Iss

2020 Band 4

Abstract: Although the diagnostic value of impulse oscillometry (IOS) in bronchiectasis for the differential diagnosis of healthy subjects has been researched, the usefulness of each IOS parameter for predicting disease severity in bronchiectasis has not been ... ...

Abstract	Although the diagnostic value of impulse oscillometry (IOS) in bronchiectasis for the differential diagnosis of healthy subjects has been researched, the usefulness of each IOS parameter for predicting disease severity in bronchiectasis has not been thoroughly investigated. In addition, the usefulness of IOS in patients with nontuberculous mycobacteria (NTM) infection has not been reported. This study aimed to determine the predictive significance of respiratory impedance and detect the other most significant IOS parameters for predicting disease severity in bronchiectasis patients and to validate the usefulness of IOS in patients with NTM infection. A total of 206 patients with bronchiectasis who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center were included. Chest high-resolution computed tomography, spirometry and IOS were performed. Hospital admissions, mortality and disease severity indices for bronchiectasis (Bronchiectasis Severity Index (BSI), FACED, and E-FACED scores) were calculated to assess disease severity. The patients were divided into subgroups with and without NTM infection, and subgroup analyses were performed. Respiratory reactance, especially resonant frequency (fres), correlated with both BSI and FACED score better than respiratory resistance. Inspiratory but not expiratory impedance was strongly correlated with BSI, FACED and E-FACED scores. Inspiratory fres was the most useful predictor, increasing as the disease became more severe. The usefulness of IOS was almost equivalent in patients both with and without NTM infection. Inspiratory reactance measured by IOS is useful for estimating disease severity in bronchiectasis. Inspiratory fres best predicts disease severity in bronchiectasis patients both with and without NTM infection.
Schlagwörter	Medicine ; R
Thema/Rubrik (Code)	610
Sprache	Englisch
Erscheinungsdatum	2020-10-01T00:00:00Z
Verlag	European Respiratory Society
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Long-Term Treatment Outcome of Progressive Mycobacterium Avium Complex Pulmonary Disease

Kiyoharu Fukushima / Seigo Kitada / Yuko Abe / Yuji Yamamoto / Takanori Matsuki / Hiroyuki Kagawa / Yohei Oshitani / Kazuyuki Tsujino / Kenji Yoshimura / Mari Miki / Keisuke Miki / Hiroshi Kida

Journal of Clinical Medicine, Vol 9, Iss 1315, p

2020 Band 1315

Abstract: Background: Multidrug therapy is essential for preventing respiratory failure in patients with highly progressive Mycobacterium avium complex pulmonary disease (MAC-PD). However, the prognosis and long-term outcome following combination therapy is poorly ...

Abstract	Background: Multidrug therapy is essential for preventing respiratory failure in patients with highly progressive Mycobacterium avium complex pulmonary disease (MAC-PD). However, the prognosis and long-term outcome following combination therapy is poorly understood. Methods: We retrospectively evaluated the clinical characteristics and long-term outcomes in patients with chemo-naïve progressive MAC-PD, hospitalized for first-line multidrug therapy. Results: Among 125 patients, 86 (68.8%) received standardized treatment (rifampicin, ethambutol, clarithromycin), 25 (20.0%) received a fluoroquinolone (FQ)-containing regimen, and 53 (42.4%) received aminoglycoside injection. The sputum conversion rate was 80.0%, and was independently associated with standardized treatment. The incidence of refractory disease (45.6%) was independently and negatively associated with standardized regimen and aminoglycoside use. Choice of an FQ-containing regimen was not associated with positive outcome. Clarithromycin resistance occurred in 16.8% and was independently associated with refractory disease. MAC-PD-associated death occurred in 3.3% of patients with non-cavitary nodular bronchiectasis (NB) and 21.3% with cavitary MAC-PD over a median follow-up period of 56.4 months. The rates of MAC-PD-associated death were comparable between cavitary-NB and fibrocavitary disease. Concurrent chronic pulmonary aspergillosis (CPA) occurred in 13 (17.3%) patients with cavitary MAC-PD, and age, diabetes mellitus, and CPA were independent risk factors for mortality. Conclusions: Standardized intensive multidrug treatment reduces disease progression and persistence in progressive MAC-PD. Cavitary NB may differ from, rather than being just an advanced stage of, non-cavitary NB. The high incidence and significant mortality of CPA in cavitary MAC-PD highlight the need for early diagnosis and treatment.
Schlagwörter	mycobacterium avium ; mycobacterium intracellulare ; nodular bronchiectasis ; non-tuberculous mycobacteria ; pulmonary aspergillosis ; rare pulmonary disease ; Medicine ; R
Thema/Rubrik (Code)	610
Sprache	Englisch
Erscheinungsdatum	2020-05-01T00:00:00Z
Verlag	MDPI AG
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Pleural Effusion Caused by Mycolicibacterium mageritense in an Immunocompetent Host

Takayuki Niitsu / Tomoki Kuge / Kiyoharu Fukushima / Yuki Matsumoto / Yuko Abe / Masashi Okamoto / Kako Haduki / Haruko Saito / Tadayoshi Nitta / Akira Kawano / Takanori Matsuki / Daisuke Motooka / Kazuyuki Tsujino / Keisuke Miki / Shota Nakamura / Hiroshi Kida / Atsushi Kumanogoh

Frontiers in Medicine, Vol

A Case Report

2021 Band 8

Abstract: Mycolicibacterium mageritense (M. mageritense) is a rare species among rapidly growing mycobacteria, and M. mageritense pleurisy is very rare. Here, we report for the first time, an immunocompetent patient with pleurisy caused by M. mageritense. The ... ...

Abstract	Mycolicibacterium mageritense (M. mageritense) is a rare species among rapidly growing mycobacteria, and M. mageritense pleurisy is very rare. Here, we report for the first time, an immunocompetent patient with pleurisy caused by M. mageritense. The patient had no history of immunodeficiency and no recurrence of lung cancer after surgery. However, 8 months after surgery, he developed a new lung shadow and pleurisy. Although whole-genome analysis of the colony cultured from the patient's pleural fluid revealed M. mageritense, we could not identify it in time, resulting in a poor outcome. M. mageritense pleurisy in this case might have occurred via a bulla rupture of the lung lesion because computed tomography of the patient's chest showed pneumothorax and a lung lesion in contact with thoracic cavity. This case emphasized that nontuberculous mycobacterial pleurisy should be considered in the differential diagnoses of pleural effusion even in immunocompetent patients. Advancement of comprehensive and rapid analyses of genomic data from clinical specimens will lead to better treatment strategies.
Schlagwörter	pleural effusion ; rapidly growing mycobacteria ; nontuberculous mycobacteria ; Mycolicibacterium mageritense ; immunocompetent ; Medicine (General) ; R5-920
Thema/Rubrik (Code)	610
Sprache	Englisch
Erscheinungsdatum	2021-11-01T00:00:00Z
Verlag	Frontiers Media S.A.
Dokumenttyp	Artikel ; Online
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Artikel ; Online: Chronic Pulmonary Disease Caused by Tsukamurella toyonakaense

Emerging Infectious Diseases, Vol 28, Iss 7, Pp 1437-

2022 Band 1441

Abstract: Unidentified Mycobacterium species are sometimes detected in respiratory specimens. We identified a novel Tsukamurella species (Tsukamurella sp. TY48, RIMD 2001001, CIP 111916T), Tsukamurella toyonakaense, from a patient given a misdiagnosis of ... ...

Abstract	Unidentified Mycobacterium species are sometimes detected in respiratory specimens. We identified a novel Tsukamurella species (Tsukamurella sp. TY48, RIMD 2001001, CIP 111916T), Tsukamurella toyonakaense, from a patient given a misdiagnosis of nontuberculous mycobacterial pulmonary disease caused by unidentified mycobacteria. Genomic identification of this Tsukamurella species helped clarify its clinical characteristics and epidemiology.
Schlagwörter	chronic pulmonary disease ; nontuberculous mycobacteria ; Tsukamurella toyonakaenses ; Tsukamurella paurometabola ; bacteria ; rapid-growing mycobacteria ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Sprache	Englisch
Erscheinungsdatum	2022-07-01T00:00:00Z
Verlag	Centers for Disease Control and Prevention
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging

Yingji Jin / Yoshito Takeda / Yasushi Kondo / Lokesh P. Tripathi / Sujin Kang / Hikari Takeshita / Hanako Kuhara / Yohei Maeda / Masayoshi Higashiguchi / Kotaro Miyake / Osamu Morimura / Taro Koba / Yoshitomo Hayama / Shohei Koyama / Kaori Nakanishi / Takeo Iwasaki / Satoshi Tetsumoto / Kazuyuki Tsujino / Muneyoshi Kuroyama /

Kota Iwahori / Haruhiko Hirata / Takayuki Takimoto / Mayumi Suzuki / Izumi Nagatomo / Ken Sugimoto / Yuta Fujii / Hiroshi Kida / Kenji Mizuguchi / Mari Ito / Takashi Kijima / Hiromi Rakugi / Eisuke Mekada / Isao Tachibana / Atsushi Kumanogoh

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Band 14

Abstract: Abstract Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged as key players in malignancy and inflammatory diseases. Here, we ... ...

Abstract	Abstract Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging, but the mechanism remains unclear. Tetraspanins have emerged as key players in malignancy and inflammatory diseases. Here, we found that CD9/CD81 double knockout (DKO) mice with a COPD-like phenotype progressively developed a syndrome resembling human aging, including cataracts, hair loss, and atrophy of various organs, including thymus, muscle, and testis, resulting in shorter survival than wild-type (WT) mice. Consistent with this, DNA microarray analysis of DKO mouse lungs revealed differential expression of genes involved in cell death, inflammation, and the sirtuin-1 (SIRT1) pathway. Accordingly, expression of SIRT1 was reduced in DKO mouse lungs. Importantly, siRNA knockdown of CD9 and CD81 in lung epithelial cells additively decreased SIRT1 and Foxo3a expression, but reciprocally upregulated the expression of p21 and p53, leading to reduced cell proliferation and elevated apoptosis. Furthermore, deletion of these tetraspanins increased the expression of pro-inflammatory genes and IL-8. Hence, CD9 and CD81 might coordinately prevent senescence and inflammation, partly by maintaining SIRT1 expression. Altogether, CD9/CD81 DKO mice represent a novel model for both COPD and accelerated senescence.
Schlagwörter	Medicine ; R ; Science ; Q
Thema/Rubrik (Code)	570
Sprache	Englisch
Erscheinungsdatum	2018-03-01T00:00:00Z
Verlag	Nature Portfolio
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Statins decrease lung inflammation in mice by upregulating tetraspanin CD9 in macrophages.

PLoS ONE, Vol 8, Iss 9, p e

2013 Band 73706

Abstract: Tetraspanins organize protein complexes in tetraspanin-enriched membrane microdomains that are distinct from lipid rafts. Our previous studies suggested that reduction in the levels of tetraspanins CD9 and CD81 may be involved in the progression of ... ...

Abstract	Tetraspanins organize protein complexes in tetraspanin-enriched membrane microdomains that are distinct from lipid rafts. Our previous studies suggested that reduction in the levels of tetraspanins CD9 and CD81 may be involved in the progression of inflammatory lung diseases, especially COPD. To search for agents that increase the levels of these tetraspanins, we screened 1,165 drugs in clinical use and found that statins upregulate CD9 and CD81 in RAW264.7 macrophages. The lipophilic statins, fluvastatin and simvastatin, reversed LPS-induced downregulation of CD9 and CD81, simultaneously preventing TNF-α and matrix metalloproteinase-9 production and spreading of RAW264.7 cells. These statins exerted anti-inflammatory effects in vitro in wild-type macrophages but not in CD9 knockout macrophages, and decreased lung inflammation in vivo in wild-type mice but not in CD9 knockout mice, suggesting that their effects are dependent on CD9. Mechanistically, the statins promoted reverse transfer of the LPS-signaling mediator CD14 from lipid rafts into CD9-enriched microdomains, thereby preventing LPS receptor formation. Finally, upregulation of CD9/CD81 by statins was related to blockade of GTPase geranylgeranylation in the mevalonate pathway. Our data underscore the importance of the negative regulator CD9 in lung inflammation, and suggest that statins exert anti-inflammatory effects by upregulating tetraspanin CD9 in macrophages.
Schlagwörter	Medicine ; R ; Science ; Q
Sprache	Englisch
Erscheinungsdatum	2013-01-01T00:00:00Z
Verlag	Public Library of Science (PLoS)
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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