Takashi Motegi

Nippon Medical School, Tokyo, Tokyo-to, Japan

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Publications (34)25.49 Total impact

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    ABSTRACT: Combined pulmonary fibrosis and emphysema (CPFE) is an under-recognized syndrome for which the diagnostic use of serum biomarkers is an attractive possibility. We hypothesized that CC16 and/or TGF-β1 or combinations with other biomarkers are useful for diagnosing CPFE. Patients with respiratory symptoms and a smoking history, with or without chronic obstructive pulmonary disease, were divided into the following three groups according to findings of high-resolution computed tomography of the chest: controls without either emphysema or fibrosis, patients with emphysema alone, and patients compatible with the diagnosis of CPFE. Serum concentrations of CC16, TGF-β1, SP-D, and KL-6 were measured in patients whose condition was stable for at least 3 months. To investigate changes in biomarkers of lung fibrosis in patients with a life-long smoking history, additional measurements were performed on the patients with idiopathic pulmonary fibrosis (IPF) of smoking history. The mean age of the first three groups was 68.0 years, whereas that of the IPF group was 71.8 years, and the groups contained 36, 115, 27, and 10 individuals, respectively. The serum concentration of CC16 in the four groups was 5.67 ± 0.42, 5.66 ± 0.35, 9.38 ± 1.04 and 22.15 ± 4.64 ng/ml, respectively, indicating that those patients with lung fibrosis had a significantly higher concentration. The combined use of CC16, SP-D, and KL-6 provided supportive diagnosis in conjunction with radiological imaging in diagnosis of CPFE. We conclude that a combination of biomarkers including CC16 could provide useful information to screen and predict the possible diagnosis of CPFE.
    COPD Journal of Chronic Obstructive Pulmonary Disease 09/2014; · 2.73 Impact Factor
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    ABSTRACT: Background and objectiveVitamin D supplementation can decrease the vulnerability to pulmonary infections. Therefore, it is speculated that the genes related to vitamin D metabolism are associated with an exacerbation-prone phenotype in chronic obstructive pulmonary disease (COPD). Because genetic variations of group component (GC) affect immunological capacity and serum vitamin D concentration, they could also affect the susceptibility to COPD exacerbation and the disease progression. We investigated the association between GC genetic variations and COPD and its exacerbation frequency in a Japanese population.Methods We performed genotype analysis of 361 COPD patients and 219 controls to identify two coding single nucleotide polymorphisms of GC, rs4588 and rs7041. We examined whether these polymorphisms were associated with the frequency of COPD exacerbation and analysed the correlation between the genotypes, COPD, emphysema severity and COPD progression, namely, the annual decline in airflow obstruction and diffusing capacity.ResultsSubjects with a C allele at rs4588 exhibited a higher frequency of exacerbations (P = 0.0048), greater susceptibility to chronic obstructive pulmonary disease (P = 0.0003), and emphysema (P = 0.0029), and a tendency for rapid decline of airflow obstruction (P = 0.0927).ConclusionsGC variations may affect exacerbation susceptibility, possibly leading to COPD worsening and its progression.
    Respirology 05/2014; 19(4). · 2.78 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the "infection-inflammation-exacerbation" axis of COPD disease progression, and may represent promising targets for therapeutic intervention.
    Cellular and Molecular Life Sciences CMLS 03/2013; · 5.62 Impact Factor
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    ABSTRACT: AIM: Age-associated changes of the lung might increase pathogenetic susceptibility to chronic obstructive pulmonary disease (COPD). Decrement in serum transforming growth factor (TGF)-β1 concentration is reported in elderly people. As impaired TGF-β1 signaling could cause emphysema-like changes, we hypothesized that decreased TGF-β1 with aging is correlated with emphysema. METHODS: Symptomatic patients with or without COPD and healthy normal subjects without COPD were recruited (COPD, n = 182; smoking controls, n = 73; normal, n = 26). We investigated the correlation between TGF-β1 and extent of emphysema and airway wall thickness, which were defined as the percentage of low-attenuation area (LAA%) and large airway wall area (WA%) on pulmonary high-resolution computed tomography, respectively. The correlation of pulmonary function test parameters and TGF-β1 was evaluated. TGF-β1 was determined by enzyme-linked immunosorbent assay. RESULTS: TGF-β1 significantly decreased with age (P = 0.0009). When the correlation between age and TGF-β1 was analyzed in each group, a significant inverse correlation was found in COPD patients and smoking controls (P = 0.0095 and 0.0132, respectively), whereas no correlation was observed in healthy older adults. Among COPD patients with severe emphysema, LAA% was inversely correlated with TGF-β1 (n = 89, P = 0.0104), whereas WA% and pulmonary function test parameters were not. CONCLUSIONS: Although no correlation was found between TGF-β1 and the severity of COPD, TGF-β1 significantly decreased as emphysema became more severe. Age-related decrease of TGF-β1 in COPD might be associated with emphysematous alterations of the lungs in elderly subjects. Geriatr Gerontol Int 2013; ●●: ●●-●●.
    Geriatrics & Gerontology International 02/2013;
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    ABSTRACT: Prediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease. To determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations. This was a 2-year prospective cohort study of COPD patients. Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared. Among 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002). For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001). Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation. In this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices.
    International Journal of COPD 01/2013; 8:259-71.
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    ABSTRACT: Historically, the progress of long term-oxygen therapy (LTOT) in Japan has been characterized by collaboration among academic groups, policy makers, and industrial companies. The public health insurance program has covered the cost of LTOT since 1985. Thomas Petty's group in Denver enthusiastically carried out the public implementation of LTOT and conveyed the concept of pulmonary rehabilitation for the processing with LTOT. Although the target diseases of LTOT in Japan tended to be chronic obstructive pulmonary disease or sequelae of primary lung tuberculosis, it was soon applied for cardiac diseases as well as other pulmonary diseases. Together with increasing medical costs for geriatric patients, the political conversion from hospital based care of a traditional style to home care system has been performed, with two background reasons: the improvement of quality of life of patients and the reduction of the medical expense. Presently, LTOT plays a pivotal role in the successful implementation of home respiratory care for elderly patients. In addition, this promotes comprehensive pulmonary rehabilitation, a team approach, and close liaisons between primary care and hospitals. Currently, the total number of patients using LTOT exceeds 150,000. In Japan, LTOT resulted in an advancement in the medical care as well as in administrative decision to introduce it as a nationwide system after analyzing the results of opinion polls of patients with respiratory failure. However, the recent great earthquake in East Japan revealed that many unresolved problems remain for these patients, and these issues are of great concern.
    Pneumonologia i alergologia polska: organ Polskiego Towarzystwa Ftyzjopneumonologicznego, Polskiego Towarzystwa Alergologicznego, i Instytutu Gruzlicy i Chorob Pluc 01/2013; 81(5):468-78.
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    ABSTRACT: This study evaluated the implementation of pulmonary rehabilitation (PR), and the extent of the collaboration between primary care and chest physicians involved in the management of chronic obstructive pulmonary disease (COPD) in Japan. The survey was conducted in 2006 via post and facsimile and included all medical institutions approved by the Japan Respiratory Society. In total, 176 institutions responded (response rate, 27%); a PR program was conducted at 55.1% of these institutions throughout Japan, but with regional differences. The mean duration of each session in an outpatient setting was 30min with 2 sessions per week, and the mean length of hospitalization was 2-3 weeks. Although 33% of the hospitals adopted PR programs, on a scale from none (0) to maximum achievement (100), the accomplishment score was 48. Similarly, the mean satisfaction level score for collaboration was 44. The main problem arising with regards to chest physicians' referral to general physicians was the reluctance of patients or family members (88%). Chest physicians believed that general physicians should perform early screening of patients and manage early exacerbations, including educating patients of the need to discontinue smoking. Most chest physicians in Japan were not satisfied with the status of long-term COPD management. PR for COPD patients and collaboration between primary care physicians and specialists remain problematic in Japan. Moreover, there are widespread regional differences in terms of implementation. Sharing and implementing appropriate clinical information with primary care physicians according to current clinical guidelines should be emphasized.
    Respiratory investigation. 09/2012; 50(3):98-103.
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    ABSTRACT: Fut8 (α1,6-Fucosyltransferase) heterozygous knock-out (Fut8(+/-)) mice had an increased influx of inflammatory cells into the lungs, and this was associated with an up-regulation of matrix metalloproteinases, MMP-2 and MMP-9, after treatment with porcine pancreatic elastase (PPE), exhibiting an emphysema-prone phenotype as compared with wild type mice (Fut8(+/+)). The present data as well as our previous data on cigarette-smoke-induced emphysema [8] led us to hypothesize that reduced Fut8 levels leads to COPD with increased inflammatory response in humans and is associated with disease progression. To test this hypothesis, symptomatic current or ex-smokers with stable COPD or at risk outpatients were recruited. We investigated the association between serum Fut8 activity and disease severity, including the extent of emphysema (percentage of low-attenuation area; LAA%), airflow limitation, and the annual rate of decline in forced expiratory volume in 1 s (FEV(1)). Association with the exacerbation of COPD was also evaluated over a 3-year period. Serum Fut8 and MMP-9 activity were measured. Fut8 activity significantly increased with age among the at risk patients. In the case of COPD patients, however, the association was not clearly observed. A faster annual decline of FEV(1) was significantly associated with lower Fut8 activity. Patients with lower Fut8 activity experienced exacerbations more frequently. These data suggest that reduced Fut8 activity is associated with the progression of COPD and serum Fut8 activity is a non-invasive predictive biomarker candidate for progression and exacerbation of COPD.
    Biochemical and Biophysical Research Communications 06/2012; 424(1):112-7. · 2.28 Impact Factor
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • Journal of Nippon Medical School 01/2012; 79(6):498-500.
  • American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado; 05/2011
  • American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado; 05/2011
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    ABSTRACT: Education is a key issue for the long-term management of chronic obstructive pulmonary disease in older patients. We tested the hypothesis that integrated care focusing on patient information needs for self-management can improve patient information needs and health outcomes.   Patients with chronic obstructive pulmonary disease (n=102) were randomized into integrated care (group I) and usual care (group U) groups. Group I underwent a program of educational sessions for 6months (integrated education period), and then repeatedly received an individually tailored education according to the Lung Information Needs Questionnaire score. Both groups were followed up monthly for 6months.   A total of 85 patients (mean age: 71.7years) were followed up for 12months. The total Lung Information Needs Questionnaire score was significantly better in group I than in group U at 12months (P<0.03). Activities of daily living scores were significantly improved in group I at 6months (P<0.03). The dyspnea score and the BODE index (body mass index, dyspnea, airflow obstruction and exercise capacity) were significantly improved in group I at 12months (P<0.01 and P<0.02, respectively). During the integrated education period, the frequency of hospitalization was significantly lower in group I than in group U (P=0.033). Integrated education for older patients with chronic obstructive pulmonary disease effectively improved patients' information needs, activities of daily living, dyspnea score, BODE index and reduced hospitalizations during the observed period. Geriatr Gerontol Int 2011; 11: 422-430.
    Geriatrics & Gerontology International 03/2011; 11(4):422-30.
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    ABSTRACT: Early diagnosis is a key factor in the management of chronic obstructive pulmonary disease (COPD). Although mass screening is widely used, little is known about its accuracy and efficacy. This study investigated whether using spirometry during mass screening to detect COPD among community residents might be ineffective because of variability in the training and experience of examiners. Both spirometry and a self-written questionnaire-based survey, including questions designed to detect respiratory symptoms, were conducted on community residents. Two separate studies were conducted on islanders living in similar environments. Study I was performed from 2004 to 2007 on Hachijyo Island residents, while study II, with a similar study design, was performed in 2003 on Inno Island residents. In study I, 3,592 subjects underwent examination over the 4-year study period; of these, 378 subjects underwent repeated examinations. Approximately 25% of the subjects had respiratory symptoms. Acceptable spirometry recordings were obtained for 62.0% (2004) to 84.1% (2006) of the subjects. In study II, 167 of the 254 subjects (65.7%) had respiratory symptoms. Acceptable assessment recordings were achieved in 254 subjects (95.5%). The suitability of the recordings was influenced by the extent/level of training of the examiners and the accompanying thoracic specialists. We concluded that the effectiveness of health check-ups for COPD evaluation using spirometry was greatly influenced by the quality of the examiners, even when the subjects had respiratory symptoms. Thus, we recommend caution when screening for early signs of COPD during health check-ups.
    Internal Medicine 01/2011; 50(19):2135-41. · 0.97 Impact Factor
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    ABSTRACT: Previous studies have suggested links between chronic obstructive pulmonary disease (COPD), cardiovascular disease, and abdominal obesity. Although abdominal visceral fat is thought to be associated with cardiovascular risk factors, the degree of visceral fat accumulation in patients with COPD has not been directly studied. The aim of this study was to investigate the abdominal visceral fat accumulation and the association between visceral fat and the severity and changes in emphysema in COPD patients. We performed clinical and laboratory tests, including pulmonary function, dyspnea score, and the six-minute walking test in COPD patients (n = 101) and control, which included subjects with a smoking history but without airflow obstruction (n = 62). We used computed tomography to evaluate the abdominal visceral fat area (VFA), subcutaneous fat area (SFA), and the extent of emphysema. The COPD group had a larger VFA than the control group. The prevalence of non-obese subjects with an increased VFA was greater in the Global Initiative for Chronic Obstructive Lung Disease Stages III and IV than in the other stages of COPD. The extent of emphysema was inversely correlated with waist circumference and SFA. However, VFA did not decrease with the severity of emphysema. VFA was positively correlated with the degree of dyspnea. COPD patients have excessive visceral fat, which is retained in patients with more advanced stages of COPD or severe emphysema despite the absence of obesity.
    International Journal of COPD 01/2011; 6:423-30.
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    ABSTRACT: To determine whether the presence of in-home caregivers is associated with changes in the health outcomes of older adults with chronic obstructive pulmonary disease (COPD). Cross-sectional study. Geriatric medical center and academic respiratory clinic in Japan. Community-dwelling adults with COPD and their caregivers. Outcome measures (pulmonary function tests, distance on the 6-minute walking test (6MWT), activities of daily living (ADLs), quality of life (Medical Outcomes Study 36-item Short Form Survey and St. George's Respiratory Questionnaire), and frequencies of emergency visits and hospitalizations of those living alone (group A), those living with one caregiver (group B), and those living with two or more caregivers (group C) were compared. Three hundred eighty-nine participants (315 men and 74 women; mean age 73.3) were enrolled. Mean predicted forced expiratory volume in 1 second was 57.5%. The numbers of participants allocated into the global initiative for chronic obstructive lung disease stages I, II, III, and IV were 105, 107, 122, and 55, respectively. Group A had 87 participants; group B, 125; and group C, 177. Instrumental ADL scores were highest in group A (P < .001), whereas 6MWT distance was longest in group B and shortest in group A. The frequency of emergency visits was highest in group A (P < .001). Participants with COPD living alone were higher functioning in terms of instrumental ADLs, but they had less exercise capacity and more-frequent emergency visits than participants in the in-home caregiver groups and no difference in hospitalizations.
    Journal of the American Geriatrics Society 01/2011; 59(1):44-9. · 4.22 Impact Factor
  • American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans; 05/2010
  • American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans; 05/2010