研究者詳細 - 中鉢　正太郎

論文 - 中鉢　正太郎

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Prognostic significance of chronic kidney disease and impaired renal function in Japanese patients with COVID-19

Tanaka H., Chubachi S., Asakura T., Namkoong H., Azekawa S., Otake S., Nakagawara K., Fukushima T., Lee H., Watase M., Sakurai K., Kusumoto T., Masaki K., Kamata H., Ishii M., Hasegawa N., Okada Y., Koike R., Kitagawa Y., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

BMC Infectious Diseases 24 （ 1 ） 2024年12月

Background: Renal impairment is a predictor of coronavirus disease (COVID-19) severity. No studies have compared COVID-19 outcomes in patients with chronic kidney disease (CKD) and patients with impaired renal function without a prior diagnosis of CKD. This study aimed to identify the impact of pre-existing impaired renal function without CKD on COVID-19 outcomes. Methods: This retrospective study included 3,637 patients with COVID-19 classified into three groups by CKD history and estimated glomerular filtration rate (eGFR) on referral: Group 1 (n = 2,460), normal renal function without a CKD history; Group 2 (n = 905), impaired renal function without a CKD history; and Group 3 (n = 272), history of CKD. We compared the clinical characteristics of these groups and assessed the effect of CKD and impaired renal function on critical outcomes (requirement for respiratory support with high-flow oxygen devices, invasive mechanical ventilation, or extracorporeal membrane oxygen, and death during hospitalization) using multivariable logistic regression. Results: The prevalence of comorbidities (hypertension, diabetes, and cardiovascular disease) and incidence of inflammatory responses (white blood counts, and C-reactive protein, procalcitonin, and D-dimer levels) and complications (bacterial infection and heart failure) were higher in Groups 2 and 3 than that in Group 1. The incidence of critical outcomes was 10.8%, 17.7%, and 26.8% in Groups 1, 2, and 3, respectively. The mortality rate and the rate of requiring IMV support was lowest in Group 1 and highest in Group 3. Compared with Group 1, the risk of critical outcomes was higher in Group 2 (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.03–1.70, P = 0.030) and Group 3 (aOR: 1.94, 95% CI: 1.36–2.78, P < 0.001). Additionally, the eGFR was significantly associated with critical outcomes in Groups 2 (odds ratio [OR]: 2.89, 95% CI: 1.64–4.98, P < 0.001) and 3 (OR: 1.87, 95% CI: 1.08–3.23, P = 0.025) only. Conclusions: Clinicians should consider pre-existing CKD and impaired renal function at the time of COVID-19 diagnosis for the management of COVID-19.

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Increased adiposity-to-muscle ratio and severity of sinusitis affect quality of life in asthma: Computed tomographic analysis

Shimizu K., Kimura H., Tanabe N., Tanimura K., Chubachi S., Iijima H., Sato S., Wakazono N., Nakamaru Y., Okada K., Makita H., Goudarzi H., Suzuki M., Nishimura M., Konno S.

Journal of Allergy and Clinical Immunology: Global 3 （ 3 ） 2024年08月

Background: Deteriorated sinusitis and increased adiposity relative to muscle mass may affect quality of life in patients with asthma. However, whether these effects are observed regardless of intrapulmonary pathology is unknown. Objectives: We evaluated the correlation of the cross-sectional ratio of abdominal visceral fat (VF) to erector spinae muscle (ESM) and sinus findings based on Lund-Mackey scoring system (LMS) on computed tomography (CT) with the impaired score of the Asthma Quality of Life Questionnaire (AQLQ), regardless of airway and parenchymal disease, in patients with asthma. Methods: We recruited participants from the Hokkaido-based severe asthma cohort who had completed AQLQ and CT examination at the entry. The participants were divided into high (highest) and low (other quartiles) groups on the bases of the extrapulmonary indices. Multivariate analysis examined the association of VF/ESM for the adiposity-to-muscle ratio and LMS with AQLQ after adjusting for the airway fractal dimension for airway index and percentage of low attenuation volume to lung volume for parenchymal index. Results: No significant differences were observed in VF/ESM and LMS in terms of sex. The AQLQ score in the high VF/ESM group and high LMS group was lower than those in low VF/ESM group and low LMS group (63 male and 100 female subjects). High VF/ESM (estimate [95% confidence interval] (−0.43 [−0.61, −0.25]) and high LMS scores (−0.22 [−0.41, −0.03]) were associated with low AQLQ scores when adjusted for age, body mass index, smoking status, blood eosinophil count, and intrapulmonary CT indices. Conclusions: Increased VF relative to ESM mass and high LMS may deteriorate asthma-related quality of life, regardless of presence of intrapulmonary disease.

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CT-derived vertebral bone mineral density is a useful biomarker to predict COVID-19 outcome

Azekawa S., Maetani T., Chubachi S., Asakura T., Tanabe N., Shiraishi Y., Namkoong H., Tanaka H., Shimada T., Fukushima T., Otake S., Nakagawara K., Watase M., Terai H., Sasaki M., Ueda S., Kato Y., Harada N., Suzuki S., Yoshida S., Tateno H., Yamada Y., Jinzaki M., Hirai T., Okada Y., Koike R., Ishii M., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

Bone 184 2024年07月

ISSN 87563282

The low vertebral bone computed tomography (CT) Hounsfield unit values measured on CT scans reflect low bone mineral density (BMD) and are known as diagnostic indicators for osteoporosis. The potential prognostic significance of low BMD defined by vertebral bone CT values for the coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to assess the impact of BMD on the clinical outcome in Japanese patients with COVID-19 and evaluate the association between BMD and critical outcomes, such as high-flow nasal cannula, non-invasive and invasive positive pressure ventilation, extracorporeal membrane oxygenation, or death. We examined the effects of COVID-19 severity on the change of BMD over time. This multicenter retrospective cohort study enrolled 1132 inpatients with COVID-19 from the Japan COVID-19 Task Force database between February 2020 and September 2022. The bone CT values of the 4th, 7th, and 10th thoracic vertebrae were measured from chest CT images. The average of these values was defined as BMD. Furthermore, a comparative analysis was conducted between the BMD on admission and its value 3 months later. The low BMD group had a higher proportion of critical outcomes than did the high BMD group. In a subanalysis stratifying patients by epidemic wave according to onset time, critical outcomes were higher in the low BMD group in the 1st–4th waves. Multivariable logistic analysis of previously reported factors associated with COVID-19 severity revealed that low BMD, chronic kidney disease, and diabetes were independently associated with critical outcomes. At 3 months post-infection, patients with oxygen demand during hospitalization showed markedly decreased BMD than did those on admission. Low BMD in patients with COVID-19 may help predict severe disease after the disease onset. BMD may decrease over time in patients with severe COVID-19, and the impact on sequelae symptoms should be investigated in the future.

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Pulmonary function and chest CT abnormalities 3 months after discharge from COVID-19, 2020–2021: A nation-wide multicenter prospective cohort study from the Japanese respiratory society

Kamata H., Takamatsu K., Fukunaga K., Chubachi S., Nakagawara K., Namkoong H., Terai H., Tanaka K., Sato S., Hagiwara E., Takei R., Kondoh Y., Takazono T., Hashimoto M., Tasaka S., Ohrui T., Tanino Y., Mineshita M., Komase Y., Miyazaki K., Nishikawa M., Ando A., Kita H., Ichihara E., Ohshimo S., Murata Y., Ishida M., Kobayashi S., Uchida T., Tateno H., Ikari J., Terashima T., Kozu Y., Tateishi T., Shinkai M., Sagara H., To Y., Ito Y., Yamamoto M., Yamamoto Y., Kita T., Ito Y., Tomii K., Fujita Y., Funaki Y., Yatera K., Yamasue M., Komiya K., Kozawa S., Manabe H., Hozumi H., Horiguchi T., Kitajima T., Nakano Y., Nagaoka T., Hojo M., Ebihara A., Kobayashi M., Takayama K., Jinta T., Sawai T., Fukuda Y., Kaneko T., Chin K., Ogura T., Mukae H., Ishii M., Yokoyama A.

Respiratory Investigation 62 （ 4 ） 572 - 579 2024年07月

ISSN 22125345

Background: No comprehensive analysis of the pulmonary sequelae of coronavirus disease 2019 (COVID-19) in Japan based on respiratory function tests and chest computed tomography (CT) has been reported. We evaluated post-COVID-19 conditions, especially focusing on pulmonary sequelae assessed by pulmonary function tests and chest CT. Methods: For this prospective cohort study, we enrolled 1069 patients who presented pneumonia at the time of admission in 55 hospitals from February 2020 to September 2021. Disease severity was classified as moderateⅠ, moderate II, and severe, defined primarily according to the degree of respiratory failure. The data on post-COVID-19 conditions over 12 months, pulmonary function, and chest CT findings at 3 months were evaluated in this study. Additionally, the impact of COVID-19 severity on pulmonary sequelae, such as impaired diffusion capacity, restrictive pattern, and CT abnormalities, was also evaluated. Results: The most frequently reported post-COVID-19 conditions at 3 months after COVID-19 were muscle weakness, dyspnea, and fatigue (48.4%, 29.0%, and 24.7%, respectively). The frequency of symptoms gradually decreased over subsequent months. In pulmonary function tests at 3 months, the incidence of impaired diffusion capacity and restrictive pattern increased depending on disease severity. There also were differences in the presence of chest CT abnormalities at the 3 months, which was markedly correlated with the severity. Conclusion: We reported a comprehensive analysis of post-COVID-19 condition, pulmonary function, and chest CT abnormalities in Japanese patients with COVID-19. The findings of this study will serve as valuable reference data for future post-COVID-19 condition research in Japan.

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Lung volume measurement using chest CT in COVID-19 patients: a cohort study in Japan

Otake S., Shiraishi Y., Chubachi S., Tanabe N., Maetani T., Asakura T., Namkoong H., Shimada T., Azekawa S., Nakagawara K., Tanaka H., Fukushima T., Watase M., Terai H., Sasaki M., Ueda S., Kato Y., Harada N., Suzuki S., Yoshida S., Tateno H., Yamada Y., Jinzaki M., Hirai T., Okada Y., Koike R., Ishii M., Hasegawa N., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

BMJ Open Respiratory Research 11 （ 1 ） 2024年04月

Objective This study aimed to investigate the utility of CT quantification of lung volume for predicting critical outcomes in COVID-19 patients. Methods This retrospective cohort study included 1200 hospitalised patients with COVID-19 from 4 hospitals. Lung fields were extracted using artificial intelligence-based segmentation, and the percentage of the predicted (%pred) total lung volume (TLC (%pred)) was calculated. The incidence of critical outcomes and posthospitalisation complications was compared between patients with low and high CT lung volumes classified based on the median percentage of predicted TLCct (n=600 for each). Prognostic factors for residual lung volume loss were investigated in 208 patients with COVID-19 via a follow-up CT after 3 months. Results The incidence of critical outcomes was higher in the low TLCct (%pred) group than in the high TLCct (%pred) group (14.2% vs 3.3%, p<0.0001). Multivariable analysis of previously reported factors (age, sex, body mass index and comorbidities) demonstrated that CT-derived lung volume was significantly associated with critical outcomes. The low TLCct (%pred) group exhibited a higher incidence of bacterial infection, heart failure, thromboembolism, liver dysfunction and renal dysfunction than the high TLCct (%pred) group. TLCct (%pred) at 3 months was similarly divided into two groups at the median (71.8%). Among patients with follow-up CT scans, lung volumes showed a recovery trend from the time of admission to 3 months but remained lower in critical cases at 3 months. Conclusion Lower CT lung volume was associated with critical outcomes, posthospitalisation complications and slower improvement of clinical conditions in COVID-19 patients.

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Asthma is a risk factor for general fatigue of long COVID in Japanese nation-wide cohort study

Sunata K., Miyata J., Terai H., Matsuyama E., Watase M., Namkoong H., Asakura T., Masaki K., Chubachi S., Ohgino K., Kawada I., Harada N., Sasano H., Nakamura A., Kusaka Y., Ohba T., Nakano Y., Nishio K., Nakajima Y., Suzuki S., Yoshida S., Tateno H., Ishii M., Fukunaga K.

Allergology International 73 （ 2 ） 206 - 213 2024年04月

ISSN 13238930

Background: Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue is frequently observed in patients with long COVID during acute and post-acute phases. This study aimed to identify the specific risk factors for general fatigue in long COVID. Methods: Hospitalized patients with COVID-19 aged over 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. Results: Among prolonged symptoms through 1-year follow-ups, general fatigue was the most interfering symptom in daily life. Patients with protracted fatigue at all follow-up periods had lower quality of life scores at the 12-month follow-up. Univariate logistic regression analysis of the presence or absence of general fatigue at the 3-month, 6-month, and 12-month follow-ups identified asthma, younger age, and female sex as risk factors for prolonged fatigue. Multivariable logistic regression analysis revealed that asthma was an independent risk factor for persistent fatigue during the 12-month follow-up period. Longitudinal changes in the symptoms of patients with or without asthma demonstrated that general fatigue, not cough and dyspnea, was significantly prolonged in patients with asthma. Conclusions: In a Japanese population with long COVID, prolonged general fatigue was closely linked to asthma. A preventive approach against COVID-19 is necessary to avoid sustained fatigue and minimize social and economic losses in patients with asthma.

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Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study

Matsubara Y., Kiyohara H., Mikami Y., Nanki K., Namkoong H., Chubachi S., Tanaka H., Azekawa S., Sugimoto S., Yoshimatsu Y., Sujino T., Takabayashi K., Hosoe N., Sato T., Ishii M., Hasegawa N., Okada Y., Koike R., Kitagawa Y., Kimura A., Imoto S., Miyano S., Ogawa S., Fukunaga K., Kanai T.

Journal of gastroenterology 59 （ 3 ） 195 - 208 2024年03月

BACKGROUND: Research on whether gastrointestinal symptoms correlate with the severity of Coronavirus Disease 2019 (COVID-19) has been inconclusive. This study aimed to clarify any associations between gastrointestinal symptoms and the prognosis of COVID-19. METHODS: We collected data from the Japanese nationwide registry for COVID-19 to conduct a retrospective cohort study. Data from 3498 Japanese COVID-19 patients, diagnosed at 74 facilities between February 2020 and August 2022, were analyzed in this study. Hospitalized patients were followed up until discharge or transfer to another hospital. Outpatients were observed until the end of treatment. Associations between gastrointestinal symptoms and clinical outcomes were investigated using multivariable-adjusted logistic regression models. RESULTS: The prevalence of diarrhea, nausea/vomiting, abdominal pain, and melena were 16.6% (581/3498), 8.9% (311/3498), 3.5% (121/3498), and 0.7% (23/3498), respectively. In the univariable analysis, admission to intensive care unit (ICU) and requirement for mechanical ventilation were less common in patients with diarrhea than those without (ICU, 15.7% vs. 20.6% (p = 0.006); mechanical ventilation, 7.9% vs. 11.4% (p = 0.013)). In the multivariable-adjusted analysis, diarrhea was associated with lower likelihood of ICU admission (adjusted odds ratio (aOR), 0.70; 95% confidence interval (CI), 0.53-0.92) and mechanical ventilation (aOR, 0.61; 95% CI, 0.42-0.89). Similar results were obtained in a sensitivity analysis with another logistic regression model that adjusted for 14 possible covariates with diarrhea (ICU; aOR, 0.70; 95% CI, 0.53-0.93; mechanical ventilation; aOR 0.62; 95% CI, 0.42-0.92). CONCLUSIONS: Diarrhea was associated with better clinical outcomes in COVID-19 patients.

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Integrated assessment of computed tomography density in pectoralis and erector spinae muscles as a prognostic biomarker for coronavirus disease 2019

Nakagawara K., Shiraishi Y., Chubachi S., Tanabe N., Maetani T., Asakura T., Namkoong H., Tanaka H., Shimada T., Azekawa S., Otake S., Fukushima T., Watase M., Terai H., Sasaki M., Ueda S., Kato Y., Harada N., Suzuki S., Yoshida S., Tateno H., Yamada Y., Jinzaki M., Hirai T., Okada Y., Koike R., Ishii M., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

Clinical Nutrition 43 （ 3 ） 815 - 824 2024年03月

ISSN 02615614

Background ＆ aims: Muscle quantification using chest computed tomography (CT) is a useful prognostic biomarker for coronavirus disease 2019 (COVID-19). However, no studies have evaluated the clinical course through comprehensive assessment of the pectoralis and erector spinae muscles. Therefore, we compared the impact of the areas and densities of these muscles on COVID-19 infection outcome. Methods: This multicenter retrospective cohort study was conducted by the COVID-19 Task Force. A total of 1410 patients with COVID-19 were included, and data on the area and density of the pectoralis and erector spinae muscles on chest CT were collected. The impact of each muscle parameter on the clinical outcome of COVID-19 was stratified according to sex. The primary outcome was the percentage of patients with severe disease, including those requiring oxygen supplementation and those who died. Additionally, 167 patients were followed up for changes in muscle parameters at three months and for the clinical characteristics in case of reduced CT density. Results: For both muscles, low density rather than muscle area was associated with COVID-19 severity. Regardless of sex, lower erector spinae muscle density was associated with more severe disease than pectoralis muscle density. The muscles were divided into two groups using the receiver operating characteristic curve of CT density, and the population was classified into four (Group A: high CT density for both muscles, Group B: low CT density for pectoralis and high for erector spinae muscle. Group C: high CT density for pectoralis and low for erector spinae muscle, Group D: low CT density for both muscles). In univariate analysis, Group D patients exhibited worse outcomes than Group A (OR: 2.96, 95% CI: 2.03–4.34 in men; OR: 3.02, 95% CI: 2.66–10.4 in women). Multivariate analysis revealed that men in Group D had a significantly more severe prognosis than those in Group A (OR: 1.82, 95% CI: 1.16–2.87). Moreover, Group D patients tended to have the highest incidence of other complications due to secondary infections and acute kidney injury during the clinical course. Longitudinal analysis of both muscle densities over three months revealed that patients with decreased muscle density over time were more likely to have severe cases than those who did not. Conclusions: Muscle density, rather than muscle area, predicts the clinical outcomes of COVID-19. Integrated assessment of pectoralis and erector spinae muscle densities demonstrated higher accuracy in predicting the clinical course of COVID-19 than individual assessments.

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Prognostic significance of hypertension history and blood pressure on admission in Japanese patients with coronavirus disease 2019: integrative analysis from the Japan COVID-19 Task Force

Sakurai K., Chubachi S., Asakura T., Namkoong H., Tanaka H., Azekawa S., Shimada T., Otake S., Nakagawara K., Fukushima T., Lee H., Watase M., Kusumoto T., Masaki K., Kamata H., Ishii M., Hasegawa N., Okada Y., Koike R., Kitagawa Y., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

Hypertension Research 47 （ 3 ） 639 - 648 2024年03月

ISSN 09169636

The effect of preexisting hypertension on coronavirus disease 2019 (COVID-19) prognosis remains controversial. Additionally, no studies have compared the association between blood pressure (BP) indices on admission and COVID-19 outcomes using preexisting hypertension status. Therefore, this study aimed to investigate the association between preexisting hypertension and COVID-19 outcomes in Japanese patients with COVID-19 and assess the impact of BP indices on admission on clinical outcomes in patients with and without preexisting hypertension. Preexisting hypertension presence was confirmed based on the patient’s clinical history. Critical outcomes were defined as high-flow oxygen use, non-invasive and invasive positive-pressure ventilation, extracorporeal membrane oxygenation, or death during hospitalization. Preexisting hypertension was observed in 64.6% of the patients. Multivariable logistic regression analysis of severe COVID-19 risk factors indicated that preexisting hypertension was independently associated with critical outcomes [adjusted odds ratio (OR): 1.35; 95% confidence interval (CI): 1.05–1.73]. Low or high BP and high pulse pressure on admission were associated with critical outcomes in patients without preexisting hypertension [OR for systolic BP < 100 mmHg: 2.13, 95% CI: 1.21–3.75; OR for high BP stage 2 (160–179 systolic and/or 100–109 mmHg diastolic BP): 2.13, 95% CI: 1.27–3.58; OR for pulse pressure ≥60 mmHg: 1.68, 95% CI: 1.14–2.48]. Preexisting hypertension is a risk factor for critical outcomes in Japanese patients with COVID-19. BP indices are useful biomarkers for predicting COVID-19 outcomes, particularly in patients without preexisting hypertension. Thus, hypertension history, systolic BP, and pulse pressure should be assessed to predict severe COVID-19 outcomes. (Figure presented.)

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Cluster analysis of long COVID in Japan and association of its trajectory of symptoms and quality of life

Ito F., Terai H., Kondo M., Takemura R., Namkoong H., Asakura T., Chubachi S., Masuzawa K., Nakayama S., Suzuki Y., Hashiguchi M., Kagyo J., Shiomi T., Minematsu N., Manabe T., Fukui T., Funatsu Y., Koh H., Masaki K., Ohgino K., Miyata J., Kawada I., Ishii M., Sato Y., Fukunaga K.

BMJ Open Respiratory Research 11 （ 1 ） 2024年02月

Background Multiple prolonged symptoms observed in patients who recovered from COVID-19 are defined as long COVID. Although diverse phenotypic combinations are possible, they remain unclear. This study aimed to perform a cluster analysis of long COVID in Japan and clarify the association between its characteristics and background factors and quality of life (QOL). Methods This multicentre prospective cohort study collected various symptoms and QOL after COVID-19 from January 2020 to February 2021. This study included 935 patients aged ≥18 years with COVID-19 at 26 participating medical facilities. Hierarchical cluster analysis was performed using 24 long COVID symptom at 3 months after diagnosis. Results Participants were divided into the following five clusters: numerous symptoms across multiple organs (cluster 1, n=54); no or minor symptoms (cluster 2, n=546); taste and olfactory disorders (cluster 3, n=76); fatigue, psychoneurotic symptoms and dyspnoea (low prevalence of cough and sputum) (cluster 4, n=207) and fatigue and dyspnoea (high prevalence of cough and sputum) (cluster 5, n=52). Cluster 1 included elderly patients with severe symptoms, while cluster 3 included young female with mild symptoms. No significant differences were observed in the comorbidities. Cluster 1 showed the most impaired QOL, followed by clusters 4 and 5; these changes as well as the composition of symptoms were observed over 1 year. Conclusions We identified patients with long COVID with diverse characteristics into five clusters. Future analysis of these different pathologies could result in individualised treatment of long COVID.

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A reference equation for lung volume on computed tomography in Japanese middle-aged and elderly adults

Tanabe N., Sato S., Shimada T., Kaji S., Shiraishi Y., Terada S., Maetani T., Mochizuki F., Shimizu K., Suzuki M., Chubachi S., Terada K., Tanimura K., Sakamoto R., Oguma T., Sato A., Kanasaki M., Muro S., Masuda I., Iijima H., Hirai T.

Respiratory Investigation 62 （ 1 ） 121 - 127 2024年01月

ISSN 22125345

Background: Effective use of lung volume data measured on computed tomography (CT) requires reference values for specific populations. This study examined whether an equation previously generated for multiple ethnic groups in the United States, including Asians predominantly composed of Chinese people, in the Multi-Ethnic Study of Atherosclerosis (MESA) could be used for Japanese people and, if necessary, to optimize this equation. Moreover, the equation was used to characterize patients with chronic obstructive pulmonary disease (COPD) and lung hyperexpansion. Methods: This study included a lung cancer screening CT cohort of asymptomatic never smokers aged ≥40 years from two institutions (n = 364 and 419) to validate and optimize the MESA equation and a COPD cohort (n = 199) to test its applicability. Results: In all asymptomatic never smokers, the variance explained by the predicted values (R2) based on the original MESA equation was 0.60. The original equation was optimized to minimize the root mean squared error (RMSE) by adjusting the scaling factor but not the age, sex, height, or body mass index terms of the equation. The RMSE changed from 714 ml in the original equation to 637 ml in the optimized equation. In the COPD cohort, lung hyperexpansion, defined based on the 95th percentile of the ratio of measured lung volume to predicted lung volume in never smokers (122 %), was observed in 60 (30 %) patients and was associated with centrilobular emphysema and air trapping on inspiratory/expiratory CT. Conclusions: The MESA equation was optimized for Japanese middle-aged and elderly adults.

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Upper Respiratory Symptoms as Long COVID: Insight from a Multicenter Cohort Study

Okada M., Ishida N., Kanzaki S., Kawada I., Nagashima K., Terai H., Hiruma G., Namkoong H., Asakura T., Masaki K., Ohgino K., Miyata J., Chubachi S., Kodama N., Maeda S., Sakamoto S., Okamoto M., Nagasaki Y., Umeda A., Miyagawa K., Shimada H., Minami K., Hagiwara R., Ishii M., Sato Y., Fukunaga K.

OTO Open 8 （ 1 ） 2024年01月

Objective: This study aimed to investigate the clinical features of long COVID cases presenting with upper respiratory symptoms, a topic not yet fully elucidated. Study Design: Prospective cohort study. Setting: A multicenter study involving 26 medical facilities in Japan. Methods: Inclusion criteria were patients aged ≥18 years old with a confirmed COVID-19 diagnosis via severe acute respiratory syndrome coronavirus 2 polymerase chain reaction or antigen testing, who were hospitalized at the participating medical facilities. Analyzing clinical information and patient-reported outcomes from 1009 patients were analyzed. The outcome measured the degree of initial symptoms for taste or olfactory disorders and assessed the likelihood of these symptoms persisting as long COVID, as well as the impact on quality of life if the upper respiratory symptoms persisted as long COVID. Results: Patients with high albumin, low C-reactive protein, and low lactate dehydrogenase in laboratory tests tended to experience taste or olfactory disorders as part of long COVID. Those with severe initial symptoms had a higher risk of experiencing residual symptoms at 3 months, with an odds ratio of 2.933 (95% confidence interval [CI], 1.282-6.526) for taste disorders and 3.534 (95% CI, 1.382-9.009) for olfactory disorders. Presence of upper respiratory symptoms consistently resulted in lower quality of life scores. Conclusion: The findings from this cohort study suggest that severe taste or olfactory disorders as early COVID-19 symptoms correlate with an increased likelihood of persistent symptoms in those disorders as long COVID.

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Epicardial adipose tissue measured from analysis of adipose tissue area using chest CT imaging is the best potential predictor of COVID-19 severity

Fukushima T., Maetani T., Chubachi S., Tanabe N., Asakura T., Namkoong H., Tanaka H., Shimada T., Azekawa S., Otake S., Nakagawara K., Watase M., Shiraishi Y., Terai H., Sasaki M., Ueda S., Kato Y., Harada N., Suzuki S., Yoshida S., Tateno H., Yamada Y., Jinzaki M., Hirai T., Okada Y., Koike R., Ishii M., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

Metabolism: Clinical and Experimental 150 2024年01月

ISSN 00260495

Background: Computed tomography (CT) imaging is widely used for diagnosing and determining the severity of coronavirus disease 2019 (COVID-19). Chest CT imaging can be used to calculate the epicardial adipose tissue (EAT) and upper abdominal visceral adipose tissue (Abd-VAT) areas. The EAT is the main source of inflammatory cytokines involved in chest inflammatory diseases; thus, the EAT area might be a more useful severity predictor than the Abd-VAT area for COVID-19. However, to the best of our knowledge, there are no large-scale reports that sufficiently consider this issue. In addition, there are no reports on the characteristics of patients with normal body mass index (BMI) and high adipose tissue. Aim: The purpose of this study was to analyze whether the EAT area, among various adipose tissues, was the most associated factor with COVID-19 severity. Using a multicenter COVID-19 patient database, we analyzed the associations of chest subcutaneous, chest visceral, abdominal subcutaneous, and Abd-VAT areas with COVID-19 outcomes. In addition, the clinical significance of central obesity, commonly disregarded by BMI, was examined. Methods: This retrospective cohort study evaluated patients with COVID-19 aged ≥18 years In Japan. Data including from chest CT images collected between February 2020 and October 2022 in four hospitals of the Japan COVID-19 Task Force were analyzed. Patient characteristics and COVID-19 severity were compared according to the adipose tissue areas (chest and abdominal subcutaneous adipose tissue [Chest-SAT and Abd-SAT], EAT, and Abd-VAT) calculated from chest CT images. Results: We included 1077 patients in the analysis. Patients with risk factors of severe COVID-19 such as old age, male sex, and comorbidities had significantly higher areas of EAT and Abd-VAT. High EAT area but not high Abd-VAT area was significantly associated with COVID-19 severity (adjusted odds ratio (aOR): 2.66, 95 % confidence interval [CI]: 1.19–5.93). There was no strong correlation between BMI and VAT. Patients with high VAT area accounted for 40.7 % of the non-obesity population (BMI < 25 kg/m2). High EAT area was also significantly associated with COVID-19 severity in the non-obesity population (aOR: 2.50, 95 % CI: 1.17–5.34). Conclusions: Our study indicated that VAT is significantly associated with COVID-19 severity and that EAT is the best potential predictor for risk stratification in COVID-19 among adipose tissue areas. Body composition assessment using EAT is an appropriate marker for identifying obesity patients overlooked by BMI. Considering the next pandemic of the global health crisis, our findings open new avenues for implementing appropriate body composition assessments based on CT imaging.

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Centrilobular emphysema and airway dysanapsis: factors associated with low respiratory function in younger smokers

Mochizuki F., Tanabe N., Shimada T., Iijima H., Sakamoto R., Shiraishi Y., Maetani T., Shimizu K., Suzuki M., Chubachi S., Ishikawa H., Naito T., Kanasaki M., Masuda I., Oguma T., Sato S., Hizawa N., Hirai T.

ERJ Open Research 10 （ 2 ） 2024年

Background Low respiratory function in young adulthood is one of the important factors in the trajectory leading to the future development of COPD, but its morphological characteristics are not well characterised. Methods We retrospectively enrolled 172 subjects aged 40–49 years with ⩾10 pack-years smoking history who underwent lung cancer screening by computed tomography (CT) and spirometry at two Japanese hospitals. Emphysema was visually assessed according to the Fleischner Society guidelines and classified into two types: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). Airway dysanapsis was assessed with the airway/lung ratio (ALR), which was calculated by the geometric mean of the lumen diameters of the 14 branching segments divided by the cube root of total lung volume on a CT scan. Results Among the subjects, CLE and PSE were observed in 20.9% and 30.8%, respectively. The mean ALR was 0.04 and did not differ between those with and without each type of emphysema. Multivariable regression analysis models adjusted for age, sex, body mass index and smoking status indicated that CLE and a low ALR were independently associated with lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (estimate −1.64 (95% CI −2.68– −0.60) and 6.73 (95% CI 4.24–9.24), respectively) and FEV1 % pred (estimate −2.81 (95% CI −5.10– −0.52) and 10.9 (95% CI 5.36–16.4), respectively). Conclusions CLE and airway dysanapsis on CT were independently associated with low respiratory function in younger smokers.

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Social impact of brain fog and analysis of risk factors: Long COVID in Japanese population

Shigematsu L., Kimura R., Terai H., Mimura Y., Ito D., Bun S., Namkoong H., Asakura T., Chubachi S., Masaki K., Ohgino K., Miyata J., Kawada I., Ishii M., Takemura R., Ueda S., Yoshiyama T., Kokuto H., Kusumoto T., Oashi A., Miyawaki M., Saito F., Tani T., Ishioka K., Takahashi S., Nakamura M., Sato Y., Fukunaga K.

Annals of Clinical and Translational Neurology 2024年

Objective: To reveal the clinical features and assess risk factors linked to brain fog and its societal implications, including labor productivity, providing valuable insights for the future care of individuals who have experienced coronavirus disease 2019 (COVID-19). Methods: We analyzed a comprehensive cohort dataset comprising 1,009 patients with COVID-19 admitted to Japanese hospitals. To assess brain fog, we analyzed patients who responded to a questionnaire indicating symptoms such as memory impairment and poor concentration. Results: The prevalence of brain fog symptoms decreased 3 months posthospitalization but remained stable up to 12 months. Neurological symptoms such as taste and smell disorders and numbness at hospitalization correlated with a higher frequency of identifying brain fog as a long COVID manifestation. Our findings indicated that advanced age, female sex, a high body mass index, oxygen required during hospitalization, chronic obstructive pulmonary disease, asthma, and elevated C-reactive protein and elevated D-dimer levels were risk factors in patients exhibiting brain fog. Additionally, we demonstrated the negative impact of brain fog on labor productivity by presenteeism scores. Interpretations: This study clarified the clinical characteristics of patients experiencing brain fog as a long COVID manifestation, specifically emphasizing neurological symptoms during hospitalization and their correlation with brain fog. Additionally, the study identified associated risk factors for its onset and revealed that the emergence of brain fog was linked to a decline in labor productivity.

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Characteristics of patients with COVID-19 who have deteriorating chest X-ray findings within 48 h: a retrospective cohort study

Kusumoto T., Chubachi S., Namkoong H., Tanaka H., Lee H., Otake S., Nakagawara K., Fukushima T., Morita A., Watase M., Asakura T., Masaki K., Kamata H., Ishii M., Hasegawa N., Harada N., Ueda T., Ueda S., Ishiguro T., Arimura K., Saito F., Yoshiyama T., Nakano Y., Mutoh Y., Suzuki Y., Edahiro R., Murakami K., Sato Y., Okada Y., Koike R., Kitagawa Y., Tokunaga K., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

Scientific Reports 13 （ 1 ） 2023年12月

The severity of chest X-ray (CXR) findings is a prognostic factor in patients with coronavirus disease 2019 (COVID-19). We investigated the clinical and genetic characteristics and prognosis of patients with worsening CXR findings during early hospitalization. We retrospectively included 1656 consecutive Japanese patients with COVID-19 recruited through the Japan COVID-19 Task Force. Rapid deterioration of CXR findings was defined as increased pulmonary infiltrates in ≥ 50% of the lung fields within 48 h of admission. Rapid deterioration of CXR findings was an independent risk factor for death, most severe illness, tracheal intubation, and intensive care unit admission. The presence of consolidation on CXR, comorbid cardiovascular and chronic obstructive pulmonary diseases, high body temperature, and increased serum aspartate aminotransferase, potassium, and C-reactive protein levels were independent risk factors for rapid deterioration of CXR findings. Risk variant at the ABO locus (rs529565-C) was associated with rapid deterioration of CXR findings in all patients. This study revealed the clinical features, genetic features, and risk factors associated with rapid deterioration of CXR findings, a poor prognostic factor in patients with COVID-19.

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Longitudinal long COVID symptoms in Japanese patients after COVID-19 vaccinations

Nakagawara K., Morita A., Namkoong H., Terai H., Chubachi S., Asakura T., Tanaka H., Ito F., Matsuyama E., Kaji M., Saito A., Takaoka H., Okada M., Sunata K., Watase M., Yagi K., Ohgino K., Miyata J., Kamata H., Kawada I., Kobayashi K., Hirano T., Inoue T., Kagyo J., Shiomi T., Otsuka K., Miyao N., Odani T., Baba R., Arai D., Nakachi I., Ueda S., Funatsu Y., Koh H., Ishioka K., Takahashi S., Nakamura M., Sato T., Hasegawa N., Kitagawa Y., Kanai T., Ishii M., Fukunaga K.

Vaccine: X 15 2023年12月

We conducted a subgroup analysis of a study on the long-term effects of COVID-19 (long COVID) in Japan to assess the effect of vaccination on long COVID symptoms. We assessed the clinical course of 111 patients with long COVID at the time of vaccination. The follow-up period was one year from the onset of COVID-19 or until the administration of the third vaccine dose. Of the 111 patients, 15 (13.5%) reported improvement, four (3.6%) reported deterioration, and 92 (82.9%) reported no change in their long COVID symptoms after vaccination. The most common long COVID symptoms before vaccination were alopecia, dyspnea, muscle weakness, fatigue, and headache among participants whose symptoms improved. Reduced dyspnea and alopecia were the most frequently reported improvements in symptoms after vaccination. Some symptoms persisted, including sleep disturbance, myalgia, and hypersensitivity. Vaccination did not appear to have a clinically important effect on patients with long COVID symptoms.

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Interaction of BMI and respiratory status in obstructive sleep apnea, a cross-sectional COPD study

Hashiguchi M.H., Chubachi S., Yamasawa W., Otsuka K., Harada N., Miyao N., Nakamura H., Asano K., Yamaguchi K., Fukunaga K.

npj Primary Care Respiratory Medicine 33 （ 1 ） 2023年12月

This cross-sectional study of 136 patients with chronic obstructive pulmonary disease (COPD) investigated the mechanism underlying overlap syndrome, defined as coexisting COPD and obstructive sleep apnea (OSA). OSA was defined as a respiratory event index (REI) ≥ 5 events/h, determined using type-3 portable monitors. The mean REI was 12.8 events/h. Most participants (60.1%) had mild OSA (REI: 5–15 events/h). The REI was positively correlated with forced expiratory volume in one second (%FEV1) (r = 0.33, p < 0.001), body mass index (BMI) (r = 0.24, p = 0.005), and fat-free mass index (r = 0.31, p = 0.005), and negatively correlated with residual volume divided by total lung capacity (r = −0.27, p = 0.003). Receiver-operating characteristic curve analysis revealed an optimal BMI cutoff of 21.96 kg/m2 for predicting moderate/severe OSA. A BMI ≥ 21.96 kg/m2 was associated with OSA among participants with %FEV1 ≥ 50%, but not those with %FEV1 < 50%. This study revealed an interaction between airflow limitation and hyperinflation, nutritional status, and OSA.

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Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study

Nakagawara K., Kamata H., Chubachi S., Namkoong H., Tanaka H., Lee H., Otake S., Fukushima T., Kusumoto T., Morita A., Azekawa S., Watase M., Asakura T., Masaki K., Ishii M., Endo A., Koike R., Ishikura H., Takata T., Matsushita Y., Harada N., Kokutou H., Yoshiyama T., Kataoka K., Mutoh Y., Miyawaki M., Ueda S., Ono H., Ono T., Shoko T., Muranaka H., Kawamura K., Mori N., Mochimaru T., Fukui M., Chihara Y., Nagasaki Y., Okamoto M., Amishima M., Odani T., Tani M., Nishi K., Shirai Y., Edahiro R., Ando A., Hashimoto N., Ogura S., Kitagawa Y., Kita T., Kagaya T., Kimura Y., Miyazawa N., Tsuchida T., Fujitani S., Murakami K., Sano H., Sato Y., Tanino Y., Otsuki R., Mashimo S., Kuramochi M., Hosoda Y., Hasegawa Y., Ueda T., Takaku Y., Ishiguro T., Fujiwara A., Kuwahara N., Kitamura H., Hagiwara E., Nakamori Y., Saito F., Kono Y., Abe S., Ishii T., Ohba T., Kusaka Y., Watanabe H., Masuda M., Watanabe H., Kimizuka Y., Kawana A., Kasamatsu Y., Hashimoto S., Okada Y., Takano T., Katayama K., Ai M., Kumanogoh A., Sato T., Tokunaga K., Imoto S., Kitagawa Y., Kimura A., Miyano S., Hasegawa N., Ogawa S., Kanai T., Fukunaga K.

BMC Pulmonary Medicine 23 （ 1 ） 2023年12月

Background: Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. Methods: We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. Results: Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil–lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. Conclusions: Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.

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Healthcare costs for hospitalized COVID-19 patients in a Japanese university hospital: a cross-sectional study

Uno S., Goto R., Honda K., Tokuda M., Kamata H., Chubachi S., Yamamoto R., Sato Y., Homma K., Uchida S., Namkoong H., Uwamino Y., Sasaki J., Fukunaga K., Hasegawa N.

Cost Effectiveness and Resource Allocation 21 （ 1 ） 2023年12月

Background: A health-economic evaluation related to COVID-19 is urgently needed to allocate healthcare resources efficiently; however, relevant medical cost data in Japan concerning COVID-19 are scarce. Methods: This cross-sectional study investigated the healthcare cost for hospitalized COVID-19 patients in 2021 at Keio University Hospital. We calculated the healthcare costs during hospitalization using hospital claims data and investigated the variables significantly related to the healthcare cost with multivariable analysis. Results: The median healthcare cost per patient for the analyzed 330 patients was Japanese yen (JPY) 1,304,431 (US dollars ~ 11,871) (interquartile range: JPY 968,349–1,954,093), and the median length of stay was 10 days. The median healthcare cost was JPY 798,810 for mild cases; JPY 1,113,680 for moderate I cases; JPY 1,643,909 for moderate II cases; and JPY 6,210,607 for severe cases. Healthcare costs increased by 4.0% for each additional day of hospitalization; 1.26 times for moderate I cases, 1.64 times for moderate II cases, and 1.84 times for severe cases compared to mild cases; and 2.05 times for cases involving ICU stay compared to those not staying in ICU. Conclusions: We clarified the healthcare cost for hospitalized COVID-19 patients by severity in a Japanese university hospital. These costs contribute as inputs for forthcoming health economic evaluations for strategies for preventing and treating COVID-19.

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中鉢 正太郎

論文 - 中鉢 正太郎

中鉢　正太郎

論文 - 中鉢　正太郎