Details of a Researcher - Asakura, Takanori

Papers - Asakura, Takanori

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Cough and sputum in long COVID are associated with severe acute COVID-19: a Japanese cohort study.

Mayuko Watase, Jun Miyata, Hideki Terai, Keeya Sunata, Emiko Matsuyama, Takanori Asakura, Ho Namkoong, Katsunori Masaki, Kazuma Yagi, Keiko Ohgino, Shotaro Chubachi, Ichiro Kawada, Takao Mochimaru, Ryosuke Satomi, Yoshitaka Oyamada, Keigo Kobayashi, Toshiyuki Hirano, Takashi Inoue, Ho Lee, Kai Sugihara, Nao Omori, Koichi Sayama, Shuko Mashimo, Yasushi Makino, Tatsuya Kaido, Makoto Ishii, Koichi Fukunaga

Respiratory research 24 ( 1 ) 283 - 283 2023.12

ISSN 14659921

BACKGROUND: Multiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by patients with long COVID during the acute and post-acute phases. This study aimed to identify specific risk factors for cough and sputum in patients with long COVID. METHODS: Hospitalized patients with COVID-19 aged 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: At the 3-, 6-, and 12-month follow-ups, there were no differences in the incidence rates of wet and dry coughs. In contrast, the proportion of patients presenting sputum without coughing increased over time compared to those with sputum and coughing. Univariate analyses of cough and sputum at all follow-up visits identified intermittent mandatory ventilation (IMV), smoking, and older age as risk factors for prolonged symptoms. At the 12-month follow-up, persistent cough and sputum were associated with the characteristics of severe COVID-19 based on imaging findings, renal and liver dysfunction, pulmonary thromboembolism, and higher serum levels of LDH, KL-6, and HbA1C. The Kaplan-Meier curves showed that the severity of acute COVID-19 infection was correlated with prolonged cough and sputum production. Multivariable logistic regression analysis showed that IMV ventilator management were independent risk factors for prolonged cough and sputum at 12 months. CONCLUSIONS: In a Japanese population with long COVID, prolonged cough and sputum production were closely associated with severe COVID-19. These findings emphasize that a preventive approach including appropriate vaccination and contact precaution and further development of therapeutic drugs for COVID-19 are highly recommended for patients with risk factors for severe infection to avoid persistent respiratory symptoms.

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Clinical utilization of artificial intelligence-based COVID-19 pneumonia quantification using chest computed tomography - a multicenter retrospective cohort study in Japan.

Hiromu Tanaka, Tomoki Maetani, Shotaro Chubachi, Naoya Tanabe, Yusuke Shiraishi, Takanori Asakura, Ho Namkoong, Takashi Shimada, Shuhei Azekawa, Shiro Otake, Kensuke Nakagawara, Takahiro Fukushima, Mayuko Watase, Hideki Terai, Mamoru Sasaki, Soichiro Ueda, Yukari Kato, Norihiro Harada, Shoji Suzuki, Shuichi Yoshida, Hiroki Tateno, Yoshitake Yamada, Masahiro Jinzaki, Toyohiro Hirai, Yukinori Okada, Ryuji Koike, Makoto Ishii, Naoki Hasegawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Respiratory research 24 ( 1 ) 241 - 241 2023.12

ISSN 14659921

BACKGROUND: Computed tomography (CT) imaging and artificial intelligence (AI)-based analyses have aided in the diagnosis and prediction of the severity of COVID-19. However, the potential of AI-based CT quantification of pneumonia in assessing patients with COVID-19 has not yet been fully explored. This study aimed to investigate the potential of AI-based CT quantification of COVID-19 pneumonia to predict the critical outcomes and clinical characteristics of patients with residual lung lesions. METHODS: This retrospective cohort study included 1,200 hospitalized patients with COVID-19 from four hospitals. The incidence of critical outcomes (requiring the support of high-flow oxygen or invasive mechanical ventilation or death) and complications during hospitalization (bacterial infection, renal failure, heart failure, thromboembolism, and liver dysfunction) was compared between the groups of pneumonia with high/low-percentage lung lesions, based on AI-based CT quantification. Additionally, 198 patients underwent CT scans 3 months after admission to analyze prognostic factors for residual lung lesions. RESULTS: The pneumonia group with a high percentage of lung lesions (N = 400) had a higher incidence of critical outcomes and complications during hospitalization than the low percentage group (N = 800). Multivariable analysis demonstrated that AI-based CT quantification of pneumonia was independently associated with critical outcomes (adjusted odds ratio [aOR] 10.5, 95% confidence interval [CI] 5.59-19.7), as well as with oxygen requirement (aOR 6.35, 95% CI 4.60-8.76), IMV requirement (aOR 7.73, 95% CI 2.52-23.7), and mortality rate (aOR 6.46, 95% CI 1.87-22.3). Among patients with follow-up CT scans (N = 198), the multivariable analysis revealed that the pneumonia group with a high percentage of lung lesions on admission (aOR 4.74, 95% CI 2.36-9.52), older age (aOR 2.53, 95% CI 1.16-5.51), female sex (aOR 2.41, 95% CI 1.13-5.11), and medical history of hypertension (aOR 2.22, 95% CI 1.09-4.50) independently predicted persistent residual lung lesions. CONCLUSIONS: AI-based CT quantification of pneumonia provides valuable information beyond qualitative evaluation by physicians, enabling the prediction of critical outcomes and residual lung lesions in patients with COVID-19.

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Clinical features of Japanese patients with gastrointestinal long-COVID symptoms.

Kazuma Yagi, Takanori Asakura, Hideki Terai, Keiko Ohgino, Katsunori Masaki, Ho Namkoong, Shotaro Chubachi, Jun Miyata, Ichiro Kawada, Nobuhiro Kodama, Satoshi Sakamoto, Akira Umeda, Takashi Ishiguro, Makoto Ishii, Koichi Fukunaga

JGH open : an open access journal of gastroenterology and hepatology 7 ( 12 ) 998 - 1002 2023.12

Gastrointestinal (GI) long-COVID symptoms, including diarrhea and abdominal pain, have been reported in patients with long-COVID. However, the clinical features of patients with GI long-COVID symptoms remain unclear. We conducted a large-scale prospective cohort study focusing on the clinical characteristics of patients with GI long-COVID symptoms in Japan. Among 943 COVID-19 patients, 58 patients (6.2%) had GI long-COVID symptoms. The health-related quality of life (QOL) parameters (the Short Form-8 [SF-8] and Euro Quality of Life 5 Dimensions 5 level [EQ-5D-5L]) at 12 months after diagnosis in patients with GI long-COVID symptoms were significantly lower than in those without GI long-COVID symptoms (P < 0.0001). Moreover, patients with GI long-COVID symptoms had more varied long-COVID symptoms compared to patients without GI long-COVID symptoms.

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

Tatsuya Kusumoto, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Ho Lee, Shiro Otake, Kensuke Nakagawara, Takahiro Fukushima, Atsuho Morita, Mayuko Watase, Takanori Asakura, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Ryuya Edahiro, Koji Murakami, Yasunori Sato, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Scientific reports 13 ( 1 ) 22054 - 22054 2023.12

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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Association between ABO blood group/genotype and COVID-19 in a Japanese population.

Tatsuya Kusumoto, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Ho Lee, Shuhei Azekawa, Shiro Otake, Kensuke Nakagawara, Takahiro Fukushima, Atsuho Morita, Mayuko Watase, Kaori Sakurai, Takanori Asakura, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Ryuya Edahiro, Hirohito Sano, Yasunori Sato, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Annals of hematology 102 ( 11 ) 3239 - 3249 2023.11

ISSN 09395555

An association between coronavirus disease 2019 (COVID-19) and the ABO blood group has been reported. However, such an association has not been studied in the Japanese population on a large scale. Little is known about the association between COVID-19 and ABO genotype. This study investigated the association between COVID-19 and ABO blood group/genotype in a large Japanese population. All Japanese patients diagnosed with COVID-19 were recruited through the Japan COVID-19 Task Force between February 2020 and October 2021. We conducted a retrospective cohort study involving 1790 Japanese COVID-19 patients whose DNA was used for a genome-wide association study. We compared the ABO blood group/genotype in a healthy population (n = 611, control) and COVID-19 patients and then analyzed their associations and clinical outcomes. Blood group A was significantly more prevalent (41.6% vs. 36.8%; P = 0.038), and group O was significantly less prevalent (26.2% vs. 30.8%; P = 0.028) in the COVID-19 group than in the control group. Moreover, genotype OO was significantly less common in the COVID-19 group. Furthermore, blood group AB was identified as an independent risk factor for most severe diseases compared with blood group O [aOR (95% CI) = 1.84 (1.00-3.37)]. In ABO genotype analysis, only genotype AB was an independent risk factor for most severe diseases compared with genotype OO. Blood group O is protective, whereas group A is associated with the risk of infection. Moreover, blood group AB is associated with the risk of the "most" severe disease.

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Comprehensive analysis of long COVID in a Japanese nationwide prospective cohort study.

Hideki Terai, Makoto Ishii, Ryo Takemura, Ho Namkoong, Kyoko Shimamoto, Katsunori Masaki, Takae Tanosaki, Shotaro Chubachi, Emiko Matsuyama, Reina Hayashi, Takashi Shimada, Lisa Shigematsu, Fumimaro Ito, Masanori Kaji, Hatsuyo Takaoka, Momoko Kurihara, Kensuke Nakagawara, Saki Tomiyasu, Kotaro Sasahara, Ayaka Saito, Shiro Otake, Shuhei Azekawa, Masahiko Okada, Takahiro Fukushima, Atsuho Morita, Hiromu Tanaka, Keeya Sunata, Masato Asaoka, Miyuki Nishie, Taro Shinozaki, Toshiki Ebisudani, Yuto Akiyama, Akifumi Mitsuishi, Shingo Nakayama, Takunori Ogawa, Kaori Sakurai, Misato Irie, Kazuma Yagi, Keiko Ohgino, Jun Miyata, Hiroki Kabata, Shinnosuke Ikemura, Hirofumi Kamata, Hiroyuki Yasuda, Ichiro Kawada, Ryusei Kimura, Masahiro Kondo, Toshiki Iwasaki, Noriyuki Ishida, Gaku Hiruma, Naoki Miyazaki, Yoshiki Ishibashi, Sei Harada, Takanori Fujita, Daisuke Ito, Shogyoku Bun, Hajime Tabuchi, Sho Kanzaki, Eisuke Shimizu, Keitaro Fukuda, Jun Yamagami, Keigo Kobayashi, Toshiyuki Hirano, Takashi Inoue, Mizuha Haraguchi, Junko Kagyo, Tetsuya Shiomi, Ho Lee, Kai Sugihara, Nao Omori, Koichi Sayama, Kengo Otsuka, Naoki Miyao, Toshio Odani, Mayuko Watase, Takao Mochimaru, Ryosuke Satomi, Yoshitaka Oyamada, Keita Masuzawa, Takanori Asakura, Sohei Nakayama, Yusuke Suzuki, Rie Baba, Satoshi Okamori, Daisuke Arai, Ichiro Nakachi, Naota Kuwahara, Akiko Fujiwara, Takenori Oakada, Takashi Ishiguro, Taisuke Isosno, Yasushi Makino, Shuko Mashimo, Tatsuya Kaido, Naoto Minematsu, Soichiro Ueda, Kazuhiro Minami, Rie Hagiwara, Tadashi Manabe, Takahiro Fukui, Yohei Funatsu, Hidefumi Koh, Takashi Yoshiyama, Hiroyuki Kokuto, Tatsuya Kusumoto, Ayano Oashi, Masayoshi Miyawaki, Fumitake Saito, Tetsuo Tani, Kota Ishioka, Saeko Takahashi, Morio Nakamura, Norihiro Harada, Hitoshi Sasano, Ai Goto, Yu Kusaka, Takehiko Ohba, Yasushi Nakano, Kazumi Nishio, Yukiko Nakajima, Shoji Suzuki, Shuichi Yoshida, Hiroki Tateno, Nobuhiro Kodama, Maeda Shunsuke, Satoshi Sakamoto, Masaki Okamoto, Yoji Nagasaki, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Kazuto Hagimura, Kengo Nagashima, Toshiro Sato, Yasunori Sato, Naoki Hasegawa, Toru Takebayashi, Jin Nakahara, Masaru Mimura, Kaoru Ogawa, Shigeto Shimmura, Kazuno Negishi, Kazuo Tsubota, Masayuki Amagai, Rei Goto, Yoko Ibuka, Yuko Kitagawa, Takanori Kanai, Koichi Fukunaga

Respiratory investigation 61 ( 6 ) 802 - 814 2023.11

ISSN 22125345

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly since 2019, and the number of reports regarding long COVID has increased. Although the distribution of long COVID depends on patient characteristics, epidemiological data on Japanese patients are limited. Hence, this study aimed to investigate the distribution of long COVID in Japanese patients. This study is the first nationwide Japanese prospective cohort study on long COVID. METHODS: This multicenter, prospective cohort study enrolled hospitalized COVID-19 patients aged ≥18 years at 26 Japanese medical institutions. In total, 1200 patients were enrolled. Clinical information and patient-reported outcomes were collected from medical records, paper questionnaires, and smartphone applications. RESULTS: We collected data from 1066 cases with both medical records and patient-reported outcomes. The proportion of patients with at least one symptom decreased chronologically from 93.9% (947/1009) during hospitalization to 46.3% (433/935), 40.5% (350/865), and 33.0% (239/724) at 3, 6, and 12 months, respectively. Patients with at least one long COVID symptom showed lower quality of life and scored higher on assessments for depression, anxiety, and fear of COVID-19. Female sex, middle age (41-64 years), oxygen requirement, and critical condition during hospitalization were risk factors for long COVID. CONCLUSIONS: This study elucidated the symptom distribution and risks of long COVID in the Japanese population. This study provides reference data for future studies of long COVID in Japan.

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Propensity-Score Matched Analysis of the Effectiveness of Baricitinib in Patients With Coronavirus Disease 2019 (COVID-19) Using Nationwide Real-World Data: An Observational Matched Cohort Study From the Japan COVID-19 Task Force.

Hiromu Tanaka, Shotaro Chubachi, Ho Namkoong, Yasunori Sato, Takanori Asakura, Ho Lee, Shuhei Azekawa, Shiro Otake, Kensuke Nakagawara, Takahiro Fukushima, Mayuko Watase, Kaori Sakurai, Tatsuya Kusumoto, Yasushi Kondo, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Yuko Kaneko, Naoki Hasegawa, Soichiro Ueda, Mamoru Sasaki, Takehiro Izumo, Minoru Inomata, Naoki Miyazawa, Yasuhiro Kimura, Yusuke Suzuki, Norihiro Harada, Masako Ichikawa, Tohru Takata, Hiroyasu Ishikura, Takashi Yoshiyama, Hiroyuki Kokuto, Koji Murakami, Hirohito Sano, Tetsuya Ueda, Naota Kuwahara, Akiko Fujiwara, Takashi Ogura, Takashi Inoue, Takahiro Asami, Yoshikazu Mutoh, Ichiro Nakachi, Rie Baba, Koichi Nishi, Mayuko Tani, Junko Kagyo, Mizuha Hashiguchi, Tsuyoshi Oguma, Koichiro Asano, Masanori Nishikawa, Hiroki Watanabe, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Open forum infectious diseases 10 ( 7 ) ofad311 2023.07

BACKGROUND: To determine the effectiveness of baricitinib in patients with coronavirus disease 2019 (COVID-19), investigate whether baricitinib prevents the need for invasive mechanical ventilation and identify patient subgroups that would benefit from baricitinib. METHODS: This observational matched-cohort study was conducted by the Japan COVID-19 Task Force, a nationwide multicenter consortium. Patients with COVID-19 aged ≥18 years were identified from 70 hospitals in Japan. Among patients with confirmed COVID-19 from February 2020 to September 2021, those receiving baricitinib were propensity-score matched with controls. RESULTS: Among 3309 patients, 144 propensity score-matched pairs were identified. Thirteen (9.0%) patients in the baricitinib group and 27 (18.8%) in the control group required invasive mechanical ventilation during the disease course (odds ratio, 0.43). Although the baricitinib group had more severe disease, there were no significant differences in the intensive care unit admission rates (odds ratio, 1.16) and mortality rates (odds ratio, 0.74) between groups. In subgroup analyses, baricitinib was associated with a significant reduction in the need for invasive mechanical ventilation in patients requiring oxygen support (odds ratio, 0.28), with rapid shadow spread on chest radiography (odds ratio, 0.11), or treated with remdesivir (odds ratio, 0.27), systemic corticosteroids (odds ratio, 0.31), or anticoagulants (odds ratio, 0.17). CONCLUSIONS: Baricitinib is effective at preventing the need for invasive mechanical ventilation in patients with COVID-19.

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Characteristics and Clinical Effectiveness of COVID-19 Vaccination in Hospitalized Patients in Omicron-dominated Epidemic Wave - A Nationwide Study in Japan.

Hiromu Tanaka, Shotaro Chubachi, Takanori Asakura, Ho Namkoong, Shuhei Azekawa, Shiro Otake, Kensuke Nakagawara, Takahiro Fukushima, Ho Lee, Mayuko Watase, Kaori Sakurai, Tatsuya Kusumoto, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 132 84 - 88 2023.07

ISSN 12019712

OBJECTIVES: Coronavirus disease (COVID-19) was severe in the Delta variant-dominated epidemic wave (fifth wave) in Japan. The clinical characteristics and effectiveness of COVID-19 vaccination are not fully understood in the Omicron variant-dominated wave (sixth and seventh waves), especially in hospitalized patients. We investigated the relationship between vaccination and disease severity in the Omicron-dominated wave and compared these variant-dominated waves. METHODS: The nationwide COVID-19 database (Japan COVID-19 Task Force) was used to compare clinical characteristics and critical outcome in patients hospitalized from Delta (5th, N=735) vs Omicron-dominated waves (6th, N=495; 7th, N=128). RESULTS: Patients in the sixth and seventh waves had a lower incidence of critical outcomes and respiratory outcomes, and a higher incidence of bacterial infection, although the mortality rate did not differ significantly between waves. In the sixth and seventh waves, 138 (27.9%) and 29 (22.7%) COVID-19 patients were unvaccinated, respectively. Multivariable analysis adjusted with previously reported factors revealed that the proportion of 1) critical outcomes and 2) respiratory outcomes decreased in a frequency-dependent manner; 1) (the number of vaccinations): 1-2 times, aOR 0.37 (95% CI; 0.20-0.69); 3-4 times: aOR 0.25 (95% CI; 0.11-0.58), 2) 1-2 times, aOR 0.43 (95% CI; 0.27-0.66); 3-4 times: aOR 0.36 (95% CI; 0.21-0.60). CONCLUSIONS: COVID-19 hospitalized patients with Omicron infections showed a lower incidence of critical outcomes than those with Delta infections, and COVID-19 vaccination may contribute to preventing respiratory failure.

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Use of the neutrophil-to-lymphocyte ratio and an oxygen requirement to predict disease severity in patients with COVID-19.

Takuya Ozawa, Takanori Asakura, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Ko Lee, Takahiro Fukushima, Shiro Otake, Kensuke Nakagawara, Mayuko Watase, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Ryuya Edahiro, Koji Murakami, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Respiratory investigation 61 ( 4 ) 454 - 459 2023.07

ISSN 22125345

We investigated the association between complete blood count, including neutrophil-to-lymphocyte ratio (NLR) in combination with patient characteristics, and coronavirus disease (COVID-19) outcomes to identify the best prognostic indicator. We analyzed data of patients with confirmed COVID-19 from the nationwide database of the Japan COVID-19 Task Force between February 2020 and November 2021. A composite outcome was defined as the most severe condition, including noninvasive positive-pressure ventilation, high-flow nasal cannula, invasive mechanical ventilation, extracorporeal membrane oxygenation, or death. Of 2425 patients in the analysis, 472 (19.5%) experienced a composite outcome. NLR was the best predictor of composite outcomes, with an area under the curve (AUC) of 0.81, and a sensitivity and specificity of 72.3% and 75.7%, respectively, using a cut-off value of 5.04. The combination of NLR and an oxygen requirement on admission had the highest AUC (0.88). This simple combination may help identify patients at risk of progression to severe disease.

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Serum KL-6 levels predict clinical outcomes and are associated with MUC1 polymorphism in Japanese patients with COVID-19.

Shuhei Azekawa, Shotaro Chubachi, Takanori Asakura, Ho Namkoong, Yasunori Sato, Ryuya Edahiro, Ho Lee, Hiromu Tanaka, Shiro Otake, Kensuke Nakagawara, Takahiro Fukushima, Mayuko Watase, Kaori Sakurai, Tatsuya Kusumoto, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

BMJ open respiratory research 10 ( 1 ) 2023.05

BACKGROUND: Krebs von den Lungen-6 (KL-6) is a known biomarker for diagnosis and monitoring of interstitial lung diseases. However, the role of serum KL-6 and the mucin 1 (MUC1) variant (rs4072037) in COVID-19 outcomes remains to be elucidated. We aimed to evaluate the relationships among serum KL-6 levels, critical outcomes and the MUC1 variant in Japanese patients with COVID-19. METHODS: This is a secondary analysis of a multicentre retrospective study using data from the Japan COVID-19 Task Force collected from February 2020 to November 2021, including 2226 patients with COVID-19 whose serum KL-6 levels were measured. An optimal serum KL-6 level cut-off to predict critical outcomes was determined and used for multivariable logistic regression analysis. Furthermore, the relationship among the allele dosage of the MUC1 variant, calculated from single nucleotide polymorphism typing data of genome-wide association studies using the imputation method, serum KL-6 levels and COVID-19 critical outcomes was evaluated. RESULTS: Serum KL-6 levels were significantly higher in patients with COVID-19 with critical outcomes (511±442 U/mL) than those without (279±204 U/mL) (p<0.001). Serum KL-6 levels ≥304 U/mL independently predicted critical outcomes (adjusted OR (aOR) 3.47, 95% CI 2.44 to 4.95). Moreover, multivariable logistic regression analysis with age and sex indicated that the MUC1 variant was independently associated with increased serum KL-6 levels (aOR 0.24, 95% CI 0.28 to 0.32) but not significantly associated with critical outcomes (aOR 1.11, 95% CI 0.80 to 1.54). CONCLUSION: Serum KL-6 levels predicted critical outcomes in Japanese patients with COVID-19 and were associated with the MUC1 variant. Therefore, serum KL-6 level is a potentially useful biomarker of critical COVID-19 outcomes.

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Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity

Edahiro R., Shirai Y., Takeshima Y., Sakakibara S., Yamaguchi Y., Murakami T., Morita T., Kato Y., Liu Y.C., Motooka D., Naito Y., Takuwa A., Sugihara F., Tanaka K., Wing J.B., Sonehara K., Tomofuji Y., Wang Q.S., Hasegawa T., Saiki R., Hyugaji T., Shimizu E., Katayama K., Kanai M., Naito T., Sasa N., Yamamoto K., Takahashi K., Harada N., Naito T., Hiki M., Matsushita Y., Takagi H., Ichikawa M., Nakamura A., Harada S., Sandhu Y., Kabata H., Masaki K., Kamata H., Ikemura S., Chubachi S., Okamori S., Terai H., Morita A., Asakura T., Sasaki J., Morisaki H., Uwamino Y., Nanki K., Uchida S., Uno S., Nishimura T., Ishiguro T., Isono T., Shibata S., Matsui Y., Hosoda C., Takano K., Nishida T., Kobayashi Y., Takaku Y., Takayanagi N., Ueda S., Tada A., Miyawaki M., Yamamoto M., Yoshida E., Hayashi R., Nagasaka T., Arai S., Kaneko Y., Sasaki K., Tagaya E., Kawana M., Arimura K., Takahashi K., Anzai T., Ito S., Endo A., Uchimura Y., Miyazaki Y., Honda T., Tateishi T., Tohda S., Ichimura N., Sonobe K., Sassa C.T., Nakajima J., Nakano Y., Nakajima Y., Anan R., Arai R., Kurihara Y., Harada Y., Nishio K., Ueda T., Azuma M., Saito R., Sado T.

Nature Genetics 55 ( 5 ) 753 - 767 2023.05

ISSN 10614036

Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.

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Diagnostic significance of secondary bacteremia in patients with COVID-19.

Kensuke Nakagawara, Hirofumi Kamata, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Ho Lee, Shiro Otake, Takahiro Fukushima, Tatsuya Kusumoto, Atsuho Morita, Shuhei Azekawa, Mayuko Watase, Takanori Asakura, Katsunori Masaki, Makoto Ishii, Akifumi Endo, Ryuji Koike, Hiroyasu Ishikura, Tohru Takata, Yasushi Matsushita, Norihiro Harada, Hiroyuki Kokutou, Takashi Yoshiyama, Kensuke Kataoka, Yoshikazu Mutoh, Masayoshi Miyawaki, Soichiro Ueda, Hiroshi Ono, Takuya Ono, Tomohisa Shoko, Hiroyuki Muranaka, Kodai Kawamura, Nobuaki Mori, Takao Mochimaru, Mototaka Fukui, Yusuke Chihara, Yoji Nagasaki, Masaki Okamoto, Masaru Amishima, Toshio Odani, Mayuko Tani, Koichi Nishi, Yuya Shirai, Ryuya Edahiro, Akira Ando, Naozumi Hashimoto, Shinji Ogura, Yuichiro Kitagawa, Toshiyuki Kita, Takashi Kagaya, Yasuhiro Kimura, Naoki Miyazawa, Tomoya Tsuchida, Shigeki Fujitani, Koji Murakami, Hirohito Sano, Yuki Sato, Yoshinori Tanino, Ryo Otsuki, Shuko Mashimo, Mizuki Kuramochi, Yasuo Hosoda, Yoshinori Hasegawa, Tetsuya Ueda, Yotaro Takaku, Takashi Ishiguro, Akiko Fujiwara, Naota Kuwahara, Hideya Kitamura, Eri Hagiwara, Yasushi Nakamori, Fukuki Saito, Yuta Kono, Shinji Abe, Tomoo Ishii, Takehiko Ohba, Yu Kusaka, Hiroko Watanabe, Makoto Masuda, Hiroki Watanabe, Yoshifumi Kimizuka, Akihiko Kawana, Yu Kasamatsu, Satoru Hashimoto, Yukinori Okada, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Atsushi Kumanogoh, Toshiro Sato, Katsushi Tokunaga, Seiya Imoto, Yuko Kitagawa, Akinori Kimura, Satoru Miyano, Naoki Hasegawa, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 29 ( 4 ) 422 - 426 2023.04

ISSN 1341321X

OBJECTIVES: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. RESULTS: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. CONCLUSIONS: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.

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Impact of accumulative smoking exposure and chronic obstructive pulmonary disease on COVID-19 outcomes: Report based on findings from the Japan COVID-19 Task Force.

Mayuko Watase, Katsunori Masaki, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Ho Lee, Takahiro Fukushima, Shiro Otake, Kensuke Nakagawara, Tatsuya Kusumoto, Takanori Asakura, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Yoshitaka Oyamada, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Ryuya Edahiro, Hirohito Sano, Yasunori Sato, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 128 121 - 127 2023.03

ISSN 12019712

OBJECTIVES: Smoking and chronic obstructive pulmonary disease (COPD) are risk factors of severe coronavirus disease 2019 (COVID-19). However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. METHODS: The study included 1266 smokers enrolled by the Japan COVID-19 Task Force between February 2020 and December 2021. PY and COPD status were self-reported by patients. Patients were classified into the non-COPD (n=1151) and COPD (n=115) groups; the non-COPD group was further classified into <10 PY (n=293), 10-30 PY (n=497), and >30 PY (n=361). The study outcome was the need for invasive mechanical ventilation (IMV). RESULTS: The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY=7.8%, 10-30 PY=12.3%, >30 PY=15.2%, COPD=26.1%; p<0.001). Significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY=2.11, COPD=4.14) and multivariate (OR: >30 PY=2.38; COPD=7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 y. CONCLUSIONS: Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.

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An epithelial-immune circuit amplifies inflammasome and IL-6 responses to SARS-CoV-2.

Katherine C Barnett*, Yuying Xie*, Takanori Asakura*, Dingka Song, Kaixin Liang, Sharon A Taft-Benz, Haitao Guo, Shuangshuang Yang, Kenichi Okuda, Rodney C Gilmore, Jennifer F Loome, Thomas H Oguin Iii, Gregory D Sempowski, Scott H Randell, Mark T Heise, Yu Leo Lei, Richard C Boucher, Jenny P-Y Ting

Cell host & microbe 31 ( 2 ) 243 - 259.e6 2023.02

ISSN 19313128

Elevated levels of cytokines IL-1β and IL-6 are associated with severe COVID-19. Investigating the underlying mechanisms, we find that while primary human airway epithelia (HAE) have functional inflammasomes and support SARS-CoV-2 replication, they are not the source of IL-1β released upon infection. In leukocytes, the SARS-CoV-2 E protein upregulates inflammasome gene transcription via TLR2 to prime, but not activate, inflammasomes. SARS-CoV-2-infected HAE supply a second signal, which includes genomic and mitochondrial DNA, to stimulate leukocyte IL-1β release. Nuclease treatment, STING, and caspase-1 inhibition but not NLRP3 inhibition blocked leukocyte IL-1β release. After release, IL-1β stimulates IL-6 secretion from HAE. Therefore, infection alone does not increase IL-1β secretion by either cell type. Rather, bi-directional interactions between the SARS-CoV-2-infected epithelium and immune bystanders stimulates both IL-1β and IL-6, creating a pro-inflammatory cytokine circuit. Consistent with these observations, patient autopsy lungs show elevated myeloid inflammasome gene signatures in severe COVID-19.

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Clinical significance of prediabetes, undiagnosed diabetes and diagnosed diabetes on critical outcomes in COVID-19: Integrative analysis from the Japan COVID-19 task force.

Takahiro Fukushima, Shotaro Chubachi, Ho Namkoong, Takanori Asakura, Hiromu Tanaka, Ho Lee, Shuhei Azekawa, Yukinori Okada, Ryuji Koike, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Diabetes, obesity & metabolism 25 ( 1 ) 144 - 155 2023.01

ISSN 14628902

AIM: Diabetes mellitus (DM) is a known risk factor for severe coronavirus disease 2019 (COVID-19), but the clinical impact of undiagnosed diabetes and prediabetes in COVID-19 are unclear particularly in Japan. We clarify the difference in clinical characteristics, including age, sex, body mass index and co-morbidities, laboratory findings and critical outcomes, in a large Japanese COVID-19 cohort without diabetes, with prediabetes, undiagnosed diabetes and diagnosed diabetes, and to identify associated risk factors. MATERIALS AND METHODS: This multicentre, retrospective cohort study used the Japan COVID-19 Task Force database, which included data on 2430 hospitalized COVID-19 patients from over 70 hospitals from February 2020 to October 2021. The prevalence of prediabetes, undiagnosed diabetes and diagnosed diabetes were estimated based on HbA1c levels or a clinical diabetes history. Critical outcomes were defined as the use of high-flow oxygen, invasive positive-pressure ventilation or extracorporeal membrane oxygenation, or death during hospitalization. RESULTS: Prediabetes, undiagnosed diabetes and diagnosed diabetes were observed in 40.9%, 10.0% and 23.0%, respectively. Similar to diagnosed diabetes, prediabetes and undiagnosed diabetes were risk factors for critical COVID-19 outcomes (adjusted odds ratio [aOR] [95% CI]: 2.13 [1.31-3.48] and 4.00 [2.19-7.28], respectively). HbA1c was associated with COVID-19 severity in prediabetes patients (aOR [95% CI]: 11.2 [3.49-36.3]), but not other groups. CONCLUSIONS: We documented the clinical characteristics and outcomes of Japanese COVID-19 patients according to HbA1c levels or diabetes co-morbidity. As well as undiagnosed and diagnosed diabetes, physicians should be aware of prediabetes related to COVID-19 severity.

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Nasopharyngeal Mycobacterium abscessus Infection: A Case Report and Literature Review.

Masanori Kaji, Ho Namkoong, Genta Nagao, Shuhei Azekawa, Kensuke Nakagawara, Hiromu Tanaka, Atsuho Morita, Takanori Asakura, Hirofumi Kamata, Yoshifumi Uwamino, Mitsunori Yoshida, Koichi Fukunaga, Naoki Hasegawa

Infection and drug resistance 16 3955 - 3963 2023

BACKGROUND: Mycobacterium abscessus (M. abscessus) is a rapidly growing bacterium (RGM) that causes refractory pulmonary and extrapulmonary infections. However, studies investigating pharyngeal and laryngeal M. abscessus infections are limited. CASE PRESENTATION: A 41-year-old immunocompetent woman complaining of bloody sputum was referred to our hospital. Although her sputum culture tested positive for M. abscessus subsp. abscessus, radiological findings were not indicative of pulmonary infection or sinusitis. Further diagnostic workup, including laryngeal endoscopy and positron emission tomography/computed tomography (PET/CT), confirmed the presence of nasopharyngeal M. abscessus infection. The patient was initially treated with intravenous amikacin, imipenem/cilastatin, azithromycin, and clofazimine for 28 days, after which the patient was provided with amikacin, azithromycin, clofazimine, and sitafloxacin for four months. After the completion of antibiotic therapy, the patient showed negative results on sputum smear and culture and normal findings on PET/CT and laryngeal endoscopy. Whole-genome sequencing of this strain revealed that it belonged to the ABS-GL4 cluster, which has a functional erythromycin ribosomal methylase gene, although it is not a major lineage in non-cystic fibrosis (CF) patients in Japan and Taiwan and in CF patients in European countries. We conducted a literature review and identified seven patients who developed pharyngeal/laryngeal non-tuberculous mycobacterium (NTM) infection. Four of the eight patients had a history of immunosuppressant use, including steroids. Seven of the eight patients responded well to their treatment regimens. CONCLUSION: Patients whose sputum culture tests are positive for NTM and who meet the diagnostic criteria for NTM infection but do not have intrapulmonary lesions should be evaluated for otorhinolaryngological infections. Our case series revealed that immunosuppressant use is a risk factor for pharyngeal/laryngeal NTM infection and that patients with pharyngeal/laryngeal NTM infections respond relatively well to antibiotic therapy.

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Epidemiological characteristics of nontuberculous mycobacteriosis and bronchiectasis: comparative study using national mortality statistics from 1970 to 2015 in Japan.

Kozo Morimoto, Kazuro Iwai, Takashi Yoshiyama, Masashi Ito, Fumiko Uesugi, Takanori Asakura, Takeshi Osawa, Koji Furuuchi, Atsuyuki Kurashima, Keiji Fujiwara, Naoki Hasegawa, Yoshiaki Tanaka, Kudoh Shoji, Yuji Shiraishi, Satoshi Mitarai, Manabu Ato, Ken Ohta

ERJ open research 9 ( 1 ) 2023

BACKGROUND: This study assessed longitudinal national data on mortality due to nontuberculous mycobacteriosis (NTMosis) and bronchiectasis and the association between the two diseases. METHODS: We analysed the national death statistics of Japan from 1970 to 2015. The International Classification of Disease (ICD) codes were used to extract the relevant data. Crude mortality, age-adjusted mortality and standardised mortality rates were calculated using vital statistics and the population in 2000. We also identified domestic publications related to NTMosis and bronchiectasis with an internet-based search system. RESULTS: The total number of bronchiectasis-related deaths remained at the same level, which was approximately 1000, for 45 years, although the number of deaths has consistently decreased in males but increased in females since the mid-1990s. A substantial increasing trend in females was also observed for NTMosis in the same period. The age-adjusted mortality data showed an increase in mortality in women due to NTMosis and confirmed the trend in bronchiectasis in women. The patterns in the number of domestic reports showed a recent slight increase in bronchiectasis and a marked increase in NTMosis. CONCLUSIONS: The trends in bronchiectasis-related mortality differed by sex. The epidemiological trends in the two diseases were associated, especially in elderly females since the mid-1990s. It is suggested that pulmonary NTMosis without pre-existing bronchiectasis might be a leading cause of postinfectious bronchiectasis in Japan.

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Chronic airway epithelial hypoxia exacerbates injury in muco-obstructive lung disease through mucus hyperconcentration

Yu Mikami, Barbara R. Grubb, Troy D. Rogers, Hong Dang, Takanori Asakura, Pradeep Kota, Rodney C. Gilmore, Kenichi Okuda, Lisa C. Morton, Ling Sun, Gang Chen, Jason A. Wykoff, Camille Ehre, Juan Vilar, Catharina van Heusden, Alessandra Livraghi-Butrico, Martina Gentzsch, Brian Button, M. Jackson Stutts, Scott H. Randell, Wanda K. O’Neal, Richard C. Boucher

Science Translational Medicine (American Association for the Advancement of Science (AAAS)) 15 ( 699 ) eabo7728 2023

Accepted, ISSN 19466234

Unlike solid organs, human airway epithelia derive their oxygen from inspired air rather than the vasculature. Many pulmonary diseases are associated with intraluminal airway obstruction caused by aspirated foreign bodies, virus infection, tumors, or mucus plugs intrinsic to airway disease, including cystic fibrosis (CF). Consistent with requirements for luminal O 2 , airway epithelia surrounding mucus plugs in chronic obstructive pulmonary disease (COPD) lungs are hypoxic. Despite these observations, the effects of chronic hypoxia (CH) on airway epithelial host defense functions relevant to pulmonary disease have not been investigated. Molecular characterization of resected human lungs from individuals with a spectrum of muco-obstructive lung diseases (MOLDs) or COVID-19 identified molecular features of chronic hypoxia, including increased EGLN3 expression, in epithelia lining mucus-obstructed airways. In vitro experiments using cultured chronically hypoxic airway epithelia revealed conversion to a glycolytic metabolic state with maintenance of cellular architecture. Chronically hypoxic airway epithelia unexpectedly exhibited increased MUC5B mucin production and increased transepithelial Na + and fluid absorption mediated by HIF1α/HIF2α-dependent up-regulation of β and γENaC (epithelial Na + channel) subunit expression. The combination of increased Na + absorption and MUC5B production generated hyperconcentrated mucus predicted to perpetuate obstruction. Single-cell and bulk RNA sequencing analyses of chronically hypoxic cultured airway epithelia revealed transcriptional changes involved in airway wall remodeling, destruction, and angiogenesis. These results were confirmed by RNA–in situ hybridization studies of lungs from individuals with MOLD. Our data suggest that chronic airway epithelial hypoxia may be central to the pathogenesis of persistent mucus accumulation in MOLDs and associated airway wall damage.

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ALK-positive lung adenocarcinoma in a patient with rheumatoid arthritis with long-term treatment for organizing pneumonia: A case report.

Kazuhito Horie, Takanori Asakura, Keita Masuzawa, Hideki Terai, Sohei Nakayama, Yusuke Suzuki

Medicine 101 ( 49 ) e32159 2022.12

ISSN 00257974

RATIONALE: Rheumatoid arthritis (RA) causes inflammation in various organs including the lungs. Pulmonary manifestations include inflammation of the pleura, vasculature, airway, and parenchyma, including interstitial lung disease (ILD). RA-organizing pneumonia (OP) is the third most common cause of RA-ILD. Cases of OP coexisting/complicated with lung cancer have been reported. Therefore, lung cancer can represent a diagnostic challenge, especially in patients with underlying pulmonary diseases including OP. PATIENT CONCERNS: An 81-year-old woman with a 12-year history of RA-OP underwent multiple transbronchial lung biopsies (TBLBs), all of which resulted in no malignant findings. She was treated with prednisolone (PSL) depending on the deteriorated infiltrations. At admission, chest computed tomography (CT) images showed exacerbation of left S8 consolidation on chest CT. Additionally, her RA activity was exacerbated, and PSL dose was increased to 30 mg/day, which resulted in improved dyspnea and consolidation. Accordingly, PSL dose was gradually decreased. However, 6 months later, when PSL dose was 11 mg/d, due to a worsening of consolidation and the joint symptoms of RA, PSL dose was increased to 20 mg/d and tacrolimus 2 mg/d was administered. 3 months after the increase in PSL dose, dyspnea improved and PSL dose was reduced to 15 mg/d; however, she was admitted to our hospital because of low back pain. DIAGNOSIS: Spinal magnetic resonance imaging showed bone metastases in the third and fifth lumbar vertebrae, and lung cancer was suspected as the primary tumor on CT. INTERVENTIONS: TBLB was performed on the left B8 infiltrate, which showed no evidence of malignancy in the previous TBLB. OUTCOMES: Pathological examination of TBLB on the left B8 revealed an adenocarcinoma that was positive for anaplastic lymphoma kinase. LESSONS: Physicians should be aware of the development of lung cancer in regions with OP, even after a partial response to corticosteroid therapy.

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Most Important Things and Associated Factors With Prioritizing Daily Life in Patients With Advanced Lung Cancer.

Naofumi Kameyama, Takashi Sato, Daisuke Arai, Daisuke Fujisawa, Mari Takeuchi, Ichiro Nakachi, Ichiro Kawada, Hiroyuki Yasuda, Shinnosuke Ikemura, Hideki Terai, Shigenari Nukaga, Yasushi Nakano, Toshiyuki Hirano, Naoto Minematsu, Takanori Asakura, Takashi Kamatani, Kyuto Tanaka, Shoji Suzuki, Masayoshi Miyawaki, Katsuhiko Naoki, Koichi Fukunaga, Kenzo Soejima

JCO oncology practice 18 ( 12 ) E1977 - E1986 2022.12

ISSN 26881527

PURPOSE: Patients' values and priorities in their lives should be appreciated from an early phase of incurable diseases such as advanced cancer. However, studies examining these characteristics have been lacking. This study attempted to determine what patients with advanced lung cancer valued most, once they had been diagnosed, and any associated factors. METHODS: Patients with newly diagnosed advanced lung cancer (N = 248) were enrolled in a questionnaire survey conducted at 16 hospitals in Japan. Their priorities were assessed using a free-text response to the question what is the most important thing to you now? at the time of diagnosis and 3 months after diagnosis. The free-text responses were classified into 10 categories for quantification. The clinical characteristics associated with the category describing daily life were further examined. RESULTS: Free-text comments were obtained from 103 (44.0%) and 66 (42.6%) patients at the time of diagnosis and at 3 months, respectively. The most frequent categories were family (at diagnosis: 50.5%; at 3 months: 50.0%) and daily life (at diagnosis: 33.0%; at 3 months: 36.4%), followed by health (at diagnosis: 32.0%; at 3 months: 27.3%) at both time points. The patients mentioning daily life, the issues related to how to spend daily life, showed significantly higher total scores and functional well-being subscale scores on the Functional Assessment of Cancer Therapy-Lung scale at both time points and lower depression scores at diagnosis and lower anxiety scores at 3 months on the Hospital Anxiety and Depression Scale. CONCLUSION: Family and daily life were highly valued by patients with advanced lung cancer at diagnosis. A better quality of life and better mood were associated with mentioning daily life, which should be taken into account in care planning to maintain patients' involvement in daily life even with incurable diseases.

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