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Autoantibodies are detected in idiopathic interstitial pneumonias (IIPs) without a clear connective tissue disease diagnosis, and their clinical significance is unclear. This study aimed to identify a novel autoantibody in IIPs. We screened 295 IIP patients using a 35S-methionine labeled protein immunoprecipitation assay. Candidate autoantigens were identified via protein array and confirmed by immunoprecipitation. Six sera from 295 IIP patients immunoprecipitated common tetrameric proteins (100 kDa). The protein array identified interferon gamma-inducible protein 16 (IFI16) as the candidate autoantigen. Patients with anti-IFI16 antibodies received immunosuppressants less frequently. Five-year survival rates were 50 %, 69 %, and 63 % (P = 0.60), and acute exacerbation-free rates were 50 %, 96 %, and 84 % (P = 0.15) for patients with anti-IFI16, anti-aminoacyl tRNA antibodies, and others. Anti-IFI16 is a novel autoantibody in IIPs. Patients with this antibody often receive less immunosuppressive therapy and could have a poor prognosis. Further research is needed to refine patient stratification and management. • The discovery of anti-IFI16 antibody in patients with IIPs. • Anti-IFI16 antibody in IIPs linked to poor prognosis. • Inflammatory mechanism is suggested in lung pathology of anti-IFI16-positive IIP. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). AE-IPF patients require optimal palliative care; however, the real-world clinical situations are poorly understood. We aimed to survey the palliative care received by AE-IPF patients, especially with respect to opioid use for dyspnea and the end-of-life discussions (EOLd).Methods: Self-administered questionnaires were dispatched to 3423 of the certified pulmonary physicians in Japan. They were asked to report a care report form of one patient each with AE-IPF who died very recently about opioid use for dyspnea and EOLd. We further explored the factors associated with the early use of opioids for dyspnea.Results: Among the 3423 physicians, 1226 (35.8%) returned the questionnaire with the report forms of 539 AE-IPF patients. Of 539 AE-IPF patients, 361 (67.0%) received opioids for dyspnea. Of the 361 patients, 72 (20.0%) received opioids during the initial treatment with an intention of recovery (early use), while 289 (80.0%) did when the recovery was deemed impossible. EOLd was held before the onset of AE in 124 patients (23.0%); however, the majority of patients had EOLd after the admission for AE-IPF. EOLd before the onset of AE was significantly associated with the early use of opioids.Conclusion: In terminally ill AE-IPF patients, opioids are usually administered when the recovery is deemed impossible, and EOLd are rarely held before the onset of AE. Further studies are warranted on the efficacy of opioids for dyspnea and the appropriate timing of EOLd. [ABSTRACT FROM AUTHOR]

The discriminative power of CURB-65 for mortality in community-acquired pneumonia (CAP) is suspected to decrease with age. However, a useful prognostic prediction model for older patients with CAP has not been established. This study aimed to develop and validate a new scoring system for predicting mortality in older patients with CAP. We recruited two prospective cohorts including patients aged ≥ 65 years and hospitalized with CAP. In the derivation (n = 872) and validation cohorts (n = 1,158), the average age was 82.0 and 80.6 years and the 30-day mortality rate was 7.6% (n = 66) and 7.4% (n = 86), respectively. A new scoring system was developed based on factors associated with 30-day mortality, identified by multivariate analysis in the derivation cohort. This scoring system named CHUBA comprised five variables: confusion, hypoxemia (SpO2 ≤ 90% or PaO2 ≤ 60 mmHg), blood urea nitrogen ≥ 30 mg/dL, bedridden state, and serum albumin level ≤ 3.0 g/dL. With regard to 30-day mortality, the area under the receiver operating characteristic curve for CURB-65 and CHUBA was 0.672 (95% confidence interval, 0.607–0.732) and 0.809 (95% confidence interval, 0.751–0.856; P < 0.001), respectively. The effectiveness of CHUBA was statistically confirmed in the external validation cohort. In conclusion, a simpler novel scoring system, CHUBA, was established for predicting mortality in older patients with CAP. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50% [1]. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown.Methods: We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) > 50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data.Results: A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N = 52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥ 2 (p = 0.0832), stage IV disease or recurrence (p = 0.0487), PD-L1 TPS 50-89% (p = 0.0657), use of steroids prior to the administration of pembrolizumab (p = 0.0243), malignant pleural effusion (p = 0.0032), and baseline C-reactive protein (CRP) levels > 1.0 mg/dL (p = 0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32-31.8; p = 0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15-6.35; p = 0.0228), and baseline CRP > 1.0 mg/dL (OR: 2.17; 95% CI: 1.03-4.68; p = 0.0402) were significantly associated with non-response to treatment.Conclusion: In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels > 1.0 mg/dL reduced the response of first-line monotherapy with pembrolizumab. [ABSTRACT FROM AUTHOR]

The typical clinical manifestation of acute eosinophilic pneumonia is acute onset of respiratory symptoms due to smoking or medication use, accompanied by bilateral ground‐glass opacity with consolidations on chest radiography. However, differential diagnosis with acute eosinophilic pneumonia should not be excluded in cases of unilateral pneumonia of postoperative lung. [ABSTRACT FROM AUTHOR]

Background: Multidisciplinary discussion (MDD), in which physicians, radiologists, and pathologists communicate and diagnose together, has been reported to improve diagnostic accuracy compared to diagnoses made solely by physicians. However, even among experts, diagnostic concordance of MDD is not always good, and some patients may not receive a specific diagnosis due to insufficient findings. A provisional diagnosis based on the ontology with a diagnostic confidence level has recently been proposed. Additionally, we developed an artificial intelligence model to differentiate idiopathic pulmonary fibrosis (IPF) from other chronic interstitial lung diseases (ILD)s, which needs validation in a broader population., Methods: This prospective nationwide ILD registry has recruited patients with newly diagnosed ILD at the referral respiratory hospitals in Japan and provides rapid MDD diagnoses and treatment recommendations through a central online MDD platform with a 3-year follow-up period. A modified diagnostic ontology is used. If no diagnosis reaches more than 50% certainty, the diagnosis is unclassifiable ILD. If multiple diseases are expected, the diagnosis with a high probability takes precedence. If the confidence levels for the top two possible diagnoses are equal, the diagnosis can be unclassifiable. The registry uses tentative diagnostic criteria for nonspecific interstitial pneumonia with organising pneumonia and smoking-related ILD not otherwise specified as possible new entities. Central MDD diagnosticians review the clinical data, test results, radiology images, and pathological specimens on a dedicated website and conduct MDD diagnoses using online meetings with a cloud-based reporting system. This study aims to (1) provide MDD diagnoses with treatment recommendations; (2) determine the overall ILD rates in Japan; (3) clarify the reasons for unclassifiable ILDs; (4) evaluate possible new disease entities; (5) identify progressive phenotypes and create a clinical prediction model; (6) measure the agreement rate between institutional and central diagnoses in ILD referral and non-referral centres; (7) identify key factors for each specific ILD diagnosis; and (8) create a new disease classification system based on treatment strategies, including the use of antifibrotic drugs., Discussion: This study will provide ILD frequencies, including new entities, using central MDD on dedicated online systems, and develop a machine learning model for ILD diagnosis and prognosis prediction., Trial Registration: UMIN-CTR Clinical Trial Registry (UMIN000040678)., (© 2024. The Author(s).)

Background: Dyspnea and desaturation during exercise are essential assessment items for pulmonary rehabilitation. Characterizing patients using these 2 factors may be important for providing more effective pulmonary rehabilitation. This study aimed to categorize subjects with interstitial lung disease (ILD) using dyspnea and desaturation at the end of the 6-min walk test (6MWT)., Methods: This was a retrospective study including 230 stable subjects with ILD who underwent 6MWT in our out-patient department at a general hospital in Japan. The modified Borg scale and oxygen saturation determined by S pO 2 at the end of the 6MWT were used for cluster analysis using the k -means method with k = 4., Results: Subjects were classified into 4 characteristic clusters. S pO 2 at the end of the 6MWT was lower in cluster 4 (80.5 ± 3.0%) than in clusters 1 (94.3 ± 2.0%), 2 (94.3 ± 1.9%), and 3 (87.9 ± 1.8%) and was lower in cluster 3 than in clusters 1 and 2. The modified Borg scale score at the end of the 6MWT was higher in clusters 2 (4 [3-8]), 3 (3 [0-9]), and 4 (4 [0-7]) than in cluster 1 (0.5 [0-2.0]) and was higher in cluster 2 than in cluster 3., Conclusions: Subjects with ILD were classified into 4 characteristic clusters using dyspnea and S pO 2 at the end of the 6MWT. The 4 clusters are characterized as follows: Cluster 1 had mild desaturation and mild dyspnea; cluster 2 had mild desaturation and severe dyspnea; cluster 3 had both moderate desaturation and dyspnea, and cluster 4 had both severe desaturation and dyspnea. These classification data offer insight for individualized pulmonary rehabilitation for patients with ILD., (Copyright © 2024 by Daedalus Enterprises.)

Background: The diagnosis of fibrotic hypersensitivity pneumonitis (fHP) from other interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF), is often difficult. This study aimed to examine computed tomography (CT) findings that were useful for differentiating between fHP and IPF and to develop and validate a radiological diagnostic model., Methods: In this study, 246 patients (fHP, n = 104; IPF, n = 142) from two institutions were included and randomly divided into the test (n = 164) and validation (n = 82) groups (at a 2:1 ratio). Three radiologists evaluated CT findings, such as pulmonary fibrosis, small airway disease, and predominant distribution, and compared them between fHP and IPF using binomial logistic regression and multivariate analysis. A prognostic model was developed from the test group and validated with the validation group., Results: Ground-glass opacity (GGO) with traction bronchiectasis (TB), honeycombing, hypoattenuation area, three-density pattern, diffuse craniocaudal distribution, peribronchovascular opacities in the upper lung, and random distribution were more common in fHP than in IPF. In multivariate analysis, GGO with TB, peribronchovascular opacities in the upper lung, and random distribution were significant features. The area under the curve of the fHP diagnostic model with the three aforementioned CT features was 0.733 (95% confidence interval [CI], 0.655-0.811, p < 0.001) in the test group and 0.630 (95% CI, 0.504-0.755, p < 0.047) in the validation group., Conclusion: GGO with TB, peribronchovascular opacities in the upper lung, and random distribution were important CT features for differentiating fHP from IPF., Competing Interests: Declaration of competing interest KK received lectures fees from Boehringer Ingelheim. YK received lectures fees from Boehringer Ingelheim. YM received grants from Boehringer Ingelheim, and lectures fees from Boehringer Ingelheim and AstraZeneca. TJ received lectures fees from Bohlinger Ingelheim, AstraZeneca, and Kyorin Inc. The other authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

An inhibitor of plasminogen activator inhibitor (PAI)-1, TM5614, inhibited thrombosis, inflammation, and fibrosis in several experimental mouse models. To evaluate the efficacy and safety of TM5614 in human COVID-19 pneumonia, phase IIa and IIb trials were conducted. In an open-label, single-arm trial, 26 Japanese COVID-19 patients with mild to moderate pneumonia were treated with 120-180 mg of TM5614 daily, and all were discharged without any notable side effects. Then, a randomized, double-blind, placebo-controlled trial was conducted in Japanese COVID-19 patients with mild to moderate pneumonia. The number of study participants was set to be 50 in each arm. Even after extension of the enrollment period, the number of study participants did not reach the initially intended sample size, and 75 patients were enrolled in the study. The total oxygenation scale from Day 1 to Day 14 as the primary endpoint was 1.5 in the TM5614 group vs 4.0 in the placebo group (p = 0.22), and the number of days of oxygen administration required as the secondary endpoint was 2.0 days in the TM5614 group vs 3.5 days in the placebo group (p = 0.34). Further studies will be necessary to verify the efficacy of PAI-1 inhibition for the treatment of COVID-19 pneumonia.Clinical trial registration: Two studies were conducted: a prospective, multicenter, open-label phase II study at https://jrct.niph.go.jp (jRCT2021200018) (First registration date 18/08/2020) and a prospective, multicenter, randomized, double-blind, placebo-controlled, phase II study at https://jrct.niph.go.jp (jRCT2021210006) (First registration date 28/05/2021)., (© 2024. The Author(s).)

Considering recently published two guidelines for the diagnosis of hypersensitivity pneumonitis (HP), the Japanese Respiratory Society (JRS) has now published its own Japanese clinical practice guide for HP. Major types of HP in Japan include summer-type, home-related, bird-related, farmer's lung, painter's lung, humidifier lung, and mushroom grower's lung. Identifying causative antigens is critical for increasing diagnostic confidence, as well as improving prognosis through appropriate antigen avoidance. This guide proposes a comprehensive antigen questionnaire including the outbreak sources reported in Japan. Drawing on the 2021 CHEST guideline, this guide highlights the antigen identification confidence level and adaptations for environmental surveys. The detection of specific antibodies against causative antigens is an important diagnostic predictor of HP. In Japan, the assessments of bird-specific IgG (pigeons, budgerigars) and the Trichosporon asahii antibody are covered by medical insurance. Although this guide adopts the 2020 ATS/JRS/ALAT guideline diagnostic criteria based on the combination of imaging findings, exposure assessment, bronchoalveolar lavage lymphocytosis, and histopathological findings, it added some annotations to facilitate the interpretation of the content and correlate the medical situation in Japan. It recommends checking biomarkers; seasonal changes in the KL-6 concentration (increase in winter for bird-related HP/humidifier lung and in summer for summer-type HP) and high KL-6 concentrations providing a basis for the suspicion of HP. Antigen avoidance is critical for disease management of HP. This guide also addresses the pharmacological management of HP, highlighting the treatment strategy for fibrotic HP including combination therapies with anti-inflammatory/immunosuppressive and antifibrotic drugs., Competing Interests: Conflict of Interest Hiromi Tomioka received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Yasunari Miyazaki received research grants from Nippon Boehringer Ingelheim Co., Ltd. and Chugai Pharmaceutical Co., Ltd. and lecture fees from Nippon Boehringer Ingelheim Co., Ltd. and Astra Zeneca Co., Ltd. Yoshikazu Inoue received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Hiroyuki Sano received lecture fees from AstraZeneca Co., Ltd., Glaxo Smith Kline Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd. and Novartis Pharma Co., Ltd.. Takeshi Johkoh received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Takeshi Hisada received lecture fees from AstraZeneca Co., Ltd. Junya Fukuoka received honoraria from National Institute of Advanced Industrial Science and Technology and Future Corporation. Yuki Iijima received a research grant from Shionogi & Co.,Ltd. Masahiro Ishizuka received a research grant from GlaxoSmithKline Co.,Ltd. Tsukasa Okamoto received endowments from Nippon Boehringer Ingelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., Wako Filter Technology Co.,Ltd., and Car Conveni Club Co.,Ltd. Toshiaki Kikuchi received lecture fees from AstraZeneca Co.,Ltd., Chugai Pharmaceutical Co.,Ltd and Nippon Boehringer Ingelheim Co., Ltd and a research grant from Astra Zeneca Co.,Ltd. and endowments from Ono Pharmaceutical Co.,Ltd, Shionogi & Co.,Ltd., Chugai Pharmaceutical Co., Ltd. and Nippon Eli Lilly Co.,Ltd. Noriho Sakamoto a research grant from PPD-SNBL Co., Ltd.. Noboru Hattori received lecture fees from Astra Zeneca Co.,Ltd, Glaxo Smith Kline Co.,Ltd., Shionogi & Co.,Ltd., Chugai Pharmaceutical Co.,Ltd and Nippon Boehringer Ingelheim Co., Ltd. and endowments from Ono Pharmaceutical Co.,Ltd, Taiho Pharmaceutical Co.,Ltd and Nippon Eli Lilly Co.,Ltd.. Hiroshi Mukae received lecture fees from Astellas Pharma Inc., Astra Zeneca Co.,Ltd., MSD Co.,Ltd., Kyorin Pharmaceutical Co.,Ltd., Shionogi & Co.,Ltd., Daiichi Sankyo Co.,Ltd., Taisho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd and Pfizer Co., Ltd. and research grants from Otsuka Pharmaceutical Co., Ltd., Shionogi & Co.,Ltd. and Nippon Boehringer Ingelheim Co., Ltd. and endowments from Astellas Pharma Inc., Kyorin Pharmaceutical Co.,Ltd., Shionogi & Co.,Ltd., Daiichi Sankyo Co.,Ltd., Taisho Pharmaceutical Co., Taiho Pharmaceutical Co.,Ltd, Chugai Pharmaceutical Co.,Ltd, FUJIFILM Toyama Chemical Co.,Ltd, and Meiji Seika Pharma Co.,Ltd. Masao Yamaguchi received lecture fees from AstraZeneca Co.,Ltd. Yoshihiro Nishimura received lecture fees from Astra Zeneca Co.,Ltd., Glaxo Smith Kline Co.,Ltd., Novartis Pharma Co.,Ltd. and Nippon Boehringer Ingelheim Co., Ltd and research grants from Teijinn Pharma Co., Ltd and endowments from Glaxo Smith Kline Co.,Ltd., Taiho Pharmaceutical Co.,Ltd, Chugai Pharmaceutical Co.,Ltd and Nippon Eli Lilly Co.,Ltd. Masayuki Hanaoka received lecture fees from AstraZeneca Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd and endowments from Bayer Pharma Co., Ltd.. Masashi Bando received lecture fees from AstraZeneca Co., Ltd. Shionogi & Co.,Ltd. and Nippon Boehringer Ingelheim Co., Ltd. Ryoko Egashira, Tetsuji Kawamura, Tamiko Takemura, Naohiko Inase, Masaru Ejima, Horoshi Ohnishi, Ryo Okuda, Susumu Sakamoto, Tsuyoshi Shirai, Kozo Suhara, Reoto Takei, Tomoya Tateishi, Kentaro Tanaka, Toshiharu Tsutsui, Yoshihisa Nukui, Haruhiko Furusawa, Yasushi Horimasu, Akemi Matsuo, Takashi Yamana, Yasuyuki Yoshizawa and Masahiro Kaneko have no conflicts of interest., (© 2023 Published by Elsevier B.V. on behalf of The Japanese Respiratory Society.)

Background: TAS-115, a novel oral multi-kinase inhibitor, showed antifibrotic effects in in vitro and in vivo animal models of idiopathic pulmonary fibrosis (IPF)., Methods: In this exploratory phase 2 study, IPF patients with a percent predicted forced vital capacity (%FVC) decline ≥5% acquired within the previous 6 months were enrolled. Patients were divided into three pre-treatment cohorts, namely, treatment-naïve, pirfenidone, or nintedanib. TAS-115 was administered orally at 200 mg/day with a 5-day on and 2-day off regimen. After 13 weeks of treatment, patients entered a 13-week extension treatment period where the efficacy was evaluated. The primary endpoint was the difference in slope of %FVC decline at Week 13 from baseline. Safety was also evaluated., Results: Between June 2018 and July 2019, 46 patients were enrolled, and 30 (65.2%) patients completed the 13-week treatment. Of these, 22 (47.8%) proceeded to extension treatment. For the primary endpoint, TAS-115 treatment lowered the slope of the %FVC decline of 0.0750%/day (95% confidence interval: 0.0341-0.1158%/day) at Week 13. Efficacy was also demonstrated at Week 26. Treatment-related adverse events were reported in 40 (88.9%) patients, but most were manageable by dose reduction, dose interruption, or symptomatic treatment., Conclusions: TAS-115 treatment was effective, assessed using intra-patient change in slope of %FVC decline as a surrogate endpoint in patients with IPF pre-treated with pirfenidone or nintedanib and treatment-naïve patients. TAS-115 showed acceptable tolerability and a manageable safety profile., Trial Registration: Japic-Clinical Trials Information, JapicCTI-183898 (first registered: March 15, 2018)., Competing Interests: Conflict of Interest AA reports a research grant and honoraria from Boehringer Ingelheim, honoraria from Toray, Kyorin Pharma, and grant from Taiho during the conduct of the study. S Homma reports a grant from Taiho during the conduct of the study. TO reports honoraria from Taiho, Nippon Boehringer Ingelheim, Shionogi, Gilead Sciences, Fujifilm, Astellas, Chugai, Meiji Seika Pharma, and Toray. YN reports a research grant and honoraria from Nippon Boehringer Ingelheim, grant from Shionogi, and grants from Taiho during the conduct of the study. KT reports honoraria from Nippon Boehringer Ingelheim, Shionogi, and Taiho. S Hisata reports a honoraria for lectures from Boehringer Ingelheim. YM, NA, S Sato, S Sakamoto, TH, HT, and KK have no conflicts of interest., (Copyright © 2023 [The Author/The Authors]. Published by Elsevier B.V. All rights reserved.)

Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF). Weight loss is recognized as an adverse event during nintedanib treatment, and is a common complication exploitable as a prognostic indicator of IPF. Here, we report a single-center, retrospective cohort study to assess body weight changes during nintedanib therapy in patients with IPF. Sixty-one patients treated with nintedanib for >6 months were included (45 males, mean age ± standard deviation 73.1 ± 7.4 years). Baseline body weight and body mass index were 60.1 ± 12.0 kg and 23.2 ± 3.5 kg/m 2 , respectively. Mean weight loss during the first 6 months of nintedanib treatment was significant (-3.2 ± 3.4 kg, p < 0.0001) with Common Terminology Criteria for Adverse Events (CTCAE) grades 0,1,2 or 3 of 30, 17, 13 and 1, respectively. Pulmonary function test records 6 months before nintedanib administration were available in a subset of patients (n = 40). Significant differences in weight change over the 6 months before-vs-after nintedanib administration were also observed in these patients [mean differences -2.5 ± 3.4 kg, 95% confidence interval (CI) -3.6, -1.4, p < 0.0001]. Multivariate analysis showed that only baseline body weight was significantly associated with weight loss of CTCAE grade ≧2 (odds ratio 0.921, 95% CI 0.854, 0.994). Median follow-up from starting nintedanib was 34.8 months. There was a significant difference in overall survival between patients with CTCAE grade ≧2-vs-grade<2 (median survival of 25.5 months and 55.2 months, p = 0.014). In the model adjusting for age, sex and lung function, weight loss CTCAE grade ≧2 was an independent predictor for all-cause mortality (hazard ratio 2.448, 95% CI 1.080-5.551). In conclusion, weight loss is an important issue for the management of patients with IPF treated with nintedanib., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A woman in her 60s with suspected multicentric Castleman's disease, who was receiving treatment with oral prednisolone, presented to our hospital with mild cough and malaise. Chest CT showed diffuse infiltrative and granular shadows, indicating exacerbation of lung lesions caused by steroid-resistant multicentric Castleman's disease. A video-assisted thoracoscopic lung and mediastinal lymph node biopsy was performed. The biopsy revealed mediastinal lymph node tissue consistent with multicentric Castleman's disease, as well as presence of Cryptococcus neoformans in the alveolar space. C. neoformans infection in immunocompromised individuals may present with diffuse lung lesions and should be noted as a mimicker of acute exacerbation of Castleman's disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Interstitial lung disease (ILD) is classified into several disease groups. Among them, idiopathic pulmonary fibrosis (IPF) has higher incidence and poor prognosis; therefore, it is important to characterize specific IPF symptoms. Exercise desaturation is a strong factor related to mortality in patients with ILD. Thus, the purpose of this study was to compare the degree of oxygen desaturation between IPF and other ILD (non-IPF ILD) patients during exercise, using the 6-minute walk test (6MWT)., Methods: This retrospective study included 126 stable patients with ILD who underwent 6MWT in our outpatient department. The 6MWT was used to assess desaturation during exercise, 6-minute walk distance (6MWD), and dyspnea at the end of exercise. In addition, patient characteristics and pulmonary function test results were recorded., Results: Study subjects were divided into 51 IPF patients and 75 non-IPF ILD patients. The IPF group had significantly lower nadir oxygen saturation determined by pulse oximetry (SpO 2 ) during 6MWT than the non-IPF ILD group (IPF, 86.5 ± 4.6%; non-IPF ILD, 88.7 ± 5.3%; p = 0.02). The significant association between the nadir SpO 2 and IPF or non-IPF ILD grouping remained even after adjusting for gender, age, body mass index, lung function, 6MWD, and dyspnea (β = -1.62; p <0.05)., Conclusion: Even after adjusting for confounding factors, IPF patients had lower nadir SpO 2 during 6MWT. Early assessment of exercise desaturation using the 6MWT may be more important in patients with IPF compared with patients with other ILDs., Competing Interests: There is no conflict of interest to disclose., (©2023 Japanese Society of Physical Therapy.)

Background: Sarcopenia, defined using abdominal computed tomography (CT), has been used as a prognostic marker for patients with idiopathic pulmonary fibrosis (IPF). However, no consensus on the impact of sarcopenia as defined using chest CT exists. Therefore, this study aimed to investigate the impact of sarcopenia, defined using CT at the carina-level, on the long-term prognosis of patients with IPF., Methods: This single-center retrospective cohort study included 117 patients with IPF. Sarcopenia was defined as skeletal muscle mass measured at the carina-level on chest CT images. All-cause mortality was analyzed using the Kaplan-Meier method, and the log-rank test was used to evaluate the differences between sarcopenia and non-sarcopenia groups. A Cox proportional hazards regression model was used to analyze the impact of sarcopenia on all-cause mortality in model 1 with adjustment for body mass index and gender-age-physiology stage as a confounding factor and in model 2 with sex, age, and% forced vital capacity (FVC)., Results: The median follow-up period was 956 days, and 57 deaths were recorded. The sarcopenia group had a significantly lower survival rate than the non-sarcopenia group. The multivariate Cox proportional hazards analysis revealed that sarcopenia was a significant predictor of all-cause mortality in models 1 and 2. In patients with no diffusing capacity for carbon monoxide (DL CO ) measurement, sarcopenia was a significant prognostic predictor of all-cause mortality independent of%FVC., Conclusion: Sarcopenia, defined at the carina level, is a risk factor for all-cause mortality in patients with IPF. Assessment of sarcopenia by CT imaging is useful and less burdensome in patients with IPF., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 SPLF and Elsevier Masson SAS. All rights reserved.)

The prognosis of patients with connective tissue disease (CTD) has improved significantly in recent years, but interstitial lung disease (ILD) associated with connective tissue disease (CTD-ILD) remains a refractory condition, which is a leading cause of mortality. Because it is an important prognostic factor, many observational and interventional studies have been conducted to date. However, CTD is a heterogeneous group of conditions, which makes the clinical course, treatment responses, and prognosis of CTD-ILD extremely diverse. To summarize the current understanding and unsolved questions, the Japanese Respiratory Society and the Japan College of Rheumatology collaborated to publish the world's first guide focusing on CTD-ILD, based on the evidence and expert consensus of pulmonologists and rheumatologists, along with radiologists, pathologists, and dermatologists. The task force members proposed a total of 27 items, including 7 for general topics, 9 for disease-specific topics, 3 for complications, 4 for pharmacologic treatments, and 4 for non-pharmacologic therapies, with teams of 2-4 authors and reviewers for each item to prepare a consensus statement based on a systematic literature review. Subsequently, public opinions were collected from members of both societies, and a critical review was conducted by external reviewers. Finally, the task force finalized the guide upon discussion and consensus generation. This guide is expected to contribute to the standardization of CTD-ILD medical care and is also useful as a tool for promoting future research by clarifying unresolved issues., Competing Interests: Conflict of Interest Dr. Yasuhiro Kondoh received honoraria from Shionogi & Co.,Ltd. and Nippon Boehringer Ingelheim Co., Ltd. Takashi Ogura received honoraria from Shionogi & Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; grant support and/ or research funding from Nippon Boehringer Ingelheim Co., Ltd.; and subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd. and the Mental Health Okamoto Memorial Foundation. Dr. Takafumi Suda received honoraria from AstraZeneca K.K. and Nippon Boehringer Ingelheim Co., Ltd.; grant support and/or research funding from AstraZeneca K.K. and Ono Pharmaceutical Co., Ltd.; subsidies or donations from Astellas Pharma Inc., MSD K.K., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., and Pfizer Japan Inc. Dr. Hiromi Tomioka received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Hirofumi Amano received grant support and/or research funding from Sumitomo Dainippon Pharma Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; subsidies or donations from Actelion Pharmaceuticals Japan Ltd., Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AYUMI Pharmaceutical Corporation, Eisai Co., Ltd., MSD K.K., Taisho Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Teijin Pharma Ltd., and Bayer Yakuhin, Ltd. Dr. Masaki Anraku belongs to endowed departments sponsored by Tokio Marine & Nichido Fire Insurance Co., Ltd. Dr. Takao Fujii, received honoraria from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Pfizer Japan Inc., Ono Pharmaciutical Cooperation Co.,Ltd., and Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Asahi Kasei Pharma Corporation, AbbVie GK, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Ono Pharmaciutical Cooperation Co., Ltd. Dr. Tomoyuki Fujisawa received grant support and/or research funding from Novartis Pharma K.K. Dr. Takahisa Gono received honoraria from Ono Pharmaceutical Co., Ltd. Dr. Masayoshi Harigai received honoraria from Chugai Pharmaceutical Co., Ltd. and subsidies or donations from Eisai Co., Ltd.; and belongs to endowed departments sponsored by AYUMI Pharmaceutical Corporation, Mitsubishi Tanabe Pharma Corporation, and Nippon Kayaku Co., Ltd. Dr. Yoshikazu Inoue received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Takeshi Johkoh received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Hideto Kameda received honoraria from Asahi Kasei Pharma Corporation, AbbVie GK, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K.; grant support and/or research funding from Astellas Pharma Inc., AbbVie GK, Gilead Sciences Inc., Novartis Pharma K.K., and Bristol-Myers Squibb K.K.; and subsidies or donations from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Chugai Pharmaceutical Co., Ltd. Dr. Kensuke Kataoka received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Yasuhiro Katsumata received subsidies or donations from Mitsubishi Tanabe Pharma Corporation and Chugai Pharmaceutical Co., Ltd. Dr. Yasushi Kawaguchi received honoraria from Actelion Pharmaceuticals Japan Ltd. and Bayer Yakuhin, Ltd. Dr. Atsushi Kawakami received honoraria from Astellas Pharma Inc., AbbVie GK, Eisai Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Pfizer Japan Inc.; grant support and/or research funding from Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taisho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Bristol-Myers Squibb K.K.; and subsidies or donations from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., and Pfizer Japan Inc. Dr. Noboru Kitamura received subsidies or donations from Ono Pharmaceutical Co., Ltd. and Chugai Pharmaceutical Co., Ltd. Dr. Kazuhiro Kurasawa received grant support and/or research funding from Pfizer Japan Inc.; and subsidies or donations from Asahi Kasei Pharma Corporation and Mitsubishi Tanabe Pharma Corporation. Dr. Yutaro Nakamura received subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd. Dr. Ran Nakashima received grant support and/or research funding from Takeda Pharmaceutical Co., Ltd. Dr. Yasuhiko Nishioka, received subsidies or donations from Asahi Kasei Pharma Corporation and Pfizer Japan Inc. Dr. Masaki Okamoto received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Fumikazu Sakai received honoraria from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd., and manuscript fees from Nippon Boehringer Ingelheim Co., Ltd. Dr. Shinji Sato received subsidies or donations from Asahi Kasei Pharma Corporation, Ono Pharmaceutical Co., Ltd., and Chugai Pharmaceutical Co., Ltd. Dr. Tohru Takeuchi received honoraria from Mitsubishi Tanabe Pharma Corporation and Bristol-Myers Squibb K.K. and subsidies or donations from Asahi Kasei Pharma Corporation, Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Teijin Pharma Ltd. Dr. Masataka Kuwana received patent royalties and/or licensing fees from Medical & Biological Laboratories Co., Ltd.; honoraria from Actelion Pharmaceuticals Japan Ltd., Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., and Janssen Pharmaceutical K.K.; grant support and/or research funding from Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., and Bayer Yakuhin, Ltd.; and subsidies or donations from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., and Bayer Yakuhin, Ltd. Dr. Drs. Shigeki Makino, Noriyuki Enomoto, Hidenori Ichiyasu, Hideya Kitamura, Tomohiro Koga, Osamu Nishiyama, Susumu Sakamoto, Toshimasa Shimizu, Noboru Takayanagi, Reoto Takei, Tamiko Takemura, Yuko Toyoda, Hidehiro Yamada, Hideaki Yamakawa, Yasuhiko Yamano, and Yoshioki Yamasaki declare no conflicts of interest associated with this article., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients., Methods: A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed., Results: In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01-1.07; IL-8, HR = 1.04, 95% CI 1.01-1.08; MIP-1α, HR = 1.19, 95% CI 1.00-1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02-1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01-1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls., Conclusions: CTACK is a novel prognostic biomarker of IPF. Trial registration None (because of no healthcare intervention).

Background: The data on smoking cessation treatment outcomes for smokers with chronic obstructive pulmonary disease (COPD) are limited. The present study assessed the effectiveness of smoking cessation interventions at our clinic., Methods: Data from a prospective registry of a 3-month smoking cessation program were evaluated. The primary outcome, smoking cessation, was defined as the complete abstinence from smoking between the 8-week and 12-week clinic visits. Pulmonary function and health-related quality of life using St. George's Respiratory Questionnaire (SGRQ) were assessed at baseline and at the end of the program., Results: Out of the 155 COPD patients with nicotine dependence (female/male = 39/116; mean age, 67.2 ± 9.8 years; mean forced expiratory volume in 1 s (FEV1), 59.7 ± 21.1% predicted), 107 participants completed the program. Among the completers, 74 achieved smoking cessation. In the multivariate analysis, mental disorders (odds ratio [OR] 3.678, 95% confidence interval [CI]: 1.182, 11.445), higher exhaled carbon monoxide (CO) level (OR 1.080, 95% CI: 1.013, 1.151) and lower FEV1/forced vital capacity (FVC) (OR 0.958, 95% CI: 0.923, 0.995) were negatively associated with successful smoking termination. Significant changes in pulmonary function were found in quitters but not in continuous smokers (increases in FEV1 by 0.09 L/s [95% CI: 0.03, 0.15] and peak expiratory flow by 0.23 L/s [95% CI: 0.01, 0.44]). SGRQ total scores improved significantly in both quitters (-5.4 [95% CI: -8.4, -2.5]) and continuous smokers (-7.0 [95% CI: -11.6, -2.5])., Conclusion: In the program completers, the exhaled CO levels, FEV1/FVC ratio, and presence of mental disorders were significantly associated with program success or failure in COPD patients with nicotine dependence., Competing Interests: Conflict of Interest The authors report no conflicts of interest for this study., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Nursing and healthcare-associated pneumonia (NHCAP), a concept of pneumonia proposed by the Japanese Respiratory Society, mostly occurs among elderly people in long-term care facilities. Similarly, the risk of urinary tract infection (UTI) also increases with age, with UTIs common among those in long-term care. Therefore, NHCAP is sometimes complicated by the presence of a UTI. However, pneumonia complicated by a UTI has not been clinically well characterized. We retrospectively analyzed 376 patients with NHCAP admitted to our hospital over a three-year period. Sixty-seven patients (17.8%) showed complications by a UTI. Patients with a UTI had lower renal function (higher blood urea nitrogen [P = 0.001], higher creatinine [P = 0.001]), lower systolic blood pressure (P = 0.04), higher A-DROP scores (P = 0.005) and higher positive blood culture rates (P = 0.03) than those without a UTI. Furthermore, based on urine, sputum and blood culture results, nearly half of the microorganisms (4/7) in blood cultures were identical with those of urine, suggesting that a concurrent UTI increases positive blood culture rates. Multivariate analysis showed that UTI was not an independent factor associated with 30-day mortality (P = 0.17), although patients with a UTI showed higher 30-day mortality (P = 0.04) than those without a UTI in univariate analysis. In summary, patients with NHCAP and a UTI were more prone to complications than those without a UTI, although UTI itself did not affect the prognosis of patients with NHCAP. A concurrent UTI had a negative impact on the severity of NHCAP., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Long-term, real-world data, as opposed to academic or research data, on outcomes of smoking cessation clinics are scarce. We assessed patient outcomes over a 10-year period at a smoking cessation clinic in a community teaching hospital in Japan and explored predictors of successful smoking cessation., Methods: We used data from a prospective registry of cigarette smokers who participated in a 3-month smoking cessation program comprising combined pharmacological treatment and cognitive behavioral therapy and explored factors associated with program execution and successful smoking cessation. The primary outcome was smoking cessation, defined by quitting completely between the 8-week and 12-week sessions, with verification according to exhaled carbon monoxide (CO) level of ≤10 ppm., Results: Between August 2007 and December 2017, 813 patients with nicotine dependence participated in the program. The number of participants decreased after Japan׳s 2010 tobacco tax increase. Among participants, 433 (53.3%) completed the program. In multivariate analysis, the number of cigarettes smoked daily (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.96, 0.99), cardiovascular disease (OR 1.75, 95% CI 1.16, 2.68), chronic obstructive pulmonary disease (OR 1.74, 95% CI 1.10, 2.78), and gastric/duodenal ulcer (OR 1.77, 95% CI 1.04, 3.08) were significantly associated with program completion. Among program completers, 288 (66.5%) achieved smoking cessation. Exhaled CO level (OR 0.94, 95% CI 0.93, 0.97) and mental disorders (OR 0.53, 95% CI 0.33, 0.85) were negatively associated with successful smoking cessation., Conclusions: Baseline exhaled CO level and mental disorders were significantly associated with either success or failure of smoking cessation., (Copyright © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

The significance of blood cultures in nursing home-acquired pneumonia (NHAP) is incompletely understood. We retrospectively analyzed the clinical and laboratory features of 515 patients with NHAP admitted to our hospital over an 11-year period. Blood cultures were obtained from 336 patients (65.2%). We compared 13 and 323 patients with positive and negative blood cultures, respectively. The former showed lower systolic blood pressure and higher blood urea nitrogen (BUN), creatinine, C-reactive protein (CRP), and A-DROP scores than the latter. With regard to A-DROP parameters, patients with positive blood cultures showed significantly higher rates of dehydration (BUN ≥ 21 mg/dL) and low blood pressure (systolic blood pressure ≤ 90 mmHg). Multivariate analysis identified CRP values and low blood pressure as independent predictors of bacteremia: CRP (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.04-1.19, P = 0.003) and low blood pressure (OR 6.03; 95% CI 1.06-34.25, P = 0.04). A receiver operating characteristic curve indicated that CRP was of moderate accuracy (area under the curve = 0.75), and its diagnostic accuracy was optimal at a cut-off point of 19.2 mg/dL (sensitivity 69%, specificity 87%). Since the probability of true bacteremia is very low in NHAP, obtaining blood cultures from all patients with NHAP is unnecessary. However, our results suggest blood cultures are warranted from patients with high CRP values (≥20 mg/dL) or low blood pressure., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)