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Background: The latest guidelines on hypersensitivity pneumonitis (HP) categorise the disease as either fibrotic or non-fibrotic because of the greater clinical utility of this stratification. However, the prevalence and incidence of fibrotic and non-fibrotic HP are unknown. This study assessed the exact prevalence and incidence of fibrotic and non-fibrotic HP in Japan in 2021., Methods: For adults, the study hospitals were selected by stratified random sampling according to numbers of beds. The sampling rate was set at about 20%. The questionnaire survey was submitted to the target hospitals. For pediatric cases, a survey was distributed to all members of the Japanese Society of Pediatric Pulmonology and Japanese Society of Pediatric Allergy and Clinical Immunology., Results: Regarding adult cases, in total, 575 facilities responded to the survey, resulting in a response rate of 36.4%. The estimated prevalence and incidence of fibrotic HP were 6.3 and 2.5 per 100,000 population, respectively, versus 3.6 and 2.0 per 100,000 population, respectively, for non-fibrotic HP. Both fibrotic and non-fibrotic HP were more prevalent in southern Japan (Kyushu) and less prevalent in northern Japan (Hokkaido). The incidence of non-fibrotic HP was significantly lower in December than in the other months (relative risk ratio = 0.36, p < 0.001). Three cases of fibrotic HP and five cases of non-fibrotic HP were identified in children., Conclusions: This study determined the prevalence and incidence of fibrotic and non-fibrotic HP in Japan for the first time., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: The prognosis of patients with coronavirus disease 2019 (COVID-19) was poor although its survival rate has been improved after the occurrence of the Omicron strain. Autoimmune pulmonary alveolar proteinosis (APAP), a lung disease caused by macrophage dysfunction induced by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF)-neutralizing autoantibodies, is characterized by the deposition of proteinaceous material in the alveolar spaces. The clinical course of COVID-19 in patients with APAP remains unclear and this study aimed to clarify it., Methods: The data of 23 patients with APAP, who were diagnosed with COVID-19 between January 2020 and May 2023 and collected through a nationwide questionnaire surveillance system, were retrospectively reviewed., Results: Based on the epidemiological frequency at disease onset, suspected strains of severe acute respiratory syndrome coronavirus 2 were Omicron (n = 18) and non-Omicron (n = 5). Fifteen patients were vaccinated. Six and three patients received anti-viral drugs and corticosteroids, respectively. One patient in the third trimester of pregnancy died despite treatment in the intensive care unit. Six patients were complicated by pneumonia and/or required supplemental oxygen. These patients were suspected to have non-Omicron strains (p = 0.087). Vaccination status showed a significant association with suspected Omicron strains. The radiological findings in four patients and shortness of breath improved in two of the four patients after COVID-19., Conclusions: The severity and prognosis of the patients were not worse than those predicted based on the results of a previous study. The transition from a non-Omicron strain to an Omicron strain and the vaccination status may have affected these results., Competing Interests: Declaration of competing interest Toru Arai received lecture fees from Boehringer Ingelheim and Shionogi for activities not connected to the submitted work; Yoshikazu Inoue is a consultant or steering/advisory committee member of Boehringer Ingelheim, Roche, SAVARA, and Taiho (not related to this study) and received lecture fees from Boehringer Ingelheim, Shionogi, Kyorin, Thermo Fisher, and GSK (not related to this study). Keiichi Akasaka has no conflict of interest; Aiko Masunaga has no conflict of interest; Masaki Fujita has no conflict of interest; Etsuo Yamaguchi has no conflict of interest; Mika Saigusa has no conflict of interest; Koji Murakami has no conflict of interest; Yu Kurahara has no conflict of interest; Kazunari Tsuyuguchi has no conflict of interest; Takuji Suzuki has no conflict of interest; Yasunari Miyazaki has no conflict of interest; Masashi Bando has no conflict of interest; Takafumi Suda has no conflict of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

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).)

Idiopathic pulmonary fibrosis (IPF) is the archetypal interstitial lung disease. It is a chronic progressive condition that is challenging to manage as the clinical course of the disease is often difficult to predict. The prevalence of IPF is rising globally and in Japan, where it is estimated to affect 27 individuals per 100,000 of the population. Greater patient numbers and the poor prognosis associated with IPF diagnosis mean that there is a growing need for disease management approaches that can slow or even reverse disease progression and improve survival. Considerable progress has been made in recent years, with the approval of two antifibrotic therapies for IPF (pirfenidone and nintedanib), the availability of Japanese treatment guidelines, and the creation of global and Japanese disease registries. Despite this, significant unmet needs remain with respect to the diagnosis, treatment, and management of this complex disease. Each of these challenges will be discussed in this review, including making a timely and differential diagnosis of IPF, uptake and adherence to antifibrotic therapy, patient access to pulmonary rehabilitation, lung transplantation and palliative care, and optimal strategies for monitoring and staging disease progression, with a particular focus on the status in Japan. In addition, the review will reflect upon how ongoing research, clinical trials of novel therapies, and technologic advancements (including artificial intelligence, biomarkers, and genomic classification) may help address these challenges in the future., Competing Interests: Declaration of competing interest Masashi Bando has received honoraria from AstraZeneca and Nippon Boehringer Ingelheim; Hirofumi Chiba has received honoraria and research funding from Nippon Boehringer Ingelheim; Yasunari Miyazaki has received honoraria and research funding from Nippon Boehringer Ingelheim; Takafumi Suda has received honoraria from AstraZeneca and Nippon Boehringer Ingelheim and research funding from Chugai Pharmaceutical and Nippon Boehringer Ingelheim.The authors did not receive payment related to the development of this manuscript. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy, as well as intellectual property considerations., (Copyright © 2024. Published by Elsevier B.V.)

Anti-neutrophil cytoplasmic antibody-associated vasculitis is triggered by infection, dust exposure, and drugs. A 73-year-old male presented with dyspnea. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection was confirmed upon admission. Exacerbation of interstitial pneumonia and renal dysfunction were observed. Analysis revealed positivity for myeloperoxidase-anti-neutrophil cytoplasmic antibody, other anti-aminoacyl transfer RNA synthetase antibodies, and anti-melanoma differentiation-associated gene 5. Renal biopsy confirmed crescentic glomerulonephritis, leading to the diagnosis of microscopic polyangiitis. Combination therapy with prednisolone and cyclophosphamide was initiated, resulting in improved respiratory and renal failure. There is a potential association between SARS-CoV-2 infection and the onset of autoimmune diseases., Competing Interests: No conflict., (© 2024 The Authors.)

Background: Central pain, characterized by neuropathic pain, can manifest due to injury to the superior spinothalamic tract. The brainstem includes sensory and motor pathways as well as nuclei of the cranial nerves, and therefore cancer metastasis in the region requires early intervention. Although stereotactic radiosurgery (SRS) is commonly employed for the treatment of brain metastasis, it poses risks of late complications like radiation necrosis (RN). RN exacerbates the progression of brain lesions within the irradiated area, and in the brainstem, it can damage multiple nerves, including the superior spinothalamic tract. Central neuropathic pain is often intractable and empirically managed with a combination of conventional drugs, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. However, their efficacy is often limited, leading to a decline in performance status (PS) and quality of life (QOL)., Case Presentation: We present the case of a 53-year-old man diagnosed with stage IV lung cancer, referred to our palliative care team for managing severe central pain resulting from SRS-related RN in the pons. Despite administration of opioids, including oxycodone and hydromorphone, and adjuvant analgesics, the patient continued to require frequent use of immediate-release opioids. The addition of methadone alone proved successful in achieving optimal pain control., Conclusions: Provided that RN in the brainstem can lead to intractable neuropathic pain, it is advisable to avoid SRS for brainstem metastasis when possible. Add-on methadone should be considered as a viable pain management medication for patients experiencing unresolved central pain., (© 2024. The Author(s).)

Background: Clinical guidance on the identification and management of connective tissue disease-associated interstitial lung disease (CTD-ILD) is needed for optimal clinical practice. We aimed to develop clinical algorithms for identifying and managing three common CTD-ILDs: those associated with systemic sclerosis (SSc-ILD), rheumatoid arthritis (RA-ILD), and polymyositis/dermatomyositis (PM/DM-ILD)., Research Design and Methods: Meetings were held October-November 2023 to create consensus-based algorithms for identifying and managing SSc-ILD, RA-ILD, and PM/DM-ILD in clinical practice, based on expert consensus statements for identification and management of CTD-ILD previously derived from a Delphi process., Results: We developed clinical algorithms for SSc-ILD, RA-ILD, and PM/DM-ILD that highlight both commonalities and differences in the identification and management of these CTD-ILDs. Importantly, ILD should be suspected in patients with SSc, RA, or PM/DM who have respiratory symptoms. Chest high-resolution computed tomography has utility for screening, diagnosis and assessment of severity. Furthermore, regular follow-up and multidisciplinary management are important. Disease-specific considerations include unique risk factors such as anti-topoisomerase I antibodies in SSc-ILD, high-titer cyclic citrullinated peptide antibodies in RA, anti-aminoacyl tRNA synthetase antibodies in PM/DM, and anti-melanoma differentiation-associated gene 5 antibody in DM., Conclusions: These algorithms may help physicians to identify and manage patients with SSc-ILD, RA-ILD, or PM/DM-ILD.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines." Because new evidence had accumulated, we formulated the "Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition)." While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress., Competing Interests: Declaration of competing interest Masashi Bando received lecture fees from AstraZeneca K.K., Shionogi & Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. Sakae Homma received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. and belongs to Endowed departments by Shionogi & Co., Ltd., Chugai Pharmaceutical Co., Ltd., Teijin Pharma Ltd. and Nippon Boehringer Ingelheim Co., Ltd. Hiroshi Date received lecture fees from Covidien Japan Inc. and Johnson & Johnson K.K. and donations from Adachi Co., Ltd., Hogy Medical Co., Ltd. and Taiho Pharmaceutical Co., Ltd. Kazuma Kishi received lecture fees from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. and research funding from MSD K. K., Taiho Pharmaceutical Co., Ltd. and Chugai Pharmaceutical Co., Ltd. and donations from Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K. and Nippon Boehringer Ingelheim Co., Ltd. Atsushi Miyamoto received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Takeo Nakayama received lecture fees from Eli Lilly Japan K.K., Pfizer Japan, Inc. and Janssen Pharmaceutical K.K. and research finding from I&H Co., Ltd., Cocokarafine Group Co., Ltd. And Konica Minolta, Inc. and donations from Cancerscan Inc. and Yuyama Manufacturing Co., Ltd. Arata Azuma received lecture fees from Taiho Pharmaceutical Co., Ltd., Toray Industries, Inc. and Nippon Boehringer Ingelheim Co., Ltd. Yasuhiro Kondoh received lecture fees from Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K. and Janssen Pharmaceutical K.K. Takeshi Johkoh received lecture fees from Nippon Boehringer Ingelheim Co., Ltd. Yasuhiko Nishioka received lecture fees from MSD K. K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. and research funding from Taiho Pharmaceutical Co., Ltd., TMS Co., Ltd., Chugai Pharmaceutical Co., Ltd. and Bonac Corporation and donations from Asahi Kasei Pharma Corporation, Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd. and Eli Lilly Japan K.K. Junya Fukuoka received research funding from National Institute of Advanced Industrial Science and Technology and Future Corporation. Yasunari Miyazaki received donations from Chugai Pharmaceutical Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd. and lecture fees from AstraZeneca K.K. and Nippon Boehringer Ingelheim Co., Ltd. Ichiro Yoshino received lecture fees from MSD K. K., AstraZeneca K.K., Intuitive Surgical G.K., Ono Pharmaceutical Co., Ltd., Covidien Japan Inc., Johnson & Johnson K.K., Daiichi Sankyo Company, Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co. and Eli Lilly Japan K.K. and donations from Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K. and Pfizer Japan, Inc. Takafumi Suda received lecture fees from AstraZeneca K.K. and Nippon Boehringer Ingelheim Co., Ltd. and research funding from Chugai Pharmaceutical Co., Nippon Boehringer Ingelheim Co. and Bristol-Myers Squibb K.K. and donations from Shionogi & Co., Ltd. and Chugai Pharmaceutical Co. Yoshihito Goto, Susumu Sakamoto and Hiroyoshi Yamauchi have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Tuberculous meningitis (TBM) is a rare disease in low-incidence countries like Japan, where general physicians have fewer experience with TBM. Despite its proper treatment and early improvement of the condition, TBM often causes paradoxical reactions (PRs), which can lead to severe complications such as stroke. As PRs in the brain are difficult to detect without regular neuroimaging surveillance and have a later onset than in other organs, delayed treatment can be fatal. We report a case of a 54-year-old, human immunodeficiency virus (HIV)-negative man who presented with TBM and miliary tuberculosis (TB) in an unconscious state. Standard anti-tuberculous therapy with adjunctive systemic high-dose dexamethasone brought rapid clinical and microbiological improvement, which allowed the dexamethasone to be tapered. However, he developed cerebral infarction with left hemiplegia due to a TBM-related PR five months after admission. Therefore, the initial high-dose dexamethasone was again added to the anti-tuberculous drugs, achieving the significant effects on the PR-related lesions. Anti-tuberculous drugs had been administered for 3 years and the dexamethasone was carefully tapered. Nevertheless, enlargement of PR-related lesions in the brain recurred 5 years later. Accordingly, the dose of corticosteroid was again increased, resulting in resolving the lesions. It is important to note that severe TBM may cause prolonged PRs, which require a long-term neuroimaging follow-up and anti-inflammatory drugs for the successful management of the TBM-related PR., Competing Interests: Declaration of competing interest The authors declare no conflict of interest (COI)., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to evaluate the Ministry of Health, Labour and Welfare (MHLW) diagnostic criteria for antineutrophil cytoplasmic antibody-associated vasculitis compared to the new American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria., Methods: Two nationwide cohort studies were used, and participants were categorised as having eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 and MHLW criteria., Results: Of the entire patient population, only 10 (2.1%) were unclassifiable according to the MHLW probable criteria, while a significant number of patients (71.3%) met at least two criteria. The MHLW probable criteria for MPA had some challenges in differentiating between MPA and eosinophilic granulomatosis with polyangiitis, and the same was true for MHLW probable criteria for GPA in differentiating MPA from GPA. Nevertheless, improved classification results were obtained when the MHLW probable criteria were applied in the order of eosinophilic granulomatosis with polyangiitis, MPA, and GPA., Conclusions: The application of MHLW criteria could categorise a substantial number of patients with antineutrophil cytoplasmic antibody-associated vasculitis into one of the three antineutrophil cytoplasmic antibody-associated vasculitis diseases. The classification was in accordance with the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria when considering the order of application., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect advancements in the field., Methods: Similar to the 2017 CPG, the Grading of Recommendations, Assessment, Development, and Evaluation system was adopted for this revision. The intended users of this CPG include patients diagnosed with MPA or GPA in Japan and their families and healthcare professionals, including specialists and non-specialists. Based on a scoping review, four clinical questions (CQs) of the 2017 guidelines were modified, and six new CQs were added., Results: We suggest a combination of glucocorticoid and cyclophosphamide or rituximab for remission induction therapy. In cases where cyclophosphamide or rituximab is used, we suggest the use of avacopan over high-dose glucocorticoid. Furthermore, we suggest against the use of plasma exchange in addition to the standard treatment in severe cases of MPA/GPA. Finally, we suggest the use of glucocorticoid and rituximab over glucocorticoid and azathioprine for remission maintenance therapy., Conclusions: The recommendations have been updated based on patient preference, certainty of evidence, benefit and risk balance, and cost., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The objective of this study was to compare the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria with the previous classification algorithm for anti-neutrophil cytoplasmic antibody-associated vasculitis., Methods: We used data from two nationwide, prospective, inception cohort studies. The enrolled patients were classified as having eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the new criteria; these criteria were compared with Watts' algorithm., Results: Among 477 patients, 10.7%, 9.9%, and 75.6% were classified as having EGPA, GPA, and MPA, respectively; 6.1% were unclassifiable. Three patients met both the EGPA and MPA criteria, and eight patients met both the GPA and MPA criteria. Of 78 patients with GPA classified using Watts' algorithm, 27 (34.6%) patients were reclassified as having MPA. Ear, nose, and throat involvement was significantly less frequent in patients reclassified as having MPA than in those reclassified as having GPA. Of 73 patients unclassifiable using Watts' algorithm, 62 were reclassified as having MPA. All patients reclassified as having MPA were myeloperoxidase-anti-neutrophil cytoplasmic antibody positive, and 46 had interstitial lung disease., Conclusion: Although the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria cause overlapping multiple criteria fulfilments in some patients, those items contribute to classifying unclassifiable patients using Watts' algorithm into MPA., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Background: Idiopathic interstitial pneumonias are an independent risk factor of lung cancer, and a chemotherapy-induced acute exacerbation is the most common lethal complication in Japanese patients. The safety and efficacy of carboplatin and weekly paclitaxel for the treatment of non-small cell lung cancer with idiopathic interstitial pneumonias has been previously reported in prospective studies. However, carboplatin + paclitaxel with bevacizumab is currently the standard therapy. We conducted a multicenter, phase II study to confirm the safety and efficacy of carboplatin + weekly paclitaxel + bevacizumab for the treatment of patients with lung cancer complicated by idiopathic interstitial pneumonias., Methods: Chemotherapy-naïve patients with advanced-stage or patients with post-operative recurrent non-squamous non-small cell lung cancer complicated by idiopathic interstitial pneumonias were enrolled. Patients received carboplatin (area under the curve: 5.0) and bevacizumab (15 mg/kg) on day 1 and paclitaxel (100 mg/m 2 ) on days 1, 8, and 15 of each 4-week cycle., Results: Seventeen patients less than the predetermined number were enrolled and received a median of four treatment cycles (range: 1-6). One patient (5.9%; 95% confidence interval: 0.1-28.7%) had acute exacerbation of interstitial pneumonia related to the study treatment which improved after corticosteroid treatment. The overall response rate was 52.9%. The median progression-free survival, median survival time, and 1-year survival were 5.7 months, 12.9 months, and 52.9%, respectively., Conclusion: The addition of bevacizumab to carboplatin and weekly paclitaxel might be safe and effective for the treatment of advanced non-small cell lung cancer complicated by idiopathic interstitial pneumonias., Clinical Trial Registration Number: UMIN000008189., Competing Interests: Conflict of Interest K.T. has received research funding from Chugai Pharmaceutical Co., Ltd.; A.G. has received speakers' bureau honoraria from Chugai Pharmaceutical Co., Ltd.; K.K. has received speakers’ bureau honoraria and a scholarship donation from Chugai Pharmaceutical Co., Ltd.; the other authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objectives: We conducted a descriptive study of the physicians' evidence-practice gap for adults covered by the 2017 clinical practice guidelines for the management of antineutrophil cytoplasmic antibody-associated vasculitis in Japan., Methods: This web-based survey, conducted between January and February 2021, involved physicians who had treated at least five patients in the preceding year at a regional core hospital. The outcome was the physicians' experience in treating patients with microscopic polyangiitis or granulomatosis with polyangiitis [prevalence with 95% confidence intervals (CIs)], defined as treating at least 60% of their patients with the recommended therapy during the year. A modified Poisson regression analysis was performed to explore the factors associated with concordance., Results: The 202 participants included 49 pulmonologists, 65 nephrologists, 61 rheumatologists, and other physicians. The concordance was 31.5% (95% CI, 25.1-38.5) of physicians who used cyclophosphamide or rituximab for the induction of remission. Rheumatology showed the highest concordance with published evidence (risk ratio = 2.4; 95% CI, 1.10-5.22, p = .03)., Conclusions: These results suggest an evidence-practice gap, which varies substantially among subspecialties. Further studies and a new promotional initiative are necessary to close this gap in clinical practice., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To identify the prevalence of risk factors for pulmonary non-tuberculous mycobacterial (NTM) disease in a Japanese population. Patients and Methods: We reviewed 337 consecutive Japanese patients (210 women) with pulmonary NTM disease, including 225 patients with Mycobacterium avium complex (MAC) disease (95.8%) at our hospital during 2006-2017. We calculated the prevalence of risk factors reported in Western countries among mycobacterial species. Results: Pulmonary MAC disease cases comprised 78.2% of pulmonary NTM patients in their 40s, increasing to 100% at age ≥80 years. Body mass index (BMI) was <18.5 in approximately 40% of patients, which was significantly higher than the prevalence of underweight in the Japanese population. The percentage of male heavy smokers (Brinkman index ≥600) was 58.2% of pulmonary NTM disease and was high for all mycobacterial species. In pulmonary MAC disease, systemic factors were observed in the order of malignant tumors (other than lung cancer), diabetes, rheumatoid arthritis, and tuberculosis. Local factors were observed in the order of bronchiectasis, chronic obstructive pulmonary disease, lung cancer, and bronchial asthma. Conclusion: The risk factors reported in Western countries were relatively highly prevalent among Japanese pulmonary NTM disease patients. This observation may help elucidate disease onset mechanisms., Competing Interests: We report no conflicts of interest., (©2023 The Japanese Association of Rural Medicine.)

Background: Numerous studies investigated patients with IPF; however, only a few examined patients with idiopathic interstitial pneumonias (IIPs)., Methods: The Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry, which was initiated in December 2016, is a multicenter prospective observational study of patients newly diagnosed with IIPs from 86 facilities treating ILDs. The plan is to enroll more than 600 new patients during the 2-year enrolment period and to follow their progress for 3 years after the last case enrolment. If additional consent is obtained, the study will continue for another 2 years. Research questions mainly focus on identifying the frequency by IIP classification, patient background, and diagnostic methods during enrolment, survival, acute exacerbation rate, changes in high-resolution CT imaging, forced vital capacity, and interstitial pneumonia markers over time. Other research questions, including those regarding disease behavior in patients with progressive fibrosing-ILD and new biomarkers associated with genetic predispositions, will be investigated., Discussion: The JIPS Registry will provide a comprehensive description of the disease progression, prognosis, treatment status, new biomarkers, and validity of guidelines and central multidisciplinary decisions for IPF and similar diseases that can be differentiated from IPF among IIPs., Ethics and Dissemination: Ethical approval was obtained from the institutional review board of Kanagawa Cardiovascular and Respiratory Center (KCRC-16-0005), and that of Jichi Medical University approved the biobank part (I18-005). Results will be published in peer-reviewed journals and will be presented at national and international conferences., Trial Registration: ClinTrials.gov Registry (NCT03041623, first posted on February 3, 2017)., Competing Interests: Conflict of Interest R. Okuda has received lecture fees from Nippon Boehringer Ingelheim Gmb. T. Ogura has received advisory board fees from Nippon Boehringer Ingelheim Gmb, Taiho Pharmaceutical Co. Ltd., Shionogi & Co. Ltd., and Bristol Myers Squibb Co. T. Ogura also has received lecture fees from Nippon Boehringer Ingelheim Gmb., Shionogi & Co. Ltd., Astellas Co., AstraZeneca K.K., and Eizai Inc. S. Hisata has received lecture fees from Nippon Boehringer Ingelheim Gmb. T. Baba has received lecture fees from Nippon Boehringer Ingelheim Gmb. Y. Kondoh has received advisory board fees and personal fees from Nippon Boehringer Ingelheim Gmb., Asahi Kasei Pharma Corp., and Shionogi & Co. Ltd., advisory board fees from Janssen Pharmaceutical K.K., Healios K.K., Chugai Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd., and personal fees from Astellas, AstraZeneca K.K., Eisai inc., KYORIN Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma, and Novartis Pharma K.K., outside the presentation work. T. Suda has received grants or lecture fees from Nippon Boehringer Ingelheim Gmb. T. Johkoh has received lecture fees from Nippon Boehringer Ingelheim Gmb. T. Iwasawa has received grants from Canon Medical systems and received grants or lecture fees from Nippon Boehringer Ingelheim Gmb. H. Tomioka has received lecture fees from Nippon Boehringer Ingelheim Gmb. M. Bando has received lecture fees from Nippon Boehringer Ingelheim Gmb. A. Azuma has received a steering committee member fee, consultant fee, and lecture fee. Y. Inoue has received payments as lecture fees, participation on the steering committees, or advisor of Boehringer Ingelheim Gmb. T. Arai has received lecture fees from Boehringer Ingelheim Gmb, and Shionogi & Co. Ltd. R. Nakamura has received grants or lecture fees from Nippon Boehringer Ingelheim Gmb. A. Miyamoto has received a lecture fee from Nippon Boehringer Ingelheim Gmb. Y. Miyazaki has received grants or lecture fees from Nippon Boehringer Ingelheim Gmb. H Chiba has received grants or lecture fees from Nippon Boehringer Ingelheim Gmb. H. Ishii has received grants or lecture fees from Nippon Boehringer Ingelheim Gmb. N. Hamada received grants from Nippon Boehringer Ingelheim Gmb. S. Sato has received grants and lecture fees from Nippon Boehringer Ingelheim Gmb. T. Suzuki has received a lecture fee from Nippon Boehringer Ingelheim Gmb. Y. Nishioka has received grants or lecture fees from Nippon Boehringer Ingelheim Gmb. N. Hattori has received grants and lecture fees from Nippon Boehringer Ingelheim Gmb. N. Hashimoto received research grants and lecture fees from Boehringer Ingelheim Gmb. K. Hagiwara has received lecture fees from Nippon Boehringer Ingelheim Gmb. K. Kobayashi has received lecture fees from AstraZeneca K.K. and Takeda Pharmaceutical Co. Y. Terasaki, I. Kuwahira, S. Kato, S. Sakamoto, N. Ichihara, H. Miyata and T. Nukiwa have no competing interests., (Copyright © 2022 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Interstitial lung disease (ILD) is a common complication of connective tissue diseases (CTD), but there are few clinical trials to guide disease management. We aimed to develop expert consensus statements and an algorithm for CTD-ILD management., Research Design and Methods: Based on a targeted literature review, we developed 109 statements on managing CTD-ILD across six domains. We used a modified Delphi process to survey 22 physicians in Japan involved in managing CTD-ILD (specialists in pulmonology, rheumatology, pathology, and radiology). These panelists participated in two rounds of web-based survey to establish consensus statements, which were used to define an algorithm. Consensus was defined as a mean value ≥70 on a scale of 0 (strong disagreement) to 100 (strong agreement)., Results: Between May-August 2022, consensus was reached on 93 statements on CTD-ILD management. The most important consensus statements included screening CTD patients for ILD (typically with high-resolution computed tomography), using imaging, pulmonary function testing and serum biomarkers for diagnosis and severity assessment, regularly following up patients, and multidisciplinary management of CTD-ILD. Consensus statements were interpreted into an algorithm for clinical guidance., Conclusions: Using the Delphi process, we have developed consensus statements and an algorithm to guide clinical decision-making for CTD-ILD.

In this study, ILDs involving IgG4-positive plasma cell infiltration were classified using the 2019 ACR/EULAR criteria. Most IgG4-positive interstitial pneumonia cases were excluded, suggesting the need for a unique treatment strategy. https://bit.ly/38GiUJM., Competing Interests: Conflict of interest: M. Komatsu has nothing to disclose. Conflict of interest: H. Yamamoto has nothing to disclose. Conflict of interest: S. Matsui has nothing to disclose. Conflict of interest: Y. Terasaki has nothing to disclose. Conflict of interest: A. Hebisawa has nothing to disclose. Conflict of interest: T. Iwasawa has nothing to disclose. Conflict of interest: T. Johkoh has nothing to disclose. Conflict of interest: T. Baba has nothing to disclose. Conflict of interest: A. Miyamoto has nothing to disclose. Conflict of interest: T. Handa has nothing to disclose. Conflict of interest: K. Tomii has nothing to disclose. Conflict of interest: Y. Waseda has nothing to disclose. Conflict of interest: M. Bando has nothing to disclose. Conflict of interest: H. Ishii has nothing to disclose. Conflict of interest: Y. Miyazaki has nothing to disclose. Conflict of interest: A. Yoshizawa has nothing to disclose. Conflict of interest: T. Takemura has nothing to disclose. Conflict of interest: Y. Kawabata has nothing to disclose. Conflict of interest: M. Hanaoka has nothing to disclose. Conflict of interest: T. Ogura has nothing to disclose., (Copyright ©The authors 2022.)

Objectives: In Japan, clinical records of patients with intractable diseases, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), are compiled into a database. This study aimed to understand the current treatment status and changes in treatment regimens from our previous survey., Methods: Using data from 2012 and 2013, patients with new-onset MPA and GPA were extracted and analysed., Results: We analysed 1278 MPA and 215 GPA patients. The average age was 71.7 and 62.7 years, respectively. Methylprednisolone pulse therapy was used in 51.2% of MPA patients and 40.5% of GPA patients; the initial prednisolone-equivalent glucocorticoid dose was 39.5 mg/day in MPA and 46.6 mg/day in GPA. Concomitant intravenous or oral cyclophosphamide (CY) was administered to 22.6% of MPA and 56.3% of GPA. Young age, bloody sputum, low serum creatinine, and high C-reactive protein levels were independently associated with CY use in MPA. Compliance with treatment protocol for Japanese patients with myeloperoxidase (MPO)-anti-neutrophilic cytoplasmic antibody-associated vasculitis study criteria or the 2011 clinical practice guidelines for rapidly progressive glomerulonephritis was 42.7% and 49.7%, respectively., Conclusions: MPA was more prevalent than GPA in the registry. Compared to patients with GPA, MPA patients were older and used CY less frequently. No apparent changes in treatment trends were observed from the previous survey., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Interstitial lung disease (ILD) carries a risk for severe pneumonia in patients with rheumatoid arthritis (RA). Bronchiectasis, another risk of severe pneumonia, has not been well elucidated in RA. We investigated the types of respiratory diseases in RA and correlated them to severe pneumonia during the course of treatment using biologic DMARDs (bDMARDs), with special attention to bronchiectasis and ILD. RA patients were examined by computed tomography before starting bDMARDs and divided into three groups: normal, bronchiectasis and ILD. The log-rank test and Dunnett's multiple comparisons test were employed for the statistical analysis. Among 424 patients, 350 were categorized as normal, 32 as having bronchiectasis, and 42 as having ILD. Two in the normal group, three in the bronchiectasis group and four in the ILD group developed severe pneumonia. The log-rank test showed a significant difference among the three groups (p < 0.0001). The pneumonia-free rates in the bronchiectasis and ILD groups were significantly lower than the normal group, respectively, with Dunnett's multiple comparison test (p < 0.0001). This study suggests that the bronchiectasis that occurs in RA carries a risk of severe pneumonia during treatment with bDMARDs that is comparable to ILD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We present a case of life-threatening pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa ) in a healthy 67-year-old man. Rapid disseminated infection resulted in the right hemorrhagic pneumonia and bacteremia. Antimicrobial therapy had limited effects, radical pneumonectomy eventually resolved the prolonged infection. Concurrently, we explored the environmental factors responsible for fulminant P. aeruginosa infection. Multi-locus sequence typing demonstrated that P. aeruginosa isolated from the patient was identical to that collected from home whirlpool bath by the common virulent factor gene. Massive inhalation of contaminated aerosol and pathogen virulence may have synergistically contributed to the severity in this case., Competing Interests: All authors declare that they have no competing interests., (© 2022 Published by Elsevier Ltd.)

We herein report the long-term changes in chest computed tomography (CT) findings from early sarcoidosis lesions to pleuroparenchymal fibroelastosis (PPFE)-like lesions in a 30-year-old man with granulomas on a transbronchial lung biopsy. Multiple bilateral micronodular and nodular opacities around the bronchovascular bundle in the upper lobes detected by chest CT in 2004 disappeared, but paradoxically, peripheral consolidations continued to grow at the periphery of the original lesions. Chest CT in 2017 confirmed the progression of bilateral shrinkage of the upper lobe, spread of peripheral consolidations and wedge-shaped opacities below the first rib, and bronchiectatic air bronchograms, confirming PPFE-like lesions.

Although interstitial pneumonia is an important respiratory manifestation in microscopic polyangiitis (MPA), no studies have examined the detailed pathogenesis of interstitial pneumonia during the clinical course of MPA. In addition, it is considered that MPA develops at a certain incidence rate from myeloperoxidase (MPO)- antineutrophil cytoplasmic antibody (ANCA) positive interstitial pneumonia. However, there is a lack of consensus among pulmonologist and rheumatologist regarding whether MPO-ANCA positive interstitial pneumonia, which does not accompany other organ damage related to ANCA-associated vasculitis (AAV) other than interstitial pneumonia, should be included in AAV. In this review article, the clinical questions regarding MPO-ANCA positive interstitial pneumonia have been set, and evidence to date and problems to be solved in future are outlined., Competing Interests: Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright: © 2021 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

Background: Bronchoscopy is a minimally invasive procedure for establishing the diagnosis of lung cancer. It sometimes fails to obtain tissue samples but readily collects cytological samples., Methods: We developed PNA-LNA dual-PCR (PLDP), which amplified mutant sequences by a high-fidelity DNA polymerase in the presence of a peptide nucleic acid (PNA) oligomer having a wild-type sequence. Mutations are detected either by locked nucleic acid (LNA) probes for quick detection of a limited number of mutations, which are EGFR, KRAS, and BRAF mutations in the current study, or by direct sequencing for a comprehensive screening. In a total of 233 lung cancer samples, the results for cytological samples by PLDP were compared with those for tissue samples by cobas® EGFR mutation test (cobas) or by the PNA-LNA PCR clamp method (P-LPC). Moreover, the performance of PLDP using cell-free DNA (cfDNA) was investigated., Results: Peptide nucleic acid-LNA dual-PCR was able to detect each synthesized mutant sequence with high sensitivity. PLDP detected EGFR mutations in 80 out of 149 clinical samples, while the cobas or the P-LPC detected in 66 matched. The correctness of PLDP was confirmed both by clinical response and by the results of sequencing using a next-generation sequencer. PLDP detected mutations from cfDNA in approximately 70% of patients who harbors mutations in the tumor., Conclusions: Peptide nucleic acid-LNA dual-PCR exhibited an excellent performance, even using cytological samples. PLDP is applicable for the investigation of cfDNA. The combination of bronchoscopy and PLDP is attractive and will expand the utility of bronchoscopy in clinical practice., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Phase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited., Methods: The retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records., Results: Nintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender-Age-Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax)., Conclusions: Real-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile., Competing Interests: Conflict of Interest Shu Hisata, Kensuke Kataoka, Yoshinobu Saito, and Motoyasu Kato received honoraria from Nippon Boehringer Ingelheim Co., Ltd.; Masashi Bando, Sakae Homma, and Takashi Ogura received honoraria from Nippon Boehringer Ingelheim Co., Ltd. and Shionogi & Co., Ltd.; Yasuhiko Nishioka received honoraria, donations, and research funding from Nippon Boehringer Ingelheim Co., Ltd.; Kazuhiro Yatera received honoraria from Nippon Boehringer Ingelheim Co., Ltd., and donations from Shionogi & Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; Hiroshi Mukae received honoraria, donations, and research funding from Nippon Boehringer Ingelheim Co., Ltd. and Shionogi & Co., Ltd.; Shinyu Izumi, Susumu Sakamoto, Kizuku Watanabe, Yasuo Shimizu, Hiromichi Hara, Yuko Waseda, Yoshinori Tanino, Seishu Hashimoto, and Naohiko Inase have no conflicts of interest to declare., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

This study suggests that IgG 4 + IP with abundant IgG 4 + cells and elevated serum IgG 4 levels could be treated differently from IgG 4 -related respiratory disease due to potential differences in disease behaviour and response to corticosteroid therapy https://bit.ly/3dUo2cu., Competing Interests: Conflict of interest: M. Komatsu has nothing to disclose. Conflict of interest: H. Yamamoto has nothing to disclose. Conflict of interest: S. Matsui has nothing to disclose. Conflict of interest: Y. Terasaki has nothing to disclose. Conflict of interest: A. Hebisawa has nothing to disclose. Conflict of interest: T. Iwasawa has nothing to disclose. Conflict of interest: T. Johkoh has nothing to disclose. Conflict of interest: T. Baba has nothing to disclose. Conflict of interest: A. Miyamoto has nothing to disclose. Conflict of interest: T. Handa has nothing to disclose. Conflict of interest: K. Tomii has nothing to disclose. Conflict of interest: Y. Waseda has nothing to disclose. Conflict of interest: M. Bando has nothing to disclose. Conflict of interest: H. Ishii has nothing to disclose. Conflict of interest: Y. Miyazaki has nothing to disclose. Conflict of interest: A. Yoshizawa has nothing to disclose. Conflict of interest: T. Takemura has nothing to disclose. Conflict of interest: Y. Kawabata has nothing to disclose. Conflict of interest: T. Ogura has nothing to disclose., (Copyright ©The authors 2021.)

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease. An increased expression of somatostatin receptor subtype 2 in patients with IPF was identified and lung fibroblasts expressed somatostatin receptors in vitro . In addition, somatostatin analogue inhibits the expression of transforming growth factor-β, insulin-like growth factor (IGF) -1, platelet-derived growth factor, and basic fibroblast growth factor. Therefore, we examined the effects of somatostatin analogue on bleomycin-induced pulmonary fibrosis in mice. In a similar model, it has been reported that administration of high-dose somatostatin analogs suppressed acute inflammation and subsequent pulmonary fibrosis. However, it was clarified that the same effect can be obtained even at the dose used in clinical practice., Methods: C57BL/6 mice received a single tracheal instillation of bleomycin. After randomly allocated, mice were treated with subcutaneous injection of either normal saline or somatostatin analogue., Results: Somatostatin analogue reduced the number of neutrophils and lymphocytes in bronchoalveolar lavage (BAL) and IGF-1 level in serum and BAL fluid and attenuated weight loss. The hydroxyproline content of the lung homogenates in somatostatin analogue treatment group was significantly lower than in that of normal saline treatment group., Conclusions: These results suggest that somatostatin analogue may attenuate pulmonary fibrosis after bleomycin treatment at the dose used in clinical practice.

Objective: Pulmonary mycobacterium avium complex (MAC) disease is increasing significantly worldwide. Several studies have investigated the clinical features of pulmonary MAC disease in the setting of cancer. Here, we aimed to clarify the clinical characteristics of patients with cancer with recent onset of pulmonary MAC disease and the effect of cancer on the onset of this disease. Patients and Methods: Of the 323 consecutive Japanese patients newly diagnosed with pulmonary MAC disease at Jichi Medical University Hospital between and 2006-2017, we retrospectively reviewed 79 consecutive patients with cancer. Results: Seventeen patients had lung cancer (21.0%), while 62 had non-lung cancer. Of the 17 patients with lung cancer, 16 had adenocarcinoma of which 10 had stage I to III disease; 8 of the 10 patients had not received chemotherapy. Sixteen patients with lung cancer had a MAC infection in the ipsilateral lung. Notably, 9 of the 11 lung cancer patients who did not undergo surgery had a MAC infection in the affected lobe. Of the 39 patients with the most common types of non-lung cancer (14 had gastric cancer, 13 had colorectal cancer, and 12 had breast cancer), 22 had stage I to III disease, and 18 of these 22 had not received chemotherapy. Conclusion: Lung cancer may act as a local factor contributing to the onset of pulmonary MAC disease in the ipsilateral lung. However, the underlying mechanism by which a history of cancer might affect the onset of pulmonary MAC disease remains unclear. Further investigation into this mechanism is needed., Competing Interests: We report no conflicts of interest., (©2021 The Japanese Association of Rural Medicine.)

Objective: Histological verification of epithelioid cell granuloma is important in diagnosing sarcoidosis; tissue sampling is a worldwide requirement. In 2006, to reduce medical expenses and avoid invasive procedures, diagnostic criteria without histological verification were permitted by the Japanese government. In 2015, new diagnostic criteria, allowed clinical diagnoses based on only respiratory, ocular, and cardiac systems with at least a two-system involvement, increasing the need to sample tissue from clinically unevaluable organs in suspected sarcoidosis. This study aimed to compare the characteristics of patients who were diagnosed with sarcoidosis according to the 2006 and 2015 criteria. Materials and Methods: Using the 2015 version, we re-evaluated the characteristics of 264 patients with diagnosed or suspected sarcoidosis according to the 2006 criteria, at Jichi Medical University Hospital between 2004 and 2012 (clinical diagnosis, 84; histological diagnosis, 117; suspected sarcoidosis 63). Results: Thirty-nine patients were diagnosed with suspected sarcoidosis due to the absence of at least a two-system involvement; two patients had insufficient laboratory data suggestive of sarcoidosis. Six patients moved from suspected sarcoidosis to a histological diagnosis because of a greater leniency in the criteria for supportive findings. The 2015 diagnostic criteria excluded patients with organ involvement without a requirement for systemic steroids from the clinical diagnosis group. A case of schwannoma, erroneously placed in the clinical diagnosis group by the 2006 criteria, was reclassified according to the 2015 criteria. Conclusion: The 2015 version is preferable for clinically diagnosing sarcoidosis, even without histological specimens, and provides guidance for indications for systemic treatment., Competing Interests: We report no conflicts of interest., (©2021 The Japanese Association of Rural Medicine.)

Background: Fiberoptic tracheal intubation (FTI) in bronchoscopy is widely performed with a conventional Portex tracheal tube (PTT). Occasionally, it is difficult for pulmonologists with limited experience to insert a tube beyond the vocal cords and advance it into the trachea. A new endotracheal tube, the Parker Flex-Tip tube (PFT), was recently designed. We compared the usefulness and safety of PFT versus PTT for FTI in bronchoscopy performed by pulmonologists with limited experience., Methods: Forty consecutive patients were enrolled and randomly assigned to either the PFT group (n = 20) or PTT group (n = 20). The time required for the tip of the endotracheal tube to pass from the mouth to the carina, the number of vomiting reflexes, the number of attempts to pass the tube through the vocal cords during intubation, complications, and technical difficulty of intubation were evaluated., Results: Both the PFT and PTT groups exhibited high intubation success rates (100% vs. 90%, respectively). The PFT group was intubated faster than the PTT group (11.5 [5-45] s vs. 22.5 [8-270] s, respectively, p < 0.01). The PFT group showed fewer vomiting reflexes and tube impingements than the PTT group (p < 0.05). Operators felt it was easier to intubate with PFT versus PTT (p < 0.01). Complications were not significantly different between the two groups., Conclusion: For pulmonologists with limited experience who perform FTI in bronchoscopy, intubation using PFT versus PTT is faster and easier, without an increase in complications., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

A 46-year-old woman with uveitis was referred to our respiratory diseases department in July 2018. Her medical history included transient bilateral hilar mediastinal lymphadenopathy (BHL) and multiple pulmonary nodules in May 2013 during pegylated interferon-alpha and ribavirin treatment for chronic hepatitis C infection. Five years post-treatment, chest X-ray revealed BHL and nodular recurrence. A biopsy of the subcutaneous buttock nodules revealed scattered non-caseating epithelioid granulomas with positive PAB immunohistochemical staining. This seem to be the first report of Propionibacterium acnes-associated sarcoidosis possibly initially triggered by interferon-alpha therapy. Understanding the mechanisms underlying interferon-triggered P. acnes-associated sarcoidosis may clarify the sarcoidosis immunopathogenesis.

Objective: To understand assumptions about and approaches to interstitial lung disease (ILD), including those of the progressive phenotype (progressive fibrosing ILD), this multinational survey assessed physicians' attitudes toward, knowledge of, and management strategies for progressive fibrosing ILD., Methods: This internet-based survey of physicians was conducted between November 2018 and February 2019. Practical management strategies for progressive fibrosing ILD, and current approaches to the assessment and treatment of ILD, were compared between countries/regions (Japan vs. United States and European Union) and specialties (pulmonologists vs. rheumatologists)., Results: The survey was completed by 574 respondents. Compared with Western countries, the progressive fibrosing phenotype concept was not widely understood by Japanese respondents, with no notable differences in the understanding of this phenotype between pulmonologists and rheumatologists. Across all regions, pulmonary function tests, diffusing capacity of the lungs for carbon monoxide assessments, and pulse oximeter measurements were commonly performed at intervals of ≤6 months. In general, physicians in the United States and European Union preferred physiologic approaches for follow-up, while those in Japan preferred imaging and blood monitoring. Compared with rheumatologists, pulmonologists performed more frequent monitoring of autoimmune ILDs, and the differences between specialties were most pronounced in Japan. Regional differences in treatment approaches were observed, probably reflecting the local availability of agents and healthcare environments., Conclusions: Awareness and management of progressive fibrosing ILD varied between specialties and regions, highlighting an unmet need for standardized diagnosis, treatment guidelines, and specialist education in this area.

Background: A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown., Methods: This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide ( D LCO ) and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability., Results: 81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was -300 mL and -123 mL, respectively (difference -178 mL, 95% CI -324--31 mL; p=0.018). Serial change in D LCO , 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups., Conclusions: Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF., Competing Interests: Conflict of interest: S. Sakamoto has nothing to disclose. Conflict of interest: K. Kataoka has nothing to disclose. Conflict of interest: Y. Kondoh reports advisory board fees and personal fees from Asahi Kasei Pharma Corp., Boehringer Ingelheim Co. Ltd and Shionogi & Co. Ltd; advisory board fees from Janssen Pharmaceutical K.K; and personal fees from Eisai Inc., Kyorin Pharmaceutical Co. Ltd, Mitsubishi Tanabe Pharma and Novartis Pharma K.K, outside the submitted work. Conflict of interest: M. Kato has nothing to disclose. Conflict of interest: M. Okamoto has nothing to disclose. Conflict of interest: H. Mukae reports grants and personal fees from Shionogi & Co, Ltd, during the conduct of the study. Conflict of interest: M. Bando reports personal fees from Shionogi & Co, Ltd, outside the submitted work. Conflict of interest: T. Suda has nothing to disclose. Conflict of interest: K. Yatera reports grants from Kirigaoka Tsuda Hospital, Tochiku Hospital, Hagiwara Central Hospital, Kurate Hospital, Saiseikai Yamaguchi Hospital, Ono Pharmaceutical Co. Ltd, Teijin Home Healthcare Limited, Taiho Pharmaceutical Co. Ltd, Daiichi Sankyo Company, Limited, GlaxoSmithKline K.K, Pfizer Japan Inc., Taisho Pharma Co. Ltd, MSD K.K, Novartis Pharma K.K, Nippon Boehringer Ingelheim Co. Ltd, Daiwa Securities Health Foundation, Actelion Pharmaceuticals Japan Ltd, Astellas Pharma Inc., AstraZeneca K.K, Eisai Co., Ltd, Shionogi & Co., Ltd, KYORIN Pharmaceutical Co. Ltd, Taisho Pharma Co. Ltd, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co. Ltd, Chugai Pharmaceutical Co. Ltd, Teijin Pharma Limited, and Eli Lilly Japan K.K, outside the submitted work. Conflict of interest: Y. Tanino has nothing to disclose. Conflict of interest: T. Kishaba has nothing to disclose. Conflict of interest: N. Hattori has nothing to disclose. Conflict of interest: Y. Taguchi has nothing to disclose. Conflict of interest: T. Saito has nothing to disclose. Conflict of interest: Y. Nishioka reports grants and personal fees from Shionogi & Co. Ltd, during the conduct of the study; and grants and personal fees from Nippon Boehringer Ingelheim Co. Ltd, MSD K.K, Ono Pharmaceutical Co. Ltd, Taiho Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd, Asahi Kasei Pharma Corporation and Eli Lilly Japan K.K, and grants from Bonac Corporation, outside the submitted work. Conflict of interest: K. Kuwano has nothing to disclose. Conflict of interest: K. Kishi reports personal fees from Shionogi, outside the submitted work. Conflict of interest: N. Inase has nothing to disclose. Conflict of interest: S. Sasaki has nothing to disclose. Conflict of interest: H. Takizawa has nothing to disclose. Conflict of interest: T. Johkoh has nothing to disclose. Conflict of interest: F. Sakai has nothing to disclose. Conflict of interest: S. Homma has nothing to disclose., (Copyright ©ERS 2021.)

We herein report a rare case of pulmonary sarcoidosis leading to chronic respiratory failure with restrictive ventilatory impairment during a 53-year-long observation period. Nine years after the histological diagnosis of stage I sarcoidosis on chest X-ray in a woman in her 20s, she developed bilateral reticular and granular opacities on chest computed tomography and was started on prednisone for 18 years. Seven years after prednisone withdrawal, these persisting opacities around the bronchovascular bundle, including a central-peripheral band, had progressed, forming traction bronchiectasis clusters and peripheral cysts, some of which developed continuously at the distal side of these clusters, with eventual upper lobe shrinkage.

Background: The number of reports on sarcoidosis complicated by hypersensitivity pneumonitis (HP) is limited, and most describe cases complicated by chronic bird-related HP. Here, we present for the first time a case with Propionibacterium acnes-associated sarcoidosis complicated by acute bird-related HP., Case Presentation: A 62-year-old man with a past medical history of sarcoidosis was admitted to our department, and chest computed tomography showed diffuse ground-glass opacities, which appeared as he rapidly increased the number of pigeons he kept for a competition. Random transbronchial lung biopsy revealed well-formed non-caseating epithelioid granulomas, which contained positively stained substances on immunohistochemistry using the PAB antibody, a specific monoclonal antibody against P. acnes lipoteichoic acid. Poorly formed non-caseating granulomas without positively stained substances were also detected., Conclusion: We describe the successful identification of this exceptionally rare case of sarcoidosis complicated by acute bird-related HP in which two morphologically and immunohistologically different types of granulomas were present in the same lung.

A 65-year-old woman had a ground glass nodule, which was suspicious for lung cancer, in her right lung S 6 by chest computed tomography. For diagnosis, video-assisted thoracoscopic surgery was performed, and the specimen showed a pathological pattern of lymphocytic interstitial pneumonia (LIP). Four years after surgery, new localized ground glass shadows gradually increased on the base of the lung. However, because she had no respiratory symptoms and had normal respiratory function, she was observed with no medication. Subsequently, no other underlying diseases associated with LIP developed. The ground glass nodule was the initial lesion of LIP., Competing Interests: The authors declare no conflicts of interest associated with this manuscript., (© 2020 The Author(s).)

The present article reports the case of a 51-year-old female patient who was clinically diagnosed with idiopathic pleuroparenchymal fibroelastosis in the initial phase of the disease. The upper and lower lobes showed a pleuroparenchymal fibroelastosis pattern and reticular shadow, respectively. Both upper and lower shadows gradually progressed. Five years following the first detection of the chest shadow, left single-lung transplantation was performed. In the multidisciplinary discussion held after the lung transplantation, most participants recognized this end-stage lung disease as unclassifiable idiopathic interstitial pneumonia though the major pathological findings showing a pleuroparenchymal fibroelastosis pattern., Competing Interests: Declaration of Competing Interest Hiroyoshi Yamauchi has no conflict of interest; Masashi Bando received lecture fees from Nippon Boehringer Ingelheim Co., Ltd., SHIONOGI & CO., LTD., AstraZeneca K·K., and SEKISUI MEDICAL CO., LTD.; Aya Shinozaki-Ushiku has no conflict of interest; Takashi Ogura received lecture fees and a research grant from Nippon Boehringer Ingelheim Co., Ltd., received lecture fees from SHIONOGI & CO., LTD.; Tamiko Takemura has no conflict of interest; Masaaki Sato has no conflict of interest; Koichi Hagiwara received patent royalties/licensing fee from LSI medience, and received donations from Taiho pharma, and Ono pharmaceutical., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: The presence of histologically evident epithelioid granuloma is required for the diagnosis of sarcoidosis worldwide. The Japan Society of Sarcoidosis and Other Granulomatous Disorders 2015 diagnostic criteria (JSSOG 2015 criteria) includes "clinically proven diagnosis" (involvement of at least 2 of 3 systems confirmed solely by clinical assessment) because of the frequency of sarcoidosis with ocular, cardiac, and respiratory involvement in Japan and the difficulty of obtaining specimens. Here, we describe in detail the clinical presentation of clinically diagnosed sarcoidosis., Methods: We enrolled 68 consecutive patients with clinically diagnosed sarcoidosis (12 men, 56 women) based on the JSSOG 2015 criteria who were treated at Jichi Medical University between December 2018 and January 2000. We analyzed age at diagnosis, organ involvement, and laboratory findings., Results: Age at diagnosis was unimodal in women. Ocular, splenic, cardiac, and skin involvement, and hypercalcemia were observed in 95.6%, 8.8%, 7.4%, 5.9%, and 35.0% of patients, respectively. High serum lysozyme and soluble interleukin-2 receptor (sIL-2R) levels, bilateral hilar lymphadenopathy on chest radiography, high-grade atrioventricular block or fatal ventricular arrhythmia, and bundle branch block were found in 18.8%, 48.3%, 95.6%, 5.0%, and 10.0% of patients, respectively., Conclusions: The age-specific distribution of clinically diagnosed sarcoidosis was similar to histologically diagnosed sarcoidosis in women, as previously reported. Rates of elevated serum lysozyme and sIL-2R levels were lower in this study than previously reported in histologically diagnosed patients in Japan., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: There is currently no consensus on the morphology of severe fibrotic pulmonary sarcoidosis, and we examined computed tomography (CT) findings and progression., Methods: We analyzed findings in 10 consecutive patients (three men, seven women) with pulmonary sarcoidosis requiring oxygen therapy for chronic respiratory failure, who were extracted from >2500 sarcoidosis patients (three hospitals, 2000-2018). Patients with comorbidities causing chronic respiratory failure were excluded., Results: Predominant findings were consolidations along the bronchovascular bundles comprising 'central-peripheral band', traction bronchiectasis, peripheral cysts/bullae, and upper lobe shrinkage. Traction bronchiectasis arose from opacities comprising 'central-peripheral band'. Clustering of traction bronchiectasis at the distal side formed honeycomb lung-like structures in three patients. Upper lobe shrinkage progressed in seven patients together with progression of consolidations, 'central-peripheral band', traction bronchiectasis clusters, and cysts, while patients without shrinkage included two patients with severe multiple cysts without traction bronchiectasis. Restrictive ventilatory impairment developed in most patients. Pulmonary hypertension (PH) was detected radiologically in five patients, and chronic progressive pulmonary aspergillosis (CPPA) in four patients., Conclusions: During progression, consolidations comprising 'central-peripheral band' progressed together with traction bronchiectasis clusters and peripheral cysts, resulting in upper lobe shrinkage. This may lead to respiratory failure with possible complications such as PH and CPPA., Competing Interests: Abbreviations: BHL: bilateral hilar-mediastinal lymphadenopathy; CT: computed tomography; GGO: Ground-grass opacity; IQR: interquartile range; PH: pulmonary hypertension; CPPA: chronic progressive pulmonary aspergillosis.

Inflammation plays a pivotal role in the pathophysiology of gastric aspiration-induced acute lung injury (ALI). However, its mechanism remains unclear. In this study, we investigated the role of NLRP3 inflammasome-driven IL-1β production in a mouse model of acid aspiration-induced inflammation and ALI. Acid aspiration-induced inflammatory responses and ALI in wild-type mice were significantly attenuated in IL-1β -/- mice, but not NLRP3 -/- mice. In vitro experiments revealed that severe acidic stress (pH 1.75) induced the processing of pro-IL-1β into its 18-kDa mature form (p18-IL-1β), which was different from the caspase-1-processed 17-kDa form (p17-IL-1β), in human THP-1 macrophages and primary murine macrophages. Deficiency of NLRP3 and caspase-1 had no effect on acidic stress-produced IL-1β. The production of IL-1β by severe acidic stress was prevented by inhibitors of serine proteases [4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride], but not of cysteine proteases (E-64), cathepsin G, or inflammasome. The cathepsin D inhibitor pepstatin A inhibited IL-1β production induced by mild acidic stress (pH 6.2) or lactic acid, but not severe acidic stress. Using mass spectrometry and processing-site mutants of pro-IL-1β, we identified D109 as a novel cleavage site of pro-IL-1β in response to severe acidic stress and calculated the theoretical molecular mass of the mature form to be 18.2 kDa. The bioactivity of acidic stress-produced IL-1β was confirmed by its ability to promote p38 phosphorylation and chemokine upregulation in alveolar epithelial cells. These findings demonstrate a novel mechanism of acid-induced IL-1β production and inflammation independent of NLRP3 inflammasome and provide new insights into the therapeutic strategies for aspiration pneumonitis and ALI., (Copyright © 2019 by The American Association of Immunologists, Inc.)

Ewing's sarcoma (ES)/primitive neuroectodermal tumors (PNETs) are highly malignant neoplasms that usually affect the bones and soft tissues in children and young adults. ES/PNET of the lung is very rare and is associated with a poor prognosis. We herein report a case of ES/PNET of the left lung in a 45-year-old man. He was treated with neoadjuvant chemotherapy and pneumonectomy, but unfortunately his disease recurred 1.5 months after surgery. He was started on pazopanib, which resulted in a five-month progression-free survival. To our knowledge, this is the first demonstration of pazopanib efficacy in ES/PNET of the lung.

Background: Although the prevalence of pneumoconiosis has been decreasing due to improvements in working conditions and regular health examinations, occupational hygiene measures are still being established. Plasterers encounter a number of hazardous materials that may be inhaled in the absence of sufficient protection., Case Presentation: A 64-year-old man who plastered without any dust protection for more than 40 years was referred to our hospital with suspected interstitial pneumonia. Mixed dust pneumoconiosis and an unusual interstitial pneumonia (UIP) pattern with fibroblastic foci were diagnosed by video-assisted thoracoscopic surgery, and an elemental analysis detected elements included in plaster work materials. Despite the cessation of plaster work and administration of nintedanib, the patient developed advanced respiratory failure., Conclusion: Plasterers are at an increased risk of pneumoconiosis and may have a poor prognosis when complicated by the UIP pattern. Thorough dust protection and careful monitoring are needed.

Objective: The Japan Research Committee for Intractable Vasculitis has fully revised the clinical practice guidelines (CPG) for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) to improve and standardize the medical treatment of the disease in Japan., Methods: The previous CPG was published in a classical review style in Japanese in 2011 and 2014. We adopted the Grading of Recommendations Assessment, Development and Evaluation system for this revision, and various stakeholders, including patients, participated in it. The expected users of this CPG are AAV patients in Japan and their families and healthcare professionals, including both AAV specialists and non-specialists. We set clinical questions concerning the three important clinical topics of remission induction therapy, plasma exchange, remission maintenance therapy, and developed eight recommendation statements., Results: For remission induction therapy for newly developed AAV, we weakly recommend glucocorticoid (GC) plus intravenous cyclophosphamide pulse (IVCY) or oral cyclophosphamide (POCY) rather than GC alone, and IVCY rather than POCY. We also weakly recommend CY rather than rituximab. In the case of AAV with severe renal impairment, we weakly recommend plasma exchange as a conjunction therapy. We weakly recommend azathioprine for remission maintenance therapy., Conclusion: The revised CPG has demonstrated evidence-based treatment recommendations for AAV.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology which accounts for a large proportion of cases of idiopathic interstitial pneumonia. It has a very poor prognosis with a 5-year survival rate of 30% or below, and so far there has been no guideline in Japan offering an established effective therapy based on evidence. In addition to the establishment of basic therapies, there is also an urgent need to establish therapies to deal with complications, as death occurs in many cases due to acute exacerbation or comorbid lung cancer. It was therefore decided to formulate a guideline in order to promote evidence-based clinical practice, to further improve the quality of medical treatment in the clinical setting, and to allow the benefits to be enjoyed by the public., (Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Pulmonary infection due to Mycobacterium heckeshornense (M. heckeshornense) in healthy adults without underlying diseases is very rare and optimal treatments have not yet been established. A 39-year-old woman was admitted to our hospital for further examinations following the identification of a pulmonary cavitary nodule. Acid-fast bacilli were cultured from specimens obtained by bronchofiberscopy, and identified with M. heckeshornense using nucleotide sequencing. Antimycobacterial chemotherapy was effective temporarily, while the nodular lesion subsequently worsened. The patient underwent lobectomy and has not relapsed thus far. A lung specimen showed marked granulomatous inflammation with extensive caseous necrosis and the preservation of some parts of alveolar septa within caseous necrosis, indicating an exudative process and resistance to chemotherapy. M. heckeshornense is strongly pathogenic and switching to surgical intervention needs to be considered when chemotherapy is insufficient., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Several studies have reported that viral infections are related to lung cancer. We previously reported the involvement of Torque teno virus (TTV) in patients with lung cancer and idiopathic pulmonary fibrosis. However, the role of TTV in lung cancer growth, and its influence on changes in TTV DNA titers due to idiopathic pulmonary fibrosis (IPF) in lung cancer patients are poorly understood., Methods: Serum TTV DNA titers were measured in serum samples obtained from patients with lung cancer. Forty-eight patients with primary lung cancer, including 8 patients with IPF, were enrolled. Serum TTV DNA titers were quantitated before and after chemotherapy. In addition, patients were classified into two groups according to the presence or absence of IPF, and clinical characteristics were compared between these two groups., Results: Among the 33 patients with partial response to treatment or stable disease in the lung cancer, the mean TTV DNA titer in 28 patients without IPF had significantly decreased after chemotherapy. In contrast, the mean TTV DNA titer in the 5 patients with IPF tended to increase after chemotherapy. In the 15 patients with progressive lung cancer, TTV DNA titers were significantly elevated in those with and without IPF., Conclusion: In lung cancer patients without IPF, changes in TTV titers may be correlated with tumor growth. However, in lung cancer patients with IPF, TTV titers were not consistently associated with chemotherapy responses. Therefore, IPF may have an influence on changes in TTV DNA titers., (Copyright © 2018. Published by Elsevier B.V.)

Background and Objective: In Japan, the classification of disease severity of idiopathic pulmonary fibrosis (IPF) (J-system) has been used in making decisions on medical care subsidies. The present J-system consists of arterial partial pressure of oxygen (PaO 2 ) and exercise desaturation in stages of I-IV. It provides a good prognostic classification in stages III and IV, but not in stages I and II. Therefore, we propose a revised system to improve discriminative ability in stages I and II., Methods: We compared the revised J-system with the present J-system using Cox proportional hazards model to predict mortality rate. We also evaluated the recently proposed GAP (Gender, Age and Physiology) system in comparison to both J-systems., Results: Two-hundred and fifteen IPF patients were studied retrospectively. A univariate model showed that the present and revised J-systems and a modified GAP system were all significant prognostic factors. The C-statistic for discriminating prognosis was higher in the revised J-system than the modified GAP system and the present J-system (0.677, 0.652 and 0.659, respectively). The C-statistics of these models produced from the 10 000 bootstrap samples were similar to those of the original models, suggesting good internal validation (0.665 (95% CI: 0.621-0.705), 0.645 (0.600-0.686) and 0.659 (0.616-0.700), respectively). Multivariate analysis revealed that the revised J-system (P = 0.0038) and the modified GAP system (P = 0.0029) were independent prognostic factors., Conclusion: The revised J-system can provide a better mortality prediction than the present one. Both the revised J-system and the modified GAP system are independent and valuable tools for prognostication and clinical management for IPF., (© 2017 Asian Pacific Society of Respirology.)

The lung develops an unique epithelial barrier system to protect host from continuous invasion of various harmful particles. Interleukin (IL-)33 released from epithelial cells in the lung drives the type 2 immune response by activating ST2- expressed immune cells in various allergic diseases. However, the involvement of memory-type ST2 + CD4 + T cells in such lung inflammation remains unclear. Here we demonstrated that intratracheal administration of IL-33 resulted in the substantial increase of numbers of tissue-resident memory-type ST2 + CD4 + T cells in the lung. Following enhanced production of IL-5 and IL-13, eosinophilic lung inflammation sequentially developed. IL-33-mediated eosinophilic lung inflammation was not fully developed in T cell-deficient Foxn1 nu mice and NSG mice. Dexamethasone treatment showed limited effects on both the cell number and function of memory-type ST2 + CD4 + T cells. Thus our study provides novel insight into the pathogenesis of eosinophilic lung disease, showing that memory-type ST2 + CD4 + T cells are involved in IL-33-induced eosinophilic inflammation and elicited steroid-resistance.

Aims: The lung lesion [immunoglobulin (Ig)G4-L] of IgG4-related disease (IgG4-RD) is a condition that occurs together with IgG4-RD and often mimics the lung lesion [idiopathic multicentric Castleman's disease (iMCD-L)] of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data., Methods and Results: Nine patients had IgG4-L (high levels of serum IgG4 and of IgG4 + cells in lung specimens; typical extrapulmonary manifestations). Fifteen patients had iMCD-L (polyclonal hyperimmunoglobulinaemia, elevated serum interleukin-6 levels and polylymphadenopathy with typical lymphadenopathic lesions). Mean values for age, serum haemoglobin levels and IgG4/IgG ratios were higher in the IgG4-L group and C-reactive protein levels were higher in the iMCD-L group. All IgG4-RD lung lesions showed myxomatous granulation-like fibrosis (active fibrosis), with infiltration of lymphoplasmacytes and scattered eosinophils within the perilymphatic stromal area, such as interlobular septa and pleura with obstructive vasculitis. All 15 lung lesions of iMCD, however, had marked accumulation of polyclonal lymphoplasmacytes in lesions with lymphoid follicles and dense fibrosis, mainly in the alveolar area adjacent to interlobular septa and pleura without obstructive vasculitis., Conclusions: Although both lesions had lymphoplasmacytic infiltration, lung lesions of IgG4-RD were characterized by active fibrosis with eosinophilic infiltration within the perilymphatic stromal area with obstructive vasculitis, whereas lung lesions of iMCD had lymphoplasmacyte proliferating lesions mainly in the alveolar area adjacent to the perilymphatic stromal area. These clinicopathological features may help to differentiate the two diseases., (© 2017 John Wiley & Sons Ltd.)