Publications by authors named "Kazuhiro Yatera"

221 Publications

Lung disorders induced by respirable organic chemicals.

J Occup Health 2021 Jan;63(1):e12240

Department of Occupational and Environmental Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

Respirable organic chemicals were originally thought to cause allergic respiratory diseases, such as bronchial asthma and hypersensitivity pneumonitis, and believed not to cause lung disorders derived from inflammatory or fibrotic processes such as pulmonary fibrosis and interstitial pneumonitis. It has recently been reported, however, that exposure to organic chemicals can cause interstitial lung diseases. In this review, we discuss the clinical features of occupational asthma and hypersensitivity pneumonitis, as well as other lung disorders, including interstitial pneumonitis, caused by humidifier disinfectants in Korea and by a cross-linked acrylic acid-based polymer (CL-PAA) in Japan.
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http://dx.doi.org/10.1002/1348-9585.12240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204092PMC
January 2021

Association between obligatory anaerobes and empyema caused by Streptococcus anginosus group bacteria.

Respir Investig 2021 Jun 10. Epub 2021 Jun 10.

Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.

Co-infections of Streptococcus anginosus group (SAG) bacteria and obligate anaerobes are observed in patients with empyema; however, their epidemiology and pathology remain unknown. A retrospective study was performed with 44 patients who underwent pleural effusion microbiota evaluation between January 2006 and March 2018, using the clone library method for detecting empyema caused by SAG bacteria. Based on culture analysis of pleural effusion, 12 patients were diagnosed with empyema caused by SAG bacteria. Obligate anaerobe phylotypes were detected in eight patients (66.7%) using the clone library method, whereas anaerobic culture analysis detected anaerobes in only two patients (16.7%). No significant difference was observed between the clinical features of SAG-mediated empyema with and without anaerobes using the clone library method, except for chest computed tomographic data. Co-infection of SAG bacteria and obligate anaerobes may be underestimated if conventional culture methods are used. SAG-mediated empyema with and without anaerobes may present different radiological features; therefore, further studies are required.
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http://dx.doi.org/10.1016/j.resinv.2021.04.009DOI Listing
June 2021

A human respiratory tract-associated bacterium with an extremely small genome.

Commun Biol 2021 May 26;4(1):628. Epub 2021 May 26.

Department of Microbiology, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.

Recent advances in culture-independent microbiological analyses have greatly expanded our understanding of the diversity of unculturable microbes. However, human pathogenic bacteria differing significantly from known taxa have rarely been discovered. Here, we present the complete genome sequence of an uncultured bacterium detected in human respiratory tract named IOLA, which was determined by developing a protocol to selectively amplify extremely AT-rich genomes. The IOLA genome is 303,838 bp in size with a 20.7% GC content, making it the smallest and most AT-rich genome among known human-associated bacterial genomes to our best knowledge and comparable to those of insect endosymbionts. While IOLA belongs to order Rickettsiales (mostly intracellular parasites), the gene content suggests an epicellular parasitic lifestyle. Surveillance of clinical samples provides evidence that IOLA can be predominantly detected in patients with respiratory bacterial infections and can persist for at least 15 months in the respiratory tract, suggesting that IOLA is a human respiratory tract-associated bacterium.
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http://dx.doi.org/10.1038/s42003-021-02162-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155191PMC
May 2021

Safety and tolerability of combination therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis: A multicenter retrospective observational study in Japan.

Respir Investig 2021 May 13. Epub 2021 May 13.

Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

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.
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http://dx.doi.org/10.1016/j.resinv.2021.04.005DOI Listing
May 2021

The role of comprehensive analysis with circulating tumor DNA in advanced non-small cell lung cancer patients considered for osimertinib treatment.

Cancer Med 2021 Jun 12;10(12):3873-3885. Epub 2021 May 12.

Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, Japan.

Background: EGFR mutations are good predictive markers of efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKI), but whether comprehensive genomic analysis beyond EGFR itself with circulating tumor DNA (ctDNA) adds further predictive or prognostic value has not been clarified.

Methods: Patients with NSCLC who progressed after treatment with EGFR-TKI, and with EGFR T790 M detected by an approved companion diagnostic test (cobas ), were treated with osimertinib. Plasma samples were collected before and after treatment. Retrospective comprehensive next-generation sequencing (NGS) of ctDNA was performed with Guardant360 . Correlation between relevant mutations in ctDNA prior to treatment and clinical outcomes, as well as mechanisms of acquired resistance, were analyzed.

Results: Among 147 patients tested, 57 patients received osimertinib, with an overall response rate (ORR) of 58%. NGS was successful in 54 of 55 available banked plasma samples; EGFR driver mutations were detected in 43 (80%) and T790 M in 32 (59%). The ORR differed significantly depending on the ratio (T790 M allele fraction [AF])/(sum of variant AF) in ctDNA (p = 0.044). The total number of alterations detected in plasma by NGS was higher in early resistance patients (p = 0.025). T790 M was lost in 32% of patients (6 out of 19) after acquired resistance to osimertinib. One patient with RB1 deletion and copy number gains of EGFR, PIK3CA, and MYC in addition to T790 M, showed rapid progression due to suspected small cell transformation.

Conclusions: NGS of ctDNA could be a promising method for predicting osimertinib efficacy in patients with advanced NSCLC harboring EGFR T790 M.
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http://dx.doi.org/10.1002/cam4.3929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209625PMC
June 2021

Paraneoplastic neuromyelitis optica spectrum disorder associated with malignant melanoma: A case report.

Thorac Cancer 2021 06 5;12(11):1775-1779. Epub 2021 May 5.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, Fukuoka, Japan.

Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune demyelinating diseases involving the central nervous system, affecting the spinal cord and optic nerves. There are few reports of paraneoplastic NMOSD associated with malignant melanoma. Here, we report a rare case of anti-aquaporin 4 (AQP4) antibody-positive NMOSD associated with malignant melanoma. A 61-year-old Japanese woman was diagnosed with malignant melanoma and lung metastasis four years after a diagnosis of anti-AQP4 antibody-positive NMOSD. When diagnosing and treating patients with NMOSD, physicians should be aware of the development of malignancy for at least several years.
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http://dx.doi.org/10.1111/1759-7714.13965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169302PMC
June 2021

Examination of Surfactant Protein D as a Biomarker for Evaluating Pulmonary Toxicity of Nanomaterials in Rat.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyusyu 807-8555, Fukuoka, Japan.

This work studies the relationship between lung inflammation caused by nanomaterials and surfactant protein D (SP-D) kinetics and investigates whether SP-D can be a biomarker of the pulmonary toxicity of nanomaterials. Nanomaterials of nickel oxide and cerium dioxide were classified as having high toxicity, nanomaterials of two types of titanium dioxides and zinc oxide were classified as having low toxicity, and rat biological samples obtained from 3 days to 6 months after intratracheal instillation of those nanomaterials and micron-particles of crystalline silica were used. There were different tendencies of increase between the high- and low-toxicity materials in the concentration of SP-D in bronchoalveolar-lavage fluid (BALF) and serum and in the expression of the SP-D gene in the lung tissue. An analysis of the receiver operating characteristics for the toxicity of the nanomaterials by SP-D in BALF and serum showed a high accuracy of discrimination from 1 week to 3 or 6 months after exposure. These data suggest that the differences in the expression of SP-D in BALF and serum depended on the level of lung inflammation caused by the nanomaterials and that SP-D can be biomarkers for evaluating the pulmonary toxicity of nanomaterials.
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http://dx.doi.org/10.3390/ijms22094635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124995PMC
April 2021

A fatal case of COVID-19-associated invasive pulmonary aspergillosis.

J Infect Chemother 2021 Jul 1;27(7):1102-1107. Epub 2021 Apr 1.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.

A 79-year-old Japanese man with polymyalgia rheumatica was admitted to hospital with coronavirus disease (COVID-19). On admission, he was treated with ciclesonide inhalation, ivermectin, and meropenem. He was intubated 6 days after admission, and methylprednisolone therapy was initiated (1000 mg/day). Hypoxemia and chest radiographic findings temporarily improved. However, chest computed tomography showed bilateral ground-glass attenuations, multiple nodules, and consolidation. Aspergillus fumigatus was cultured from the tracheal aspirate and he was diagnosed with COVID-19-associated invasive pulmonary aspergillosis (CAPA) and treated with liposomal amphotericin B. However, he died 28 days after admission.
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http://dx.doi.org/10.1016/j.jiac.2021.03.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015426PMC
July 2021

Evaluation of four commercial severe acute respiratory coronavirus 2 antibody tests.

J Infect Chemother 2021 Jul 15;27(7):1033-1038. Epub 2021 Mar 15.

Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.

Introduction: Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital.

Methods: This study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses.

Results: The varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11-15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed.

Conclusions: Our results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis.
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http://dx.doi.org/10.1016/j.jiac.2021.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959261PMC
July 2021

Exposure to PM is a risk factor for acute exacerbation of surgically diagnosed idiopathic pulmonary fibrosis: a case-control study.

Respir Res 2021 Mar 12;22(1):80. Epub 2021 Mar 12.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu-city, Fukuoka, 807-8555, Japan.

Background: Short-term exposure to ozone and nitrogen dioxide is a risk factor for acute exacerbation (AE) of idiopathic pulmonary fibrosis (AE-IPF). The comprehensive roles of exposure to fine particulate matter in AE-IPF remain unclear. We aim to investigate the association of short-term exposure to fine particulate matter with the incidence of AE-IPF and to determine the exposure-risk time window during 3 months before the diagnosis of AE-IPF.

Methods: IPF patients were retrospectively identified from the nationwide registry in Japan. We conducted a case-control study to assess the correlation between AE-IPF incidence and short-term exposure to eight air pollutants, including particulate matter < 2.5 µm (PM). In the time-series data, we compared monthly mean exposure concentrations between months with AE (case months) and those without AE (control months). We used multilevel mixed-effects logistic regression models to consider individual and institutional-level variables, and also adjusted these models for several covariates, including temperature and humidity. An additional analysis with different monthly lag periods was conducted to determine the risk-exposure time window for 3 months before the diagnosis of AE-IPF.

Results: Overall, 152 patients with surgically diagnosed IPF were analyzed. AE-IPF was significantly associated with an increased mean exposure level of nitric oxide (NO) and PM 30 days prior to AE diagnosis. Adjusted odds ratio (OR) with a 10 unit increase in NO was 1.46 [95% confidence interval (CI) 1.11-1.93], and PM was 2.56 (95% CI 1.27-5.15). Additional analysis revealed that AE-IPF was associated with exposure to NO during the lag periods lag 1, lag 2, lag 1-2, and lag 1-3, and PM during the lag periods lag 1 and lag 1-2.

Conclusions: Our results show that PM is a risk factor for AE-IPF, and the risk-exposure time window related to AE-IPF may lie within 1-2 months before the AE diagnosis. Further investigation is needed on the novel findings regarding the exposure to NO and AE-IPF.
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http://dx.doi.org/10.1186/s12931-021-01671-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955640PMC
March 2021

Emerald Sign for Diagnosing Tracheobronchial Amyloidosis.

Intern Med 2021 Mar 1. Epub 2021 Mar 1.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan.

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http://dx.doi.org/10.2169/internalmedicine.6738-20DOI Listing
March 2021

The Japanese respiratory society guidelines for the management of cough and sputum (digest edition).

Respir Investig 2021 May 26;59(3):270-290. Epub 2021 Feb 26.

Tokyo Women's Medical University, Japan.

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough.
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http://dx.doi.org/10.1016/j.resinv.2021.01.007DOI Listing
May 2021

Impact of Corticosteroid Administration within 7 Days of the Hospitalization for Influenza Pneumonia with Respiratory Failure: A Propensity Score Analysis Using a Nationwide Administrative Database.

J Clin Med 2021 Jan 31;10(3). Epub 2021 Jan 31.

Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.

Influenza pneumonia, which causes acute respiratory distress syndrome and multiple organ failure, has no established management protocol. Recently, corticosteroid therapy was used to treat coronavirus disease 2019 with respiratory failure; however, its effectiveness as a treatment for influenza pneumonia remains controversial. To investigate the impact of corticosteroid therapy for the early phase of severe influenza pneumonia, we compared influenza pneumonia patients with respiratory failure treated with or without corticosteroids within 7 days after hospital admission using a Japanese nationwide administrative database. The primary endpoint was the mortality rate. The secondary endpoints were duration of intensive-care unit management, invasive mechanical ventilation, and hospital stay. The inverse probability weighting method with estimated propensity scores was used to minimize the data collection bias. We included 3519 patients with influenza pneumonia with respiratory failure. Of these, 875 were treated with corticosteroids. There was no significant difference between the groups regarding 30-day and 90-day mortality, duration of intensive-care unit management, invasive mechanical ventilation, and hospital stay. However, the in-hospital mortality rate was higher in the corticosteroid group. The use of systematic corticosteroid therapy in patients with influenza pneumonia was associated with a higher in-hospital mortality rate.
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http://dx.doi.org/10.3390/jcm10030494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866855PMC
January 2021

Immune checkpoint inhibitors-induced eosinophilic pneumonia: A case report.

Thorac Cancer 2021 03 21;12(5):720-724. Epub 2021 Jan 21.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

A 78-year-old male with renal cell carcinoma was treated with combined immunotherapy of nivolumab and ipilimumab. After four courses of the treatment, a chest computed tomography (CT) revealed newly formed ground-glass opacities (GGOs) in both the lower lung lobes; drug-induced pneumonia was speculated. Eosinophil counts were elevated in both peripheral blood and bronchoalveolar lavage fluid. Both the immune checkpoint inhibitors (ICIs) were discontinued, following which the chest CT findings improved. Based on these findings, a diagnosis of ICI-induced eosinophilic pneumonia was made. Hence, clinicians should be wary of the risk of eosinophilic pneumonia during ICI-anticancer therapy.
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http://dx.doi.org/10.1111/1759-7714.13848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919115PMC
March 2021

Chronic obstructive pulmonary disease severity in middle-aged and older men with osteoporosis associates with decreased bone formation.

Osteoporos Sarcopenia 2020 Dec 24;6(4):179-184. Epub 2020 Nov 24.

Department of Orthopedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Objectives: Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers.

Methods: We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV), which reflects COPD severity, and we examined the relationships between %FEV and serum levels of bone metabolism biomarkers.

Results: All subjects were diagnosed with osteoporosis based on T-scores. %FEV correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV independent of other factors.

Conclusions: The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.
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http://dx.doi.org/10.1016/j.afos.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783073PMC
December 2020

Paraneoplastic Sensory Polyneuropathy Related to Anti-PD-L1-including Anticancer Treatment in a Patient with Lung Cancer.

Intern Med 2021 May 15;60(10):1577-1581. Epub 2020 Dec 15.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan.

Paraneoplastic neurological syndromes (PNS), such as sensory polyneuropathy, are rare, and serum neuronal antibodies that are used for diagnosing this syndrome are occasionally positive. Similarly, neurological immune-related adverse events due to immune checkpoint inhibitors (ICIs) are also rare. However, their etiologies and the relationship between them remain unclear. We herein report a patient with suspected small cell lung cancer who showed sensory polyneuropathy after treatment with atezolizumab in combination with cytotoxic agents (carboplatin and etoposide) and was doubly positive for serum anti-Hu and anti-SOX-1 antibodies. Treatment with ICI and cytotoxic agents may sometimes lead to the development of PNS.
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http://dx.doi.org/10.2169/internalmedicine.5629-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188014PMC
May 2021

[A Case of Papillary Thyroid Cancer Diagnosed as Recurrent Pulmonary Metastases Diagnosed by Transbronchial Biopsies 18 Years After Surgery].

J UOEH 2020 ;42(4):353-358

Department of Respiratory Medicine, School of Medicine,University of Occupational and Environmental Health, Japan.

We report a 79-year-old woman, who had undergone surgery for papillary thyroid carcinoma 18 years previously and lung adenocarcinoma 15 years previously. She didn't receive any follow-up because she had no recurrence for 5 years in both diseases. She visited a local doctor with precordial pain and thorax discomfort as her chief complaints, where chest computed tomography indicated a 14 mm-sized nodule in the right lower lobe and 5-7 mm-sized small nodules in both lungs. Using endobronchial ultrasonography with a guide sheath (EBUS-GS) for the diagnosis in our department, the lesions were confirmed by ultrasonography, and a transbronchial biopsy was carried out under fluoroscopy. Pathologically, a sufficient amount of tumor cells were collected, and the findings of adenocarcinoma were obtained. Her condition was diagnosed as recurrent pulmonary metastases of thyroid papillary carcinoma because of the atypical columnar epithelial cells with nuclear variants and the papillary proliferation of intranuclear inclusion, and because of the positive findings in immunohistochemical staining for thyroglobulin. Since papillary thyroid carcinoma is positive for thyroid transcription factor-1 (TTF-1), which is widely used as a marker of lung adenocarcinoma, it cannot be used to differentiate between the two. It is often difficult to diagnose papillary thyroid carcinoma by bronchoscopy, because its progress is slow and the origin of the metastatic lung tumor is not in the bronchus, unlike primary lung cancer. However, a devised transbronchial biopsy procedure for slowly progressive metastatic lung tumors such as papillary thyroid carcinoma is considered to be a useful technique for diagnosis.
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http://dx.doi.org/10.7888/juoeh.42.353DOI Listing
February 2021

[A Case of a Bronchial Foreign Body (Artificial Tooth) in the Right Middle Bronchus Without Respiratory Symptoms].

J UOEH 2020 ;42(4):347-352

Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Japan.

Patients with bronchial foreign bodies often present with subjective symptoms, mainly cough, and removing the foreign bodies is difficult. Bronchial foreign bodies are mostly located in the right lower bronchus, and rarely in the right middle bronchus. An 85-year-old man had no subjective symptoms. He aspirated an artificial tooth during dental treatment the day before visiting our clinic, and consulted his home doctor. He was admitted to our hospital because a chest radiograph indicated the presence of a foreign body in the right middle and lower lung field. Chest computed tomography showed that the bronchial foreign body was located in the right middle bronchus, and it was accompanied by an artifact in the circumference of the lesion, and it seemed to be the metal piece of an artificial tooth. Three-dimensional CT showed the root of the artificial tooth located in center side of the right middle bronchus, and, considering the invasiveness, we decided to remove the tooth by flexible bronchoscopy. The bronchoscopy revealed a metal piece occluding the right middle bronchus without granulation, and we could remove the tooth immediately by grasping the root of the tooth with alligator forceps. We experienced a case of a foreign body located in the right middle bronchus without respiratory symptoms. It is important to carry out image examinations, because elderly patients may not exhibit respiratory symptoms.
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http://dx.doi.org/10.7888/juoeh.42.347DOI Listing
February 2021

Respiratory Failure after the Use of a New Hair Spray.

Intern Med 2021 Apr 9;60(7):1129-1131. Epub 2020 Nov 9.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan.

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http://dx.doi.org/10.2169/internalmedicine.5829-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079899PMC
April 2021

Novel device to prevent droplets in bronchoscopy during the SARS-CoV-2 pandemic.

Thorac Cancer 2021 01 4;12(1):137-139. Epub 2020 Nov 4.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan.

We modified the method of protection to reduce the exposure of health-care workers (droplets) without restricting operability during bronchoscopy. Our method is inexpensive, simple, utilizes disposable materials and prevents interpatient infections. Its routine use during transoral bronchoscopy may be considered due to its simplicity.
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http://dx.doi.org/10.1111/1759-7714.13729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779194PMC
January 2021

Impaired B-Cell Differentiation in a Patient With Gain-of-Function Mutation.

Front Immunol 2020 29;11:557521. Epub 2020 Sep 29.

Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.

Hypogammaglobulinemia is a rare complication of gain-of-function (GOF) mutations. We report an adult patient diagnosed with hypogammaglobulinemia caused by B-cell depletion during the treatment of disseminated cryptococcosis. The patient carried the GOF mutation (c.820C>T, p.R274W). The flow cytometric analysis of his bone marrow revealed that B-cell differentiation was blocked in the stages between pre-B1b and pre-B2 cells. On the other hand, his brother who carried the same mutation displayed normal B-cell counts, thereby indicating that the unrecognized variants in same or other gene might be associated with abnormal B-cell differentiation in the patients. In conclusion, impaired B-cell differentiation in the bone marrow can cause hypogammaglobulinemia in patients with GOF mutations.
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http://dx.doi.org/10.3389/fimmu.2020.557521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550620PMC
May 2021

An autopsy case of a patient with systemic sclerosis who developed marked pulmonary hypertension because of pulmonary tumor thrombotic microangiopathy caused by gastric carcinoma.

Mod Rheumatol Case Rep 2020 01 22;4(1):56-62. Epub 2019 Nov 22.

The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.

We performed an autopsy on a patient with systemic sclerosis who developed uncontrollable pulmonary hypertension due to pulmonary tumour thrombotic microangiopathy (PTTM) caused by gastric carcinoma. The case was of a 62-year-old woman with systemic sclerosis who was admitted to the intensive care unit (ICU) with severe pulmonary hypertension accompanied by respiratory insufficiency. Pulmonary hypertension could not be controlled despite aggressive medical treatment including vasodilators. Approximately 10 days after admission, a unilateral pleural effusion developed. Thoracentesis was performed, and cytology examination of the pleural fluid revealed carcinomatous pleurisy. Because of the presence of a known gastric carcinoma, PTTM was clinically diagnosed. Although chemotherapy was administered, she died 33 days after ICU admission. An autopsy revealed diffuse fibrocellular intimal thickening of the peripheral pulmonary arterioles, which indicated PTTM. In patients with connective tissue disease complicated with pulmonary hypertension, it is necessary to differentiate not only pulmonary arterial hypertension but also other pathological conditions such as PTTM.
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http://dx.doi.org/10.1080/24725625.2019.1690767DOI Listing
January 2020

Predictive Biomarkers for the Ranking of Pulmonary Toxicity of Nanomaterials.

Nanomaterials (Basel) 2020 Oct 15;10(10). Epub 2020 Oct 15.

Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan. 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.

We analyzed the mRNA expression of chemokines in rat lungs following intratracheal instillation of nanomaterials in order to find useful predictive markers of the pulmonary toxicity of nanomaterials. Nickel oxide (NiO) and cerium dioxide (CeO) as nanomaterials with high pulmonary toxicity, and titanium dioxide (TiO) and zinc oxide (ZnO) as nanomaterials with low pulmonary toxicity, were administered into rat lungs (0.8 or 4 mg/kg BW). (), (), (), (), and () were selected using cDNA microarray analysis at one month after instillation of NiO in the high dose group. The mRNA expression of these five genes were evaluated while using real-time quantitative polymerase chain reaction (RT-qPCR) from three days to six months after intratracheal instillation. The receiver operating characteristic (ROC) results showed a considerable relationship between the pulmonary toxicity ranking of nanomaterials and the expression of , , and at one week and one month. The expression levels of these three genes also moderately or strongly correlated with inflammation in the lung tissues. Three chemokine genes can be useful as predictive biomarkers for the ranking of the pulmonary toxicity of nanomaterials.
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http://dx.doi.org/10.3390/nano10102032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602652PMC
October 2020

A Case of Smoke Bomb-induced Acute Lung Injury.

Intern Med 2021 Mar 14;60(6):965-966. Epub 2020 Oct 14.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan.

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http://dx.doi.org/10.2169/internalmedicine.5708-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024971PMC
March 2021

Selection of microRNAs in extracellular vesicles for diagnosis of malignant pleural mesothelioma by in vitro analysis.

Oncol Rep 2020 Nov 22;44(5):2198-2210. Epub 2020 Sep 22.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807‑8555, Japan.

Malignant pleural mesothelioma (MPM) is a malignant tumor which is a challenge for diagnosis and is associated with a poor patient prognosis. Thus, early diagnostic interventions will improve the quality of life and life expectancy of these patients. Recently, cellular microRNAs (miRNAs) have been found to be involved in maintaining homeostasis, and abnormal miRNA expression has often been observed in various diseases including cancer. Extracellular vesicles (EVs) released by many cells contain proteins and nucleic acids. miRNAs are secreted from all cells via EVs and circulate throughout the body. In this study, culture media were passed sequentially through membrane filters 220‑50 nm in size, and EVs with diameters of 50 to 220 nm (EVcap50/220) were collected. miRNAs (EV50‑miRNAs) in EVcap50/220 were purified, and microarray analysis was performed. EV50‑miRNA expression profiles were compared between MPM cells and a normal pleural mesothelial cell line, and six EV50‑miRNAs were selected for further investigation. Of these, hsa‑miR‑193a‑5p and hsa‑miR‑551b‑5p demonstrated higher expression in MPM‑derived EVcap50/220. These miRNAs reduced the expression of several genes involved in cell‑cell interactions and cell‑matrix interactions in normal pleural mesothelial cells. Our data suggest that hsa‑miR‑193a‑5p and hsa‑miR‑551b‑5p in EVcap50/220 could be diagnostic markers for MPM.
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http://dx.doi.org/10.3892/or.2020.7778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551269PMC
November 2020

Hyper-progressive disease after immune checkpoint inhibitor in SMARCA4-deficient small-cell lung carcinoma.

Respirol Case Rep 2020 Nov 21;8(8):e00667. Epub 2020 Sep 21.

Department of Respiratory Medicine University of Occupational and Environmental Health Fukuoka Japan.

SMARCA4 (switch/sucrose non-fermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4)-deficient thoracic tumours have shown poor prognosis in clinical settings. Although the optimal treatment for SMARCA4-deficient thoracic tumours remains unclear, existing studies indicate a favourable response of these tumours to immune checkpoint inhibitors (ICIs). However, there are no reports of fatality in SMARCA4-deficient small-cell lung carcinoma (SCLC) with hyper-progressive disease (HPD) upon treatment with ICIs. Herein, we report a patient with SMARCA4-deficient SCLC who had HPD after the first ICI treatment. A 35-year-old man was treated with nivolumab, subsequent to cytotoxic chemotherapy. A week after nivolumab initiation, chest computed tomography revealed marked increase in pleural effusion in the right lung and chest wall dissemination of the tumour, which concur with the definition of HPD. This is the first study to report the occurrence of HPD after treatment with ICIs in a patient with SMARCA4-deficient SCLC. Analysis of additional data is necessary to determine the optimal treatment for these patients.
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http://dx.doi.org/10.1002/rcr2.667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506996PMC
November 2020

Influential Factors for Assessing Endobronchial Ultrasound Elastography.

Respiration 2020 7;99(12):1154-1155. Epub 2020 Sep 7.

Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu City, Japan.

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http://dx.doi.org/10.1159/000510643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949213PMC
February 2021

Drastic change in the lung microbiome induced by mechanical ventilation.

Respir Investig 2020 Sep 3. Epub 2020 Sep 3.

Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.

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http://dx.doi.org/10.1016/j.resinv.2020.07.005DOI Listing
September 2020

Pembrolizumab-induced Radiation Recall Pneumonitis After the Resolution of Typical Asymptomatic Radiation Pneumonitis.

J UOEH 2020 ;42(3):261-266

Department of Radiology, School of Medicine, University of Occupational and Environmental Health, Japan.

Radiation recall pneumonitis is a phenomenon in which a recall-triggering drug induces an acute inflammatory reaction in the lungs, corresponding to a previously irradiated area. Radiation recall reactions have been reported to occur following treatments with various cytotoxic anticancer agents and molecular-targeting drugs; however, only a few reports have described immune checkpoint inhibitor-induced radiation recall pneumonitis. We report a case of radiation recall pneumonitis induced by pembrolizumab in a patient with the postoperative local recurrence of non-small cell lung cancer. This case demonstrated that pembrolizumab might cause severe radiation recall pneumonitis, even after typical radiation pneumonitis has been resolved.
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http://dx.doi.org/10.7888/juoeh.42.261DOI Listing
September 2020

Pseudoaneurysm after total arch replacement mimicking malignant lymphadenopathy.

Respirol Case Rep 2020 Oct 19;8(7):e00645. Epub 2020 Aug 19.

Department of Respiratory Medicine University of Occupational and Environmental Health, Japan Kitakyushu Japan.

Pseudoaneurysm should be considered in the differential diagnosis when the computed tomography (CT) findings show a mediastinal mass in patients with a history of cardiovascular surgery even if such surgery occurred over two decades previously.
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http://dx.doi.org/10.1002/rcr2.645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438812PMC
October 2020
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