Publications by authors named "Eri Hagiwara"

98 Publications

Patients with Terminal Interstitial Pneumonia Require Comparable or More Palliative Pharmacotherapy for Refractory Dyspnea than Patients with Terminal Lung Cancer.

Palliat Med Rep 2021 16;2(1):188-193. Epub 2021 Jun 16.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama City, Japan.

Dyspnea is a severe symptom of terminal-stage interstitial pneumonia (IP). We commonly use continuous morphine or midazolam for terminal refractory dyspnea. We aimed to determine whether there is a difference in the use of continuous morphine and midazolam for terminal dyspnea between IP patients and lung cancer (LC) patients. This is a single-center retrospective study. We retrospectively examined the clinical records of IP and LC patients who had died in our hospital. These patients were divided into the IP and LC groups to compare the use of morphine and midazolam. Continuous morphine was administered to 50.0% of those in the IP group and 38.0% of those in the LC group for terminal dyspnea. There was no difference in the effect at six hours after morphine initiation between the two groups, but the concomitant use of continuous midazolam and morphine was more common in the IP group than in the LC group. The dose of continuous midazolam was significantly higher in the IP group than in the LC group, and the survival time after morphine initiation was significantly shorter in the IP group. The efficacy of continuous morphine administration for terminal dyspnea in IP patients was similar to that in LC patients for a short time after initiation, but just before death, more patients in the IP group required concomitant use of midazolam and morphine. Thus, IP patients require comparable or more palliative treatment than LC patients.
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http://dx.doi.org/10.1089/pmr.2021.0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244508PMC
June 2021

Asbestos exposure and tuberculous pleurisy as developmental causes of progressive unilateral upper-lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis.

Respir Investig 2021 Jun 22. Epub 2021 Jun 22.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

Background: Unilateral upper-lung field pulmonary fibrosis (upper-PF), which is radiologically consistent with pleuroparenchymal fibroelastosis, develops after thoracic surgery. In most patients with unilateral upper-PF, aberrant intra-/extra thoracic air commonly emerges and an autopsy shows chronic pleuritis, which indicates that pleural involvement is associated with upper-PF development. If so, there may be patients with unilateral upper-PF who have a history of pleural involvement, including tuberculous pleurisy (TP) or asbestos exposure (AE). This study aimed to examine this supposition.

Methods: We examined the radiological reports of all consecutive patients from 2012 to 2018 to investigate whether there were patients having unilateral upper-PF and a history of TP or AE.

Results: Eight patients were included in the study. Five patients had a history of TP, and the remaining three had that of AE. All patients were men and had respiratory symptoms, and seven patients presented with restrictive ventilatory impairment. The interval between TP or last AE and upper-PF development was long, with a median of over 20 years. The upper-PF lesion was commonly located in the right lung, and aberrant intrathoracic air was observed in five patients during their clinical course. Additionally, the upper-PF lesion transformed into a cystic lesion in six patients, which resulted in Aspergillus infection in two patients. The prognosis was poor, with a median overall survival of 38 months.

Conclusions: Unilateral upper-PF developed even in patients with a history of pleural involvement. Our results indicate that pleural involvement plays an important role in the development of unilateral upper-PF.
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http://dx.doi.org/10.1016/j.resinv.2021.05.010DOI Listing
June 2021

Spontaneous regression following endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients.

Respir Investig 2021 Jun 16. Epub 2021 Jun 16.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Spontaneous regression (SR) is defined as a complete or partial, temporary or permanent disappearance of a tumor without anticancer treatment, which potentially develops after surgery or biopsy for primary and metastatic tumors despite unknown incidence rate. Here, we report the incidence rate of SR after endobronchial ultrasound-guided transbronchial nodal needle aspiration (EBUS-TBNA) in lung cancer patients. Among 96 patients evaluable with chest CT before and after EBUS-TBNA, SR was found in three patients (3.1%). With regards to patient characteristics, two patients had small cell lung cancer (SCLC), and one patient had adenocarcinoma. All patients had stage 3 disease with a bulky N2 stage and a history of smoking. Two patients also had interstitial lung disease. Notably, SR was observed not only at the biopsied site, but also at the non-biopsied site. Our results indicate that SR can develop following EBUS-TBNA in a substantial proportion of lung cancer patients.
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http://dx.doi.org/10.1016/j.resinv.2021.05.003DOI Listing
June 2021

Imaging of COVID-19: An update of current evidences.

Diagn Interv Imaging 2021 May 25. Epub 2021 May 25.

Department of Diagnostic Radiology, Yokohama City University Graduate School of Medicine, 236-0004 Yokohama, Kanagawa, Japan.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported as a global emergency. As respiratory dysfunction is a major clinical presentation of COVID-19, chest computed tomography (CT) plays a central role in the diagnosis and management of patients with COVID-19. Recent advances in imaging approaches using artificial intelligence have been essential as a quantification and diagnostic tool to differentiate COVID-19 from other respiratory infectious diseases. Furthermore, cardiovascular involvement in patients with COVID-19 is not negligible and may result in rapid worsening of the disease and sudden death. Cardiac magnetic resonance imaging can accurately depict myocardial involvement in SARS-CoV-2 infection. This review summarizes the role of the radiology department in the management and the diagnosis of COVID-19, with a special emphasis on ultra-high-resolution CT findings, cardiovascular complications and the potential of artificial intelligence.
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http://dx.doi.org/10.1016/j.diii.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148573PMC
May 2021

Serum Krebs von den Lungen-6 levels are associated with mortality and severity in patients with coronavirus disease 2019.

Respir Investig 2021 Apr 27. Epub 2021 Apr 27.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan. Electronic address:

Background: The serum Krebs von den Lungen-6 (KL-6) level is a predictive factor for acute respiratory distress syndrome (ARDS). The development of ARDS has been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to determine whether serum KL-6 levels are associated with mortality and severity in patients with COVID-19.

Methods: Among 361 Japanese patients with COVID-19 who were hospitalized at Kanagawa Cardiovascular and Respiratory Center between February 2020 and December 2020, 356 patients with data on serum KL-6 levels were enrolled and their medical records were retrospectively analyzed.

Results: A negative correlation was observed between KL-6 levels and the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen on admission. The KL-6 levels on admission and the maximal KL-6 levels were higher in patients with severe disease (n = 60) than in those with nonsevere disease (n = 296). Furthermore, the maximal KL-6 levels were higher in nonsurvivors (n = 6) than in survivors (n = 350). In nonsurvivors, the KL-6 levels increased as the disease progressed. The optimal cutoff value of the maximal KL-6 level for discriminating between survivors and nonsurvivors was 684 U/mL, with a sensitivity of 83.3%, a specificity of 90.5%, and an area under the curve of 0.89.

Conclusions: The serum KL-6 level was associated with disease severity. Patients with KL-6 levels ≥684 U/mL had a significantly poorer outcome than those with KL-6 levels <684 U/mL.
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http://dx.doi.org/10.1016/j.resinv.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075813PMC
April 2021

Identification and Characteristics of Co-isolation of Multiple Nontuberculous Mycobacteria.

Intern Med 2021 Apr 26. Epub 2021 Apr 26.

Division of Pulmonary Medicine, Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Objective Although multiple non-tuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.
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http://dx.doi.org/10.2169/internalmedicine.5300-20DOI Listing
April 2021

Clinical characteristics of Japanese patients with moderate to severe COVID-19.

J Infect Chemother 2021 Jun 4;27(6):895-901. Epub 2021 Mar 4.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. Electronic address:

Introduction: Although several reports on the risk factors for severe disease of COVID-19 already exist, reports on effective early indicators are still limited, especially from Japan. This study was conducted to clarify the patient's characteristics whose disease progressed to severe status.

Methods: The medical records of all consecutive 300 Japanese patients hospitalized at our institution between February and November 2020 were retrospectively reviewed. The clinical characteristics were evaluated to compare between mild (no oxygen needed), moderate (oxygen needs of 1-4 L/min), and severe diseases (oxygen needs of 5 L/min or more).

Results: The median age was 68 years old, with 123 (41.0%) males and 177 (59.0%) females. Of these, 199 patients (66.3%), 55 patients (18.3%), 46 patients (15.3%) patients were in the mild disease, moderate disease, severe disease groups, respectively. Patients with severe disease were more likely to be older, have more comorbidities, and tended to have higher body mass index. In laboratory data, lymphocyte count, levels of C-reactive protein (CRP), LDH, and AST on admission were significantly associated with the severity. In multivariate analysis, age and CRP were the independent risk factors for severe disease (OR = 1.050, 1.130, respectively). The optimal cut-off value for age was 74 years old and that for CRP was 3.15 mg/dL.

Conclusions: Age and CRP were independently associated with disease severity of COVID-19 in multivariate analysis. Additionally, the numbers of underlying disease, lymphocyte count, and inflammatory markers such as LDH and D-dimer may also be related to disease severity.
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http://dx.doi.org/10.1016/j.jiac.2021.02.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931728PMC
June 2021

A case of exogenous lipoid pneumonia diagnosed by transbronchial lung cryobiopsy.

Respir Investig 2021 Jul 5;59(4):555-558. Epub 2021 Mar 5.

Kanagawa Cardiovascular and Respiratory Center, Department of Respiratory Medicine, Tomioka-Higashi 6-16-1, Kanazawa-ku, Yokohama, 236-0051, Japan.

A 57-year-old man visited a referral physician due to abnormal chest shadows. Transbronchial lung biopsy (TBLB) failed to diagnose his condition. As antibiotics and systemic steroids did not improve the condition, he was referred to our hospital. A second TBLB in our hospital also failed to diagnose the disease. Transbronchial lung cryobiopsy (TBLC) was performed using radial endobronchial ultrasound with guide sheath (EBUS-GS), and the patient was diagnosed with lipoid pneumonia. Right upper lobe resection was performed, and lipoid pneumonia was confirmed from the surgical specimen. We report a case of lipoid pneumonia diagnosed by EBUS-GS TBLC.
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http://dx.doi.org/10.1016/j.resinv.2021.02.001DOI Listing
July 2021

Predictive factors for the long-term use of pirfenidone in patients with fibrosing interstitial lung disease.

Respir Investig 2021 Jul 19;59(4):414-420. Epub 2021 Feb 19.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. Electronic address:

Background: Pirfenidone is an anti-fibrotic agent approved for idiopathic pulmonary fibrosis (IPF), and long-term treatment data and the effect of continuation after disease progression have been reported. The efficacy and safety of pirfenidone in fibrosing interstitial lung disease (ILD) patients without IPF have been recently reported in clinical trials; therefore, the benefits of long-term treatment are also expected. This study aims to analyze the long-term treatment data of pirfenidone and clarify the predictive factors for long-term use of pirfenidone in non-IPF patients.

Methods: We retrospectively reviewed the records of consecutive fibrosing ILD patients who started using pirfenidone between 2008 and 2014.

Results: Of the 266 fibrosing ILD patients, 167 patients had IPF, and 99 had non-IPF. Despite the non-significant differences in body size and pulmonary function between IPF and non-IPF patients, the non-IPF patients had better overall survival than the IPF patients (median 4.06 years vs. 2.09 years, p < 0.0001). In addition, the non-IPF patients had a significantly longer time to treatment discontinuation than the IPF patients (median 2.20 years vs. 1.20 years, p = 0.002). Multivariate logistic regression analysis for ≥2 years of use of pirfenidone showed that the percent predicted forced vital capacity (%FVC) and age were predictive factors common to both IPF and non-IPF patients.

Conclusions: Our results indicate that non-IPF patients can continue using pirfenidone for longer durations than IPF patients. Initiation of pirfenidone for fibrosing ILD patients with higher %FVC and younger age would lead to long-term use of pirfenidone.
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http://dx.doi.org/10.1016/j.resinv.2021.01.002DOI Listing
July 2021

Development of an Automated Chemiluminescence Assay System for Quantitative Measurement of Multiple Anti-SARS-CoV-2 Antibodies.

Front Microbiol 2020 15;11:628281. Epub 2021 Jan 15.

Department of Microbiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Objectives: Serological tests for COVID-19 have been instrumental in studying the epidemiology of the disease. However, the performance of the currently available tests is plagued by the problem of variability. We have developed a high-throughput serological test capable of simultaneously detecting total immunoglobulins (Ig) and immunoglobulin G (IgG) against nucleocapsid protein (NP) and spike protein (SP) and report its performance in detecting COVID-19 in clinical samples.

Methods: We designed and prepared reagents for measuring NP-IgG, NP-Total Ig, SP-IgG, and SP-Total Ig (using N-terminally truncated NP (ΔN-NP) or receptor-binding domain (RBD) antigen) dedicated automated chemiluminescent enzyme immunoassay analyzer AIA-CL1200. After determining the basal thresholds based on 17 sera obtained from confirmed COVID-19 patients and 600 negative sera, the clinical validity of the assay was evaluated using independent 202 positive samples and 1,000 negative samples from healthy donors.

Results: All of the four test parameters showed 100% specificity individually (1,000/1,000; 95%CI, 99.63-100). The sensitivity of the assay increased proportionally to the elapsed time from symptoms onset, and all the tests achieved 100% sensitivity (153/153; 95%CI, 97.63-100) after 13 days from symptoms onset. NP-Total Ig was the earliest to attain maximal sensitivity among the other antibodies tested.

Conclusion: Our newly developed serological testing exhibited 100% sensitivity and specificity after 13 days from symptoms onset. Hence, it could be used as a reliable method for accurate detection of COVID-19 patients and to evaluate seroprevalence and possibly for surrogate assessment of herd immunity.
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http://dx.doi.org/10.3389/fmicb.2020.628281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843449PMC
January 2021

Pulmonary vascular enlargement and lesion extent on computed tomography are correlated with COVID-19 disease severity.

Jpn J Radiol 2021 May 27;39(5):451-458. Epub 2021 Jan 27.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama, Kanagawa, 236-8651, Japan.

Purpose: To assess the relationships among pulmonary vascular enlargement, computed tomography (CT) findings quantified with software, and coronavirus disease (COVID-19) severity.

Materials And Methods: Ultra-high-resolution (UHR) CT images of 87 patients (50 males, 37 females; median age, 63 years) with COVID-19 confirmed using real-time polymerase chain reaction were analyzed. The maximum subsegmental vascular diameter was measured on CT. Total CT lung volume (CTLV total) and lesion extent (ratio of lesion volume to CTLV total) of ground-glass opacities, reticulation, and consolidation were measured using software. Maximum pulmonary vascular diameter and lesion extent were analyzed using Spearman's correlation analysis. Logistic regression analysis was performed on CT results to predict disease severity. We also assessed changes in these measures on follow-up scans in 16 patients.

Results: All 23 patients with severe and critical illness had vascular enlargement (> 4 mm). Pulmonary vascular enlargement (odds ratio 3.05, p = 0.018) and CT lesion extent (odds ratio 1.07, p = 0.002) were independent predictors of disease severity after adjustment for age and comorbidities. On follow-up CT, vascular diameter and CT lesion volume decreased (p = 0.001, p = 0.002; respectively), but CTLV total did not change significantly.

Conclusion: Subsegmental vascular enlargement is a notable finding to predict acute COVID-19 disease severity.
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http://dx.doi.org/10.1007/s11604-020-01085-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838849PMC
May 2021

Beneficial impact of weight loss on respiratory function in interstitial lung disease patients with obesity.

Respir Investig 2021 Mar 12;59(2):247-251. Epub 2020 Nov 12.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Background: Interstitial lung disease (ILD) patients commonly become obese or overweight due to deteriorated daily living activities and the adverse effects of prednisolone. This study aimed to clarify the effect of weight loss on pulmonary function test (PFT) in ILD patients with obesity.

Methods: Among all consecutive ILD patients with a body mass index (BMI) ≥ 27 kg/m who received nutrition education for improving obesity between June 2014 and December 2018, we retrospectively included patients who successfully decreased their body weight by over 2 kg and underwent follow-up PFT within 6 months. The results of PFT at baseline and follow-up and the level of Krebs von den Lungen-6 (KL-6) were compared.

Results: Eleven patients (5 men and 6 women; median BMI of 34.1 kg/m), were enrolled. For PFT at baseline, the percentages of forced vital capacity (%FVC), functional residual capacity (%FRC), and diffusing capacity of the lung for carbon monoxide (%DLCO) were 69.3%, 59.9%, and 54%, respectively. The median KL-6 was 1035 U/mL. The median interval from baseline to the follow-up PFTs was 41 days. Compared to the baseline results of PFT, %FVC, %FRC, and %DLCO significantly increased (p = 0.018, 0.0006, and 0.024, respectively), and the changes in body weight and FVC were strongly correlated (p = 0.0004). In addition, the median serum level of KL-6 at follow-up tended to decrease by 206.5 U/mL (p = 0.083).

Conclusion: In ILD patients with obesity, weight loss is important and potentially improves their disease course.
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http://dx.doi.org/10.1016/j.resinv.2020.10.002DOI Listing
March 2021

Evaluation of lymphocytic infiltration in the bronchial glands of Sjögren's syndrome in transbronchial lung cryobiopsy.

BMC Pulm Med 2020 Oct 23;20(1):277. Epub 2020 Oct 23.

Department of Respiratory medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama city, Kanagawa, 236-0051, Japan.

Background: Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by deteriorated exocrine gland function with associated lymphocytic infiltration. However, there are few pathological studies on bronchial glands in SS. In this study, we aimed to clarify pathological features of bronchial glands in SS.

Methods: We retrospectively evaluated infiltration of lymphocytes in the bronchial glands incidentally collected by transbronchial lung cryobiopsy (TBLC), which were performed for the diagnosis of diffuse lung diseases. The degrees of lymphocyte infiltration in the bronchial glands were classified into four grades (grade 0-3). We compared the degrees of infiltration of SS with those of other diffuse lung diseases.

Results: TBLC for diagnosis of diffuse lung diseases were performed on 432 cases during the study period. The samples of 50 cases included bronchial glands. Of those, 20 cases were excluded due to insufficient size or influence of therapy. The remaining 30 cases included 17 of idiopathic interstitial pneumonias, 5 of chronic hypersensitivity pneumonia, 6 of connective tissue disease (SS; n = 4, systemic sclerosis; n = 1, dermatomyositis; n = 1) and 2 of other diseases. In SS, infiltration of lymphocytes was observed in all cases; grade 1 in one, grade 2 in one, and grade 3 in two cases. In contrast, 11 of 26 in other diseases showed no lymphocytes infiltration, with the remaining 15 of grade 1 infiltration. Grade 2 or more infiltration were found only in SS but not in other diseases.

Conclusion: Our results suggested that high-grade lymphocytic infiltration of bronchial glands is a distinct characteristics in SS.
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http://dx.doi.org/10.1186/s12890-020-01318-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585306PMC
October 2020

COVID-19 Pneumonia Resembling an Acute Exacerbation of Interstitial Pneumonia.

Intern Med 2020 Dec 21;59(24):3207-3211. Epub 2020 Oct 21.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

An 84-year-old man was admitted with hypoxemia and ground-glass opacities with traction bronchiectasis in both lungs and mild fibrosis on computed tomography. We first suspected that he had acute exacerbation of interstitial pneumonia and initiated methylprednisolone pulse therapy. On day 4, he was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia. Although the ground-glass opacities were improved with corticosteroid treatment alone, the hypoxemia persisted, and the plasma D-dimer level increased. Anticoagulant therapy was initiated, and the hypoxemia was improved. COVID-19 pneumonia may result in radiological findings similar to those of acute exacerbation of interstitial pneumonia, and corticosteroids and anticoagulant therapy may lead to favorable outcomes.
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http://dx.doi.org/10.2169/internalmedicine.5630-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807128PMC
December 2020

Pneumothorax in a COVID-19 Pneumonia Patient without Underlying Risk Factors.

Intern Med 2020 Nov 7;59(22):2921-2925. Epub 2020 Oct 7.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

Coronavirus disease 2019 (COVID-19) has been recognized as a worldwide pandemic. However, the clinical course of COVID-19 remains poorly characterized. Although some cases of pneumothorax have been reported, they all had pulmonary complications or were managed with mechanical ventilation. We herein report a case of pneumothorax that developed even though the patient had no pulmonary underlying diseases and had never been managed with mechanical ventilation. In the present case, a lung bulla was found on chest computed tomography during treatment for COVID-19. We concluded that COVID-19 affected the formation of the lung bulla and induced the complication of pneumothorax.
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http://dx.doi.org/10.2169/internalmedicine.5731-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725644PMC
November 2020

Inhalation challenge test using pigeon eggs for chronic hypersensitivity pneumonitis.

Clin Exp Allergy 2020 12 18;50(12):1381-1390. Epub 2020 Oct 18.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

Background: Chronic hypersensitivity pneumonitis (CHP) remains a diagnostic challenge. The process of collecting and extracting serum and droppings from causative animals for the inhalation challenge test is complicated and the risk of inducing disease progression exists.

Objective: To investigate the utility and safety of an inhalation challenge test using pigeon eggs.

Methods: Pigeon eggs were pasteurized and mixed with a saline solution to produce an inhalation fluid. An inhalation challenge test was conducted on 19 patients with bird-related CHP and 17 patients with interstitial lung disease other than bird-related CHP. To identify antigens in pigeon eggs, the antigen-antibody responses of the pigeon eggs and serum from patients were evaluated using Western blotting.

Results: The mean changes in C-reactive protein, alveolar-arterial oxygen difference, erythrocyte sedimentation rate, and lactate dehydrogenase significantly increased by 0.32 mg/dL (P = .014), 7.8 Torr (P = .002), 1.4 mm/h (P = .012), and 5.4 U/mL (P = .0019), respectively, in bird-related CHP group compared to the control 24 hours after the inhalation challenge test. Furthermore, within 24 hours of the inhalation test, the mean forced vital capacity decreased by 2.3% in the bird-related CHP group compared with a decline of 0.05% in the control group (P = .035). Serum collected from seven bird-related CHP patients who underwent the inhalation challenge test and reacted to antigens with molecular weights of 37-75 KDa, and these molecular weights were consistent with egg albumin and globulin.

Conclusion: Since a mild response was observed after the inhalation challenge test using pigeon eggs, this test was an obvious candidate for diagnosing bird-related CHP.
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http://dx.doi.org/10.1111/cea.13752DOI Listing
December 2020

Outcome of early-stage combination treatment with favipiravir and methylprednisolone for severe COVID-19 pneumonia: A report of 11 cases.

Respir Investig 2020 Aug 28. Epub 2020 Aug 28.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. Electronic address:

Although the use of corticosteroids is not recommended in the World Health Organization statement for the treatment of coronavirus disease 2019 (COVID-19), steroid therapy may be indicated for critical cases in specific situations. Here, we report the successful treatment of 11 cases of severe COVID-19 pneumonia with favipiravir and methylprednisolone. All cases were severe and patients required oxygen administration or had a blood oxygen saturation ≤93% on room air. All were treated with favipiravir and methylprednisolone, and 10 of 11 patients responded well and required no further oxygen supplementation or ventilator management. This study shows the importance of the early-stage use of a combination of favipiravir and methylprednisolone in severe cases to achieve a favorable clinical outcome.
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http://dx.doi.org/10.1016/j.resinv.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455106PMC
August 2020

Relationship of flow-volume curve pattern on pulmonary function test with clinical and radiological features in idiopathic pulmonary fibrosis.

BMC Pulm Med 2020 Aug 12;20(1):214. Epub 2020 Aug 12.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan.

Background: The flow-volume (FV) curve pattern in the pulmonary function test (PFT) for obstructive lung diseases is widely recognized. However, there are few reports on FV curve pattern in idiopathic pulmonary fibrosis (IPF). In this study, we investigated the relationship between FV curve pattern and clinical or radiological features in IPF.

Methods: The FV curves on PFTs and chest high-resolution computed tomography (HRCT) images of 130 patients with IPF were retrospectively evaluated. The FV curves were divided into four groups based on the presence or absence of the convex and concave patterns: convex/concave, non-convex/concave, convex/non-concave, and non-convex/non-concave. Using a computer-aided system, CT honeycombing area (%HA) and subtracted low attenuation area (%sLAA) were quantitatively measured. To assess the distribution of CT findings, the lung area was divided into upper, lower, central, and peripheral areas. The relationships of FV curve patterns with patient characteristics, spirometry results, and quantitative CT findings were evaluated.

Results: The patients with convex pattern was identified in 93 (71.5%) and concave pattern in 72 (55.4%). Among the four groups, patients with the convex/non-concave pattern had significantly lower forced vital capacity (FVC) and higher %HA of the upper/peripheral lung area (p = 0.018, and p = 0.005, respectively). The convex/non-concave pattern was a significant predictor of mortality for IPF (hazard ratio, 2.19; p = 0.032).

Conclusions: Patients with convex/non-concave pattern in FV curve have lower FVC and poorer prognosis with distinct distribution of fibrosis. Hence, FV curve pattern might be a useful predictor of mortality in IPF.
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http://dx.doi.org/10.1186/s12890-020-01254-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424671PMC
August 2020

In reply.

Jpn J Radiol 2020 11 29;38(11):1109-1110. Epub 2020 Jul 29.

Respiratory Medicine in Kanagawa Cardiovascular and Respiratory Center, 6-16-1, Tomioka-higashi, Kanazawa-ku, Yokohama, 236-8651, Japan.

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http://dx.doi.org/10.1007/s11604-020-01022-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387872PMC
November 2020

Small-cell lung carcinoma transformation of lung adenocarcinoma diagnosed by pericardial effusion: A case report.

Mol Clin Oncol 2020 Aug 3;13(2):129-132. Epub 2020 Jun 3.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa 236-0051, Japan.

The present report describes a case of a 68-year-old male patient with epidermal growth factor receptor (EGFR)-mutant non-small cell lung carcinoma (NSCLC). After cytotoxic chemotherapy of three regimens following 22 months of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, the patient underwent S-1 treatment. Despite a decrease in carcinoembryonic antigen 1 month after initiating S-1 treatment, the patient developed cardiac tamponade. The evaluation of pericardial effusion confirmed small-cell lung carcinoma (SCLC) transformation. Subsequently, a combination therapy of carboplatin and etoposide was administered, which led to a marked improvement in imaging. In patients with NSCLC who develop pericardial effusion after long-term EGFR-TKI therapy, including osimertinib treatment, it is important to investigate whether SCLC transformation occurs or not as a treatable entity.
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http://dx.doi.org/10.3892/mco.2020.2059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366234PMC
August 2020

Unilateral upper lung-field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis after thoracic surgery: Clinical and radiological courses with autopsy findings.

Respir Investig 2020 Jul 10. Epub 2020 Jul 10.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

Background: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by pleural and parenchymal involvements predominantly in the upper lobes. Unilateral upper-lung field pulmonary fibrosis (upper-PF) radiologically consistent with PPFE was recently reported in patients with a history of open thoracotomy and presented with impaired thoracic movements in the operated side with unknown mechanisms. This retrospective study aimed to elucidate the clinical and radiological courses and pathological findings of unilateral upper-PF.

Methods: All the consecutive patients diagnosed as having unilateral upper-PF between March 2012 and April 2018 were included. Radiological images and clinical courses before and after the diagnosis were thoroughly reviewed.

Results: Fourteen patients were included. Unilateral upper-PF was diagnosed after a median of 4.8 years from the open thoracotomy or video-assisted thoracic surgery for treating lung or esophageal cancer, or bronchiectasis. Before or at diagnosis, 12 (85.7%) of 14 patients developed aberrant intrathoracic/extrathoracic air suggestive of pleural fistula, although the degree was slight. Of note, the upper-PF lesion apparently deteriorated once aberrant air emerged in all the patients. After diagnosis, the upper-PF lesion transformed into cystic lesion in 9 patients, 4 of whom eventually developed pulmonary aspergillosis. The prognosis was poor, with a median overall survival of 49.3 months. The autopsy in one patient demonstrated findings consistent with PPFE and chronic pleuritis.

Conclusions: Unilateral upper-PF developed after thoracic surgeries and had many clinical, radiological, and pathological characteristics in common with idiopathic PPFE. Our results indicate that the commonly observed aberrant air may be correlated with disease development and progression.
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http://dx.doi.org/10.1016/j.resinv.2020.05.001DOI Listing
July 2020

Miliary lung metastases from ROS1-rearranged lung adenocarcinoma: A case report.

Mol Clin Oncol 2020 Jul 4;13(1):80-82. Epub 2020 May 4.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa 236-0051, Japan.

Miliary lung metastases are a rare form of metastasis of non-small-cell lung carcinoma. Miliary lung metastases commonly develop in lung adenocarcinoma with epidermal growth factor receptor mutation. In the present study, we present a case of miliary lung metastases from lung adenocarcinoma with ROS1 rearrangement. The patient, who had a history of surgery for stage IIIA lung adenocarcinoma, presented to our hospital with cough, dyspnea, and severe hypoxia. Chest computed tomography showed numerous tiny, randomly distributed nodules throughout both lungs. No metastases were observed in other organs. Molecular profiling of the surgical specimens was positive for ROS1 rearrangement. The results suggest that chest physicians should be aware that miliary lung metastases can develop in patients with lung adenocarcinoma with ROS1 rearrangement.
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http://dx.doi.org/10.3892/mco.2020.2040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241238PMC
July 2020

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma with Smoking History: A Single-Center Experience.

Int Arch Allergy Immunol 2020 19;181(7):522-528. Epub 2020 May 19.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

Introduction: Bronchial thermoplasty (BT) improves asthma-related quality of life and decreases the number of asthma exacerbations. However, the effectiveness of BT in the treatment of severe asthma with smoking history is unclear because previous studies have excluded patients with smoking history of more than 10 pack-years.

Objective: The aim of the study was to clarify the effectiveness and safety of BT for severe asthma with smoking history.

Methods: We retrospectively reviewed patients who received BT and compared its effectiveness and safety with and without smoking history.

Results: Seven patients were assigned to the smoking group and 9 to the nonsmoking group. Before BT, despite Global Initiative for Asthma step 4 or 5 treatment including oral corticosteroids (OCS) or monoclonal antibody drugs, most patients in both groups had asthma-related symptoms every day (85.7 vs. 77.8%; p = 0.475) and frequent asthma exacerbations. After BT, in the smoking group, 3 patients could discontinue or reduce OCS and all 3 patients treated with monoclonal antibody drugs could discontinue them. In the smoking group, 6 patients (85.7%) experienced a reduction in the rate of symptoms, of which 3 patients (42.9%) had a disappearance of symptoms, similar to the nonsmoking group. BT was effective in 5 patients (83.3%) in the smoking group and 6 patients (75.0%) in the nonsmoking group. There were no severe complications.

Conclusions: BT was found to be effective and safe for treatment of severe asthma with smoking history. Our results suggest that BT may be a therapeutic option for asthma-chronic obstructive pulmonary disease overlap.
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http://dx.doi.org/10.1159/000507446DOI Listing
November 2020

Five cases of V600E-mutant lung adenocarcinoma with high expression of programmed death ligand 1.

Respir Med Case Rep 2020 1;30:101071. Epub 2020 May 1.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

We reported consecutive five patients with V600E-mutant recurrent or advanced non-small cell lung cancer who were identified between April 2016 and June 2019. All five patients had high programmed death ligand 1 (PD-L1) tumor proportion scores (50, 55, 75, 95 and 100%). Four of the five patients received regimens including pembrolizumab. Of them, one patient experienced a partial response, but two patients experienced progressive disease and one patient was not evaluable. Three of the four patients received regimens including pemetrexed were able to continue long-term treatment. The presence of a mutation may be associated with higher levels of PD-L1 expression. The effect of immune checkpoint inhibitors therapy in patients with mutation was similar to the previous reports in patients with previously treated advanced non-small cell lung cancer with PD-L1 tumor proportion score ≥50%. Chemotherapy regimens including pemetrexed may have a positive effect in patients with V600E-mutant lung adenocarcinoma. Accumulation of additional Case series is necessary to confirm our results.
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http://dx.doi.org/10.1016/j.rmcr.2020.101071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218153PMC
May 2020

Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia.

Jpn J Radiol 2020 May 31;38(5):394-398. Epub 2020 Mar 31.

Department of Respiratory Medicine, Kanagawa Cardiovascular & Respiratory Centerr, Yokohama, Japan.

Purpose: To review the chest computed tomography (CT) findings on the ultra-high-resolution CT (U-HRCT) in patients with the Novel coronavirus disease 2019 (COVID-19).

Materials And Methods: In February 2020, six consecutive patients with COVID-19 pneumonia (median age, 69 years) underwent U-HR CT imaging. U-HR-CT has a larger matrix size of 1024 × 1024 thinner slice thickness of 0.25 mm and can demonstrate terminal bronchioles in the normal lungs; as a result, Reid's secondary lobules and their abnormalities can be identified. The distribution and hallmarks (ground-glass opacity, consolidation with or without architectural distortion, linear opacity, crazy paving) of the lung opacities on U-HRCT were visually evaluated on a 1 K monitor by two experienced reviewers. The CT lung volume was measured, and the ratio of the measured lung volume to the predicted total lung capacity (predTLC) based on sex, age and height was calculated.

Results: All cases showed crazy paving pattern in U-HRCT. In these lesions, the secondary lobules were smaller than those in the un-affected lungs. CT lung volume decreased in two cases comparing predTLC.

Conclusion: U-HRCT can evaluate not only the distribution and hallmarks of COVID-19 pneumonia but also visualize local lung volume loss.
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http://dx.doi.org/10.1007/s11604-020-00956-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110271PMC
May 2020

Pleural Sarcoidosis Visualized by Three-dimensional Computed Tomography.

Intern Med 2020 06 19;59(12):1577-1578. Epub 2020 Mar 19.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

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http://dx.doi.org/10.2169/internalmedicine.4324-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364252PMC
June 2020

Pulmonary Malignant Ameloblastoma without Local Recurrence 31 Years after Primary Resection: A Case Report and Literature Review.

Intern Med 2020 Jun 5;59(11):1423-1426. Epub 2020 Mar 5.

Respiratory Medicine, Tokyo Metropolitan Toshima Hospital, Japan.

A 78-year-old man with a history of surgical resection for ameloblastoma 31 years earlier visited our hospital for prolonged cough. Chest computed tomography showed multiple nodules in both lungs. Although there was no local recurrence in the mandible, the specimen taken from a transbronchoscopic bronchial biopsy showed recurrent ameloblastoma. Despite receiving no treatment, the disease in our patient remained clinically stable for 8.4 years. Chest physicians should be aware that pulmonary malignant ameloblastoma can first relapse several decades after curative surgery. In addition, pulmonary malignant ameloblastoma without local recurrence may be associated with a good prognosis.
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http://dx.doi.org/10.2169/internalmedicine.3716-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332631PMC
June 2020

Clinical, radiological, and pathological features of anti-asparaginyl tRNA synthetase antibody-related interstitial lung disease.

Respir Investig 2020 May 22;58(3):196-203. Epub 2020 Feb 22.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomiokahigashi, Kanazawa-ku, Yokohama 236-0051, Japan.

Background: Myositis and interstitial lung disease (ILD) frequently occur in patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies. Nearly half of ARS-ILD patients have the acute or subacute form of the disease, and one-third of these patients show a deterioration in pulmonary function over the long-term course because of frequent recurrences and refractoriness to therapy. Several reports recently described different characteristics depending on the individual anti-ARS antibodies, and the anti-asparaginyl tRNA synthetase (KS) antibody was strongly linked to ILD rather than to myositis. We therefore hypothesized that KS-ILD may have clinical characteristics that differ from those of other ARS-ILDs. The aim of this study was to clarify the clinical, radiological, and pathological features of KS antibody-positive ILD.

Methods: We retrospectively analyzed 19 consecutive patients with KS-ILD who underwent initial clinical measurements and high-resolution computed tomography and pathological assessments. We also analyzed disease behavior based on pulmonary function test results during the follow-up period.

Results: Our KS-ILD cohort included patients with dermatomyositis (10.5%), primary Sjögren syndrome (5.3%), and idiopathic ILD (84.2%). Most patients presented with chronic onset (89.5%) and a nonspecific pattern of interstitial pneumonia at each radiological and pathological assessment (89.4% and 85.7%, respectively). The pulmonary function test results showed that the mean changes from the initial %forced vital capacity and %diffusing capacity of the lung for carbon monoxide at 3 years were 3.7% ± 2.9% and 9.35% ± 3.0%, respectively.

Conclusions: Most KS-ILD patients showed a tendency for chronic disease onset and long-term stabilization of pulmonary function.
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http://dx.doi.org/10.1016/j.resinv.2019.12.003DOI Listing
May 2020

A case of intrathoracic desmoid tumor with pulmonary disease.

Respir Med Case Rep 2020 20;29:101001. Epub 2020 Jan 20.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.

A 68-year-old man who was on treatment for pulmonary complex complained a worsening of sputum. Although he archived negative sputum culture two months ago, sputum culture tests revealed the newly isolation of repeatedly. Chest computed tomography showed newly-appeared extra-pulmonary mass lesion in contact with a cyst at the bottom of his right lung. From the results of contrast-enhanced magnetic resonance imaging, we first suspected loculated pleural effusion due to infection. A thoracoscopic examination was performed as the right pneumothorax developed, and the pleural lesion was successfully resected and diagnosed as an intrathoracic desmoid tumor. Intrathoracic desmoid tumor is very rare, and this is the first report of a case with pulmonary disease.
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http://dx.doi.org/10.1016/j.rmcr.2020.101001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992532PMC
January 2020
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