Language：English   Publishing type：Research paper (scientific journal)  

Sarcoidosis is a multisystem disease with an unknown etiology and is characterized by the formation of noncaseating granulomas in the affected organs. We present the case of a 69-year-old male Japanese patient with bilateral hilar lymphadenopathy on chest radiographs for more than 10 years, left without further investigation. The patient reported no clinical symptoms. Chest computed tomography revealed ground-glass opacities and reticular shadows in both lungs, along with bilateral hilar and mediastinal lymphadenopathy. Lymphocytosis was observed in bronchoalveolar lavage fluid. Pathological examination of transbronchial lung biopsy revealed noncaseating, epithelioid granulomas congruous with sarcoidosis, together with other findings. There were no abnormalities on electrocardiogram, echocardiogram, and ophthalmic examination.For progressive dyspnea on exertion, systemic corticosteroid therapy with oral prednisolone (25 mg/day) was initiated in 2017 and gradually tapered. Despite this intervention, the decline in forced vital capacity (FVC) was accelerated. Three years later, the patient noticed swelling in his right wrist. Further investigation revealed elevated anti-cyclic citrullinated peptide antibodies and absence of noncaseating epithelioid granuloma on surgical biopsy, leading to the diagnosis of rheumatoid arthritis (RA). Thereafter, the anti-fibrotic agent nintedanib was initiated, because interstitial lung disease (ILD) was considered to have converted into a progressive fibrosing phenotype (PF-ILD) with overlapping RA-associated lung involvement. With treatment, the progression of decline in FVC was slowed, although home oxygen therapy was introduced.

DOI： 10.1177/17534666231158279

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Some of the most common causes of chronic cough include cough variant asthma (CVA), bronchial asthma (BA), and asthma-COPD overlap (ACO). Although there is some overlap in the etiology of these diseases, it is clinically important to attempt an early differential diagnosis due to treatment strategies and prognoses. Spirometry and impulse oscillometry (IOS) before and after bronchodilator inhalation were analyzed for clinically diagnosed CVA (cCVA, n = 203), BA (cBA, n = 222), and ACO (cACO, n = 61).A significant difference in ΔFEV1 was observed between cBA and cCVA (ΔFEV1 improvement of 122.5 mL/5.4% and 65.7mL/2.2%, respectively), but no difference was observed in ΔPEF, ΔV50, or ΔV25. Except for R20 (resistance at 20 Hz), significant differences between the three groups were observed in IOS. In IOS, cCVA and cBA showed comparable peripheral airway response to bronchodilator which was thought to be commensurate with changes in V50 and V25. cACO improved ΔFEV1 improvement of 81.0 mL/6.2% and was distinguished by a downward Xrs (respiratory system reactance) waveform with a limited bronchodilator response. FEV1/FVC, %FEV1, and %V25 had relatively strong correlations with the three IOS parameters, X5 (reactance at 5 Hz), Fres (resonant frequency), and ALX (low-frequency reactance area), in the correlation between IOS and spirometers.Changes in IOS parameters were more sensitive in this study than changes in FEV1 or the flow-volume curve. Considering the benefits and relevance of the two different tests, simultaneous IOS and spirometry testing were useful in the diagnosis of asthmatic cough.

DOI： 10.1080/02770903.2022.2094803

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Background The role of inhaled corticosteroid (ICS) in chronic obstructive pulmonary disease (COPD) is unclear. Hence, this study aimed to evaluate the efficacy of ICS as an add-on to long-acting muscarinic antagonist (LAMA)/long-acting beta 2 agonist (LABA), which was assessed using the impulse oscillation system (IOS), in patients with COPD. Methodology We included patients with COPD whose treatment was changed from LAMA/LABA (≥four weeks) to ICS/LAMA/LABA between April 2019 and March 2021. To gain insight into the effect and safety of ICS-containing triple therapy for COPD, pulmonary function; Short-Form 36, St. George's Respiratory Questionnaire, COPD Assessment Test, and modified Medical Research Council scores; and airway resistance assessed using the IOS from one week before LAMA/LABA was switched to ICS/LAMA/LABA therapy until more than eight but less than twelve weeks after switching were evaluated. Results In total, 46 patients with COPD (mean age: 72.28 ± 7.81 years) were included in the study. None of the pulmonary function test parameters significantly changed from baseline values (mean difference in forced expiratory volume in one second [FEV1.0]: +0.032, P = 0.12; percentage FEV1.0 [FEV1.0%]/forced vital capacity [FVC]: -0.58, P = 0.42; and FVC: +0.087, P = 0.058). Meanwhile, the IOS showed that resonant frequency (mean difference from baseline: -2.12, P < 0.0001) and bodily pain scores in the St. George's Respiratory Questionnaire (mean difference: -7.03, P = 0.031) significantly decreased. Conclusions Switching from LAMA/LABA to ICS/LAMA/LABA therapy reduces airway elasticity-to-inertial resistance ratios, which may lead to structural airway improvements in patients with COPD.

DOI： 10.7759/cureus.19168

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

The patient was a 65-year-old man who developed dyspnea after 6 courses of S-1 and oxaliplatin(SOX)chemotherapy for advanced stomach cancer. The chemotherapy regimen consisted of SOX chemotherapy. The patient developed hypoxemia, and chest radiography revealed ground-glass opacity in both lungs. Bronchoscopy and DLST led to a diagnosis of druginduced lung injury caused by S-1. Although steroid pulse therapy was administered, the patient's condition deteriorated rapidly and was ultimately fatal. Based on the clinical course and histopathological findings, a DAD-type lung disorder was diagnosed. This description of a DAD-type drug-induced lung injury caused by S-1, for which histopathological findings were available in the early stages, is clinically valuable. We report this case along with a review of the relevant literature.

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BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) is 8.6% in Japan and 10% worldwide. Unfortunately, many patients with COPD are not correctly identified and appropriately educated regarding the condition. In this paper, we demonstrate that some citizens of Ebina City with symptoms suspicious for COPD, such as cough, sputum production, and shortness of breath, have undiagnosed COPD. We describe our activities to raise awareness of COPD through a 10-year campaign. METHODS: From 2006 to 2015, we developed activities to raise awareness of COPD, including public lectures, utilization of pulmonary function tests, and questionnaires on subjective symptoms and knowledge of COPD. RESULTS: Among 1,206 participants aged>40 years, COPD was suspected in 5.6%, as indicated by airway obstruction (i.e. forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio (FVC) <0.70). However, most of these participants were not diagnosed with COPD. Furthermore, half of these participants had not consulted a medical institution despite demonstrating symptoms. Results of the COPD awareness questionnaire, which was administered to 1,055 people, indicated that 65% of survey respondents were unaware of COPD. CONCLUSIONS: There are individuals with symptoms suspicious for COPD who are unaware of the disease at the Plaza in Ebina City. Clinicians have a responsibility to raise public awareness of COPD and to reduce the prevalence of COPD and its associated mortality.

DOI： 10.1272/jnms.JNMS.2019_86-6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Flu vaccinations are administered worldwide every winter for prevention. We herein describe a case of acute lung injury resulting from a pathologically confirmed alveolar hemorrhage, which may have been closely related to a preceding vaccination for pandemic influenza A of 2009/10. The present patient had been hospitalized with an acute lung injury after flu vaccination one year prior to the present hospitalization, however, he received another flu vaccination. We should consider a vaccine-related adverse reaction as a potential cause of pulmonary disease if patients present with this illness during the winter season.

DOI： 10.2169/internalmedicine.54.4894

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Histiocytes of Langerhans cell type are recovered from the bronchoalveolar lavage fluid (BALF) of patients with interstitial lung diseases in a nonspecific manner. Langerhans cells (LCs) can be identified through immunostaining for S-100, CD1a, and, more specifically, langerin. To evaluate the diagnostic value of BALF in pulmonary Langerhans cell histiocytosis (PLCH), we performed a retrospective clinicopathological study of 5 patients with biopsy- confirmed PLCH or Hand-Schuller-Christian disease involving the lung. As a control study, we examined BALF cells from 23 patients with various diseases, including sarcoidosis, hypersensitivity pneumonitis, collagen vascular disease, idiopathic pulmonary fibrosis, and adenocarcinoma of the lung. Cytospins obtained from BALF were stained withGiemsa or Papanicoloau and others were immunostained. In general, cytospins showed a monomorphous and dispersed cell population containing mononucleated or binucleated and occasionally multinucleated histiocytes. LCs recovered from BALF were characterized by clear and velvety cytoplasm
oval or kidney-shaped, vesicular nuclei with irregular shapes
nucleoli
and frequent grooves and indentations. Radiography and high-resolution computed tomography showed multiple bilateral nodular or cystic lesions in the middle and upper lung zones. The mean percentage of LCs in 9 lavages from the 5 patients was 8.0%, whereas that from the control group was only 0.3% (maximum, 1.6%). The percentage of cells positive for S-100 or CD1a was comparable to the percentage of Langerhans-like histiocytes stained with Giemsa stain. The present results indicate that the survey of LCs in BALF with the aid of immunocytochemical evaluation and corresponding clinical data could play a critical role in establishing the diagnosis of PLCH, thus providing a less invasive approach than lung biopsy, which carries a risk of complications.

DOI： 10.1272/jnms.76.84

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IVYSPRING INT PUBL  

Background. The value of bronchoalveolar lavage (BAL) still remains controversial, prompting a need for further improvement. The purpose of this study was to develop and evaluate a sequential analysis of cell content in fractional BAL (FBAL) from the airways and alveolar sacs with incorporation of the cellular morphologic features. Methods. Initially, 30 ml saline was infused into a subsegmental lobe of the lung and the recovered fluid was assigned as FBAL-I being mainly originated from whole airways. The second and third lavages (FBAL-II and FBAL-III) each were performed using 50 ml saline being from more distal portions of airways and alveolar sacs respectively in the same lobe. Total cell number/ml and percentages of macrophages, lymphocytes, neutrophils, and eosinophils in each fraction together with their morphological alterations and mast cells, basophils and Masson bodies were assessed. Results. In the 12 controls, percentage of neutrophils was high and lymphocytes and macrophages were low in FBAL-I while in FBAL-III, neutrophils decreased to nearly nil and lymphocytes and macrophages were increased. Analysis of FBAL from 76 patients with sarcoidosis and 14 with hypersensitivity pneumonitis (HP) revealed that a predominance of small, round and well-differentiated lymphocytes with relative absence of neutrophils, basophils and Masson bodies correlated best with sarcoidosis. In contrast, neutrophil predominance and presence of lymphocytes having deep nuclear indentations and abundant cytoplasm with a process resembling a "hand-mirror" correlated well with HP. Conclusions. Evaluation of FBAL together with cellular morphological features especially characteristics of lymphocytes provides valuable information for establishing the diagnosis in interstitial lung diseases.

DOI： 10.7150/ijms.6.1

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Language：Japanese   Publisher：克誠堂出版(株)  

われわれはBAL法で3回吸引する各回収液の細胞を分析するfractional analysis of BAL(FBAL)法により、胞領領域における炎症程度を気道系から分離することで、末梢肺野の病態を評価してきた。通常の麻酔処置の後、初回に30ml(FBAL-I)の生食水を、2度、3度目にそれぞれ50ml(FBAL-II,III)を用いて洗浄・回収した。それぞれの回収率、総細胞数を算定後、遠心分離し、ギムザ染色およびパパニコロー染色で観察した。また肺胞腔内の被包化されたMasson bodyの有無やリンパ球、好中球分画比、そしてリンパ球形態に着目した結果、サルコイドーシスと過敏性肺炎(HP)に顕著な特徴があることを見出した。(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2009023916

Language：Japanese   Publisher：克誠堂出版  

CiNii Books

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Asthma is a chronic inflammatory disease characterized by airway wall remodeling in which vascular remodeling is thought to be a main contributor. Vascular endothelial growth factor ( VEGF) is known as a major regulator of angiogenesis and enhancer of vascular permeability. Here, we define the spatial nature of vascular remodeling and the role of VEGF and its receptors (Flt-1 and Flk-1) in the allergic response in mice (A/J) susceptible to the development of allergen-induced airway hyperresponsiveness using morphometric and quantitative approaches. Increased vascularity, vasodilatation, and endothelial cell proliferation were found in the tracheal and bronchial walls in the early and late phases of asthma. Vascular changes were observed not only in small vessels but also in larger vessels. In contrast to normal control, lung tissue from the asthma model showed dual expression for CD31 and von Willebrand factor in the endothelial cells and alpha-smooth muscle actin and desmin in the mural cells of the vessels, suggesting a phenotypic and functional transformation. The mRNA levels of VEGF isoforms, VEGF 164 and VEGF 188, were significantly increased in the tracheal and lung tissue, respectively. In addition, the mRNA level of VEGF receptor Flk-1 was significantly increased in the trachea. These results establish the existence of vascular remodeling in the airways in a mouse model of allergic asthma and support a key role for the expression of unique VEGF isoform genes as mediators of structural changes. Copyright (c) 2008 S. Karger AG, Basel

DOI： 10.1159/000113794

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The vascular endothelial cells (ECs) express various antigens related to coagulation factors, including factor VIII-related antigen or von Willebrand factor (vWF) in the cytoplasm and thrombomodulin (TM
a thrombin receptor) along the plasma membrane. CD34 (a hematogenic stem cell marker) is also expressed along the surface membrane of the ECs. Using these EC markers and fluorescein-isothiocyanate-labeled dextran (FITC-dextran) (Sigma Co., St. Louis, MO), we attempted to demonstrate the complex network of microvessels and their EC phenotypes in tracheo-bronchial trees and lung parenchyma of the normal adult ICR male mice. Under anesthesia, saline with heparin was infused slowly through left ventricle to drain off the blood. Following brief fixation with 4% buffered paraformaldehyde solution (PFA) through the same route, one group of animals received, 1) FITC-dextran injection via left ventricle, and the large airways and lungs were further fixed in PFA, or 2) The airways and lungs of the other group were rapidly frozen, and the thin sections were stained with two antibodies of vWF and Alexa Fluor 594-labeled CD34. The vWF antibody was later labeled by FITC. The microvessels of airways and lungs were observed by a laser scanning confocal microscope (TC-SP, Leica, Heidelberg, Germany). The phenotypic characteristics of microvessel ECs appeared mostly identical with those described previously in the human lung 12, although CD34 was applied instead of TM in the present study. The topographical heterogeneity of immunohistochemical properties of ECs would suggest functional differences at different sites of the lung, that would provide a novel insight for understanding the pathogenesis of human lung diseases.

DOI： 10.1272/jnms.72.314

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J04260&link_issn=&doc_id=20220307420006&doc_link_id=10.1272%2Fmanms.18.37&url=https%3A%2F%2Fdoi.org%2F10.1272%2Fmanms.18.37&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：(株)癌と化学療法社  

症例は65歳、男性。進行胃癌に対しS-1+oxaliplatin(SOX)療法を6コース施行後に呼吸困難が出現し、低酸素血症と胸部CTで両側上葉優位にすりガラス陰影を認めた。気管支鏡検査、DLSTを施行しS-1による薬剤性肺障害と診断した。ステロイドパルス療法を行うも急速に呼吸状態が悪化し死亡した。臨床経過と病理組織学的所見よりDAD型肺障害と診断した。本例は発症早期の病理所見が得られたS-1によるDAD型薬剤性肺障害の貴重な症例であり、文献的考察を含め報告する。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00296&link_issn=&doc_id=20190919200021&doc_link_id=%2Fab8gtkrc%2F2019%2F004609%2F022%2F1457-1460%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2019%2F004609%2F022%2F1457-1460%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：日本結核病学会関東支部学会・日本呼吸器学会関東地方会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：特定非営利活動法人日本臨床細胞学会  

CiNii Books

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：日本サルコイドーシス  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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