Publications by authors named "Kei Yamasaki"

104 Publications

A Case of Empyema with Rare Chest Findings.

Intern Med 2020 03 18;59(5):753-754. Epub 2019 Nov 18.

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

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http://dx.doi.org/10.2169/internalmedicine.3500-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086310PMC
March 2020

Bullous Pemphigoid in a Patient Treated with Pembrolizumab.

Intern Med 2020 01 11;59(1):139-140. Epub 2019 Sep 11.

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

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http://dx.doi.org/10.2169/internalmedicine.3264-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995718PMC
January 2020

Pulmonary Artery Intimal Sarcoma Mimicking a Pulmonary Thromboembolism.

Intern Med 2019 12 28;58(24):3599-3600. Epub 2019 Aug 28.

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

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http://dx.doi.org/10.2169/internalmedicine.3246-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949436PMC
December 2019

Temporal echocardiographic assessment of pulmonary hypertension in idiopathic pulmonary fibrosis patients treated with nintedanib with or without oxygen therapy.

BMC Pulm Med 2019 Aug 22;19(1):157. Epub 2019 Aug 22.

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

Background: Nintedanib is an inhibitor of receptor tyrosine kinases, including vascular endothelial growth factor receptor, but its effects on pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) patients with chronic hypoxia were unclear.

Methods: This study included a nintedanib prospective study and historical control study. In the nintedanib prospective study, pulmonary artery systolic pressure (PASP) measured using transthoracic echocardiography was evaluated at six points during 48 weeks in 16 IPF patients in whom nintedanib was started. In the historical control study, adjusted annual change in PASP was compared between patients treated with (n = 16) and without (n = 15) nintedanib.

Results: In the nintedanib prospective study, the mean PASP at 48 weeks after starting nintedanib was significantly higher compared to that at baseline. When IPF patients were divided into two groups, IPF patients with or without long-term oxygen treatment (LTOT), mean PASP at 48 weeks was significantly higher than that at baseline only in IPF patients receiving LTOT (P = 0.001). In the historical control study, adjusted annual change in PASP in IPF patients treated with nintedanib was significantly lower than that in patients treated with no antifibrotic agents when considering patients without LTOT (0.26 mmHg vs 7.05 mmHg; P = 0.011).

Conclusions: We found differential effects of nintedanib on PH between IPF patients with or without LTOT. Nintedanib may have a disadvantageous effect on PH in IPF patients with LTOT. Conversely, nintedanib treatment may be beneficial to PH in IPF patients without LTOT.
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http://dx.doi.org/10.1186/s12890-019-0918-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704493PMC
August 2019

Poor oral hygiene is associated with the detection of obligate anaerobes in pneumonia.

J Periodontol 2020 01 21;91(1):65-73. Epub 2019 Oct 21.

Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: Oral cavity is a reservoir of various respiratory pathogens, and poor oral hygiene is associated with an increase in anaerobic bacteria in oral cavity. In addition, it positively relates higher risk of developing pneumonia and increased pneumonia-related mortality. However, the association between poor oral hygiene and increase in obligate anaerobes in the lungs of pneumonia patients is unclear.

Methods: A total of 39 patients with pneumonia in whom bronchoscopic examination and oral hygiene evaluation were performed were prospectively enrolled. The microbiota of the bronchoalveolar lavage fluid (BALF) directly obtained from the pneumonia lesion was analysed by the clone library analysis. In addition, oral hygiene evaluations were performed using oral hygiene index (OHI), tongue coating score, oral dryness, and community periodontal index of treatment needs (CPITN). The association between the detection of oral streptococci and obligate anaerobes and oral hygiene status was evaluated.

Results: Using the clone library analysis of BALF, the phylotypes of oral streptococci and obligate anaerobes were detected in 31 (79.5%) and 26 (66.7%) patients, respectively. Increased oral dryness, OHI, and CPITN, but not the tongue coating score, significantly correlated with higher rate of detection of obligate anaerobes, although no significant associations between the detection of oral streptococci in the lungs and each oral hygiene evaluation were observed. Significantly higher number of obligate anaerobes were detected in the lungs in patients with total oral hygiene score of ≥ 5 (P = 0.008).

Conclusion: Poor oral hygiene is associated with increased obligate anaerobes in the lungs of patients with pneumonia.
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http://dx.doi.org/10.1002/JPER.19-0043DOI Listing
January 2020

Distribution and annual changes in the proportion of Streptococcus pneumoniae serotypes in Japanese adults with pneumococcal pneumonia from 2011 to 2017.

J Infect Chemother 2019 Nov 24;25(11):925-929. Epub 2019 Jul 24.

Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan.

In 2014, vaccinations with 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13) were implemented in Japan for all adults aged ≥65 years. We previously clarified reductions in the proportions of PCV7-, PCV13-, and PPSV23-covered serotypes in patients with pneumococcal pneumonia after the initiation of PCV7 and PCV13 vaccinations for Japanese children; however, information about the annual changes in the proportion of Streptococcus pneumoniae serotypes in patients with pneumococcal pneumonia after the initiation of routine PPSV23 vaccinations remains unclear. We retrospectively studied 229 adults with pneumococcal pneumonia which S. pneumoniae was cultured from their lower respiratory tract samples between 2011 and 2017 and investigated the annual changes in the proportion of S. pneumoniae serotypes. The proportion of PPSV23-covered serotypes decreased from 71.4% in 2011 to 52.2% in 2014, but it remained essentially unchanged from 2015 to 2017. The proportions of PCV7-covered serotypes decreased from 46.4% in 2011 to 4.3% in 2014; however, this rate increased beginning in 2015 and reached 20.6% in 2017. Among the PCV7-covered serotypes, the proportion of the 19F serotype increased from 2015 to 2017. In conclusion, there were no obvious changes in the proportion of PPSV23-covered and PCV13-covered serotypes in patients with pneumococcal pneumonia after the initiation of routine PPSV23 vaccinations.
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http://dx.doi.org/10.1016/j.jiac.2019.07.007DOI Listing
November 2019

A Case of Lemierre Syndrome Complicated with Empyema.

Intern Med 2019 12 22;58(23):3485-3486. Epub 2019 Jul 22.

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

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http://dx.doi.org/10.2169/internalmedicine.3332-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928514PMC
December 2019

[A Case of Left Upper Lobe Lung Cancer Successfully Diagnosed by Transesophageal Endoscopic Ultrasound with Bronchoscope-Guided Fine Needle Aspiration Alone].

J UOEH 2019 ;41(2):243-248

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

A 58-year-old Japanese woman with fever and cough visited A hospital. Her chest X-ray and CT showed a tumor attached to the mediastinum in the left upper lobe with mediastinal lymphadenopathy (#4R). After an introduction from A hospital to our hospital, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the mediastinal lymphadenopathy and a simultaneous approach to the mass lesion in the left upper lobe were performed. In spite of twice aspiration by EBUS-TBNA for mediastinal lymphadenopathy, we failed to obtain enough specimens, and, as the mass lesion in the left upper lobe was invisible in the endobronchial ultrasound, we could not approach it. Then using the same ultrasound bronchoscope, we subsequently performed a transesophageal endoscopic ultrasound with bronchoscope-guided fine needle aspiration (EUS-B-FNA) to the mass lesion in the left upper lobe twice, with the result that sufficient tissues were obtained. Then we changed from the ultrasound bronchoscope to a normal bronchoscope and we performed brushing and transbronchial lung biopsy for the left upper lobe mass lesion. Pathological results revealed that only the specimens obtained by EUS-B-FNA were diagnostic for adenocarcinoma; the other specimens obtained using EBUS-TBNA and normal bronchoscope failed to be diagnostic. EUS-B-FNA in combination with EBUS-TBNA has been recommended for the diagnosis of mediastinal and near-mediastinal lesions in the guidelines of the American College of Chest Physicians in 2013, but EUS-B-FNA has not been widely used in Japan. As shown in our present patient who was successfully diagnosed as having lung cancer by EUS-B-FNA alone, respiratory physicians should be aware of being skillful at performing EUS-B-FNA to accurately and effectively approach target lesions.
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http://dx.doi.org/10.7888/juoeh.41.243DOI Listing
December 2019

[Evaluation of the Influence of the Experience and Training of EBUS-TBNA on Diagnostic Rate and Safety].

J UOEH 2019 ;41(2):179-184

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

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely used in Japan. The guidelines of the American College of Chest Physicians has recommended that EBUS-TBNA should be performed by well-trained operators who can perform highly accurate procedures, but the indicators of the degree of experience and training are unclear. In our department, physicians who do not have enough experience perform EBUS-TBNA under the supervision of bronchoscopic instructors who have EBUS-TBNA techniques (Board Certified Member of the Japan Society for Respiratory Endoscopy) after guidance and training in EBUS-TBNA using a simulator as an operator and helper. In order to evaluate the influence of the experience and training of EBUS-TBNA on diagnostic accuracy and safety, we retrospectively compared the diagnostic accuracy and safety of EBUS-TBNA performed by physicians within one year of experience of EBUS-TBNA and those performed by physicians with more than one year of experience. A total of 111 cases (148 lesions) who were eventually diagnosed as having primary lung cancer and underwent EBUS-TBNA in our department between April 2014 and January 2016 were divided into two groups. Group A (43 cases, 57 lesions) was examined by third-year doctors within one year of experience of EBUS-TBNA, and group B (68 cases, 91 lesions) was examined by doctors with four or more years of experience and with more than one year of experience of EBUS-TBNA. Diagnostic rate, examination time, and complications were evaluated. There were no significant differences between the two groups in the diagnostic rate (A, 89.5% vs. B, 90.1%, P = 1.0) or examination time (A, 27 min vs. B, 23 min, P = 0.149), and no complications were observed in either group. This study suggests that even less-experienced physicians may safely perform EBUS-TBNA as well as moderately-experienced physicians with more than 1 year experience of EBUS-TBNA with similar diagnostic rates when proper training and supervision are supplied.
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http://dx.doi.org/10.7888/juoeh.41.179DOI Listing
December 2019

Induction of plasmid-mediated AmpC β-lactamase DHA-1 by piperacillin/tazobactam and other β-lactams in Enterobacteriaceae.

PLoS One 2019 8;14(7):e0218589. Epub 2019 Jul 8.

Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki City, Nagasaki, Japan.

Chromosomal AmpC β-lactamase induction by several types of β-lactams has been reported, but not enough data are available on DHA-1 β-lactamase, a plasmid-mediated AmpC β-lactamase. Therefore, we evaluated the DHA-1 β-lactamase induction by various antibiotics including piperacillin/tazobactam (PIP/TZB) in this study. Six strains (Enterobacter cloacae 2 strains, Citrobacter freundii 1 strain, Serratia marcescens 2 strain, and Morganella morganii 1 strain) possessing chromosomal inducible AmpC β-lactamase were used as controls. Four strains (Escherichia coli 2 strains, Klebsiella pneumoniae 1 strain, and C. koseri 1 strain) possessing DHA-1 β-lactamase were used. The β-lactamase activities were determined by a spectrophotometer using nitrocefin. β-lactamase induction by PIP, PIP/TZB was not observed in any strains and β-lactamase induction by third- and fourth-generation cephems was not observed in most strains. The induction ratios of the chromosomal AmpC β-lactamase in the reference group by PIP/TZB were <1.51, and those of the DHA-1 β-lactamase were <1.36, except for K. pneumoniae Rkp2004 (2.22). The β-lactamase induction by first- and second-generation cephems, flomoxef, and carbapenem differed in each strain. Cefmetazole (CMZ) strongly induced β-lactamase. This study demonstrated that the induction of DHA-1 β-lactamase was similar to that of chromosomal AmpC using various Enterobacteriaceae, although the induction of β-lactamase in both groups by PIP/TZB was low. We also reported that the induction of PIP/TZB, a β-lactamase inhibitor combination antibiotic, against various AmpC-producing Enterobacteriaceae, including DHA-1 producers, was low.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218589PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613692PMC
February 2020

[A Case of Drug-Induced Lung Injury Caused by Kamikihito].

J UOEH 2019 ;41(1):51-56

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

An eighty-nine-year-old Japanese male was admitted to our hospital due to dry cough and dyspnea. Respiratory symptoms appeared soon after an administration of an oriental medicine, Kamikihito for tinnitus. Upon admission, chest computed tomography showed patchy consolidations and ground-glass opacities in the right upper lobe of the lungs, and ground-glass opacities in the bilateral lower lobes. Sulbactam-ampicillin combination (SBT/ABPC, 3 g × 2/day) was started in addition to the change or cessation of several other drugs, including Kamikihito, resulting in respiratory symptoms and chest radiographic exacerbations. Bronchoalveolar lavage fluid obtained from the right S showed an increase in the total cell number of lymphocytes. A drug lymphocyte stimulation test (DLST) for Kamikihito was also positive. Kamikihito-induced lung injury was most likely, and treatment with prednisolone (50 mg/day) was started. His respiratory symptoms and chest radiographic findings improved rapidly soon after initiating oral prednisolone. This is the first report of Kamikihito-induced lung injury.
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http://dx.doi.org/10.7888/juoeh.41.51DOI Listing
April 2019

The Successful Removal of a Broken Needle as an Unusual Complication of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA): A Case Report and Literature Review.

J UOEH 2019 ;41(1):35-40

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

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is recommended for the diagnosis of mediastinal lymph nodes by the American College of Chest Physicians guidelines; however, the guidelines state that this procedure should only be performed by a trained bronchoscopist. Complications related to needle malfunction during the EBUS-TBNA procedure have recently been reported. We herein describe a rare case involving the successful management of a needle breakage that occurred as an unusual complication of EBUS-TBNA. An 81-year-old male patient with a medical history of myocardial infarction was introduced to our institution to undergo an evaluation for mediastinal and right hilar lymphadenopathy on chest computed tomography (CT). We performed EBUS-TBNA in a 14×10 mm subcarinal lymph node station using a 22 G aspiration needle (NA-201SX-4022, Vizishot®, Olympus, Japan) for diagnosing and staging of the patient's lung cancer. After the second aspiration, we noticed that the needle tip was broken and that it was stuck in the right main bronchus. We immediately removed the broken needle tip from the right main bronchus by flexible bronchoscopy using an ID 8.5 mm tracheal tube without cuff inflation. The length of the needle tip was 13 mm and it was considerably bent. The EBUS scope did not suffer any apparent damage. The patient did not have any other procedure-related complications. Needle breakage during EBUS-TBNA is rare; however, inhaling or swallowing of a broken needle tip has the potential to cause serious complications. Bronchoscopists should therefore be aware of the possibility of needle breakage, which is an important complication during EBUS-TBNA.
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http://dx.doi.org/10.7888/juoeh.41.35DOI Listing
April 2019

Pulmonary Nocardiosis Caused by Nocardia exalbida in a Patient with Lung Cancer and Radiation Pneumonitis: A Case Report and Literature Review.

Intern Med 2019 Jun 1;58(11):1605-1611. Epub 2019 Feb 1.

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

We report a case of Nocardia exalbida (N.exalbida)-induced pneumonia in a 70-year old Japanese man with lung cancer and radiation pneumonitis. He initially received doripenem (1.5 g/day) for pneumonia treatment, and N.exalbida was identified by a clone library analysis of bronchoalveolar lavage fluid obtained from the pneumonia lesion. The doripenem dosage was therefore increased to 3.0 g/day with adjunctive trimethoprim/sulfamethoxazole, and his pneumonia improved. N. exalbida is susceptible to antibiotics; thus, in nocardiosis, N. exalbida infection might be associated with a good response to treatment, although its clinical findings are non-specific and similar to those of other Nocardia infections.
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http://dx.doi.org/10.2169/internalmedicine.2177-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599924PMC
June 2019

Utility of the Quick Sequential Organ Failure Assessment in Japanese patients with nursing- and healthcare-associated pneumonia.

Geriatr Gerontol Int 2019 Mar 16;19(3):177-183. Epub 2018 Dec 16.

Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Aim: To clarify the utility of sepsis evaluation using the Quick Sequential Organ Failure Assessment (qSOFA) tool in addition to the Pneumonia Severity Index (PSI); age, dehydration, respiration, orientation and blood pressure (A-DROP) index; and immunodeficiency, respiration, orientation, age and dehydration (I-ROAD) scoring systems, and risk factor evaluation of potentially drug-resistant (PDR) pathogens are suggested in the 2017 guidelines for pneumonia of the Japanese Respiratory Society in nursing- and healthcare-associated pneumonia patients.

Methods: We included 289 hospitalized nursing- and healthcare-associated pneumonia patients between April 2016 and March 2017, and investigated the ability of PSI, A-DROP, I-ROAD and qSOFA to predict pneumonia-related mortality. We also evaluated the associations among the risk factors for PDR pathogens, the detection ratio of PDR pathogens and pneumonia-related mortality.

Results: The mortality rate of pneumonia during hospitalization was 6.9% (20/289). The area under the curve for pneumonia-related mortality predicted using PSI, A-DROP, I-ROAD and qSOFA was 0.697 (95% confidence interval [CI] 0.59-0.80), 0.63 (95% CI 0.51-0.76), 0.61 (95% CI 0.52-0.70) and 0.701 (95% CI 0.59-0.81), respectively. In addition, higher areas under the curve were observed for pneumonia-related mortality predicted according to a combination of PSI and hypoalbuminemia (<2.5 g/dL) (0.75, 95% CI 0.64-0.86), and qSOFA and hypoalbuminemia (0.74, 95% CI 0.62-0.86) than for PSI and qSOFA alone. No significant associations were observed among the risk factors for PDR pathogens, the detection ratios of PDR pathogens and pneumonia-related mortality.

Conclusions: qSOFA and the combination of qSOFA and hypoalbuminemia might be simple and useful evaluation tools for predicting pneumonia-related mortality in nursing- and healthcare-associated pneumonia patients. Geriatr Gerontol Int 2019; 19: 177-183.
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http://dx.doi.org/10.1111/ggi.13581DOI Listing
March 2019

Lung Macrophage Phenotypes and Functional Responses: Role in the Pathogenesis of COPD.

Int J Mol Sci 2018 Feb 15;19(2). Epub 2018 Feb 15.

Centre for Heart Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, BC V6Z1Y6, Canada.

Lung macrophages (LMs) are essential immune effector cells that are pivotal in both innate and adaptive immune responses to inhaled foreign matter. They either reside within the airways and lung tissues (from early life) or are derived from blood monocytes. Similar to macrophages in other organs and tissues, LMs have natural plasticity and can change phenotype and function depending largely on the microenvironment they reside in. Phenotype changes in lung tissue macrophages have been implicated in chronic inflammatory responses and disease progression of various chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). LMs have a wide variety of functional properties that include phagocytosis (inorganic particulate matter and organic particles, such as viruses/bacteria/fungi), the processing of phagocytosed material, and the production of signaling mediators. Functioning as janitors of the airways, they also play a key role in removing dead and dying cells, as well as cell debris (efferocytic functions). We herein review changes in LM phenotypes during chronic lung disease, focusing on COPD, as well as changes in their functional properties as a result of such shifts. Targeting molecular pathways involved in LM phenotypic shifts could potentially allow for future targeted therapeutic interventions in several diseases, such as COPD.
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http://dx.doi.org/10.3390/ijms19020582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855804PMC
February 2018

The role of beta-blockers in the management of chronic obstructive pulmonary disease.

Expert Rev Respir Med 2018 02 27;12(2):125-135. Epub 2017 Dec 27.

a Centre for Heart Lung Innovation, St. Paul´s Hospital, & Department of Medicine , University of British Columbia , Vancouver , BC , Canada.

Introduction: The use of beta-blockers in chronic obstructive pulmonary disease (COPD) is controversial, primarily due to concerns that they may worsen lung function and attenuate bronchodilator response. Areas covered: This review summarizes the reasons for and against the use of beta-blockers in COPD by evaluating the literature on the effects of these drugs on lung function, exacerbation rate, and mortality. The safety of beta-blockers in COPD patients with concomitant heart failure, an entity that is not always distinguishable from COPD exacerbations, is also explored. Expert commentary: The use of cardioselective beta-blockers appears safe in the management of cardiac comorbidities associated with COPD and may lower exacerbation and mortality risk. There is a growing body of evidence demonstrating the safety of beta-blockers in patients with acute heart failure, acute respiratory failure or sepsis, entities that could occur simultaneously with COPD exacerbations. However, randomized controlled trials are still lacking to confirm these results.
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http://dx.doi.org/10.1080/17476348.2018.1419869DOI Listing
February 2018

Frequency of detection of Chlamydophila pneumoniae using bronchoalveolar lavage fluid in patients with community-onset pneumonia.

Respir Investig 2017 Nov 22;55(6):357-364. Epub 2017 Sep 22.

Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki city, Nagasaki 852-8501, Japan. Electronic address:

Background: Chlamydophila pneumoniae is a causative pathogen of lower respiratory tract infection, which generally infects healthy, young people. However, it is often difficult to evaluate acute C. pneumoniae infection using upper respiratory tract specimens and/or sputum samples due to its persistent infection or colonization. The interpretation of frequency of detection of C. pneumoniae seems to be insufficient in community-onset pneumonia. The aim of this study was to evaluate the presence of C. pneumoniae using bronchoalveolar lavage fluid (BALF) samples.

Methods: BALF samples from 147 patients with pneumonia were retrospectively evaluated using C. pneumoniae-specific polymerase chain reaction (PCR) primers.

Results: None of the samples had positive PCR results for C. pneumoniae using two different sets of specific primers. Single and paired serological analyses were performed in 54 (36.7%) and 37 (25.2%) patients, respectively. These analyses revealed that 1 of 37 (2.7%) patients had a presumptive acute infection with C. pneumoniae, 8 of the 54 (14.8%) patients were suspected of having a C. pneumoniae infection, and 7 of the 37 (18.9%) patients were suspected of having past C. pneumoniae infection. In addition, cultivation and/or 16S rRNA gene sequencing detected Haemophilus influenzae in the presumptive case using the serological method.

Conclusions: The results of the present study revealed that C. pneumoniae might be a minor causative agent of community-onset pneumonia according to an evaluation of specimens obtained from the lower respiratory tract.
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http://dx.doi.org/10.1016/j.resinv.2017.08.003DOI Listing
November 2017

Bacteriological incidence in pneumonia patients with pulmonary emphysema: a bacterial floral analysis using the 16S ribosomal RNA gene in bronchoalveolar lavage fluid.

Int J Chron Obstruct Pulmon Dis 2017 20;12:2111-2120. Epub 2017 Jul 20.

Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki City, Nagasaki, Japan.

Pulmonary emphysema is an important radiological finding in chronic obstructive pulmonary disease patients, but bacteriological differences in pneumonia patients according to the severity of emphysematous changes have not been reported. Therefore, we evaluated the bacteriological incidence in the bronchoalveolar lavage fluid (BALF) of pneumonia patients using cultivation and a culture-independent molecular method. Japanese patients with community-acquired pneumonia (83) and healthcare-associated pneumonia (94) between April 2010 and February 2014 were evaluated. The BALF obtained from pneumonia lesions was evaluated by both cultivation and a molecular method. In the molecular method, ~600 base pairs of bacterial 16S ribosomal RNA genes in the BALF were amplified by polymerase chain reaction, and clone libraries were constructed. The nucleotide sequences of 96 randomly selected colonies were determined, and a homology search was performed to identify the bacterial species. A qualitative radiological evaluation of pulmonary emphysema based on chest computed tomography (CT) images was performed using the Goddard classification. The severity of pulmonary emphysema based on the Goddard classification was none in 47.4% (84/177), mild in 36.2% (64/177), moderate in 10.2% (18/177), and severe in 6.2% (11/177). Using the culture-independent molecular method, was significantly more frequently detected in moderate or severe emphysema patients than in patients with no or mild emphysematous changes. The detection rates of and were unrelated to the severity of pulmonary emphysematous changes, and species - except for the group and - were detected more frequently using the molecular method we used for the BALF of patients with pneumonia than using culture methods. Our findings suggest that is more frequently detected in pneumonia patients with moderate or severe emphysema than in those with no or mild emphysematous changes on chest CT. may play a major role in patients with pneumonia complicating severe pulmonary emphysema.
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http://dx.doi.org/10.2147/COPD.S140901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530061PMC
April 2018

Two Cases of Tuberous Sclerosis Complex Suggestive of Complicating Multifocal Micronodular Pneumocyte Hyperplasia: A Case Report.

J UOEH 2017;39(2):133-141

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

Multifocal micronodular pneumocyte hyperplasia (MMPH) is pathologically characterized by multifocal nodular hyperplasia of type Ⅱ pneumocyte-like cells. MMPH is usually complicated with tuberous sclerosis complex (TSC). MMPH patients tend to be asymptomatic or only slightly symptomatic. MMPH tends to progress slowly and needs no treatment. We herein describe two cases of MMPH with its characteristic radiological features and clinical manifestations of TSC. Case 1: a 20-year-old female with definitive TSC in infancy. Chest CT at the age of 18 revealed multiple nodular opacities and ground-glass attenuations in a scattered and random distribution in the bilateral lungs. Case 2: a 44-year-old female with probable TSC at 36 years of age. Chest CT at the age of 43 showed random areas of small ground-glass attenuations, predominantly in the upper lung fields. Case 1 and Case 2 have had no respiratory symptoms or radiographic changes in the recent two years and four years, respectively. Although pathological examinations of the lung were not performed because consent for surgical lung biospies was unobtainable, we considered that these pulmonary manifestations were most likely MMPH with TSC because of these characteristic radiographical findings of multiple nodular opacities and ground-glass attenuations of 10 mm or less in size and their scattered distribution, and because there have been no abnormal laboratory data or changes in their chest radiological findings for years. Neither patient is under treatment for pulmonary lesions. Although MMPH is a rare disease, multiple nodules and ground-glass attenuations on lung imaging findings should be considered as pulmonary manifestations in patients with TSC.
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http://dx.doi.org/10.7888/juoeh.39.133DOI Listing
October 2017

Determining the Possible Etiology of Hospital-Acquired Pneumonia Using a Clone Library Analysis in Japan.

Tohoku J Exp Med 2017 05;242(1):9-17

Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences.

Obtaining precise etiological information regarding causative bacteria is important for the proper use of antimicrobials in hospital-acquired pneumonia (HAP), which is associated with a high rate of mortality. The aim of this study was to comparatively investigate the bacterial diversity in bronchoalveolar lavage fluid (BALF) in Japanese patients with HAP by the clone library method using the 16S rRNA gene. This study included Japanese patients with HAP who were treated at our hospital and referring hospitals. BALF specimens were obtained from pneumonia lesions identified on chest radiographs and/or computed tomography. Sputum specimens were also evaluated in patients with sputum production. Sixty-eight patients were ultimately enrolled. BALF cultivation revealed bacterial positivity in 53 of 68 (77.9%) patients, and Staphylococcus aureus (30.9%) was the most frequently isolated, followed by Pseudomonas aeruginosa (16.2%), and Escherichia coli (10.3%). In contrast, the clone library analysis identified the presence of some bacterial phenotype in 65 of 68 (95.6%) patients, and streptococci (16.2%), Corynebacterium species (11.8%), anaerobes (10.3%) were frequently detected as the predominant phylotypes. Both methods tended to detect S. aureus, Klebsiella pneumoniae, and E. coli in patients with late-onset pneumonia. In addition, the cases that phylotypes of S. aureus and P. aeruginosa were found to account for > 5% of the bacterial flora of each case were 42.9% and 72.7%, respectively. These results indicate that attention should be paid to the roles of gram-positive bacilli such as streptococci, Corynebacterium species and anaerobes, in addition to Gram-negative bacilli, in the pathogenesis of HAP.
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http://dx.doi.org/10.1620/tjem.242.9DOI Listing
May 2017

The utility of electron microscopy in detecting asbestos fibers and particles in BALF in diffuse lung diseases.

BMC Pulm Med 2017 04 21;17(1):71. Epub 2017 Apr 21.

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

Background: In patients with diffuse lung diseases, differentiating occupational lung diseases from other diseases is clinically important. However, the value of assessing asbestos and particles in bronchoalveolar lavage fluid (BALF) in diffuse lung diseases by electron microscopy (EM) remains unclear. We evaluated the utility of EM in detecting asbestos fibers and particles in patients with diffuse lung diseases.

Methods: The BALF specimens of 107 patients with diffuse lung diseases were evaluated. First, detection of asbestos by EM and light microscopy (LM) were compared. Second, the detection of asbestos using surgically obtained lung tissues of 8 of 107 patients were compared with the results of EM and LM in BALF. Third, we compared the results of mineralogical components of particles in patients with (n = 48) and without (n = 59) a history of occupational exposure to inorganic dust.

Results: BALF asbestos were detected in 11 of 48 patients with a history of occupational exposure by EM; whereas asbestos as asbestos bodies (ABs) were detected in BALF in 4 of these 11 patients by LM. Eight of 107 patients in whom lung tissue samples were surgically obtained, EM detected BALF asbestos at a level of >1,000 fibers/ml in all three patients who had ABs in lung tissue samples by LM at a level of >1,000 fibers/g. The BALF asbestos concentration by EM and in lung tissue by LM were positively correlated. The particle fractions of iron and phosphorus were increased in patients with a history of occupational exposure and both correlated with a history of occupational exposure by a multiple regression analysis.

Conclusions: EM using BALF seemed to be superior to LM using BALF and displayed a similar sensitivity to LM using surgically-obtained lung tissue samples in the detection of asbestos. Our results also suggest that detection of elements, such as iron and phosphorus in particles, is useful for evaluating occupational exposure. We conclude that the detection of asbestos and iron and phosphorus in particles in BALF by EM is very useful for the evaluation of occupational exposure.
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http://dx.doi.org/10.1186/s12890-017-0415-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5401470PMC
April 2017

Multiple Tracheobronchial Polyposis Caused by Tracheobronchopathia Osteochondroplastica.

Intern Med 2016;55(21):3165-3167. Epub 2016 Nov 1.

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

Tracheobronchopathia osteochondroplastica (TO) is a rare benign airway disease that is characterized by the presence of multiple rock-garden-like nodules on bronchoscopy. TO is a slowly progressive disease of the trachea and major bronchi, which is typically characterized by such symptoms as a persistent nonproductive cough, dyspnea and wheezing. The clinical features of TO are variable, and asymptomatic patients may incidentally be diagnosed during the work-up for other diseases. We herein report a rare case of TO accompanying multiple tracheobronchial polyposis in which bronchoscopic resection of the airway polyp using a high-frequency snare was successfully performed.
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http://dx.doi.org/10.2169/internalmedicine.55.6774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5140868PMC
January 2017

IgG4-related Lung Disease Associated with Autoimmune Hemolytic Anemia: A Case Report and a Literature Review.

Intern Med 2016 1;55(17):2469-74. Epub 2016 Sep 1.

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

We herein report a case of IgG4-related lung disease (IgG4-RLD) associated with autoimmune hemolytic anemia (AIHA). A 73-year-old Japanese female visited our hospital for an examination following an abnormal chest X-ray in 1999. She was diagnosed with bronchiolitis and AIHA, and treatment with prednisolone was started. After seven years, she visited our department due to a cough. Chest computed tomography (CT) demonstrated focal consolidation with ground-glass attenuations and thickened bronchial walls in the bilateral lungs. She was clinically diagnosed and treated for bronchial asthma. CT findings had shown no changes, and a lung biopsy was performed using video-assisted thoracic surgery at eleven years from the first diagnosis of AIHA. The pathological findings demonstrated the presence of peribronchovascular lymphoplasmacytic infiltrates with stromal fibrotic changes, admixed with many IgG4-positive plasma cells. Furthermore, the patient's serum IgG4 level was high, and her CT findings did not show any obvious abnormal findings in the any organs other than the lungs. She was diagnosed with IgG4-RLD based on the findings. We believe that this case report of IgG4-RLD associated with AIHA is clinically helpful for a better understanding of these diseases, although there are five reported cases of IgG4-related disease associated with AIHA.
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http://dx.doi.org/10.2169/internalmedicine.55.6499DOI Listing
March 2017

The Importance of Obligate Anaerobes and the Streptococcus anginosus Group in Pulmonary Abscess: A Clone Library Analysis Using Bronchoalveolar Lavage Fluid.

Respiration 2016 23;92(2):80-9. Epub 2016 Aug 23.

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

Background: Appropriate antibiotic use reduces the mortality of patients with lung abscess; however, 40-60% of the bacterial etiologies in these patients have remained unknown with the culture methods. Obligate anaerobes and the Streptococcus anginosus group are common pathogens in lung abscess, but a precise evaluation of these bacteria by ordinary culture methods seems to be difficult due to upper respiratory tract contamination.

Objectives: The aim of this study was to assess the microbiota of lung abscess by bronchoalveolar lavage fluid (BALF) using the molecular method in comparison to culture methods.

Methods: BALF samples obtained from the affected lesions and sputum samples of 59 patients with lung abscess were evaluated. The microbiota in BALF was analyzed according to the molecular method using the 16S ribosomal RNA gene.

Results: Fifty-six of the 59 BALF samples were positive in polymerase chain reaction analysis. Fusobacterium spp. (23.7%) were most frequently detected, followed by the S. anginosus group (15.3%), as the predominant phylotypes. Obligate anaerobes were detected in 42.4% of the BALF specimens as the predominant phylotypes, whereas the detection rate of obligate anaerobes was 13.6% by culture methods using BALF. In addition, the detection rate among those patients in whom the phylotype of obligate anaerobes was detected in >5% of the lung microbiota according to the molecular method was 86.5% in the 'mixed-bacterial' infection group.

Conclusions: The findings by the molecular method suggest that obligate anaerobes play important roles in the pathogenesis of lung abscess and provide additional bacterial information regarding conventional culture methods.
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http://dx.doi.org/10.1159/000447976DOI Listing
September 2017

Disseminated Mycobacterium abscessus Complex Infection Manifesting as Multiple Areas of Lymphadenitis and Skin Abscess in the Preclinical Stage of Acute Lymphocytic Leukemia.

Intern Med 2016 1;55(13):1787-91. Epub 2016 Jul 1.

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

A 37-year-old woman was admitted to a hospital due to a prolonged fever and a rash on her legs. She had systemic lymphadenitis and a skin abscess on her left leg. Pathological findings of a left leg skin biopsy revealed abscess formation with granulomatous dermatitis, Mycobacterium abscessus complex was cultured from the resected left supraclavicular lymph node, and disseminated M. abscessus complex infection was diagnosed. She was treated with combination treatment with antimicrobials and percutaneous drainage, and her clinical findings improved. Four months later, she developed acute lymphocytic leukemia. Leukemia is a risk factor for disseminated M. abscessus complex infection, even before developing leukemia.
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http://dx.doi.org/10.2169/internalmedicine.55.6759DOI Listing
February 2017

Adrenal Insufficiency Associated with Small Cell Lung Cancer: A Case Report and Literature Review.

J UOEH 2016 Jun;38(2):155-62

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

A 78-year-old Japanese man with fatigue, appetite loss, skin hyperpigmentation, hypotension and hypoglycemia, visited our hospital to evaluate an abnormal chest X-ray and adrenal gland swelling in echography in February 2015. Chest computed tomography showed a mass lesion in the right lower lobe and bilateral adrenal swellings, and small cell lung cancer (SCLC) with bilateral adrenal metastasis was diagnosed after bronchoscopy. According to low levels of serum cortisol, elevated adrenocorticotropic hormone (ACTH) and rapid ACTH test, the diagnosis of adrenal insufficiency associated with SCLC was made. Treatment with hydrocortisone (20 mg/day) was started in addition to systemic chemotherapy with carboplatin and etoposide. The patient's symptoms were slightly improved, however, systemic chemotherapy was discontinued according to the patient's request after 1 course of chemotherapy. Thereafter, he received only supportive care, and his general condition gradually worsened and he ultimately died in August 2015. Adrenal insufficiency associated with SCLC, which is caused by tissue destruction more than 90% of the adrenal glands, is rare although adrenal metastasis is not rare in patients with lung cancer. The findings such as general fatigue, appetite loss, hypotension, and hyponatremia are often got follow up as findings of advanced cancer, but appropriate therapy for adrenal insufficiency, supplement of the adrenal corticosteroid hormone, may lead to a significant improvement in the symptoms and quality of life in clinical practice of lung cancer. Therefore, physicians must consider potential adrenal insufficiency in lung cancer patients with bilateral adrenal metastasis.
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http://dx.doi.org/10.7888/juoeh.38.155DOI Listing
June 2016

The significance of oral streptococci in patients with pneumonia with risk factors for aspiration: the bacterial floral analysis of 16S ribosomal RNA gene using bronchoalveolar lavage fluid.

BMC Pulm Med 2016 May 11;16(1):79. Epub 2016 May 11.

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

Background: Aspiration pneumonia has been a growing interest in an aging population. Anaerobes are important pathogens, however, the etiology of aspiration pneumonia is not fully understood. In addition, the relationship between the patient clinical characteristics and the causative pathogens in pneumonia patients with aspiration risk factors are unclear. To evaluate the relationship between the patient clinical characteristics with risk factors for aspiration and bacterial flora in bronchoalveolar lavage fluid (BALF) in pneumonia patients, the bacterial floral analysis of 16S ribosomal RNA gene was applied in addition to cultivation methods in BALF samples.

Methods: From April 2010 to February 2014, BALF samples were obtained from the affected lesions of pneumonia via bronchoscopy, and were evaluated by the bacterial floral analysis of 16S rRNA gene in addition to cultivation methods in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). Factors associated with aspiration risks in these patients were analyzed.

Results: A total of 177 (CAP 83, HCAP 94) patients were enrolled. According to the results of the bacterial floral analysis, detection rate of oral streptococci as the most detected bacterial phylotypes in BALF was significantly higher in patients with aspiration risks (31.0 %) than in patients without aspiration risks (14.7 %) (P = 0.009). In addition, the percentages of oral streptococci in each BALF sample were significantly higher in patients with aspiration risks (26.6 ± 32.0 %) than in patients without aspiration risks (13.8 ± 25.3 %) (P = 0.002). A multiple linear regression analysis showed that an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≥3, the presence of comorbidities, and a history of pneumonia within a previous year were significantly associated with a detection of oral streptococci in BALF.

Conclusions: The bacterial floral analysis of 16S rRNA gene revealed that oral streptococci were mostly detected as the most detected bacterial phylotypes in BALF samples in CAP and HCAP patients with aspiration risks, especially in those with a poor ECOG-PS or a history of pneumonia.
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http://dx.doi.org/10.1186/s12890-016-0235-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864928PMC
May 2016

Clinical impact of methicillin-resistant staphylococcus aureus on bacterial pneumonia: cultivation and 16S ribosomal RNA gene analysis of bronchoalveolar lavage fluid.

BMC Infect Dis 2016 Apr 16;16:155. Epub 2016 Apr 16.

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

Background: Determining whether methicillin-resistant Staphylococcus aureus (MRSA) is a true causative pathogen or reflective of colonization when MRSA is cultured from the respiratory tract remains important in treating patients with pneumonia.

Methods: We evaluated the bacterial microbiota in bronchoalveolar lavage fluid (BALF) using the clone library method with a 16S ribosomal RNA (rRNA) gene analysis in 42 patients from a pneumonia registry who had MRSA cultured from their sputum or BALF samples. Patients were divided into two groups: those treated with (Group A) or without (Group B) anti-MRSA agents, and their clinical features were compared.

Results: Among 248 patients with pneumonia, 42 patients who had MRSA cultured from the respiratory tract were analyzed (Group A: 13 patients, Group B: 29 patients). No clones of S. aureus were detected in the BALF of 20 out of 42 patients. Twenty-eight of 29 patients in Group B showed favorable clinical outcomes, indicating that these patients had non-MRSA pneumonia. Using a microflora analysis of the BALF, the S. aureus phylotype was predominant in 5 of 28 (17.9%) patients among the detected bacterial phylotypes, but a minor population (the percentage of clones ≤ 10%) in 19 (67.9%) of 28 patients. A statistical analysis revealed no positive relationship between the percentage of clones of the S. aureus phylotype and risk factors of MRSA pneumonia.

Conclusions: The molecular method using BALF specimens suggests that conventional cultivation method results may mislead true causative pathogens, especially in patients with MRSA pneumonia. Further studies are necessary to elucidate these clinically important issues.
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http://dx.doi.org/10.1186/s12879-016-1493-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833912PMC
April 2016

Successful Additional Corticosteroid Treatment in a Patient with Mycoplasma pneumoniae Pneumonia in whom a Monobacterial Infection was Confirmed by a Molecular Method Using Bronchoalveolar Lavage Fluid.

Intern Med 2016 15;55(6):703-7. Epub 2016 Mar 15.

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

A 23-year-old Japanese woman was admitted to A hospital due to pneumonia. IgM for Mycoplasma pneumoniae was positive, and the patient was treated with imipenem/cilastatin, clindamycin, pazufloxacin and minocycline. However, both the chest radiological findings and the symptoms became exacerbated, and she was therefore transferred to our hospital. The bronchoalveolar lavage fluid was obtained, and a 16S rRNA gene sequencing analysis revealed a monobacterial infection of Mycoplasma pneumoniae. Therefore, corticosteroid treatment in addition to minocycline was administered, and the patients symptoms, laboratory data and chest radiographs improved. Corticosteroid therapy may therefore be considered for patients with refractory M. pneumoniae pneumonia.
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http://dx.doi.org/10.2169/internalmedicine.55.5124DOI Listing
October 2016
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