Infectious respiratory pathogens among patients with acute exacerbation of idiopathic pulmonary fibrosis during the coronavirus disease 2019 pandemic in Japan.

BACKGROUND: Few studies have investigated the prevalence of pathogens in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), specifically, the interactions between respiratory pathogens and AE-IPF during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVES: We aimed to analyze pathogens in patients with AE-IPF between September 2020 and December 2022. METHODS: This retrospective observational study was conducted at our hospital between September 2020 and December 2022. In patients with AE-IPF, pre-hospitalization polymerase chain reaction (PCR) tests for respiratory pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were performed using multiplex PCR or Smart Gene assay with nasopharyngeal swab specimens. Microbiological assays, including Gram staining, sputum cultures, blood cultures, and urinary antigen tests for Streptococcus pneumoniae and Legionella pneumophila, were also performed. RESULTS: Forty-nine patients with AE-IPF were included. The median age was 75 years old and 42 (86 %) were male. Only one of the 49 patients (2 %) was positive for SARS-CoV-2. Two of 28 patients (7 %) were positive for human rhinovirus/enterovirus. No bacteria were detected in sputum culture, blood culture, or urinary antigen tests. CONCLUSIONS: The detection frequency of SARS-CoV-2 infection in patients with AE-IPF was lower than that of human rhinovirus/enterovirus. Continuous analysis for the presence of pathogens is necessary for appropriate infection control because respiratory viruses may increase as the coronavirus pandemic subsides.

Epidemiologic evaluation of pulmonary paragonimiasis in Japan using a Japanese nationwide administrative database.

BACKGROUND: Paragonimiasis is a parasitic disease primarily contracted through consumption of undercooked freshwater crustaceans or wild boar meat. Large-scale nationwide epidemiological data on paragonimiasis are lacking. In this study, we aimed to investigate the nationwide epidemiology of hospitalized patients with paragonimiasis in Japan using a comprehensive nationwide Japanese administrative database. METHODS: We evaluated the Japanese Diagnosis Procedure Combination (DPC) data of patients diagnosed with pulmonary paragonimiasis between April 1, 2012 and March 30, 2020. The patients' address and information, including age, sex, treatment (medication: praziquantel; surgery: open thoracotomy or intracranial mass extirpation), Japan coma scale, comorbidities, and length of hospital stay, were extracted. RESULTS: Of the 49.6 million hospitalized patients, data were extracted on 73 patients with paragonimiasis, of whom 36 were male and 37 were female. The mean age was 49.7 years and the mean length of stay was 12.5 days. The most frequent comorbidity was pleural effusion (31.5 %), followed by pneumothorax (13.7 %). The sites of ectopic paragonimiasis in organs other than the lung included the liver (5.5 %), skin (4.1 %), and brain (2.7 %). Geographically, most patients were from the Kyushu region (54.8 %), followed by the Kanto region (22.0 %). Fukuoka Prefecture had the highest number of patients (22.0 %) by prefecture. During the study period, an average of 9.1 patients/year were hospitalized with lung paragonimiasis in Japan. CONCLUSION: Paragonimiasis has not completely disappeared in Japan; thus, physicians should be aware of paragonimiasis in the Kyushu region, especially in the Fukuoka Prefecture.

Efficacy and safety of lascufloxacin for nursing- and healthcare-associated pneumonia: A single-arm, open-label clinical trial.

BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.

Sarcoidosis Associated with Enlarged Mediastinal Lymph Nodes with the Detection of Streptococcus gordonii and Cutibacterium acnes Using a Clone Library Method.

A 77-year-old Japanese woman with mediastinal lymphadenopathy and uveitis was diagnosed with sarcoidosis. The bacterial flora in biopsied samples from mediastinal lymph nodes was analyzed using a clone library method with Sanger sequencing of the 16S rRNA gene, and Streptococcus gordonii (52 of 71 clones) and Cutibacterium acnes (19 of 71 clones) were detected. No previous study has conducted a bacterial floral analysis using the Sanger method for the mediastinal lymph node in sarcoidosis, making this case report the first to document the presence of S. gordonii and C. acnes in the mediastinal lymph node of a patient with sarcoidosis.

Plastic bronchitis caused by Haemophilus influenzae.

Plastic bronchitis is characterized by sputum obstructing the bronchus and causing atelectasis. Bronchoscopic removal of the clogged bronchial cast is typically performed, but small-diameter bronchoscopes with narrow suction ports cannot achieve adequate suction. Suction using a bronchoscope as a guide sheath may be effective for treating plastic bronchitis in children.

Disseminated Mycobacterium genavense Infection Mimicking Sarcoidosis: A Case Report and Review of Literature on Japanese Patients.

Sarcoidosis is a systemic inflammatory disease characterized by noncaseating epithelioid cell granulomas. However, certain infections can exhibit similar histological findings. We present a case of a 69-year-old man who was initially diagnosed with sarcoidosis and later was confirmed, through 16S rRNA sequencing, to have disseminated Mycobacterium genavense infection. Acid-fast bacteria were detected in the bone marrow biopsy using Ziehl-Neelsen staining, but routine clinical tests did not provide a definitive diagnosis. The patient tested negative for HIV, anti-interferon-gamma antibodies, and genetic immunodeficiency disorders. He was treated with multiple drugs, including aminoglycosides and macrolides, but showed no improvement in fever and pancytopenia. However, these clinical signs responded favorably to steroid therapy. We reviewed 17 Japanese cases of M. genavense infection. All cases were in males; 7/17 (41%) were HIV-negative; and 12/17 (71%) had a decreased CD4 count. Genetic analysis confirmed M. genavense isolation, and macrolides were used universally. Mycobacterium genavense infection is challenging to identify and mimics other systemic inflammatory diseases such as sarcoidosis. There are no standard treatment protocols. Our case report and Japanese case review contribute to understanding this rare disease.

Clinical characteristics and antimicrobial susceptibility of non-vaccine serotype Streptococcus pneumoniae in adult Japanese patients with pneumonia.

BACKGROUND: Non-vaccine serotype (NVT) pneumococcal pneumonia in Japan has increased with the spread of pneumococcal vaccinations. However, there is no data regarding the clinical background and antimicrobial susceptibility of NVT isolates compared with those of vaccine serotype (VT) isolates in adult pneumococcal pneumonia. METHODS: The serotypes and antimicrobial susceptibilities of pneumococcal isolates obtained from patients with pneumonia at the University of Occupational and Environmental Health, Japan, from January 2011 to December 2020 were retrospectively evaluated along with the patients' clinical information. RESULTS: In total, 252 patients with pneumococcal pneumonia (98 NVT and 154 VT isolates) were included. Among NVTs, the most common serotype was 35B, followed by 15A, 34, 6C, 23A, and 15C. The MIC50 and MIC90 of each antibiotic in 35B and 15A tend to be higher than those in 34, 6C, and 23A. Regarding background characteristics, the percentages of patients with dementia and liver disease were significantly higher in patients in the VT group than in those in the NVT group (p = 0.048 and p = 0.012, respectively). There were no significant differences in the severity of pneumonia and mortality rate between patients with the VT and NVT isolates. This study first demonstrated that NVT isolates included those with reduced susceptibility to antibiotics in adult pneumonia in Japan. The data of the present study can be useful in optimizing treatment strategies for pneumococcal pneumonia because of the increasing number of NVT cases in Japan.

Reduced phagocytic activity of human alveolar macrophages infected with Mycobacterium avium complex.

INTRODUCTION: Co-infection of nontuberculous mycobacteria (NTM) with other bacteria is associated with increased frequency of hospitalization and reduced quality of life. However, the clinical significance of co-infection with NTM and other bacteria remains unclear. Here, we investigated the distribution of alveolar macrophage populations, characterized their phagocytic function in bronchoalveolar lavage fluid (BALF), and assessed the bactericidal function of macrophages infected with NTM using cell lines. METHODS: BALF samples were prospectively obtained from 30 patients with suspected NTM lung disease to evaluate phagocytic activities of macrophages using immunostaining. Bactericidal activities of Staphylococcus aureus (S. aureus) and Mycobacterium intracellulare (M. intracellulare)-infected or -non-infected macrophages were evaluated using macrophage cell lines. RESULTS: Eleven patients with Mycobacterium avium complex (MAC) infection and 19 patients with chronic lower respiratory tract infections except for NTM infection (controls) were enrolled. The percentage of non-polarized (HLA-DR+, CD40-, and CD163-) macrophages in patients infected with MAC was significantly higher than that in controls; non-polarized macrophages demonstrated an impaired ability to phagocytose S. aureus. In vitro experiments revealed higher intracellular S. aureus colony-forming unit counts and proinflammatory cytokine levels in M. intracellulare-infected macrophages than in non-NTM-infected macrophages. Electron microscopy showed morphologically damaged macrophages and M. intracellulare and S. aureus growing in the same phagosome. CONCLUSION: The proportion of alveolar macrophages (HLA-DR+, CD40-, and CD163-) with impaired phagocytosis increased in MAC-infected individuals. M. intracellulare-infected macrophages reduced bactericidal activity in vitro. Dysfunction of alveolar macrophages may contribute to persistent infection by other bacteria, leading to MAC lung disease progression.

Comparative study of bacterial flora in bronchoalveolar lavage fluid of pneumonia patients based on their pneumonia subtypes and comorbidities using 16S ribosomal RNA gene analysis.

INTRODUCTION: The culture method is the gold standard for identifying pathogenic bacteria in patients with pneumonia but often does not reflect the exact bacterial flora in pulmonary lesions of pneumonia, partly owing to easiness or difficulties in culturing certain bacterial species. We aimed to evaluate bacterial flora in bronchoalveolar lavage fluid (BALF) samples directly obtained from pneumonia lesions using 16S ribosomal RNA (rRNA) gene analysis to compare the results of the BALF culture method in each category of pneumonia. METHODS: Bacterial florae were detected by a combination of the culture method, and the clone library method using the 16S rRNA gene sequencing in BALF directly obtained from pneumonia lesions in pneumonia patients from April 2010 to March 2020 at the University of Occupational and Environmental Health, Japan, and affiliated hospitals. Clinical information of these patients was also collected, and lung microbiome was evaluated for each pneumonia category. RESULTS: Among 294 pneumonia patients (120 with community-acquired pneumonia (CAP), 101 with healthcare-associated pneumonia (HCAP), and 73 with hospital-acquired pneumonia (HAP)), significantly higher percentages of obligate anaerobes were detected in CAP than in HCAP and HAP patients by the clone library method. Corynebacterium species were significantly highly detected in HAP patients and patients with cerebrovascular diseases than in patients without, and Streptococcus pneumoniae was frequently detected in patients with diabetes mellitus. CONCLUSION: Obligate anaerobes may be underestimated in patients with CAP. Corynebacterium species should be regarded as the causative bacteria for pneumonia in patients with HAP and cerebrovascular diseases.

Combined Radiographic Features and Age Can Distinguish Mycoplasma pneumoniae Pneumonia from Other Bacterial Pneumonias: Analysis Using the 16S rRNA Gene Sequencing Data.

The study objective was to evaluate chest radiographic features that distinguish Mycoplasma pneumoniae pneumonia (MPP) from other bacterial pneumonias diagnosed based on the bacterial floral analysis with 16S rRNA gene sequencing, using bronchoalveolar lavage fluid samples directly obtained from pneumonia lesions. Patients were grouped according to the dominant bacterial phenotype; among 120 enrolled patients with CAP, chest CT findings were evaluated in 55 patients diagnosed with a mono-bacterial infection (one bacterial phylotype occupies more than 80% of all phylotypes in a sample) by three authorized respiratory physicians. Among this relatively small sample size of 55 patients with CAP, 10 had MPP, and 45 had other bacterial pneumonia and were categorized into four groups according to their predominant bacterial phylotypes. We created a new scoring system to discriminate MPP from other pneumonias, using a combination of significant CT findings that were observed in the M. pneumoniae group, and age (<60 years) (MPP−CTA scoring system). When the cutoff value was set to 1, this scoring system had a sensitivity of 80%, a specificity of 93%, a positive predictive value of 73%, and a negative predictive value of 95%. Among the CT findings, centrilobular nodules were characteristic findings in patients with MPP, and a combination of chest CT findings and age might distinguish MPP from other bacterial pneumonias.

Impaired B-Cell Differentiation in a Patient With STAT1 Gain-of-Function Mutation.

Hypogammaglobulinemia is a rare complication of STAT1 gain-of-function (GOF) mutations. We report an adult patient diagnosed with hypogammaglobulinemia caused by B-cell depletion during the treatment of disseminated cryptococcosis. The patient carried the STAT1 GOF mutation (c.820C>T, p.R274W). The flow cytometric analysis of his bone marrow revealed that B-cell differentiation was blocked in the stages between pre-B1b and pre-B2 cells. On the other hand, his brother who carried the same mutation displayed normal B-cell counts, thereby indicating that the unrecognized variants in same or other gene might be associated with abnormal B-cell differentiation in the patients. In conclusion, impaired B-cell differentiation in the bone marrow can cause hypogammaglobulinemia in patients with STAT1 GOF mutations.

Negative photochromism of a blue cyanine dye.

We found a novel blue cyanine dye that exhibits negative photochromism. Upon photoexcitation of the dye solution, the blue colour visibly disappeared, and after several hours the absorbance of the solution recovered completely, indicating that the dye has high stability.

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

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.

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

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.

Fatal Acute Exacerbation of Familial Interstitial Pneumonia Complicated with Dyskeratosis Congenita after Influenza Virus B Infection.

Dyskeratosis congenita (DC) is occasionally complicated in patients with familial interstitial pneumonia (FIP). However, there have been no reports of FIP patients with DC that develop acute exacerbation (AE). We herein report a FIP patient with DC that showed AE of FIP after influenza virus B infection. Although DC is a rare disease in clinical practice, physicians should keep in mind that FIP combined with DC has the potential to cause AE.

Solvent-Dependent Reaction Pathways Operating in Copper(II) Tetrafluoroborate Promoted Oxidative Ring-Opening Reactions of Cyclopropyl Silyl Ethers.

Oxidative ring-opening reactions of benzene-fused bicyclic cyclopropyl silyl ethers, promoted by copper(II) tetrafluoroborate, were investigated. The regioselectivity of cyclopropane ring-opening as well as product distributions were found to be highly dependent on the nature of the solvent. In alcohols, dimeric substances arising from external bond cleavage are major products. Radical rearrangement products are also formed in solvents such as ether and ethyl acetate. On the contrary, nucleophile addition to carbocation intermediates, generated by internal bond cleavage, occurs mainly in reactions taking place in acetonitrile. It is proposed that the observed solvent effects that govern the reaction pathways followed are a consequence of varying solvation of copper intermediates, which governs their reactivity and redox properties. In addition, the influence of counteranions of the copper salts, organonitriles, cyclic dienes, and substrate structures on the pathways followed in these reactions was also examined.