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

BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS. METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA. RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters. CONCLUSION: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

DOI： 10.1186/s12931-024-02921-z

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DOI： 10.1016/j.bbagen.2024.130565

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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Pulmonary function tests (PFTs) aid in evaluating the disease status of IPF. The clinical significance of oscillometry measurements in interstitial lung diseases has recently been reported. Our previous study showed that respiratory reactance (Xrs) measured by oscillometry reflected disease severity and predicted subsequent lung capacity decline in patients with IPF. However, the direct impact of Xrs on survival needs to be determined, and there are currently no reference values in oscillometry to predict prognosis. Therefore, this study aimed to investigate the association between oscillometry measurements, particularly Xrs, and survival in patients with IPF and to determine the cutoff values of Xrs that predict 3-year survival. METHODS: We analyzed the relationship between the measured values of PFT and oscillometry derived from 178 patients with IPF. Univariate and multivariate Cox proportional hazards analyses were performed to investigate the relationships between clinical indices at the time of the first oscillometry and survival. We performed the time-dependent receiver operating characteristic (ROC) curve analysis to set the optimized cutoff values of Xrs for 3-year survival prediction. We examined the discriminating power of cutoff values of Xrs on survival using the Kaplan-Meier method and the log-rank test. RESULTS: Xrs components, especially in the inspiratory phase (In), significantly correlated with the PFT values. In the multivariate analyses, Xrs (all of reactance at 5 Hz [X5], resonant frequency [Fres], and low-frequency reactance area [ALX] in the inspiratory phase) had a significant impact on survival (X5, p = 0.003; Fres, p = 0.016; ALX, p = 0.003) independent of age, sex, and other prognostic factors derived from the univariate analysis. The area under the ROC curve was 0.765, 0.759, and 0.766 for X5 In, Fres In, and ALX In, with cutoff values determined at - 0.98, 10.67, and 5.32, respectively. We found significant differences in survival after dividing patients using each of the cutoff values of Xrs. CONCLUSIONS: In patients with IPF, Xrs measured by oscillometry significantly impacted survival. We also determined the cutoff values of Xrs to discriminate patients with poor prognoses.

DOI： 10.1186/s12890-023-02776-y

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BACKGROUND: Mycobacterium lentiflavum is a slow-growing nontuberculous mycobacterium that is widely distributed in soil and water systems, but it is sometimes pathogenic to humans. Although cases of M. lentiflavum infections are rare, 22 isolates of M. lentiflavum were identified at a single hospital in Japan. We suspected a nosocomial outbreak; thus, we conducted transmission pattern and genotype analyses. METHODS: Cases of M. lentiflavum isolated at Kushiro City General Hospital in Japan between May 2020 and April 2021 were analyzed. The patient samples and environmental culture specimens underwent whole-genome sequencing (WGS). Additionally, we retrospectively collected clinical data from patient medical records. RESULTS: Altogether, 22 isolates of M. lentiflavum were identified from sputum and bronchoalveolar lavage samples. Clinically, the instances with M. lentiflavum isolates were considered contaminants. In the WGS analysis, 19 specimens, including 18 patient samples and 1 environmental culture from the hospital's faucet, showed genetic similarity. The frequency of M. lentiflavum isolation decreased after we prohibited the use of taps where M. lentiflavum was isolated. CONCLUSIONS: WGS analysis identified that the cause of M. lentiflavum pseudo-outbreak was the water used for patient examinations, including bronchoscopy.

DOI： 10.1017/ice.2023.68

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

Ichushi

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

Ichushi

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Pellagra is caused by abnormal intake and/or use of nicotinic acid and is known in part to be induced by the use of medications such as isoniazid or pirfenidone. We previously investigated atypical phenotypes of pellagra, such as nausea, using a mouse model of pellagra and found that gut microbiota play an important role in the development of these phenotypes. Here, we investigated the effect of Bifidobacterium longum BB536 on pellagra-related nausea caused by pirfenidone in our mouse model. Our pharmacological data indicated that pirfenidone (PFD) causes modulation of the gut microbiota profile, which appeared to play an important role in the development of pellagra-related nausea. A gut microbiota-mediated protective effect of B. longum BB536 against nausea caused by PFD was also identified. Finally, the urinary ratio of nicotinamide/N-methylnicotinamide was shown to be a biomarker of pellagra-like adverse effects induced by PFD, and it may contribute to the prevention of these effects in patients with idiopathic pulmonary fibrosis.

DOI： 10.12938/bmfh.2022-042

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BACKGROUND/AIM: The lung-specific soluble lectins, SP-A and SP-D have been clinically used to diagnose interstitial lung disease, but their clinical significance in COVID-19 remains controversial. This study was undertaken to determine their association with other lectins (MBL and FCN1), disease severity, and radiographs in COVID-19 patients. PATIENTS AND METHODS: A total of 131 patients with COVID-19 admitted in the Sapporo Medical University Hospital between May 22 and September 19, 2021, were enrolled in the study. Data including demographics, medical history, symptoms, signs, laboratory findings, and radiological images were collected from the patients' medical records. Chest computed tomography (CT) scanning was performed at admission. Serum levels of surfactant protein A and D (SP-A and SP-D), mannose-binding lectin (MBL) and ficolin1 (FCN1) were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Compared to the control group, the COVID-19 group had significantly higher serum SP-A and FCN1 levels on admission (SP-A: 59.60±38.89 vs. 35.61±11.22 ng/ml; p<0.01, FCN1: 542.45±506.04 vs. 250.6±161.1 ng/ml; p<0.01). The severe group in COVID-19 had significantly higher serum SP-D and lower MBL levels than the non-severe group (SP-D: 141.7±155.7 vs. 61.41±54.54 ng/ml; p<0.01, MBL: 1,670±1,240 vs. 2,170±1,140 ng/ml; p<0.05). SP-D strongly reflected the degree of imaging findings, whereas SP-A showed a significant correlation, albeit slightly weaker than SP-D. Conversely, MBL and FNC1 were not significantly correlated with imaging findings. CONCLUSION: Among soluble serum lectins, SP-A and SP-D may be more sensitive to CT findings than reported disease biomarkers such as IL-6, LDH, and CRP due to their lung-specific characteristics.

DOI： 10.21873/invivo.13259

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BACKGROUND/AIM: Coronavirus disease 2019 (COVID-19) is more likely to be severe in men than in women. Its association with sex hormones as an aggravating factor for male patients has been attracting attention. This study aimed to investigate whether serum testosterone is associated with the aggravation of COVID-19. PATIENTS AND METHODS: Serum testosterone concentrations in 116 male patients with COVID-19 and residual serum were measured and examined upon their admission to Sapporo Medical University Hospital between February 1, 2020 and March 31, 2021. RESULTS: Blood samples collected from these patients with COVID-19 were analyzed. The serum testosterone levels were 2.19±1.35, 1.29±0.88, and 0.75±0.58 ng/ml in mild, moderate, and severe groups, respectively. Patients with severe COVID-19 on admission had lower testosterone levels (p<0.001). At a cutoff level of 1.31 ng/ml, the area under the curve for the comparison of severe with non-severe cases was 0.825. Furthermore, serum testosterone levels negatively correlated with C-reactive protein and serum amyloid A levels but positively correlated with calcium, zinc, C3, and C4. CONCLUSION: In male patients with COVID-19, low serum testosterone levels correlated with disease severity, accompanied by a strong inflammatory reaction and proportion of complement consumption.

DOI： 10.21873/invivo.13334

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Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who developed Pneumocystis jirovecii pneumonia (PJP) following coronavirus disease 2019 (COVID-19) infection. Case 1: A 69-year-old man on 10 mg of prednisolone (PSL) daily for IP developed new pneumonia shortly after his COVID-19 infection improved and was diagnosed with PJP based on chest computed tomography (CT) findings and elevated serum β-D-glucan levels. Trimethoprim-sulfamethoxazole (TMP-SMZ) was administered, and the pneumonia resolved. Case 2: A 70-year-old woman taking 4 mg/day of PSL for IP and rheumatoid arthritis developed COVID-19 pneumonia, which resolved mildly, but her pneumonia flared up and was diagnosed as PJP based on CT findings, elevated β-D-glucan levels, and positive polymerase chain reaction for P. jirovecii DNA in the sputum. The autopsy revealed diffuse alveolar damage, increased collagen fiver and fibrotic foci, mucinous component accumulation, and the presence of a P. jirovecii cyst. In conclusion, steroids and immunosuppressive medications are well-known risk factors for PJP. Patients with IP who have been taking these drugs for a long time are frequently treated with additional steroids for COVID-19; thus, PJP complications should be avoided in such cases.

DOI： 10.3390/medicina58091151

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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. The decline in forced expiratory volume in one second (FEV1) is considered to be one of the most important outcome measures for evaluating disease progression. However, the only intervention proven to improve COPD prognosis is smoking cessation. This study therefore investigated the factors associated with annual FEV1 decline in COPD. METHODS: This retrospective study followed up 65 patients treated for COPD for 5 years: 13 current smokers and 52 former smokers, 25 with pneumonia, 24 with asthma, 18 with cancer, and 17 with cardiovascular disease. The patients were divided into groups based on clinical cutoff parameters of the impulse oscillometry system (IOS): 11 high and 54 low R5, 8 high and 57 low R20, 21 high and 44 low R5-R20, 26 high and 39 low X5, 38 high and 27 low Fres, and 36 high and 29 low AX. We investigated whether the decline in FEV1 was associated with comorbidities and IOS parameters. RESULTS: The annual change in FEV1 over 5 years was significantly affected by smoking status (current - 66.2 mL/year vs. former - 5.7 mL/year, p < 0.01), pneumonia (with - 31.5 mL/year vs. without - 8.9 mL/year, p < 0.05), asthma (with - 30.2 mL/year vs. - 10.8 mL/year, p < 0.01), but not by cancer and cardiovascular disease. In the groups defined by IOS results, only the high AX group had significantly more annual decline in FEV1 and %FEV1 than the low AX group (- 22.1 vs. - 12.8, p < 0.05 and - 0.20 vs. 0.40, p < 0.05, respectively). CONCLUSIONS: Continuing smoking as well as complications in pneumonia and asthma would be risk factors for the progression of COPD. AX might be a suitable parameter to predict the prognosis of patients with COPD.

DOI： 10.1186/s12890-022-01980-6

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Language：Japanese   Publisher：(公社)日本化学療法学会  

Ichushi

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

Ichushi

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MET, the receptor for the hepatocyte growth factor (HGF), is strongly associated with resistance to tyrosine kinase inhibitors, key drugs that are used in the therapy of non-small cell lung cancer. MET contains 11 potential N-glycosylation sites, but the site-specific roles of these N-glycans have not been elucidated. We report herein that these N-glycans regulate the proteolytic processing of MET and HGF-induced MET signaling, and that this regulation is site specific. Inhibitors of N-glycosylation were found to suppress the processing and trafficking of endogenous MET in H1975 and EBC-1 lung cancer cells and exogenous MET in CHO-K1 cells. We purified the recombinant extracellular domain of human MET and determined the site-specific N-glycan structures and occupancy using mass spectrometry. The results indicated that most sites were fully glycosylated and that the dominant population was the complex type. To examine the effects of the deletion of N-glycans of MET, we prepared endogenous MET knockout Flp-In CHO cells and transfected them with a series of N-glycan-deletion mutants of MET. The results showed that several N-glycans are implicated in the processing of MET. The findings also suggested that the N-glycans of the SEMA domain of MET positively regulate HGF signaling, and the N-glycans of the region other than the SEMA domain negatively regulate HGF signaling. Processing, cell surface expression, and signaling were significantly suppressed in the case of the all-N-glycan-deletion mutant. The overall findings suggest that N-glycans of MET affect the status and the function of the receptor in a site-specific manner.

DOI： 10.1111/cas.15278

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PURPOSE: We aimed to compare the efficacy of the VIO soft coagulation system (VSCS) for the treatment of air leaks by sealing with fibrin glue, and also assess the histological alterations that occur after soft coagulation. METHODS: A mouse pulmonary air leak model was designed. The pulmonary fistula was subsequently coagulated with the VSCS or sealed with fibrin glue with polyglycolic acid (PGA) sheets. The burst pressure at air leak recurrence was measured in each group, and the results were compared. We also evaluated the histological alterations in the mouse pulmonary air leak model after soft coagulation with the VSCS. RESULTS: The burst pressure in the soft coagulation group (80 W/Effect 5) (median 42.8; range 35.4-53.8 cmH2O) was similar to that in the fibrin glue group (median 41.5; range 34.6-43.9 cmH2O) (p = 0.21). Histological examinations revealed that the visceral pleura remained torn, the structure of the pulmonary alveolus was maintained, and the coagulated fistula was covered with a fibrin membrane in the soft coagulation group. CONCLUSIONS: The pressure resistance following soft coagulation was equivalent to that after sealing using fibrin glue with PGA sheets. The air leaks were likely controlled by covering the fistula with a fibrin membrane after soft coagulation with the VSCS.

DOI： 10.1007/s00595-021-02251-3

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Endoplasmic reticulum (ER) stress has been reported in a variety of diseases. Although ER stress can be detected using specific markers, it is still difficult to quantitatively evaluate the degree of stress and to identify the cause of the stress. The ER is the primary site for folding of secretory or transmembrane proteins as well as the site where glycosylation is initiated. This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress. Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress. The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone. Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress. Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics. Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.

DOI： 10.1021/acs.biochem.0c00969

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

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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BACKGROUND: Coronavirus disease (COVID-19) emerged in January 2020 in Sapporo city, and the outbreak has shown two peaks. METHODS: A total of 260 COVID-19 patients were enrolled and categorized into three groups according to the pandemic pattern, jobs and situation, and disease severity. We compared clinical characteristics according to these categories. RESULTS: We found two pandemic peaks, and the proportion of patients and health providers who were infected in other hospitals had increased in the latter two periods (period 2: 49.6%, period 3: 32.7%). Particularly, the proportion of infected health providers was 27% in period 2, and they tended to be younger females with a mild condition. Severity of the disease (requirement of oxygen and/or mechanical ventilation) was associated with advanced age, and all the patients who died during admission were over 60 years old. CONCLUSIONS: We reported the temporal dynamics and characteristics of the COVID-19 pandemic in Sapporo city, Japan. This survey from the viewpoint of the hospital provides a new insight into and a better guide for the further management of the COVID-19 pandemic.

DOI： 10.1016/j.resinv.2020.11.008

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We report a case of acute eosinophilic pneumonia (AEP) triggered by coronavirus disease 2019 (COVID-19) infection. A 77-year-old man experienced left-sided chest pain and shortness of breath. Reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) revealed a positive result, and he was treated with favipiravir, ciclesonide, and lascufloxacin, but he showed poor improvement. On the other hand, computed tomography (CT) images were atypical for COVID-19 infection, and the elevation of eosinophil was found in blood and the fluid obtained by bronchoscopy. So, we clinically diagnosed this case as AEP. Administration of prednisolone dramatically improved the patient's clinical condition and chest radiograph findings, which were consistent with the clinical course of AEP. This case suggests the importance of considering the complications of AEP when treating patients with COVID-19 infection.

DOI： 10.1002/rcr2.683

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

Ichushi

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BACKGROUND: Surfactant proteins (SP) A and D belong to collectin family proteins, which play important roles in innate immune response in the lung. We previously demonstrated that cigarette smoke (CS) increases the acrolein modification of SP-A, thereby impairing the innate immune abilities of this protein. In this study, we focused on the effects of CS and its component, acrolein, on the innate immunity role of another collectin, SP-D. METHODS: To determine whether aldehyde directly affects SP-D, we examined the lungs of mice exposed to CS for 1 week and detected aldehyde-modified SP-D using an aldehyde reactive probe. The structural changes in CS extract (CSE) or acrolein-exposed recombinant human (h)SP-D were determined by western blot, liquid chromatography-electrospray ionization tandem mass spectrometry, and blue native-polyacrylamide gel electrophoresis analyses. Innate immune functions of SP-D were determined by bacteria growth and macrophage phagocytosis. RESULTS: Aldehyde-modified SP-D as well as SP-A was detected in the lungs of mice exposed to CS for 1 week. Exposure of hSP-D to CSE or acrolein induced an increased higher-molecular -weight of hSP-D and acrolein induced modification of five lysine residues in hSP-D. These modifications led to disruption of the multimer structure of SP-D and attenuated its ability to inhibit bacterial growth and activate macrophage phagocytosis. CONCLUSION: CS induced acrolein modification in SP-D, which in turn induced structural and functional defects in SP-D. GENERAL SIGNIFICANCE: These results suggest that CS-induced structural and functional defects in SP-D contribute to the dysfunction of innate immune responses in the lung following CS exposure.

DOI： 10.1016/j.bbagen.2020.129699

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

Ichushi

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

Ichushi

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Language：Japanese   Publisher：(公社)日本生化学会  

Ichushi

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

BACKGROUND: Bronchial asthma (BA) has different phenotypes, and it requires a clinically effective subtype classification system. The impulse oscillometry system (IOS) is an emerging technique device used in respiratory functional tests. However, its efficacy has not been validated. Therefore, this study aimed to assess the relationship between BA and the IOS parameters, and the difference in the therapeutic effects of inhaled corticosteroids (ICSs) among the subtype classifications was evaluated using the IOS. METHODS: Of the 245 patients with bronchial asthma who were screened, 108 were enrolled in this study. These patients were divided based on three subtypes according to the IOS result as follows: central predominant type (n = 34), peripheral predominant type (n = 58), and resistless type (n = 16). Then, the following ICSs were randomly prescribed in daily medical care: coarse-particle ICS (fluticasone propionate [FP]), fine-particle ICS (mometasone furoate [MF]), and moderate-particle ICS (budesonide [BUD]). The treatment effects were assessed using the Asthma Health Questionnaire (AHQ) and the Asthma Control Test (ACT) and were compared among the three subtypes. RESULTS: In the central predominant type, the AHQ score of the MF group was significantly higher than that of the FP group (15.4 vs. 3.6, p < 0.01) and the BUD group (15.4 vs. 8.8, p < 0.05); the ACT score of the FP group was significantly higher than that of the MF and BUD groups (24.3 vs. 21.7, 22.3, respectively, p < 0.05) at 4 weeks after treatment. In the peripheral predominant type, the AHQ score of the FP group was significantly higher than that of the MF group (14.1 vs. 3.4, p < 0.05); the ACT score of the FP group was lower than that of the MF and BUD groups (22.8 vs. 24.6, 24.4, respectively, p < 0.01) at 4 weeks after treatment. CONCLUSIONS: An association was observed between IOS subtype classification and ICS particle size in terms of therapeutic efficacy in BA. This result indicates that the IOS could be an effective tool in the selection of ICS and the evaluation of the BA phenotype.

DOI： 10.1186/s12931-020-01494-x

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

Ichushi

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

Ichushi

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DOI： 10.21203/rs.3.rs-22555/v2

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DOI： 10.21203/rs.3.rs-22555/v1

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media {LLC}  

DOI： 10.1186/s12931-019-1005-2

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BACKGROUND: The incidence of infectious disease caused by nontuberculous mycobacteria is increasing worldwide. Pulmonary Mycobacterium avium complex (MAC) disease is difficult to treat with chemotherapy, and its mechanism of infection, infection route, disease onset, and severity remain unknown. Ficolins are oligomeric defense lectins. L-ficolin plays an important role in innate immunity. This study's aim was to identify L-ficolin's role in patients with pulmonary MAC disease. METHODS: Between April 2011 and September 2017, 61 Japanese patients with pulmonary MAC disease were seen at our hospital. A control group, comprising 30 healthy individuals, without respiratory disease were enrolled in our study. The relationship between serum L-ficolin levels and disease severity was assessed, and L-ficolin's antibacterial role was examined. RESULTS: Serum L-ficolin levels were significantly lower in patients with pulmonary MAC disease than in healthy subjects (1.69 ± 1.27 μg/ml vs. 3.96 ± 1.42 μg/ml; p < 0.001). The cut-off value, based on receiver operating characteristic (ROC) analysis results, was 2.48 μg/ml (area under the curve (AUC) 0.90, sensitivity and specificity 83.6 and 86.7%, respectively). Serum L-ficolin levels were significantly lower in the patients with nodular bronchiectatic type disease compared with the patients with fibrocavitary type disease and were lower in the high-resolution computed tomography high-scoring group compared with low-scoring group. An in vitro analysis showed that purified recombinant L-ficolin bound to M. avium and its major cell wall component, lipoarabinomannan, in a concentration-dependent manner. In addition, recombinant L-ficolin suppressed M. avium growth in a concentration-dependent manner. CONCLUSIONS: Insufficient serum L-ficolin is associated with disease progression in pulmonary MAC disease, and the level of serum L-ficolin is a possible biomarker. TRIAL REGISTRATION: This study is registered with UMIN ( UMIN000022392 ).

DOI： 10.1186/s12931-019-1185-9

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Language：Japanese   Publisher：(公社)日本生化学会  

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We herein report a case of autoimmune pulmonary alveolar proteinosis (PAP) diagnosed after one-time exposure to silica powder. Owing to the misuse of a silica-containing fire extinguisher and the inhalation of large amounts of its powder, the patient experienced prolonged cough and visited our hospital. The findings of chest computed tomography and surgical lung biopsy specimens led to the diagnosis of PAP. Interestingly, the presence of anti-GM-CSF antibody was detected; therefore, both autoimmune characteristics and exposure to large amounts of silica may have caused the development of PAP in this patient. This case provides important insight into the mechanisms leading to the onset of PAP.

DOI： 10.2169/internalmedicine.1557-18

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Distal airway stem cells (DASCs) in the mouse lung can differentiate into bronchioles and alveoli. However, it remains unclear whether the same stem cells exist in the human lung. Here, we found that human lung epithelial (HuL) cells, derived from normal, peripheral lung tissue, in monolayer, mostly express both the N-terminally truncated isoform of p63 (∆Np63), a marker for airway basal cells, and thyroid transcription factor-1 (TTF-1), a marker for alveolar epithelial cells, even though these two molecules are usually expressed in a mutually exclusive way. Three-dimensionally cultured HuL cells differentiated to form bronchiole-like and alveolus-like organoids. We also uncovered a few bronchiolar epithelial cells expressing both ∆Np63 and TTF-1 in the human lung, suggesting that these cells are the cells of origin for HuL cells. Taken together, ΔNp63+ TTF-1+ peripheral airway epithelial cells are possibly the human counterpart of mouse DASCs and may offer potential for future regenerative medicine.

DOI： 10.1016/j.yexcr.2018.09.020

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BACKGROUND: Interstitial lung diseases (ILD) are severe respiratory diseases, and ILD patients are treated with corticosteroid and immunosuppressive agents. However, it is unclear whether these medications influence the response of pneumococcal vaccine. OBJECTIVES: We examined the immunogenicity of pneumococcal vaccines (PPSV23 and PCV13) in ILD patients undergoing immunosuppressive treatment. METHODS: ILD patients who were regularly followed at the outpatient clinic were enrolled. Sera were collected before and 4-8 weeks after vaccination. Serotype-specific immunoglobulin G (IgG) concentrations against pneumococcal serotype 19F were measured by ELISA. RESULTS: IgG concentrations to serotype 19F were increased in all groups in response to the vaccine. Both PCV13 and PPSV23 induced IgG concentrations in patients immunized for the first time. Response rates for the ILD group were comparable with those for the ILD group undergoing corticosteroid therapy. Only idiopathic pulmonary fibrosis patients undergoing immunosuppressive therapy had a significantly lower response.

DOI： 10.1016/j.vaccine.2018.06.062

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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. Although IPF has not been thought to be associated with bacterial communities, recent papers reported the possible role of microbiome composition in IPF. The roles of microbiomes in respiratory functions and as clinical biomarkers for IPF remain unknown. In this study, we aim to identify the relationship between the microbial environment in the lung and clinical findings. METHODS: Thirty-four subjects diagnosed with IPF were included in this analysis. The 16S rDNA was purified from bronchoalveolar lavage fluid obtained at the time of diagnosis and analyzed using next-generation sequencing techniques to characterize the bacterial communities. Furthermore, microbiomes from mice with bleomycin-induced lung fibrosis were analyzed. RESULTS: The most prevalent lung phyla were Firmicutes, Proteobacteria and Bacteroidetes. Decreased microbial diversity was found in patients with low forced vital capacity (FVC) and early mortality. Additionally, the diversity and relative abundance of Firmicutes, Streptococcaceae, and Veillonellaceae were significantly associated with FVC, 6-min walk distance, and serum surfactant protein D. Bleomycin-induced lung fibrosis resulted in decrease of diversity and alteration of microbiota in PCoA analysis. These results support the observations in human specimens. CONCLUSIONS: This study identified relationships between specific taxa in BALF and clinical findings, which were also supported by experiments in a mouse model. Our data suggest the possibility that loss of microbial diversity is associated with disease activities of IPF.

DOI： 10.1186/s12931-018-0736-9

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Language：Japanese   Publisher：生命科学系学会合同年次大会運営事務局  

Ichushi

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Language：Japanese   Publisher：生命科学系学会合同年次大会運営事務局  

Ichushi

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DOI： 10.1038/onc.2017.253

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Web of Science

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DOI： 10.1074/jbc.M117.800771

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DOI： 10.1016/j.rmed.2017.08.021

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DOI： 10.1073/pnas.1621172114

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DOI： 10.1038/s41598-017-08588-5

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DOI： 10.4049/jimmunol.1502626

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DOI： 10.1016/j.bbrc.2017.02.028

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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DOI： 10.1016/j.ccm.2016.04.007

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DOI： 10.1152/ajplung.00363.2015

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DOI： 10.1126/scitranslmed.aac8577

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DOI： 10.1038/onc.2014.20

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DOI： 10.1038/onc.2015.266

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

DOI： 10.1074/jbc.M112.380287

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

DOI： 10.1074/jbc.M111.308056

PubMed

Web of Science

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J05061&link_issn=&doc_id=20111102360008&doc_link_id=%2Fdi5inter%2F2011%2F004200%2F010%2F0032-0032%26dl%3D2&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdi5inter%2F2011%2F004200%2F010%2F0032-0032%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

Ichushi

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

DOI： 10.4049/jimmunol.1100024

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

DOI： 10.1074/jbc.M109.074765

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

Ichushi

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

J-GLOBAL

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本環境感染学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本環境感染学会  

Ichushi

J-GLOBAL

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

Ichushi

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

Ichushi

J-GLOBAL

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

Ichushi

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

Ichushi

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Language：Japanese   Publisher：日本感染症学会東日本地方会・日本化学療法学会東日本支部  

Ichushi

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Language：Japanese   Publisher：日本感染症学会東日本地方会・日本化学療法学会東日本支部  

Ichushi

J-GLOBAL

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Language：Japanese   Publisher：日本感染症学会東日本地方会・日本化学療法学会東日本支部  

Ichushi

J-GLOBAL

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

J-GLOBAL

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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

Ichushi

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

Ichushi

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

Ichushi

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

Ichushi

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

Ichushi

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J-GLOBAL

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Language：Japanese   Publisher：(有)科学評論社  

Ichushi

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Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

Ichushi

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

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

Ichushi

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

Ichushi

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

Ichushi

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

Ichushi

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Language：Japanese   Publisher：COSMIC  

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Other Link:： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00276&link_issn=&doc_id=20210210250003&doc_link_id=10.11150%2Fkansenshogakuzasshi.95.17&url=https%3A%2F%2Fdoi.org%2F10.11150%2Fkansenshogakuzasshi.95.17&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Ichushi

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

Ichushi

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Language：Japanese   Publisher：(公社)日本生化学会  

Ichushi

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

Ichushi

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

Ichushi

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

Ichushi

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

Ichushi

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

Ichushi

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Language：Japanese   Publisher：(株)先端医学社  

Other Link:： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J03102&link_issn=&doc_id=20200527590022&doc_link_id=%2Fae6bkybd%2F2020%2F002401%2F022%2F0084-0087%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6bkybd%2F2020%2F002401%2F022%2F0084-0087%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本生化学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本生化学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本生化学会  

Ichushi

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Language：Japanese   Publisher：(株)先端医学社  

Ichushi

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

Ichushi

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

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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J-GLOBAL

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Language：Japanese   Publisher：(株)最新医学社  

Other Link:： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00516&link_issn=&doc_id=20181010030016&doc_link_id=%2Fap7saisa%2F2018%2F007310%2F017%2F1388-1391%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fap7saisa%2F2018%2F007310%2F017%2F1388-1391%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本生化学会  

Ichushi

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Language：Japanese  

Ichushi

J-GLOBAL

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Language：Japanese  

Ichushi

J-GLOBAL

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Language：Japanese  

Ichushi

J-GLOBAL

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Language：Japanese  

Ichushi

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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

Ichushi

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

Ichushi

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

Ichushi

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

Ichushi

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Language：Japanese   Publisher：生命科学系学会合同年次大会運営事務局  

Ichushi

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(株)先端医学社  

Other Link:： https://search.jamas.or.jp/link/ui/2017202278

CiNii Research

Ichushi

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Language：Japanese   Publisher：札幌医科大学医療人育成センター  

Other Link:： http://search.jamas.or.jp/link/ui/2017208111

Ichushi

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Language：Japanese   Publisher：(株)先端医学社  

Other Link:： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J03102&link_issn=&doc_id=20170317390021&doc_link_id=%2Fae6bkybd%2F2017%2F002101%2F021%2F0080-0083%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6bkybd%2F2017%2F002101%2F021%2F0080-0083%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：Japanese   Publisher：(株)先端医学社  

Other Link:： http://search.jamas.or.jp/link/ui/2017202262

Ichushi

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

Ichushi

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Language：Japanese   Publisher：(一社)日本感染症学会  

Ichushi

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Language：Japanese   Publisher：日本肺サーファクタント・界面医学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本生化学会  

Ichushi

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Language：Japanese  

J-GLOBAL

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

Ichushi

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Language：Japanese   Publisher：(株)先端医学社  

Other Link:： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J03102&link_issn=&doc_id=20160414600034&doc_link_id=%2Fae6bkybd%2F2016%2F002001%2F034%2F0120-0123%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae6bkybd%2F2016%2F002001%2F034%2F0120-0123%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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

Ichushi

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Language：Japanese   Publisher：(株)先端医学社  

Other Link:： https://search.jamas.or.jp/link/ui/2016238688

CiNii Research

Ichushi

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

Ichushi

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J-GLOBAL

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Language：English   Publisher：(公社)日本生化学会  

Ichushi

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Ichushi

J-GLOBAL

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Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

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Language：Japanese  

Ichushi

J-GLOBAL

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Language：Japanese  

Ichushi

J-GLOBAL

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Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

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Language：English   Publisher：(公社)日本生化学会  

Ichushi

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Language：English   Publisher：(公社)日本生化学会  

Ichushi

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Language：English   Publisher：(公社)日本生化学会  

Ichushi

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J-GLOBAL

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

Ichushi

J-GLOBAL

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Language：Japanese   Publisher：市立函館病院  

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

Other Link:： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J03150&link_issn=&doc_id=20091022230018&doc_link_id=10026272769&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10026272769&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Ichushi

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Language：Japanese  

Other Link:： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J02926&link_issn=&doc_id=20090630460008&doc_link_id=http%3A%2F%2Fid.nii.ac.jp%2F1599%2F00011753%2F&url=http%3A%2F%2Fid.nii.ac.jp%2F1599%2F00011753%2F&type=%8ED%96y%88%E3%89%C8%91%E5%8Aw%81F%8ED%96y%88%E3%89%C8%91%E5%8Aw%8Aw%8Fp%8B%40%8A%D6%83%8A%83%7C%83W%83g%83%8A_ikor&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80183_3.gif

Ichushi

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

Other Link:： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J02926&link_issn=&doc_id=20080512450006&doc_link_id=http%3A%2F%2Fid.nii.ac.jp%2F1599%2F00007979%2F&url=http%3A%2F%2Fid.nii.ac.jp%2F1599%2F00007979%2F&type=%8ED%96y%88%E3%89%C8%91%E5%8Aw%81F%8ED%96y%88%E3%89%C8%91%E5%8Aw%8Aw%8Fp%8B%40%8A%D6%83%8A%83%7C%83W%83g%83%8A_ikor&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80183_3.gif

Ichushi

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Ichushi

J-GLOBAL

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Ichushi

J-GLOBAL

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Ichushi

J-GLOBAL

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Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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Language：English   Presentation type：Poster presentation  

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