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Semi-quantitative CT score is generally used for evaluating the disease status of Mycobacterium abscessus (Mab) Pulmonary disease (Mab-PD). However, its accuracy and clinical usefulness are limited, since the CT score is largely affected by coexisting lung disease. Hence, we hypothesized that numerical change in CT score during the observation period may be useful for evaluating disease activity of Mab-PD. Patients diagnosed with Mab-PD based on the official ATS/ERS/ESCMID/IDSA statement at Jikei University Hospital and Jikei Daisan Hospital between 2015 January 1 and 2021 July 31 were included (n = 32). We reviewed the medical records, and bacteriological and laboratory data of the patients. Chest CT was performed at diagnosis in all 32 cases. In 18 cases, chest CT images within 4 years before diagnosis were available. The numerical change in CT score between two time points was calculated and the association of the CT scores with sputum Gaffky score and serum CRP was examined. CT score at diagnosis was not correlated with sputum Gaffky score nor serum CRP, while the difference of absolute value and change rate in CT score between at diagnosis and immediate past CT were well correlated with both sputum Gaffky score and serum CRP. Chronological change in CT score may more precisely reflect the disease activity of airway mycobacterial burden and systemic inflammation in Mab-PD at the timing of diagnosis.

Background Accumulation of profibrotic myofibroblasts in fibroblastic foci (FF) is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis (IPF) pathogenesis, and transforming growth factor (TGF)-β plays a key regulatory role in myofibroblast differentiation. Reactive oxygen species (ROS) has been proposed to be involved in the mechanism for TGF-β-induced myofibroblast differentiation. Metformin is a biguanide antidiabetic medication and its pharmacological action is mediated through the activation of AMP-activated protein kinase (AMPK), which regulates not only energy homeostasis but also stress responses, including ROS. Therefore, we sought to investigate the inhibitory role of metformin in lung fibrosis development via modulating TGF-β signaling. Methods TGF-β-induced myofibroblast differentiation in lung fibroblasts (LF) was used for in vitro models. The anti-fibrotic role of metfromin was examined in a bleomycin (BLM)-induced lung fibrosis model. Results We found that TGF-β-induced myofibroblast differentiation was clearly inhibited by metformin treatment in LF. Metformin-mediated activation of AMPK was responsible for inhibiting TGF-β-induced NOX4 expression. NOX4 knockdown and N-acetylcysteine (NAC) treatment illustrated that NOX4-derived ROS generation was critical for TGF-β-induced SMAD phosphorylation and myofibroblast differentiation. BLM treatment induced development of lung fibrosis with concomitantly enhanced NOX4 expression and SMAD phosphorylation, which was efficiently inhibited by metformin. Increased NOX4 expression levels were also observed in FF of IPF lungs and LF isolated from IPF patients. Conclusions These findings suggest that metformin can be a promising anti-fibrotic modality of treatment for IPF affected by TGF-β.

Background Mycobacterium avium complex pulmonary disease (MAC-PD) is considered to be increasing worldwide. In Japan, the number of elderly MAC-PD patients requiring treatment is also expected to increase due to the aging society. However, reduced organ function in elderly patients makes it often difficult to continue or complete multidrug treatment due to adverse drug reactions (ADRs). Therefore, this study aimed to identify clinical factors associated with treatment tolerability, efficacy, and ADRs in elderly MAC-PD patients. Methods We retrospectively reviewed the medical records of 102 patients with MAC-PD aged ≥ 75 years between January 2014 and March 2023. Forty-six patients were treated with multidrug regimens (treatment group), and 56 were observed without treatment (observation group). The treatment group was divided into the treatment continuation group ( n  = 28) who were treated without interruption for ≥ 12 months, and the treatment interruption group ( n  = 18). A comparative study was conducted in each group to examine tolerability, efficacy, and ADRs. Results A two-drug regimen of ethambutol (EB) and macrolides without rifampicin (RFP) was associated with treatment continuation ( p  = 0.026). The treatment continuation group was superior to the observation group regarding symptoms change, sputum conversion rate, and chest computed tomography scores. The most common ADRs were gastrointestinal disorders, which may be related to RFP. Treatment efficacy of the two-drug regimen was non-inferior, and no cases of macrolide resistance were observed. Conclusions The two-drug regimen of EB and macrolide without RFP may be a tolerable and effective treatment for elderly MAC-PD patients.

Background The T-SPOT. TB assay is widely used for the adjunctive diagnosis of tuberculosis (TB). However, clinicians often encounter false-negative T-SPOT. TB results. The extent of TB spread may influence host immune functions, which can influence the results of the T-SPOT. TB test. However, few previous reports have investigated the association between radiologic pulmonary tuberculosis (PTB) severity and T-SPOT. TB test results. Methods We retrospectively investigated patients with culture-confirmed pulmonary TB (PTB) at the Jikei University Daisan Hospital between September 2016 and December 2021. We aimed to clarify the association of PTB severity, according to computed tomography (CT), with the false-negative results of the T-SPOT. TB test. Results Among 193 patients with PTB, 43 (22.3%) had false-negative T-SPOT. TB results. High rates of false-negative results were noted for 7/18 (38.9%) patients with PTB spread in two lung segments (mild PTB) and 16/39 (41.0%) patients with PTB spread in 19 lung segments (severe PTB). Multivariate logistic regression analysis showed that mild or severe PTB (odds ratio [OR]: 3.23; 95% confidence interval [CI]: 1.46–7.13; P  = 0.004) and lymphopenia (OR: 3.33; 95% CI: 1.20–9.26; P  = 0.02) were statistically significant risk factors for false-negative results. Conclusions Mild or severe intrapulmonary lesions on chest CT might be associated with the false-negative results of the T-SPOT. TB assay. Additionally, estimating the intrapulmonary spread of PTB using chest CT could serve as a useful supplementary tool in diagnosing patients with PTB who receive false-negative results on the T-SPOT.TB test.

Coronavirus disease 2019 (COVID-19) pneumonia can have prolonged sequelae and lead to respiratory dysfunction, mainly because of impaired diffusion capacity for carbon monoxide (DLCO). The clinical factors associated with DLCO impairment, including blood biochemistry test parameters, remain unclear. Patients with COVID-19 pneumonia who underwent inpatient treatment between April 2020 and August 2021 were included in this study. A pulmonary function test was performed 3 months after onset, and the sequelae symptoms were investigated. Clinical factors, including blood test parameters and abnormal chest shadows on computed tomography, of COVID-19 pneumonia associated with DLCO impairment were investigated. In total, 54 recovered patients participated in this study. Twenty-six patients (48%) and 12 patients (22%) had sequelae symptoms 2 and 3 months after, respectively. The main sequelae symptoms at 3 months were dyspnea and general malaise. Pulmonary function tests showed that 13 patients (24%) had both DLCO <80% predicted value (pred) and DLCO/alveolar volume (VA) <80% pred, and appeared to have DLCO impairment not attributable to an abnormal lung volume. Clinical factors associated with impaired DLCO were investigated in multivariable regression analysis. Ferritin level of >686.5 ng/mL (odds ratio: 11.08, 95% confidence interval [CI]: 1.84-66.59; p = 0.009) was most strongly associated with DLCO impairment. Decreased DLCO was the most common respiratory function impairment, and ferritin level was a significantly associated clinical factor. Serum ferritin level could be used as a predictor of DLCO impairment in cases of COVID-19 pneumonia.

We report a case of infective endocarditis (IE) due to nasal septal perforation during Home oxygen therapy (HOT). A 64‐year‐old man with a history of interstitial pneumonia (IP) and on HOT was hospitalized for dyspnea. Methicillin‐sensitive Staphylococcus aureus (MSSA) was repeatedly detected in blood cultures. Echocardiography revealed tricuspid valve vegetation and regurgitation. The patient was diagnosed with IE, according to the modified Duke criteria. A full‐body examination revealed nasal septal perforation and MSSA was isolated from the nasal cavity. The patient was treated with cefazolin and clindamycin. However, he developed aspiration pneumonia and subsequently died. The portal of entry of MSSA was damaged nasal mucosa, caused by dryness and curettage of the dried nasal mucus during HOT. Nasal septal perforation, a potential complication of HOT, may cause severe bacterial infections. Consequently, diligent nasal care is crucial during HOT. We report a case of infective endocarditis (IE) due to nasal septal perforation during Home oxygen therapy (HOT).

Background Although cigarette smoking may have a negative impact on the clinical outcome of pulmonary tuberculosis (PTB), few studies have investigated the impact of smoking-associated lung diseases. Emphysema is a major pathological finding of smoking-related lung damage. We aimed to clarify the effect of emphysema on sputum culture conversion rate for Mycobacterium tuberculosis (MTB). Methods We retrospectively studied 79 male patients with PTB confirmed by acid-fast bacillus smear and culture at Jikei University Daisan Hospital between January 2015 and December 2018. We investigated the sputum culture conversion rates for MTB after starting standard anti-TB treatment in patients with or without emphysema. Emphysema was defined as Goddard score ≥ 1 based on low attenuation area < − 950 Hounsfield Unit (HU) using computed tomography (CT). We also evaluated the effect on PTB-related CT findings prior to anti-TB treatment. Results Mycobacterial median time to culture conversion (TCC) in 38 PTB patients with emphysema was 52.0 days [interquartile range (IQR) 29.0–66.0 days], which was significantly delayed compared with that in 41 patients without emphysema (28.0 days, IQR 14.0–42.0 days) ( p  < 0.001, log-rank test). Multivariate Cox proportional hazards analysis showed that the following were associated with delayed TCC: emphysema [hazard ratio (HR): 2.43; 95% confidence interval (CI): 1.18–4.97; p  = 0.015), cavities (HR: 2.15; 95% CI: 1.83–3.89; p  = 0.012) and baseline time to TB detection within 2 weeks (HR: 2.95; 95% CI: 1.64–5.31; p  < 0.0001). Cavities and consolidation were more often identified by CT in PTB patients with than without emphysema (71.05% vs 43.90%; p  = 0.015, and 84.21% vs 60.98%; p  = 0.021, respectively). Conclusions This study suggests that emphysema poses an increased risk of delayed TCC in PTB. Emphysema detection by CT might be a useful method for prediction of the duration of PTB treatment required for sputum negative conversion.

Cigarette smoke induces damage to proteins and organelles by oxidative stress, resulting in accelerated epithelial cell senescence in the lung, which is implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Although the detailed molecular mechanisms are not fully understood, cellular energy status is one of the most crucial determinants for cell senescence. Creatine kinase (CK) is a constitutive enzyme, playing regulatory roles in energy homeostasis of cells. Among two isozymes, brain-type CK (CKB) is the predominant CK in lung tissue. In this study, we investigated the role of CKB in cigarette smoke extract (CSE)-induced cellular senescence in human bronchial epithelial cells (HBECs). Primary HBECs and Beas2B cells were used. Protein carbonylation was evaluated as a marker of oxidative protein damage. Cellular senescence was evaluated by senescence-associated β-galactosidase staining. CKB inhibition was examined by small interfering RNA and cyclocreatine. Secretion of IL-8, a hallmark of senescence-associated secretary phenotype, was measured by ELISA. CKB expression levels were reduced in HBECs from patients with COPD compared with that of HBECs from nonsmokers. CSE induced carbonylation of CKB and subsequently decreased CKB protein levels, which was reversed by a proteasome inhibitor. CKB inhibition alone induced cell senescence, and further enhanced CSE-induced cell senescence and IL-8 secretion. CSE-induced oxidation of CKB is a trigger for proteasomal degradation. Concomitant loss of enzymatic activity regulating energy homeostasis may lead to the acceleration of bronchial epithelial cell senescence, which is implicated in the pathogenesis of COPD.

Respiratory infection is a major cause of exacerbation in chronic obstructive pulmonary disease (COPD). Infectious contributions to exacerbations remain incompletely described. We therefore analyzed respiratory tract samples by comprehensive real-time polymerase chain reaction (PCR) in combination with conventional methods. We evaluated multiple risk factors for prolonged hospitalization to manage COPD exacerbations, including infectious agents. Over 19 months, we prospectively studied 46 patients with 50 COPD exacerbations, collecting nasopharyngeal swab and sputum samples from each. We carried out real-time PCR designed to detect six bacterial species and eleven viruses, together with conventional procedures, including sputum culture. Infectious etiologies of COPD exacerbations were identified in 44 of 50 exacerbations (88%). Infections were viral in 17 of 50 exacerbations (34%). COPD exacerbations caused by Gram-negative bacilli, including enteric and nonfermenting organisms, were significantly associated with prolonged hospitalization for COPD exacerbations. Our results support the use of a combination of real-time PCR and conventional methods for determining both infectious etiologies and risk of extended hospitalization.

We herein report a case of allergic bronchopulmonary aspergillosis (ABPA) that occurred in a man treated with adalimumab for ankylosing spondylitis (AS). A 69‐year‐old man with a history of ankylosing spondylitis treated by adalimumab, an anti‐tumour necrosis factor‐α (TNF‐α) antibody, developed cough and wheezing. Chest computed tomography showed obstruction of dilated left upper lobe bronchus by high attenuation mucus as well as central bronchiectasis. Both Aspergillus‐specific immunoglobulin E (IgE) and Aspergillus precipitating antibody were positive and Aspergillus fumigatus was detected in a sputum culture. According to the new diagnostic criteria, the patient was diagnosed with ABPA. His condition rapidly improved after the withdrawal of adalimumab and initiation of prednisolone and itraconazole. Anti‐TNF‐α antibody might cause ABPA through both aggravation of the host's T‐helper 2 immunological response and anti‐fungal response. We report a case of allergic bronchopulmonary aspergillosis (ABPA) that occurred in a man receiving adalimumab for ankylosing spondylitis. This case suggests that anti‐tumour necrosis factor‐α (TNF‐α) antibody might cause ABPA in terms of disruption of the Th2/Th1 balance and the anti‐fungal response.