Clinical utility of thoracoscopy in elderly tuberculous pleurisy patients under local anesthesia.

INTRODUCTION: Diagnosing tuberculous pleurisy is important in Japan because it currently has a moderate tuberculosis prevalence. However, physicians often have difficulty making a diagnosis. It was reported that thoracoscopy under local anesthesia is useful for the diagnosis of tuberculous pleurisy, but there are no reports focusing on elderly patients. METHODS: In this study, the usefulness of thoracoscopy under local anesthesia was evaluated in elderly patients. Among 170 patients who underwent thoracoscopy under local anesthesia at our hospital during 11 years from January 2008 to December 2018, those aged 75 years or older (n = 75) were investigated retrospectively. RESULTS: A total of 55 patients underwent thoracoscopy under local anesthesia for detailed examination of pleural effusion of unknown cause. Of these, 18 were diagnosed as tuberculous pleurisy. The median age was 82 years (range: 75-92 years). The diagnosis of tuberculous pleurisy was made in 11 patients in whom Mycobacterium tuberculosis was detected and in four patients whose pathological findings indicated epithelioid granuloma accompanied by caseous necrosis. Clinical diagnosis was made in the remaining three patients based on thoracoscopic findings of the pleural cavity and a high level of adenosine deaminase in pleural fluid. No serious complications attributable to the examination were observed in any patient. CONCLUSIONS: Thoracoscopy under local anesthesia was useful for the diagnosis of tuberculous pleurisy in elderly patients, with useful information being also obtained for the treatment of tuberculosis.

Efficacy of benralizumab for patients with severe eosinophilic asthma: a retrospective, real-life study.

BACKGROUND: Benralizumab, an anti-interleukin-5 (IL-5) receptor α monoclonal antibody, significantly reduces the number of annual exacerbations and oral corticosteroid (OCS) maintenance doses for patients with severe eosinophilic asthma (SEA). However, few studies on the efficacy of this biologic in real life are available. The aim was to elucidate the efficacy of benralizumab by evaluating changes in clinical parameters after benralizumab treatment in patients with SEA. METHODS: From July 2018 to December 2019, 24 Japanese patients with SEA received benralizumab at Jikei University Hospital. We retrospectively evaluated the patients' characteristics, parameters, numbers of exacerbations and maintenance OCS doses. RESULTS: Among the 24 patients, eleven patients had received mepolizumab treatment and were directly switched to benralizumab. The peripheral blood eosinophil and basophil counts significantly decreased after benralizumab treatment regardless of previous mepolizumab treatment. Pulmonary function, Asthma Control Test scores, the numbers of annual exacerbations and maintenance OCS doses in patients without previous mepolizumab treatment tended to improve without significant differences. Fourteen patients (58%) were responders according to the Global Evaluation of Treatment Effectiveness (GETE) score. The proportion of GETE responders among patients with aspirin-exacerbated respiratory disease (AERD) tended to be lower than that among patients without AERD (p = 0.085). After benralizumab treatment, the change in the forced expiratory volume in 1 s from baseline was 200 ml or greater in eight patients (33%), including three patients who were switched from mepolizumab. CONCLUSION: Benralizumab treatment improved and controlled asthma symptoms based on the GETE score.

Impact of emphysema on sputum culture conversion in male patients with pulmonary tuberculosis: a retrospective analysis.

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.

Efficacy of mepolizumab for patients with severe asthma and eosinophilic chronic rhinosinusitis.

BACKGROUND: Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice. OBJECTIVE: To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma. METHODS: From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations. RESULTS: The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [- 71.3 ± 37.0% vs - 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [- 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5-336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14). CONCLUSION: Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.

Risk factors of postoperative pulmonary complications in patients with asthma and COPD.

BACKGROUND: Postoperative pulmonary complications (PPC) in patients with pulmonary diseases remain to be resolved clinical issue. However, most evidence regarding PPC has been established more than 10 years ago. Therefore, it is necessary to evaluate perioperative management using new inhalant drugs in patients with obstructive pulmonary diseases. METHODS: April 2014 through March 2015, 346 adult patients with pulmonary diseases (257 asthma, 89 chronic obstructive pulmonary disease (COPD)) underwent non-pulmonary surgery except cataract surgery in our university hospital. To analyze the risk factors for PPC, we retrospectively evaluated physiological backgrounds, surgical factors and perioperative specific treatment for asthma and COPD. RESULTS: Finally, 29 patients with pulmonary diseases (22 asthma, 7 COPD) had PPC. In patients with asthma, smoking index (≥ 20 pack-years), peripheral blood eosinophil count (≥ 200/mm3) and severity (Global INitiative for Asthma(GINA) STEP ≥ 3) were significantly associated with PPC in the multivariate logistic regression analysis [odds ratio (95% confidence interval) = 5.4(1.4-20.8), 0.31 (0.11-0.84) and 3.2 (1.04-9.9), respectively]. In patients with COPD, age, introducing treatment for COPD, upper abdominal surgery and operation time (≥ 5 h) were significantly associated with PPC [1.18 (1.00-1.40), 0.09 (0.01-0.81), 21.2 (1.3-349) and 9.5 (1.2-77.4), respectively]. CONCLUSIONS: History of smoking or severe asthma is a risk factor of PPC in patients with asthma, and age, upper abdominal surgery, or long operation time is a risk factor of PPC in patients with COPD. Adequate inhaled corticosteroids treatment in patients with eosinophilic asthma and introducing treatment for COPD in patients with COPD could reduce PPCs.

Pirfenidone inhibits myofibroblast differentiation and lung fibrosis development during insufficient mitophagy.

BACKGROUND: Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation. In this study, the effect of PFD on autophagy/mitophagy activation in lung fibroblasts (LF) was evaluated, specifically the anti-fibrotic property of PFD for modulation of myofibroblast differentiation during insufficient mitophagy. METHODS: Transforming growth factor-ß (TGF-ß)-induced or ATG5, ATG7, and PARK2 knockdown-mediated myofibroblast differentiation in LF were used for in vitro models. The anti-fibrotic role of PFD was examined in a bleomycin (BLM)-induced lung fibrosis model using PARK2 knockout (KO) mice. RESULTS: We found that PFD induced autophagy/mitophagy activation via enhanced PARK2 expression, which was partly involved in the inhibition of myofibroblast differentiation in the presence of TGF-ß. PFD inhibited the myofibroblast differentiation induced by PARK2 knockdown by reducing mitochondrial ROS and PDGFR-PI3K-Akt activation. BLM-treated PARK2 KO mice demonstrated augmentation of lung fibrosis and oxidative modifications compared to those of BLM-treated wild type mice, which were efficiently attenuated by PFD. CONCLUSIONS: These results suggest that PFD induces PARK2-mediated mitophagy and also inhibits lung fibrosis development in the setting of insufficient mitophagy, which may at least partly explain the anti-fibrotic mechanisms of PFD for IPF treatment.

[A CASE OF SUBPHRENIC ABSCESS WITH PARADOXICAL RESPONSE CAUSED BY MYCOBACTERIUM TUBERCULOSIS].

A 40-year-old woman was admitted to our hos- pital with cough and sputum production. A chest computed tomography (CT) scan revealed a diffuse nodular shadow in the upper lung. The patient was diagnosed with pulmonary tuberculosis, based on a positive T-SPOT®.TB test result of peripheral blood and a positive polymerase chain reaction (PCR) test result for Mycobacterium tuberculosis in gastric aspirates. M.tuberculosis was subsequently isolated from the gastric aspirate specimen. After 2 months of treatment with antituberculous medication, the patient developed a low grade fever and left-sided chest pain. A CT scan revealed a left pleural effusion and a right subphrenic abscess. Tuber- culous pleurisy with paradoxical response was diagnosed on the basis of an increased lymphocyte count and increased adenosine deaminase activity in the pleural fluid exudate. A percutaneous ultrasound-guided needle biopsy of the sub- phrenic abscess was performed. Histological analysis revealed epithelioid cell granulomas with necrosis and PCR for M. tuberculosis using puncture needle washing fluid returned positive results. Based on these findings, a diagnosis of subphrenic abscess with paradoxical response, caused by M. tuberculosis, was made. Subphrenic abscess caused by M. tuberculosis is an important consideration during antituber- culous therapy.

Pulmonary and retroperitoneal lesions induced by methotrexate-associated lymphoproliferative disorder in a patient with rheumatoid arthritis.

A 78-year-old man had fatigue and appetite loss for 5 months. He had been receiving low-dose methotrexate for rheumatoid arthritis. Computed tomography revealed multiple pulmonary infiltrations and muddiness of the fatty tissue surrounding the right kidney, ureter wall thickening, and hydroureter/nephrosis, which were suspected retroperitoneal fibrosis. Lung biopsy revealed polymorphic/lymphoplasmacytic lymphoproliferative disorder. Methotrexate withdrawal resulted in spontaneous regression. Therefore, retroperitoneal lesion may account for the diagnosis as having retroperitoneal lymphoproliferative disorder, not retroperitoneal fibrosis.

Clinical features in patients with COVID-19 treated with biologics for severe asthma.

Background: Few studies have reported the clinical features of patients with coronavirus disease 2019 (COVID-19) who were treated with biologics for severe asthma (SA). Objective: We sought to elucidate the clinical features and mutual interaction between COVID-19 and SA in terms of disease severity during the Omicron epidemic. Methods: A retrospective study among patients with SA who received any biologic therapy from January 2022 to February 2023 at Jikei University Hospital (Tokyo, Japan) was performed. Results: Among 99 patients with SA, 22 women and 6 men suffered from COVID-19, and 1 woman was reinfected. The severity of COVID-19 was mild in 26 cases and moderate in 3 cases. The number of vaccinations among patients with mild COVID-19 was significantly higher than that among patients with moderate COVID-19 (3.0 ± 1.4 vs 1.0 ± 1.0; P = .03). Asthmatic exacerbations were mild in 9 cases and moderate in 7 cases. The severity of asthmatic exacerbations was significantly associated with the Asthma Control Test score at baseline (no/mild/moderate exacerbation = 23.0 ± 2.3/18.1 ± 5.3/15.0 ± 4.3; P = .004; Kruskal-Wallis test). By means of a multivariate logistic regression analysis, a lower number of vaccinations was a significant risk factor for COVID-19 progression (odds ratio, 0.64; 95% CI, 0.46-0.91; P = .006). Conclusions: During the Omicron epidemic, the onset and severity of COVID-19 were related to the number of vaccinations, and the severity of asthmatic exacerbations caused by COVID-19 was associated with the Asthma Control Test score at baseline and the number of vaccinations but not with the use of biologics.

Infective endocarditis due to nasal septal perforation during home oxygen therapy.

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.

Ultrasonic humidifier lung with a reversed halo sign: A case report.

The reversed halo sign was initially reported as a representative computed tomography scan finding of cryptogenic organizing pneumonia. Since then, however, it has been reported in various diseases and is now considered a nonspecific finding. However, there are no cases of humidifier lung with the reversed halo sign. An 82-year-old Japanese male patient presented with moving difficulties 48 days after starting darolutamide treatment for prostate cancer. He was admitted to the hospital due to acute pneumonia, which presented as bilateral extensive nonsegmental ground-glass opacities in the peripheral regions and extensive areas of ground-glass opacity with a circumferential halo of consolidation, with the reversed halo sign on computed tomography scan. After darolutamide discontinuation with the concomitant administration of antibiotics, the patient's pneumonia improved, and he was discharged from the hospital. However, within a few days, he was again admitted to the hospital due to pneumonia. He was found to have been using an ultrasonic humidifier at home and was then diagnosed with humidifier lung based on the bronchoscopy and provocative testing findings. Hence, ultrasonic humidifier lung should be considered as a differential diagnosis in patients presenting with the reversed halo sign, and a detailed medical history must be taken.

Apoptosis inhibitor of macrophage (AIM) expression in alveolar macrophages in COPD.

BACKGROUND: Marked accumulation of alveolar macrophages (AM) conferred by apoptosis resistance has been implicated in pathogenesis of chronic obstructive pulmonary disease (COPD). Apoptosis inhibitor of macrophage (AIM), has been shown to be produced by mature tissue macrophages and AIM demonstrates anti-apoptotic property against multiple apoptosis-inducing stimuli. Accordingly, we attempt to determine if AIM is expressed in AM and whether AIM is involved in the regulation of apoptosis in the setting of cigarette smoke extract (CSE) exposure. METHODS: Immunohistochemical evaluations of AIM were performed. Immunostaining was assessed by counting total and positively staining AM numbers in each case (n = 5 in control, n = 5 in non-COPD smoker, n = 5 in COPD). AM were isolated from bronchoalveolar lavage fluid (BALF). The changes of AIM expression levels in response to CSE exposure in AM were evaluated. Knock-down of anti-apoptotic Bcl-xL was mediated by siRNA transfection. U937 monocyte-macrophage cell line was used to explore the anti-apoptotic properties of AIM. RESULTS: The numbers of AM and AIM-positive AM were significantly increased in COPD lungs. AIM expression was demonstrated at both mRNA and protein levels in isolated AM, which was enhanced in response to CSE exposure. AIM significantly increased Bcl-xL expression levels in AM and Bcl-xL was involved in a part of anti-apoptotic mechanisms of AIM in U937 cells in the setting of CSE exposure. CONCLUSIONS: These results suggest that AIM expression in association with cigarette smoking may be involved in accumulation of AM in COPD.

[A case of Legionella pneumophila pneumonia accompanied by acute respiratory distress syndrome and epilepsy].

A 32-year-old female with epilepsy presented at our hospital with high-grade fever, seizures, and unconsciousness. She was initially treated for aspiration pneumonia with ampicillin/sulbactam. Despite antibiotic therapy, her chest X-ray findings dramatically worsened, showing extension to the bilateral lung field. Her PaO2/FiO2 ratio decreased to 70.6. Rapid progression of hypoxia, unconsciousness, and hyponatremia led to the suspicion of Legionella pneumonia; however, it was difficult to make a definitive diagnosis because she had denied using a whirlpool spa and the initial urinary Legionella antigen test results were negative. Therefore, we repeated the Legionella urinary antigen test, which was positive. On the basis of these results, sputum polymerase chain reaction findings, and the four-fold elevation of paired antibodies, the patient was diagnosed as having Legionella pneumonia accompanied by acute respiratory distress syndrome. We considered administering fluoroquinolone antibiotics, that are recommended for severe Legionella pneumonia, although quinolones have a potential risk for causing convulsions. In this case, we carefully administered ciprofloxacin. The patient recovered consciousness after treatment without any relapse of epileptic seizures. We also administered a corticosteroid for severe pneumonia with the expectation of clinical improvement and to avoid intubation. We emphasize the importance of aggressive workup and empirical therapy for patients with Legionella pneumonia with rapidly worsening symptoms and clinical features such as unconsciousness, epilepsy, and hyponatremia and in whom fluoroquinolone and corticosteroid therapy are effective despite the presence of epilepsy.

Simultaneous diagnosis of allergic bronchopulmonary aspergillosis and Mycobacterium avium complex lung disease.

Allergic bronchopulmonary aspergillosis (ABPA) and Mycobacterium avium complex lung disease (MAC-LD) often coexist because bronchiectasis, caused by ABPA or MAC, might be an important predisposing factor for both conditions. Here, we describe a man with asthma symptoms who had centrilobular small nodules and mucoid impaction on chest CT. We diagnosed the patient with simultaneous ABPA and MAC-LD on the basis of bronchoscopy findings. Itraconazole monotherapy led to substantial clinical improvement, avoiding the adverse effects of systemic corticosteroids. Sputum culture conversion of MAC was achieved after switching from itraconazole monotherapy to combination therapy comprising clarithromycin, rifampicin and ethambutol. ABPA recurred but was controlled by reinitiation of itraconazole. Overall, corticosteroid management was avoided for 38 months. Itraconazole monotherapy may be selected as initial treatment for ABPA with chronic infection, including MAC.

The usefulness of change in CT score for evaluating the activity of Mycobacterium abscessus (Mab) pulmonary disease (Mab-PD).

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association between serum ferritin level and decreased diffusion capacity 3 months after the onset of COVID-19 pneumonia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Involvement of creatine kinase B in cigarette smoke-induced bronchial epithelial cell senescence.

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 ß-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.

Long-Term Efficacy and Clinical Remission After Benralizumab Treatment in Patients with Severe Eosinophilic Asthma: A Retrospective Study.

Background: Few studies on the long-term efficacy of benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, have been conducted for patients with severe eosinophilic asthma (SEA), especially regarding the improvement of pulmonary function and clinical remission in a real-world setting. Objective: To elucidate the long-term efficacy and clinical remission rate (CRR) in patients with SEA. Methods: From July 2018 to July 2022, 23 Japanese patients with SEA received benralizumab for two years or more at Jikei University Hospital. We retrospectively evaluated the patients' characteristics, biomarkers, number of exacerbations, pulmonary function, asthma symptoms, maintenance oral corticosteroid (OCS) dose and CRR. Results: The mean observation period was 38.3 (24-49) months. Among the 23 patients, 10 patients switched from mepolizumab to benralizumab. After administration of benralizumab, the forced expiratory volume in one second (FEV1) increased and was maintained for two years in the biologic-naïve group and in the switching group (177 ± 404 and 151 ± 236 [mL], respectively, P = 0.80). In all patients, the %FEV1 improved from 76.7 ± 22.9% to 84.3 ± 18.4% (P = 0.016), and the number of annual exacerbations decreased from 2.5 ± 3.3 to 0.74 ± 1.7 (P = 0.014). Furthermore, the Asthma Control Test score significantly improved, and the reduction in OCS dose was maintained for three years. Ultimately, five patients met the clinical remission criteria and exhibited stabilization of pulmonary function, no exacerbation, no OCS use and well-controlled symptoms. The CRR was significantly higher in patients with a blood basophil count (BBC) ≥ 22 than in those with a BBC < 22 (/µL) (38.5% vs 0%, respectively, P = 0.046). Conclusion: Long-term treatment with benralizumab significantly improved pulmonary function, alleviated asthma symptoms and decreased the number of exacerbations at two years in a real-world setting. The CRR may be associated with the BBC at baseline.

Real-World Effectiveness of Dupilumab for Patients with Severe Asthma: A Retrospective Study.

Background: Treatment with dupilumab, an anti-interleukin (IL)-4 receptor α monoclonal antibody that blocks both the IL-4 and IL-13 pathways, has demonstrated efficacy for the treatment of severe asthma (SA) with type 2 inflammation. However, few studies have focused on the efficacy of this biologic for the treatment of SA in a real-world setting. Methods: From April 2019 to December 2021, 26 Japanese patients with SA received dupilumab at Jikei University Hospital. We retrospectively evaluated the number of moderate-to-severe exacerbations, pulmonary function, maintenance dose of corticosteroids, biomarkers, and adverse events. Results: During a mean follow-up period of 12.6 months, 10 patients received dupilumab as the first biologic, and 16 switched to dupilumab from other biologics. Dupilumab treatment significantly reduced the number of annual exacerbations from 3.4 ± 4.1 to 1.6 ± 2.7 (/person-year, p < 0.01) at the last follow-up regardless of previous biologic use. The Asthma Control Test score significantly improved in all patients by six months after administration but tended to worsen by 24 months in patients with previous biologic use. On the other hand, blood eosinophil counts (BECs) transiently increased and peaked three to six months after administration. The peak timing can be affected by previous biologic use. Adverse events included wheezing immediately after injection, hypereosinophilia, mild conjunctivitis, and relapse of chronic eosinophilic pneumonia in the patient switched from benralizumab. Conclusion: Dupilumab treatment was useful for patients with SA in a real-world setting. However, the BEC should be monitored carefully, especially in patients who previously received anti-IL-5/IL-5 receptor antibody.

Impact of emphysema on the prognosis of Mycobacterium avium complex pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major comorbid disease of Mycobacterium avium complex pulmonary disease (MAC-PD). Emphysema is one of the main pathological findings in COPD, a risk factor for chronic pulmonary aspergillosis (CPA), and is associated with poor prognosis. We aimed to clarify the effect of emphysema on mortality in MAC-PD. METHODS: We retrospectively analyzed 203 patients with MAC-PD at The Jikei Daisan Hospital between January 2014 and December 2018. We investigated the mortality and CPA development rates after MAC-PD diagnosis in patients with or without emphysema. RESULTS: Multivariate Cox proportional hazards regression analysis showed the following negative prognostic factors in patients with MAC-PD: emphysema (hazard ratio [HR]: 11.46; 95% confidence interval [CI]: 1.30-100.90; P = 0.028); cavities (HR: 3.12; 95% CI: 1.22-7.94; P = 0.017); and low body mass index (<18.5 kg/m2) (HR: 4.62; 95% CI: 1.63-13.11; P = 0.004). The mortality and occurrence of CPA were higher in MAC-PD patients with than without emphysema (log-rank test, P < 0.0001 and P < 0.0001). CONCLUSION: Our study findings showed that emphysema detected by computed tomography was associated with an increased risk of CPA development and mortality in MAC-PD.