Improvement in Frailty in a Patient With Severe Chronic Obstructive Pulmonary Disease After Ninjin'yoeito Therapy: A Case Report

Frailty is a poor prognostic factor in patients with chronic obstructive pulmonary disease (COPD). Although various studies have assessed the effects of conventional treatment with bronchodilators, nutritional support, and pulmonary rehabilitation for frailty in patients with COPD, none have addressed the effects of traditional Japanese medicine (Kampo medicine). Herein, we report the successful management of frailty using Ninjin'yoeito therapy in a 76-year-old patient with COPD. Despite being prescribed multiple bronchodilators, nutritional supplement therapy, patient education, and pulmonary rehabilitation, the patient exhibited unintentional weight loss, low energy, and low physical activity. Ninjin'yoeito was prescribed and these subjective symptoms began to improve 1 month after treatment initiation. In 6 months, the patient reported no frailty, had increased muscle mass, and had achieved an almost normal healthy state. Ninjin'yoeito has been associated with both physical effects, such as improvement in overall physical strength and appetite, and reduction in fatigue, and psychological effects, such as greater motivation and reduction of depression and anxiety symptoms. Physicians have usually treated COPD primarily with organ-specific treatments, such as bronchodilators; however, addressing both the physiological and psychological vulnerability has been difficult. This case report illustrates the potential usefulness of Ninjin'yoeito treatment for frailty in patients with COPD

Long-term follow-up of production of IgM and IgG antibodies against SARS-CoV-2 among patients with COVID-19

The patients diagnosed with coronavirus disease 2019 （COVID-19） produce IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2）. However, the frequency and duration of antibody production still need to be fully understood. In the present study, we investigated the duration of antibody production after SARS-CoV-2 infection. The patients diagnosed with COVID-19 were monitored over twelve months for the production of SARS-CoV-2 IgM and IgG antibodies, and the characteristics of these patients were examined. Forty-five patients diagnosed with COVID-19 were enrolled, and thirty-four patients were followed up until they tested negative for SARS-CoV-2 IgM and IgG antibodies or up to twelve months after the date of a negative SARS-CoV-2 polymerase chain reaction （PCR） result. The positivity rates of SARS-CoV-2 IgM and IgG antibodies were 27.3％ and 68.2％ when SARS-CoV-2 PCR was negative, 20.6％ and 70.6％ after one month, 8.8％ and 52.9％ after three months, and 0.0％ and 14.7％ after six months, respectively. Moreover, we compared patients with milder conditions who did not require oxygen administration with those with severe conditions which required oxygen administration. The positivity rate of SARS-CoV-2 IgG antibodies was significantly higher in patients with severe conditions than in those with milder conditions on the date of a negative SARS-CoV-2 PCR result and after one month and three months, but not after six months. Patients with more severe COVID-19 produced more SARS-CoV-2 IgG antibodies. Moreover, it is suggested that the duration of IgG antibody production is independent of COVID-19 severity

Safety and Efficacy of Nontuberculous Mycobacteria Treatment among Elderly Patients

Background and objectives: Incidence rates of pulmonary nontuberculous mycobacterial (NTM) disease have been increasing, especially in the elderly population. Given the limited evidence regarding the safety and efficacy of NTM treatment, this study aimed to evaluate the same among elderly patients. Material and methods: Patients diagnosed with NTM disease at a tertiary hospital from January 2007 to December 2017 were enrolled and data were then retrospectively collected. Data of elderly patients who received antimycobacterial treatment were then analyzed. Results: A total of 161 patients satisfied the diagnostic criteria for NTM disease. There were 40 elderly patients who received treatments. Of the patients, 60% received the guideline oriented standard regimens. Single drug regimens were administered to 22.5% of patients. Only 55.0% of the patients were able to continue any treatment. Treatment-related discontinuation was observed in 44.4% of discontinued or changed patients. There were no significant differences in the characteristics of patients with or without adverse events. Patients who were able to continue the treatment for >12 months had a lower proportion of activities of daily living (ADL) disability (nine in 18, 50.0% vs. three in 22, 13.6%, p = 0.018) and heart disease (six in 18, 33.3% vs. 1/22, 4.6%, p = 0.033). Sputum culture conversion was achieved in 28 out of 40 (70.0%) elderly patients treated, and those who achieved sputum culture conversion had more standard regimens prescribed than those who failed sputum culture conversion (21 in 28, 75% vs. 3 in 12, 25%; p = 0.005). Conclusion: Age may not be an obstacle for receiving the benefits of the treatment of NTM disease with a precise evaluation of patient’s comorbidities. Furthermore, elderly patients without heart disease and ADL disability may have better rate of continuing the NTM treatment. The current study suggested that selecting standard regimens to treat pulmonary NTM is important for elderly patients

Indirect Comparison of Dupilumab and Mepolizumab Treatments for Uncontrolled Eosinophilic Asthma-Bayesian Analysis of Randomized Controlled Trials-

The efficacy and safety of dupilumab, a humanized interleukin （IL）-4 receptor alfa monoclonal antibody （mAb） that inhibits the signaling of the type 2 cytokines IL-4 and IL-13, for the treatment of uncontrolled eosinophilic asthma remains to be fully characterized, particularly in comparison to other therapeutic mAbs. Therefore, we conducted a meta-analysis of randomized controlled trials （RCTs） to indirectly compare the efficacy and safety of dupilumab with those of mepolizumab, a humanized anti-IL-5 mAb, in patients with uncontrolled eosinophilic asthma. Comparisons were made using the Bayesian statistical method. This meta-analysis complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses （PRISMA） guidelines. Six RCTs were eligible for this study: two RCTs focused on dupilumab and four on mepolizumab. The primary efficacy outcome was a change in the forced expiratory volume at 1.0 second （FEV1.0）, and the primary safety outcome was the incidence of severe adverse effects （SAE）. The mean difference in changes in the FEV1.0 following treatment with dupilumab versus mepolizumab was 0.133 （95% CI, 0.016-0.252）. There was no significant difference between these two agents in the incidence of SAE （OR, 1.99; 95% CI, 0.19-11.16）. These results strongly indicate that dupilumab is more effective than mepolizumab and is generally well-tolerated in patients with uncontrolled eosinophilic asthma

Interleukin-34 induces pulmonary inflammation in a murine model of lipopolysaccharide-induced acute lung injury

The cytokine interleukin-34 （IL-34） was recently described. However, its role in the lungs is not well understood. IL-34 binds to the colony stimulating factor-1 receptor, thereby enhancing tissue macrophage maturation and differentiation. Macrophages are essential to the airway inflammation process and acute lung injury （ALI）. This study aimed to evaluate the role of IL-34 in ALI establishment. C57BL/6 male mice were stimulated intratracheally with lipopolysaccharide （LPS） and sacrificed on day 1, 3, 5, or 7. Additionally, the mice were treated with an anti-IL-34 antibody intranasally before LPS stimulation. The bronchoalveolar lavage fluid （BALF） and lung tissues were collected. The cells of the human peripheral blood monocyte cell line THP-1 and the human airway epithelial cell line BEAS-2B were cultured with LPS in vitro. The total cell number in BALF was higher in the LPS-stimulated mice than in the control mice. The BALF IL-34 level was significantly elevated in BALF on days 1 and 3. IL-34 expression was detected in the pulmonary epithelium in the LPS-stimulated mice on day 1. Anti-IL-34 antibody suppressed the number of macrophages in BALF. IL-34 blockade resulted in pulmonary fibrosis reduction in LPS-stimulated mice on day 5. LPS stimulation in vitro induced the production of tumor necrosis factor-α （TNF-α） in THP-1 cells. Furthermore, TNF-α stimulation induced the IL-34 production in BEAS-2B cells. These results suggest that IL-34 induction in the epithelial cells may enhance pulmonary inflammation and fibrosis in the murine model of LPS-induced acute lung injury

Fetal Lung Cells Transfer Improves Emphysematous Change in a Mouse Model of Neutrophil Elastase-Induced Lung Emphysema

Recently, several studies for lung regeneration have been reported. However, regenerating the lung tissue by the transfer of any cells directly to the lung has been hardly successful. The aim of this study was to evaluate the effect of fetal lung cells (FLCs) in a mouse model of lung emphysema. C57BL/6 mice were stimulated with neutrophil elastase (NE) intra-tracheally (i.t.) to generate lung emphysema. To collect fetal lung cells, C57BL/6-Tg (CAG-EGFP) mice were bred for 14 days. Before delivery, the bred mice were euthanized, and fetal lungs were harvested from the fetal mice and the cells were collected. The FLCs were transferred i.t. 24 h after the NE instillation. Four weeks after the NE instillation, mice were euthanized, and the samples were collected. The mean linear intercept (MLI) was significantly prolonged in the NE instillation group compared to the control group. However, in the FLCs transfer group stimulated with NE, the MLI became shorter than the NE-stimulated group without an FLCs transfer. This result shows that an FLCs transfer inhibited the progression of lung emphysema. Additionally, motility of the mice was also improved by the FLCs transfer. These results indicate that transfer of the FLCs, which were presumed to be progenitor cells for lung tissue, may improve the emphysematous change

Correlation of Arterial CO2 and Respiratory Impedance Values among Subjects with COPD

Chronic obstructive pulmonary disease (COPD) is a respiratory illness characterized by airflow limitation and chronic respiratory symptoms with a global prevalence estimated to be more than 10% in 2010 and still on the rise. Furthermore, hypercapnic subject COPD leads to an increased risk of mortality, morbidity, and poor QoL (quality of life) than normocapnic subjects. Series of studies showed the usefulness of the forced oscillation technique (FOT) to measure small airway closure. Traditional findings suggested that hypercapnia may not be the main treating targets, but recent findings suggested that blood stream CO2 may lead to a worse outcome. This study aimed to seek the relationship between CO2 and small airway closure by using FOT. Subjects with COPD (n = 124; hypercapnia 22 and normocapnia 102) were analyzed for all pulmonary function values, FOT values, and arterial blood gas analysis. Student’s t-test, Spearman rank correlation, and multi linear regression analysis were used to analyze the data. COPD subjects with hypercapnia showed a significant increase in R5, R20, Fres, and ALX values, and a greater decrease in X5 value than normocapnic patients. Also, multiple linear regression analysis showed R5 was associated with hypercapnia. Hypercapnia may account for airway closure among subjects with COPD and this result suggests treating hypercapnia may lead to better outcomes for such a subject group