Involvement of Muscarinic M3 Receptor in the Development of M2 Macrophages in Allergic Inflammation.

INTRODUCTION: The muscarinic M3 receptor antagonist, tiotropium, has a bronchodilatory effect on asthma patients. Additionally, tiotropium inhibits allergic airway inflammation and remodeling in a murine asthma model. However, the underlying mechanisms of this M3 receptor antagonist remain unclear. Therefore, we investigated the effect of muscarinic M3 receptor blockage on M2 macrophage development during allergic airway inflammation. METHODS: BALB/c mice were sensitized and challenged with ovalbumin to develop a murine model of allergic airway inflammation mimicking human atopic asthma. During the challenge phase, mice were treated with or without tiotropium. Lung cells were isolated 24 h after the last treatment and gated using CD68-positive cells. Relm-α and Arginase-1 (Arg1) (M2 macrophage markers) expression was determined by flow cytometry. Mouse bone marrow mononuclear cell-derived macrophages (mBMMacs) and human peripheral blood mononuclear cells (PBMCs)-derived macrophages were stimulated with IL-4 and treated with a muscarinic M3 receptor antagonist in vitro. RESULTS: The total cells, eosinophils, and IL-5 and IL-13 levels in BAL fluids were markedly decreased in the asthma group treated with tiotropium compared to that in the untreated asthma group. The Relm-α and Arg1 expression in macrophages was reduced considerably in the asthma group treated with tiotropium compared to that in the untreated asthma group, suggesting that the development of M2 macrophages was inhibited by muscarinic M3 receptor blockage. Additionally, muscarinic M3 receptor blockage in vitro significantly inhibited M2 macrophage development in both mBMMacs- and PBMCs-derived macrophages. CONCLUSIONS: Muscarinic M3 receptor blockage inhibits M2 macrophage development and prevents allergic airway inflammation. Moreover, muscarinic M3 receptors might be involved in the differentiation of immature macrophages into M2 macrophages.

[EPIPEN INSTRUCTIONS FOR ANAPHYLAXIS PATIENTS DURING DISPENSING: FACTORS RELATED TO THE QUALITY OF PHARMACISTS' INSTRUCTIONS].

BACKGROUND AND AIM: We previously reported that pharmacists working in pharmacies don't have enough knowledge and enough experience teaching anaphylaxis (An) and EpiPen use. We administered a questionnaire survey to pharmacists with experience handling EpiPen prescriptions. We investigated the relationship between the questionnaire results and the factors in the pharmacists' background regarding the explanation and guidance to patients. RESULTS: The percentage of pharmacists working in pharmacies who provided guidance using visual information and demonstrations was insufficient. Moreover, this figure decreased after the second guidance session. Objective confirmation of patient understanding was also insufficient. The results indicated that self-examination and participation in drug information sessions were important background factors for pharmacists who provided detailed guidance to patients. DISCUSSION: For appropriate long-term management of their condition, An patients must master the EpiPen technique. Pharmacists' guidance plays a critical role in this regard. A support system should be established for proper instruction of pharmacy patients by improving pharmacists' self-education and other educational opportunities.

[SURVEY OF KNOWLEDGE ABOUT ANAPHYLAXIS AND GUIDANCE WHEN DISPENSING EPIPEN FOR PHARMACISTS WORKING IN PHARMACIES].

BACKGROUND/PURPOSE: Anaphylactic shock is a serious and life-threatening condition, and affected patients should be quickly and effectively treated with an EpiPen. Although the correct use of an EpiPen is greatly affected by a user's proficiency level and the instructions accompanying the EpiPen, there has been almost no investigation into the knowledge of the EpiPen and the actual situation of the accompanying instructions for use. Therefore, we conducted this nationwide survey to elucidate these issues. METHODS: A questionnaire survey was conducted among pharmacists registered as members of the system of a research company outside the university and working at pharmacies with experience in handling EpiPen prescriptions. RESULTS: Many of the pharmacists surveyed knew that the EpiPen is the first-line treatment for anaphylactic shock. However, they did not have sufficient knowledge of administration routes and candidates for second-line treatment. Both their occasions and experiences of dealing of EpiPen were found to be low. CONSIDERATION: It is desirable to learn at conferences regarding allergology/clinical allergy and seminars for medical professionals including pharmacists in order to acquire the skills and knowledge to consult with patients with allergic diseases, including action plans presented by doctors in preparation for recurrence of anaphylaxis.

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.

Comprehensive Gene Expression Signature Using RNA-Seq in Airways of Mouse Model of Severe Asthma with Fungal Sensitization.

INTRODUCTION: Inhalation of fungal allergens induces airway epithelial damage following airway inflammation and excessive mucus secretion, which can lead to severe asthma with fungal sensitization (SAFS). Comprehensive gene expression analysis in Alternaria-exposed mouse airways, a model of SAFS, has not been conducted. METHODS: BALB/c mice received intranasal administration of Alternaria extract or phosphate-buffered saline twice a week for 6 weeks. Lung sections and bronchoalveolar lavage fluid were obtained to assess airway inflammation. RNA-Seq in the central airway was performed, and gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted for pathway analyses. An in vitro experiment using human airway epithelial cell 16HBE14o- was performed to validate the RNA-Seq findings. RESULTS: Eosinophilic airway inflammation with mucus overproduction and airway remodeling was observed in mice exposed to Alternaria. RNA-Seq analysis revealed 403 upregulated and 108 downregulated genes in airways of Alternaria-exposed mice. In GO analysis, the functions of immunoglobulin (Ig) receptor binding, Ig production, inflammatory response, and T-cell activation were upregulated, while those of keratinization and defense response to other organisms were downregulated. GSEA revealed positive enrichment in T-cell receptor complex, immunological synapse, antigen binding, mast cell activation, and Ig receptor binding, and negative enrichment in keratinization and cornification in Alternaria-exposed mice relative to control. Alternaria exposure to 16HBE14o- cells validated the downregulation of epithelial keratinization-related genes, including SPRR1A, SPRR1B, and KRT6B. CONCLUSION: RNA-Seq analysis showed that Alternaria exposure induced inflammatory response and impaired defense mechanisms in mice airway epithelium, which might be therapeutic targets for SAFS.

Investigating Patient and Family Satisfaction with the Respiratory Status in Patients with Chronic Obstructive Pulmonary Disease.

The current chronic obstructive pulmonary disease (COPD) management aims to improve the patients' quality of life and healthy life expectancy; however, few studies have evaluated the level of satisfaction with the patients' current respiratory status in COPD patients and their families. This study aimed to examine the level of patient and family satisfaction with the patients' current respiratory status and to identify the clinical factors closely linked to dissatisfaction.This multicenter, cross-sectional study included 454 outpatients with COPD and 296 family members. Patients and families were allocated to the satisfied and dissatisfied groups based on their satisfaction with the patients' current respiratory status. Patients' health status, dyspnoea, appetite, respiratory function, and mood disorders were assessed.Among the participants of this study, 67% of patients and 60% of their families were dissatisfied with the patients' current respiratory status. The COPD assessment test (CAT) was the most sensitive marker of dissatisfaction compared to other clinical factors (p < 0.01). The statistical cut-off value of CAT for predicting patient dissatisfaction was 11. CAT reflected patient dissatisfaction independent of age, sex, dyspnoea, appetite, mood disorders, body mass index, and respiratory function (odds ratio: CAT; 1.12 (1.07-1.19): p < 0.01).Many patients and families are dissatisfied with the patients' respiratory status, and the patients' CAT score is useful to predict dissatisfaction. Our findings are consistent with the Global Initiative for Chronic Obstructive Lung Disease indicating that treatment should be enhanced in patients with a CAT score ≥10. Furthermore, treatment strategies targeting CAT may contribute to an improved patient satisfaction.

The Effect of Bronchoconstriction by Methacholine Inhalation in a Murine Model of Asthma.

INTRODUCTION: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. OBJECTIVE: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. METHODS: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. RESULTS: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-ß in the lung. This result indicates that the production of TGF-ß is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. CONCLUSIONS: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.

Inhibition of Virus-Induced Cytokine Production from Airway Epithelial Cells by the Late Addition of Budesonide.

BACKGROUND: Viral infection is the main cause of asthma and COPD (chronic obstructive pulmonary disease) exacerbation and accumulate inflammatory cells to airway tissue. We have reported poly I:C, a mimic product of the virus and ligand of toll-like receptor 3 (TLR3), induced inflammatory chemokines from airway epithelial cells and found prior incubation with corticosteroids diminishes the effect of TLR3 activation. In clinical practice, mild asthma is recommended as-needed budesonide (BUD) when symptoms occur following a viral infection, etc. However, many questions still surround BUD's usefulness if taken after a virus has already infected airway tissue. OBJECTIVE: The aim of this study was to investigate the inhibitory effects of BUD on inflammatory cytokines induced by viral infection. Methods: Normal human bronchial epithelial (NHBE) cells were stimulated with poly I:C or infected with human rhinovirus-16 (HRV16) and BUD was added after the initial stimulation. Expression of both thymic stromal lymphopoietin (TSLP) and CCL26/eotaxin-3 was quantified by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Knockdown study was performed. Results: Pre-or post-incubation with BUD inhibited both poly I:C- and HRV16-induced mRNAs and proteins of both thymic stromal lymphopoietin (TSLP) and CCL26 with significance. Knockdown of the glucocorticoid receptor diminished these effects of BUD. Under the same conditions of BUD's experiment, post-incubation with neither fluticasone propionate nor dexamethasone suppressed expression of both TSLP and CCL26, which induced by poly I:C. CONCLUSION: Post-addition of BUD inhibited the virus-induced TSLP and CCL26 from the airway epithelial cells. These results suggest that inhalation of BUD after viral infection has beneficial effects on asthma. CONCLUSION: Late addition of BUD may benefit among patient with viral infection and type 2 allergic airway disease such as asthma.

[A CASE OF ANAPHYLAXIS DUE TO STINGING OF A Brachyponera chinensis].

The case involved a man in his forties. While working at the restaurant that the patient runs, the patient experienced a stab-like pain on the left shoulder and developed systemic pruritic eruptions. He was diagnosed with anaphylaxis upon visiting our emergency department. Conjunctival hyperemia, lip swelling, cold sweats, and nausea presented later. A cap fluorescence enzyme immunoassay using the serum of the patient showed specific immunoglobulin E (IgE) positivity for wasps; therefore, we hypothesized that he had anaphylaxis caused by the insect's sting. Insects of the same species as that by which the patient had been stung were collected and finally identified as the Asian needle ant (Brachyponera chinensis). The freeze-dried insects' bodies were sonicated into powders and stored for following examinations. Next, a basophil activation test was performed using the patient's whole blood treated with the reagent above, which showed positivity. Furthermore, a skin prick test using the same reagent showed a positive result, and the reaction increased in a concentrationdependent manner. Based on these results, the patient was diagnosed with anaphylaxis after a sting by the ant. Based on the results of the allergen component specific IgE test, we speculated that the pathogens in this case was group5 allergen of the Asian needle ant. Anaphylaxis following insect stings by this ant has been reported frequently in South Korea. However, it is quite rare in Japan, although the ant is native to Japan. Clinicians should consider that this allergy can occur indoors, unlike allergies to other types of venom.

Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. OBJECTIVE: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. METHOD: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). RESULTS: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. CONCLUSION: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.

Predicting future risk of exacerbations in Japanese patients with adult asthma: A prospective 1-year follow up study.

BACKGROUND: To avoid future risk is a definitive goal of long-term asthma management. Exacerbations are considered to be the most relevant future risk in real life asthma management. Few comparative studies have evaluated the risk factors associated with exacerbations in Japanese patients with asthma. METHODS: We performed the prospective 1-year follow up study in Japanese patients with adult asthma. A total of 189 patients with asthma were enrolled and followed up for 1 year. Finally, 181 patients completed the study protocol. RESULTS: Of 181 patients, 43 patients (23.8%) had exacerbations during the follow-up period. Among the 45 patients who had exacerbations during the preceding year, 32 patients (71.1%) had exacerbations. Prevalence of patients with previous exacerbations and those with previous admissions were significantly higher in patients with exacerbations than those with no exacerbation. Logistic regression analysis also identified a significant association between exacerbations during the follow-up period and exacerbations during the preceding year, admissions during the preceding 3 years, ACT score below 20, low %FVC (<80%), or low FEV1 (<70%), respectively. Of the 55 patients with severe asthma, 29 patients (52.7%) had exacerbations. Among the 36 patients with severe asthma with previous exacerbations, 26 patients (72.2%) had exacerbations. The history of exacerbations during the preceding year was associated with a significantly increased risk of exacerbations both among the patients with severe asthma and those with non-severe asthma. CONCLUSIONS: This study implicated that exacerbations during the preceding year reliably predict future risk of exacerbations in Japanese patients with asthma.

Prevalence and Impact of Social Frailty in Patients with Chronic Obstructive Pulmonary Disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) are more inclined to have a high level of social vulnerability due to their physical and psychological burden. However, to date, there have been no study on social frailty in patients with COPD. This study aimed to investigate the prevalence, characteristics, and impact of social frailty in patients with COPD. Methods: Social frailty was assessed using five items in a questionnaire. A patient was diagnosed with social frailty if responses to two or more items were positive. Four hundred and five patients with COPD were assessed for social frailty, dyspnea, and appetite. We also prospectively examined the number of acute exacerbation and unexpected hospitalization for 1 year. Results: Thirty-six percent of patients with COPD had social frailty. They had reduced appetite and more severe dyspnea [Simplified Nutritional Appetite Questionnaire score: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.69‒0.95, p < 0.01; modified Medical Research Council score: OR 1.42, 95% CI 1.05‒1.93, P = 0.02] than patients without social frailty. Social frailty was not a risk factor for moderate acute exacerbation of COPD but a risk factor for severe acute exacerbation and all-cause unexpected hospitalization (severe acute exacerbation: ß, standardized regression coefficient: 0.13, 95% CI 0.01‒0.25, P = 0.04, unexpected hospitalization: ß 0.17, 95% CI 0.05‒0.29, P = 0.01). Conclusion: The prevalence of social frailty is 36%; however, social frailty has a marked clinical impact in patients with COPD.

Utility of SpO2/FiO2 ratio for acute hypoxemic respiratory failure with bilateral opacities in the ICU.

Acute hypoxemic respiratory failure (AHRF) with bilateral opacities causes fatalities in the intensive care unit (ICU). It is often difficult to identify the causes of AHRF at the time of admission. The SpO2 to FiO2 (S/F) ratio has been recently used as a non-invasive and alternative marker of the PaO2/FiO2 (P/F) ratio in acute respiratory failure. This retrospective cohort study was conducted from October 2010 to March 2019 at the Showa University Hospital, Tokyo, Japan. We enrolled 94 AHRF patients who had bilateral opacities and received mechanical ventilation in ICU to investigate their prognostic markers including S/F ratio. Significant differences were observed for APACHE II, S/F ratio, PaO2/FiO2 (P/F) ratio, and ventilator-free-days at day 28 for ICU mortality, and for age, S/F ratio, P/F ratio, duration of mechanical ventilation, and ventilator-free days at day 28 for hospital mortality. Multivariate logistic regression analysis showed that the S/F ratio was significantly and independently associated with the risk of death during in ICU (p = 0.003) and hospitalization (p = 0.002). The area under the receiver operating characteristic curves (AUC) based on the S/F ratio were significantly greater than those based on simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) for ICU mortality (0.785 in S/F ratio vs. 0.575 in SAPS II, p = 0.012; 0.785 in S/F ratio vs 0.594 in SOFA, p = 0.021) and for hospital mortality (0.701 in S/F ratio vs. 0.502 in SAPS II, p = 0.012; 0.701 in S/F ratio vs. 0.503 in SOFA, p = 0.005). In the subanalysis for bacterial pneumonia and interstitial lung disease groups, the AUC based on the S/F ratio was the greatest among all prognostic markers, including APACHE II, SAPS II, and SOFA. The S/F ratio may be a useful and noninvasive predictive prognostic marker for acute hypoxemic respiratory failure with bilateral opacities in the ICU.

Fatal rupture of pulmonary artery pseudoaneurysm after thoracic radiation therapy against lung squamous cell carcinoma: A case report and literature review.

Pulmonary artery pseudoaneurysm is a rare but fatal condition. It has been associated with lung cancer, abscesses, and radiation therapy. Identification in patients with hemoptysis is critical, and timely interventional therapy is warranted.

Serum creatinine/cystatin C ratio as a surrogate marker for sarcopenia in patients with chronic obstructive pulmonary disease.

BACKGROUND & AIMS: Sarcopenia is common in patients with chronic obstructive pulmonary disease (COPD). Serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a surrogate marker for sarcopenia but has not been adequately studied in patients with COPD. Thus, the purpose of this study was to investigate the validity of serum Cr/CysC ratio as a predictor of sarcopenia, evaluate a statistical cut-off value, and assess the relationship between Cr/CysC ratio and clinical factors. METHODS: In this prospective observational study, we enrolled 234 male outpatients with COPD. We determined the relevance of serum Cr/CysC ratio as a surrogate maker for sarcopenia by comparing it with various biomarkers and prospectively investigated the relationship of Cr/CysC ratio with the annual exacerbation rate. RESULTS: Serum Cr/CysC was significantly correlated with handgrip strength (r = 0.53, P < 0.01) and muscle mass (r = 0.44, P < 0.01). The area under the curve for sarcopenia was significantly larger for serum Cr/CysC ratio than for other biomarkers (Cr/CysC: 0.87, CysC: 0.63, Cr: 0.61, albumin: 0.57). Multivariate analysis showed no significant difference in the frequency of acute exacerbations between patients in the low- and high-Cr/CysC group, defined by the cutoff value 0.71; however, the frequency of severe acute exacerbations was significantly higher in the low-Cr/CysC group. CONCLUSION: Serum Cr/CysC ratio can be used accurately, inexpensively, and easily to evaluate sarcopenia in male patients with COPD. Our study shows that patients with Cr/CysC below 0.71 have poor physical clinical factors and are at high risk of severe acute COPD exacerbations.

Characteristics of and reasons for patients with chronic obstructive pulmonary disease to continue smoking, quit smoking, and switch to heated tobacco products.

INTRODUCTION: Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the most effective treatment for patients with COPD. However, few studies have investigated the continuation/cessation of smoking and heated tobacco products (HTP) in patients with COPD. The objective of this study was to examine the characteristics of patients with COPD, those who are current smokers and those who switched from cigarettes to HTP, and to examine the reason for the continuation or cessation of smoking. METHODS: This multicenter, cross-sectional study included 411 outpatients with COPD. Data for this study were part of a study conducted for a comprehensive evaluation of the smoking status and clinical factors in patients with COPD and their families. RESULTS: Logistic regression analysis revealed that a younger age, longer duration of smoking, fewer daily cigarettes, and lower modified Medical Research Council (mMRC) dyspnea score, and a lower Simplified Nutritional Appetite Questionnaire (SNAQ) score for appetite, were characteristics of current smokers (age OR=0.94; duration of smoking OR=1.07; number of cigarettes per day OR=0.94; mMRC OR=0.68; SNAQ OR=0.83; p<0.05). The logistic regression analysis model showed that a younger age and higher education level were associated with the use of HTP (age OR=0.83; higher education level OR=4.63; p<0.05). Many of the current smokers displayed smoking behaviors that are not guaranteed to be safe, such as reducing smoking or switching to lighter cigarettes or HTP. CONCLUSIONS: Patients with COPD who continue smoking tended to have low appetite as well as smoking behaviors that are not guaranteed to be safe. Physicians should provide appropriate guidance to these patients on smoking cessation.

The Relationship Between the "Adherence Starts with Knowledge-20" Questionnaire and Clinical Factors in Patients with COPD: A Multi-Center, Cross-Sectional Study.

Purpose: Inhaler therapy is the mainstay of chronic obstructive pulmonary disease (COPD) management. Poor adherence causes disease exacerbation and affects patient mortality. Although the Adherence Starts with Knowledge-20 (ASK-20) questionnaire is a reliable tool for assessing medication adherence, the relationship between the ASK-20 and clinical factors in patients with COPD remains unknown. We investigated the relationship between the ASK-20 and clinical factors, and assessed real-world inhaler therapy use. Patients and Methods: A multicenter, cross-sectional study of outpatients with COPD undergoing inhaler treatment who completed the ASK-20 questionnaire was performed. We investigated COPD-related health status using the COPD Assessment Test (CAT), psychological status using the Hospital Anxiety and Depression Scale (HADS-anxiety and HADS-depression), respiratory function, patient satisfaction levels, and real-world inhaler therapy use. Results: Of the total 319 patients, 87% were male with a median age of 74 years. Most patients had mild or moderate COPD, according to Global Initiative for Chronic Obstructive Lung Disease stage. The total ASK-20 scores correlated significantly with the CAT, HADS-anxiety, and HADS-depression scores (r = 0.27, 0.33, and 0.29, respectively, p < 0.01). Multivariable analysis showed that CAT and HADS-anxiety scores had an independent and significant impact on the ASK-20 scores [ß, standardized regression coefficient: 0.18 (95% CI, 0.03-0.35; p = 0.02), and 0.29 (95% CI, 0.17-0.42; p < 0.01), respectively]; however, the ASK-20 scores were not correlated with age, sex, body mass index, cohabitation, modified Medical Research Council Dyspnea Scale score, pulmonary function, disease duration, number of COPD exacerbations per year, comorbidities, inhaler numbers, nor inhaler components. Conclusion: The ASK-20 scores in patients with COPD were significantly associated with CAT and HADS scores. In Japan, Respimat was prescribed to younger patients and patients with lower CAT scores. The ASK-20, a simple evaluation method, is useful for identifying clinical factors affecting adherence in patients with COPD.

Combination treatment of short-course systemic corticosteroid and favipiravir in a successfully treated case of critically ill COVID-19 pneumonia with COPD.

Use of systemic corticosteroids for the treatment for coronavirus disease 2019 (COVID-19) among chronic obstructive pulmonary disease (COPD) patients is not well described. A 58-year-old man with fever and progressive dyspnea was admitted to the Showa University Hospital, and showed severe respiratory failure which needed mechanical ventilation. His chest computed tomography scanning showed emphysema and bilateral ground-glass opacity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. He received 30 mg prednisolone for five days with antiviral drug of favipiravir, and was successfully extubated on day five. A SARS-CoV-2 polymerase chain reaction (PCR) test became negative on day 15. He was discharged on day 21. Serum IgM and IgG antibodies against SARS-CoV-2 converted to positive on day 7 and they kept positive on day 54 for both IgM and IgG. Combination treatment of short-course systemic corticosteroid and favipiravir might improve the prognosis for critically ill COVID-19 pneumonia with COPD without negative influence on viral clearance or antibody production.