Inhaled Corticosteroids May Not Affect the Clinical Outcomes of Pneumonia in Patients with Chronic Obstructive Pulmonary Disease.

Background: Although inhaled corticosteroids (ICS) is reportedly associated with a higher risk of pneumonia in chronic obstructive pulmonary disease (COPD), the clinical implications of ICS have not been sufficiently verified to determine their effect on the prognosis of pneumonia. Methods: The electronic health records of patients hospitalized for pneumonia with underlying COPD were retrospectively reviewed. Pneumonia was confirmed using chest radiography or computed tomography. The clinical outcomes of pneumonia in patients with COPD who received ICS and those who received long-acting bronchodilators other than ICS were compared. Results: Among the 255 hospitalized patients, 89 met the inclusion criteria. The numbers of ICS and non-ICS users were 46 and 43, respectively. The CURB-65 scores at the initial presentation of pneumonia were comparable between the two groups. The proportions of patients with multilobar infiltration, pleural effusion, and complicated pneumonia in the radiological studies did not vary between the two groups. Additionally, the defervescence time, proportion of mechanical ventilation, intensive care unit admission, length of hospital stays, and mortality rate at 30 and 90 days were not significantly different between the two groups. ICS use and blood eosinophils count were not associated with all pneumonia outcomes and mortality in multivariate analyses. Conclusion: The clinical outcomes of pneumonia following ICS use in patients with COPD did not differ from those in patients treated without ICS. Thus, ICS may not contribute to the severity and outcomes of pneumonia in patients with COPD.

Inhaled Corticosteroids and the Risk of Nontuberculous Mycobacterial Pulmonary Disease in Chronic Obstructive Pulmonary Disease: Findings from a Nationwide Population-Based Study.

Studies have shown increased nontuberculous mycobacterial pulmonary disease (NTM) incidence with inhaled corticosteroid (ICS) use in patients with chronic respiratory diseases; however, this association in chronic obstructive pulmonary disease (COPD) remains insufficiently studied. Using a nationwide population-based database of the Korean National Health Insurance Service, newly diagnosed COPD patients (2005-2018) treated with inhaled bronchodilators were selected. An NTM case was defined by the presence of the first diagnostic code following inhaled bronchodilator use. Results indicated that ICS users did not have an increased risk of NTM disease compared to non-ICS users (hazard ratio (HR), 1.121; 95% confidence interval (CI), 0.950-1.323; p = 0.176). However, in a subgroup analysis, the highest quartile of the cumulative ICS dose was associated with the development of NTM (1.200, 0.950-1.323, p = 0.050). Medium (1.229, 1.008-1.499, p = 0.041) and high daily doses of ICS (1.637, 1.241-2.160, p < 0.001) were associated with an increased risk of NTM disease. There was no difference in the risk of NTM according to ICS type. ICS use may increase the risk of developing NTM disease in patients with COPD. Physicians should weigh the potential benefits and risks of ICS, especially when using high doses and prolonged durations.

Adherence to Long-Acting Inhaler Use for Initial Treatment and Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study.

We aimed to determine the effect of long-acting inhaler use adherence on acute exacerbations in treatment-naïve patients with chronic obstructive pulmonary disease (COPD) using claims data from the Korean Health Insurance Review and Assessment Service from July 2015−December 2016. Patients with COPD aged ≥ 40 years who used long-acting inhalers were enrolled and observed for 6 months. Medication adherence was determined by the medication possession ratio (MPR); patients were categorized to adherence (MPR ≥ 80%) and non-adherence (MPR < 80%) groups. Ultimately, 3959 patients were enrolled: 60.4% and 39.6% in the adherence and non-adherence groups, respectively. The relative risk of acute exacerbation in the non-adherence group was 1.58 (95% confidence interval [CI] 1.25−1.99) compared with the adherence group. The adjusted logistic regression analysis revealed a relative risk of acute exacerbation in the non-adherence vs. adherence group of 1.68 (95% CI 1.32−2.14) regarding the number of inhalers used. Poor adherence to long-acting inhalers influenced increased acute exacerbation rates among patients with COPD. The acute exacerbation of COPD risk requiring hospitalization or ED visits was high in the non-adherence group, suggesting that efforts to improve medication adherence may help reduce COPD exacerbations even in the initial management of treatment-naïve patients.

Selection of Representative Questionnaire Items from the Asthma Control Test.

Asthma is a disease characterized by the appearance of transient or persistent symptoms in response to allergens, viral upper respiratory infections, and cold air. Asthma treatment aims to control, rather than cure, and digital systems can be useful in this regard. However, conventional assessment methods for asthma control are not suitable for digital healthcare. Therefore, we aimed to select representative questionnaire items suitable for digitally assessing the asthma control status. We analyzed the Asthma Control Test (ACT) and selected representative items. Throughout the year 2020, ACT results (2019 in total) collected from patients (>18 years old) with a principal diagnosis of asthma were analyzed. Individual questionnaire items were tested using Pearson's correlation and receiver operating characteristic curves. Of the five questionnaire items, Q1, Q2, Q3, and Q5 yielded significant findings. Among these questionnaires, Q2 was the most descriptive and correlated questionnaire. Q5 was also significant but it was excluded since it was unable to apply to the digital health care system for asthma assessment method. The remaining three questionnaire items were selected and their sensitivity and specificity were assessed. Eight methods were analyzed, and the sum of scores of Q1−Q3 had the highest sensitivity and specificity (97% and 91%, respectively). The results suggested that, instead of the full items of ACT, the sum of Q1−Q3 can be used to assess the asthma control status. These findings will serve as the foundation for developing digital asthma control assessment tools.

Prevalence of chronic rhinosinusitis and its relating factors in patients with bronchiectasis: findings from KMBARC registry.

BACKGROUND/AIMS: Patients with bronchiectasis often present with respiratory symptoms caused by chronic rhinosinusitis (CRS). However, studies on the prevalence of CRS and its relationship with bronchiectasis are limited. METHODS: The baseline characteristics of patients with bronchiectasis recruited from the Korean Multicenter Bronchiectasis Audit and Research Collaboration were analyzed. CRS diagnosis was determined by a physician, on the basis of medical records, upper airway symptoms, and/or radiologic abnormalities. Questionnaires for quality of life, fatigue, and depression were administered when patients were stable for a minimum of 4 weeks after the bronchiectasis exacerbation. RESULTS: The prevalence of CRS was 7.1% (66/931). Patients with CRS were significantly younger than those without CRS (60.5 ± 10.7 years vs. 64.6 ± 9.3 years, p = 0.001). Idiopathic bronchiectasis was more common in patients with CRS compared to those without CRS (53.0% vs. 36.0%, p = 0.006). Lung function, inflammatory markers, exacerbations, bronchiectasis severity, and scores for quality of life, fatigue, and depression did not differ between the two groups. In a logistic regression analysis, CRS was associated with age of bronchiectasis diagnosis (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.94 to 0.99; p = 0.003) and idiopathic bronchiectasis (OR, 1.95; 95% CI, 1.12 to 3.34; p = 0.018). CONCLUSION: The prevalence of CRS was relatively low. CRS was not associated with the severity or clinical outcomes of bronchiectasis. Early diagnosis and idiopathic etiology were associated with CRS. Our findings reflect the low recognition of CRS in the clinical practice of bronchiectasis and highlight the need for awareness of CRS by adopting objective diagnostic criteria.

Risk of Tuberculosis Caused by Fluticasone Propionate versus Budesonide in Chronic Obstructive Pulmonary Disease: A Nationwide Population-Based Study.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICSs) are recommended for use by patients with frequent exacerbations and blood eosinophilia. However, ICSs are often inappropriately prescribed and overused. COPD studies have reported an increased risk of tuberculosis among ICS users. This study aimed to compare the risk of tuberculosis according to the different ICS components. METHODS: This study was conducted using a nationwide, population-based cohort. Patients newly diagnosed with COPD between 2005 and 2018, and treated with either fluticasone propionate or budesonide, were selected. The patients were followed up until the development of tuberculosis. RESULTS: After propensity score matching, 16,514 fluticasone propionate and 16,514 budesonide users were identified. The incidence rate of tuberculosis per 100,000 person-years was 274.73 for fluticasone propionate and 214.18 for budesonide. The hazard ratio of tuberculosis in fluticasone propionate compared with budesonide was 1.28 (95% confidence interval 1.05-1.60). The risk of tuberculosis for fluticasone propionate increased with higher ICS cumulative doses: 1.01 (0.69-1.48), 1.16 (0.74-1.81), 1.25 (0.79-1.97), and 1.82 (1.27-2.62) from the lowest to highest quartiles, respectively. CONCLUSION: Fluticasone propionate is associated with a higher risk of tuberculosis than budesonide. ICS components can differently affect the risk of tuberculosis in patients with COPD.

Comparison of Risk of Pneumonia Caused by Fluticasone Propionate versus Budesonide in Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study.

INTRODUCTION: Inhaled corticosteroids (ICSs) play an important role in lowering the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD). However, ICSs are known to increase the risk of pneumonia. Moreover, previous studies have shown that the incidence rate of pneumonia varies depending on the type of ICS. In this study, the risk of pneumonia according to the type of ICS was investigated in a population-based cohort. METHODS: A retrospective cohort study was conducted using claims data of the entire population from the Korean National Health Insurance Service. Patients who were newly diagnosed with COPD and prescribed fluticasone propionate or budesonide were enrolled as study subjects. Cumulative doses of ICSs were classified into categorical variables to analyze the risk of pneumonia within identical ICS doses. RESULTS: A total of 47,473 subjects were identified and allocated as 14,518 fluticasone propionate and 14,518 budesonide users through 1:1 propensity score matching. Fluticasone propionate users were more likely to develop pneumonia than budesonide users (14.22% vs 10.66%, p<0.0001). The incidence rate per 100,000 person-years was 2,914.77 for fluticasone propionate users and 2,102.90 for budesonide users. The hazard ratio (HR) of pneumonia in fluticasone propionate compared to budesonide was 1.34 (95% CI 1.26-1.43, p<0.0001). The risk of pneumonia for fluticasone propionate compared to budesonide increased with higher ICS cumulative doses: 1.06 (0.93-1.21), 1.41 (1.19-1.66), 1.41 (1.23-1.63), and 1.49 (1.33-1.66) from the lowest to highest quartiles, respectively. CONCLUSION: ICS types and doses need to be carefully considered during treatment with ICSs in patients with COPD.

Prevalence of depression and its associated factors in bronchiectasis: findings from KMBARC registry.

BACKGROUND: With the emergence of bronchiectasis as a common respiratory disease, epidemiological data have accumulated. However, the prevalence and impact of psychological comorbidities were not sufficiently evaluated. The present study examined the prevalence of depression and its associated factors in patients with bronchiectasis. METHODS: This study involved a multicenter cohort of bronchiectasis patients recruited from 33 pulmonary specialist hospitals. The baseline characteristics and bronchiectasis-related factors at enrollment were analyzed. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). RESULTS: Of the 810 patients enrolled in the study, 168 (20.7%) patients had relevant depression (PHQ-9 score ≥ 10), and only 20 (11.9%) patients had a diagnosis of depression. Significant differences were noted in the depressive symptoms with disease severity, which was assessed using the Bronchiectasis Severity Index and E-FACED (all p < 0.001). Depressive symptoms inversely correlated with quality-of-life (r = - 0.704, p < 0.001) and positively correlated with fatigue severity score (r = 0.712, p < 0.001). Multivariate analysis showed that depression was significantly associated with the modified Medical Research Council dyspnea scale ≥ 2 (OR 2.960, 95% CI 1.907-4.588, p = < 0.001) and high number of exacerbations (≥ 3) in the previous year (OR 1.596, 95% CI 1.012-2.482, p = 0.041). CONCLUSIONS: Depression is common, but its association with bronchiectasis was underrecognized. It negatively affected quality-of-life and presented with fatigue symptoms. Among the bronchiectasis-related factors, dyspnea and exacerbation were closely associated with depression. Therefore, active screening for depression is necessary to optimize the treatment of bronchiectasis. TRIAL REGISTRATION: The study was registered at Clinical Research Information Service (CRiS), Republic of Korea (KCT0003088). The date of registration was June 19th, 2018.

Imaging Assessment of Visceral Pleural Surface Invasion by Lung Cancer: Comparison of CT and Contrast-Enhanced Radial T1-Weighted Gradient Echo 3-Tesla MRI.

OBJECTIVE: To compare the diagnostic performance of contrast-enhanced radial T1-weighted gradient-echo 3-tesla (3T) magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of visceral pleural surface invasion (VPSI). Visceral pleural invasion by non-small-cell lung cancer (NSCLC) can be classified into two types: PL1 (without VPSI), invasion of the elastic layer of the visceral pleura without reaching the visceral pleural surface, and PL2 (with VPSI), full invasion of the visceral pleura. MATERIALS AND METHODS: Thirty-three patients with pathologically confirmed VPSI by NSCLC were retrospectively reviewed. Multidetector CT and contrast-enhanced 3T MRI with a free-breathing radial three-dimensional fat-suppressed volumetric interpolated breath-hold examination (VIBE) pulse sequence were compared in terms of the length of contact, angle of mass margin, and arch distance-to-maximum tumor diameter ratio. Supplemental evaluation of the tumor-pleura interface (smooth versus irregular) could only be performed with MRI (not discernible on CT). RESULTS: At the tumor-pleura interface, radial VIBE MRI revealed a smooth margin in 20 of 21 patients without VPSI and an irregular margin in 10 of 12 patients with VPSI, yielding an accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F-score for VPSI detection of 91%, 83%, 95%, 91%, 91%, and 87%, respectively. The McNemar test and receiver operating characteristics curve analysis revealed no significant differences between the diagnostic accuracies of CT and MRI for evaluating the contact length, angle of mass margin, or arch distance-to-maximum tumor diameter ratio as predictors of VPSI. CONCLUSION: The diagnostic performance of contrast-enhanced radial T1-weighted gradient-echo 3T MRI and CT were equal in terms of the contact length, angle of mass margin, and arch distance-to-maximum tumor diameter ratio. The advantage of MRI is its clear depiction of the tumor-pleura interface margin, facilitating VPSI detection.

Association between airflow limitation and prognosis in patients with chronic pulmonary aspergillosis.

BACKGROUND: Previous studies have shown that reduced levels of lung function, characterized by forced expiratory volume in 1 second (FEV1), are associated with higher respiratory events and mortality in general population and some chronic lung diseases. Chronic pulmonary aspergillosis (CPA) is a destructive, fatal lung disease caused by Aspergillus infection in non-immunocompromised patients with suboptimal pulmonary function. However, there is limited information on the status and features of CPA according to FEV1. METHODS: We performed a retrospective observational study to investigate the FEV1 and airflow limitation in patients with CPA between March 2017 and February 2019 at a tertiary hospital in South Korea. RESULTS: Of the 144 CPA patients, 104 underwent spirometry, demonstrating median forced vital capacity (FVC) and FEV1 of 2.35 L (68%) and 1.43 L (62%), respectively. Among them, 56 patients had airflow limitation on PFT, with median FVC, and FEV1 of 2.47 L (73%) and 1.11 L (47%), respectively. Low body mass index (BMI) (20.1 vs. 22.1 kg/m2; P=0.011), breathlessness (60% vs. 20%; P=0.002), and bilateral pulmonary lesions (33.3% vs. 4%; P=0.006) were more common in patients with moderate to very severe airflow limitation than in those with normal to mild airflow limitation. CONCLUSIONS: Moderate to very severe airflow limitation was observed in 43.3% of patients with CPA. Additionally, low BMI, breathlessness, and bilateral pulmonary lesions contributing to poor prognosis were more common in patients with moderate to very severe airflow limitation than in those with normal to mild airflow limitation. Our findings suggest that airflow limitation can be associated with the prognosis of CPA. Further investigations are needed to demonstrate the clinical significance of this association.

Safety and Utility of Rush Immunotherapy with Aqueous Allergen Extracts for Treatment of Respiratory Allergies.

BACKGROUND: Generally, allergen immunotherapy must be administered for three to five years. Meanwhile, rush immunotherapy (RIT) shortens the required duration for the build-up phase, thereby improving the therapy's convenience compared with conventional immunotherapy (CIT). However, RIT is often performed with modified allergens. Therefore, this study aimed to investigate the safety and utility of RIT with aqueous allergens. METHODS: Medical records of 98 patients sensitized with at least one inhalant allergen who had received subcutaneous immunotherapy for allergic rhinitis with or without asthma were retrospectively reviewed. All patients were classified into three groups: depot-RIT (n = 25), receiving RIT with depot allergen; aqueous-RIT (n = 48), receiving RIT with aqueous allergen; and aqueous-CIT (n = 25), receiving CIT with aqueous allergen. Patients who had received immunotherapy targeting only house dust mites were excluded. RESULTS: The proportions of patients presenting with a systemic reaction to depot-RIT, aqueous-RIT, or aqueous-CIT were 80.0%, 85.4%, and 48.0%, respectively (P = 0.002). The proportions of patients experiencing severe systemic reaction were 4.0%, 16.7%, and 8.0% in depot-RIT, aqueous-RIT and aqueous-CIT, respectively (P = 0.223). The proportions of depot-RIT and aqueous-RIT patients presenting with systemic reaction or severe systemic reaction did not differ significantly (P = 0.553 and P = 0.118, respectively). Significantly fewer depot-RIT (1.0 ± 0.2) and aqueous-RIT patients (2.0 ± 1.3) required outpatient clinical visits during the build-up phase, compared to those administered aqueous-CIT (13.6 ± 1.9; P < 0.001). Moreover, the build-up phase decreased to 17.4 ± 1.8 days in depot-RIT and 23.7 ± 10.9 days in aqueous-RIT, compared to 92.0 ± 12.5 days in aqueous-CIT (P < 0.001). CONCLUSION: RIT with aqueous allergen reduced the build-up phase duration and frequency of hospital visits, with acceptable safety levels. RIT with aqueous allergen may, therefore, be suitable for broad application to patients with respiratory allergies.

Direct Switch from Tiotropium to Indacaterol/Glycopyrronium in Chronic Obstructive Pulmonary Disease Patients in Korea.

BACKGROUND: Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 µg to indacaterol/glycopyrronium (IND/GLY) 110/50 µg once-daily in COPD patients in Korea. METHODS: This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 µg once-daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted postbronchodilator forced expiratory volume in 1 second (FEV1) ≥50%, post-bronchodilator FEV1/forced vital capacity <0.7 and smoking history of ≥10 pack-years were included. Eligible patients were randomized in a 1:1 ratio to either IND/GLY or TIO. The primary objective was to demonstrate superiority of IND/GLY over TIO in pre-dose trough FEV1 at week 12. Secondary endpoints included transition dyspnea index (TDI) focal score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment. RESULTS: Of the 442 patients screened, 379 were randomized and 347 completed the study. IND/GLY demonstrated superiority in pre-dose trough FEV1 versus TIO at week 12 (least squares mean treatment difference [Δ], 50 mL; p=0.013). Also, numerical improvements were observed with IND/GLY in the TDI focal score (Δ, 0.31), CAT total score (Δ, -0.81), and rescue medication use (Δ, -0.09 puffs/day). Both treatments were well tolerated by patients. CONCLUSION: A direct switch from TIO to IND/GLY provided improvements in lung function and other patient-reported outcomes with an acceptable safety profile in patients with mild-to-moderate airflow limitation.

Polysomnographic phenotype as a risk factor for cardiovascular diseases in patients with obstructive sleep apnea syndrome: a retrospective cohort study.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with the development of cardiovascular diseases caused by hypoxemia during sleeping. We classified OSAS phenotypes based on polysomnographic findings and aimed to evaluate that the unique phenotypes would be differentially associated with risk of cardiovascular disease. METHODS: This retrospective and observational study assessed adult patients who underwent polysomnography at the Wonju Severance Christian Hospital from November 2008 to February 2018. The OSAS phenotypes were classified as apnea-predominant, hypopnea-predominant, and respiratory effort-related arousal (RERA)-predominant based on the polysomnography results. The polysomnographic data were collected and analysed, and clinical features such as medical history and comorbidities were assessed by a review of the electronic medical records. RESULTS: A total of 860 adult patients were classified as apnea-predominant (n=220), hypopnea-predominant (n=119), or RERA-predominant (n=275). The hypopnea-predominant group had significantly higher rates of hyperlipidaemia (P<0.001), heart failure (15.5%, P<0.001), and coronary artery disease (20.9%, P=0.005) than the other groups. After classifying the patients according to severity of the hypopnea index, logistic regression analyses adjusted for age, sex, and smoking history revealed that the hypopnea index increased the risk for coronary artery disease and heart failure. CONCLUSIONS: The hypopnea-predominant group would be a specific phenotype that has a differential association with the risks for coronary artery disease and heart failure.

LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database. METHODS: Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction. RESULTS: We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&2 (LOXL1& LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11). CONCLUSIONS: LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities.

Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure.

BACKGROUND: Adenosine deaminase (ADA) activity is typically elevated in patients with tuberculous pleural effusion (TPE), but low ADA has occasionally been reported in patients with TPE. The characteristics of these patients are not well-known, and erroneous exclusion of the possibility of TPE can result in a delayed diagnosis. This study investigated the characteristics of patients with TPE who had low ADA activity. METHODS: We retrospectively reviewed patients with microbiologically or pathologically confirmed TPE between 2012 to 2018 in a tertiary hospital in South Korea. Patients were categorised into two groups: high ADA (≥40 IU/L) and low ADA (< 40 IU/L). Clinical characteristics and Sequential Organ Failure Assessment (SOFA) scores were compared between groups. RESULTS: A total of 192 patients with TPE were included; 36 (18.8%) had ADA < 40 IU/L with a mean ADA activity level of 20.9 (±9.2) IU/L. Patients with low ADA were older (75.3 vs. 62.0 years, p < 0.001) and had a lower mean lymphocyte percentage (47.6% vs. 69.9%, p < 0.001) than patients with high ADA. Patients in the low ADA group had a significantly higher mean SOFA score (2.31 vs. 0.68, p < 0.001), and patients with organ dysfunction were significantly more common in the low ADA group (p < 0.001). Patients with 2 or ≥ 3 organ dysfunctions constituted 19.4 and 13.9% of the patients in the low ADA group, whereas they constituted 7.1 and 1.3% of the patients in the high ADA group (p < 0.001). Multivariate logistic regression analyses showed that older age (odds ratio = 1.030, 95% confidence interval 1.002-1.060, p = 0.038) and a higher SOFA score (odds ratio = 1.598, 95% confidence interval 1.239-2.060, p < 0.001) were significantly associated with low ADA activity in patients with TPE. CONCLUSIONS: ADA activity can be low in patients with TPE who are elderly, critically ill, and exhibit multiorgan failure. Low ADA activity cannot completely exclude the diagnosis of TPE, and physicians should exercise caution when interpreting pleural fluid exams.

Risk of Pneumonia Associated with Inhaled Corticosteroid in Patients with Chronic Obstructive Pulmonary Disease: A Korean Population-Based Study.

Introduction: Inhaled corticosteroids (ICSs) are recommended for patients with frequent exacerbation of chronic obstructive pulmonary disease (COPD). However, accumulating evidence has indicated the risk of pneumonia from the use of ICS. This study aimed to investigate the association between ICS and pneumonia in the real-world clinical setting. Methods: A retrospective cohort study was performed using nationwide population data from the Korea National Health Insurance Service. Subjects who had a new diagnosis of COPD and who received inhaled bronchodilators without a diagnosis of pneumonia before the initiation of bronchodilators were identified. Subjects were followed up until their first diagnosis of pneumonia. The risk of pneumonia in ICS users was compared to that in non-ICS users. Results: A total of 87,594 subjects were identified and 1:1 matched to 22,161 ICS users and non-ICS users. More ICS users were diagnosed with pneumonia compared to non-ICS users (33.73% versus 24.51%, P<0.0001). The incidence rate per 100,000 person-years was 8904.98 for ICS users and 6206.79 for non-ICS users. The hazard ratio (HR) of pneumonia for ICS users was 1.62 (95% CI 1.54-1.70). The HR of subjects prescribed with the lowest ICS cumulative dose was 1.35 (1.27-1.43). The HR increased to 1.51 (1.42-1.60), 1.96 (1.85-2.09), and 2.03 (1.89-2.18) as the cumulative dose increased. Pneumonia was strongly associated with fluticasone propionate (1.79 (1.70-1.89)) and fluticasone furoate (1.80 (1.61-2.01)) use, compared to the use of other types of ICS. Conclusion: ICS increases the risk of pneumonia in patients with COPD. Hence, ICS should be carefully prescribed in patients with risk factors for pneumonia while considering the cumulative doses and subtypes of ICS.

Prevalence and Clinical Features of Drug Reactions With Eosinophilia and Systemic Symptoms Syndrome Caused by Antituberculosis Drugs: A Retrospective Cohort Study.

PURPOSE: Although there have been reported cases of drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome caused by antituberculosis drugs, there has been no research to examine its prevalence. This study assessed the prevalence and clinical characteristics of DRESS syndrome caused by antituberculosis drugs. METHODS: The electronic medical records of a cohort consisting of adult patients diagnosed with tuberculosis between July 2006 and June 2010 were reviewed and retrospectively inspected. We searched the surveillance system for adverse drug reactions and the electronic medical records to identify patients who reported severe cutaneous adverse reactions to antituberculosis drugs. These patients were then re-assessed using a European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) scoring system. Clinical characteristics, including the symptoms and latency of DRESS syndrome, the therapeutic dosage and period of steroids, and the final duration of tuberculosis therapy, were examined. RESULTS: Of the 1,253 adult patients with tuberculosis receiving antituberculosis drugs, 15 were identified as potential cases of DRESS syndrome (prevalence of 1.2%). Ethambutol was the most frequently used drug (53.5%), followed by rifampicin (26.7%), pyrazinamide (20.0%), streptomycin (13.3%), and isoniazid (6.7%). The median latency after day 1 of antituberculosis medication was 42 days. The median daily dose of steroids, expressed in prednisone-equivalent units, was 33-mg/day, and the median dosing period was 14 days. The duration of tuberculosis treatment was 76 days longer than the standard treatment period of 180 days. There was a significant difference in the peak eosinophil counts of DRESS syndrome patients according to RegiSCAR scores. Moreover, there was a significant quantitative correlation between the RegiSCAR score and peak eosinophil count. A negative correlation was also found between the RegiSCAR score and latency. CONCLUSIONS: This study confirmed the prevalence of DRESS syndrome in a cohort of adult patients with tuberculosis.

Early readmission and mortality in acute exacerbation of chronic obstructive pulmonary disease with community-acquired pneumonia.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are important causes of hospital admission and mortality. Pneumonia is a major contributor to hospitalization for AECOPD and has a close relationship with poor outcomes. We performed a prospective cohort study to evaluate the prognosis of AECOPD patients with or without community-acquired pneumonia (CAP) who hospitalized from January 2012 to December 2015. We investigated mortality and readmission rates within 6 months after the first admission between two groups and analyzed the difference of survival rate according to readmission duration (≤30 vs. >30 days) or intensive care unit (ICU) treatment. Total 308 AECOPD patients (134 with CAP and 174 without CAP) were enrolled. The mean age was 72.3 ± 9.5 years old, and 235 patients (76.3%) were male. The 180-day mortality was higher in AECOPD with CAP than without CAP (24.6% vs. 13.2%; hazard ratio (HR): 1.982; 95% CI: 1.164-3.375; p = 0.012). However, readmission rate showed no significant difference between two groups (51.5% vs. 46.6%; HR: 1.172; 95% CI: 0.850-1.616; p = 0.333). It showed a significantly lower survival rate in AECOPD with CAP rather than without CAP when were readmitted within 30 days (HR: 1.738; 95% CI:1.063-3.017; p = 0.031). According to ICU treatment, survival rate was not significantly different between two groups. Multivariate analysis revealed the readmission within 30 days ( p < 0.001), serum hemoglobin concentration ( p = 0.010), and albumin level ( p = 0.049) were significantly associated with 180-day mortality of AECOPD with CAP. AECOPD with CAP showed lower survival rate than AECOPD without CAP during 6 months. Early readmission within 30 days was significantly associated with an increased risk of mortality.

Increased Risk of Exacerbation in Asthma Predominant Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome.

BACKGROUND: Obstructive airway disease patients with increased variability of airflow and incompletely reversible airflow obstruction are often categorized as having asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). ACOS is heterogeneous with two sub-phenotypes: asthma-ACOS and COPD-ACOS. The objective of this study was to determine the difference in risk of exacerbation between the two sub-phenotypes of ACOS. METHODS: A total of 223 patients exhibiting incompletely reversible airflow obstruction with increased variability (spirometrically defined ACOS) were enrolled. These patients were divided into asthma-ACOS and COPD-ACOS according to their physician's diagnosis and smoking history of 10 pack-years. Within-group comparisons were made for asthma-ACOS versus COPD-ACOS and light smokers versus heavy smokers. RESULTS: Compared to patients with COPD-ACOS, patients with asthma-ACOS experienced exacerbation more often despite their younger age, history of light smoking, and better lung function. While the light-smoking group showed better lung function, they made unscheduled outpatient clinic visits more frequently. On multivariate analysis, asthma-ACOS and poor inhaler compliance were significantly associated with more than two unscheduled clinic visits during the previous year. CONCLUSION: Spirometrically defined ACOS includes heterogeneous subgroups with different clinical features. Phenotyping of ACOS by physician's diagnosis could be significant in predicting future risk of exacerbation.

Brief report: Preliminary study on evaluation of spasticity in patients with brain lesions using mechanomyography.

BACKGROUND: Electromyography and the modified Ashworth scale (MAS) are among the most effective methods for evaluating spasticity; however, these are often inappropriate for clinical use, owing to the complicated procedure and subjective evaluation outcomes. METHODS: A passive stretch reflex test was performed on 10 subjects with brain lesions. Furthermore, mechanomyography and electromyography were conducted on the vastus lateralis muscle (agonist) and semitendinosus muscle (antagonist) of the subjects with brain lesions. A new equation to define the normalized hull area; that is, the mechanomyography (MMG) ratio, was applied to quantify the triaxial motion of the agonist muscle versus antagonist muscles, reflecting the electromyographic firing point of the spastic muscle. FINDINGS: The MMG ratio was proposed, which statistically distinguishes the spastic and normal muscles (p = 0.01) and exhibits a concordance with the conventional mean MAS (r = 0.69, p = 0.01). INTERPRETATION: Patients suspected to have spasticity of 0 to 1+ grade can be quantitatively evaluated using the normalized hull area ratio, which can be used as an additional clinical indicator for spasticity evaluation. REGISTRATION OF CLINICAL TRIALS: The study was conducted in conformity with the Helsinki declaration principles and performed in the Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); 2010; KCT0002385; A new approach of spasticity measurement using mechanomyography in patients with brain lesions: A randomized pilot study for a parallel randomized controlled trial; October 8, 2015 [Cited on July 21, 2017]; [1 screen]. Available from: https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=7805<ype=&rtype=.