Cardiovascular Events According to Inhaler Therapy and Comorbidities in Chronic Obstructive Pulmonary Disease.

Background: COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities. Methods: This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174). Results: Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04-1.43), heart failure (HR: 1.45, 95% CI: 1.14-1.84), arrhythmia (HR: 1.72, 95% CI: 1.41-2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64-3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05). Conclusion: Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.

Current status of platelet manufacturing in 3D or bioreactors.

Blood shortages for transfusion are global issues of grave concern. As in vitro manufactured platelets are promising substitutes for blood donation, recent research has shown progresses including different cell sources, different bioreactors, and three-dimensional materials. The first-in-human clinical trial of cultured platelets using induced pluripotent stem cell-derived platelets began in Japan and demonstrated its quality, safety, and efficacy. A novel bioreactor with fluid motion for platelet production has been reported. Herein, we discuss various cell sources for blood cell production, recent advances in manufacturing processes, and clinical applications of cultured blood.

The Impact of Inhaled Corticosteroids on the Prognosis of Chronic Obstructive Pulmonary Disease.

Background: A comprehensive analysis of the effects of inhaled corticosteroids (ICS) on COPD in a real-world setting is required due to safety concerns regarding ICS in COPD. This study aimed to explore the impact of ICS on the prognosis of Asian COPD patients in the real-life world. Methods: We examined 978 COPD patients registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database and with their data linked to Health Insurance and Review Assessment (HIRA) data. The outcome measures were ascertained by HIRA from January 1, 2009, to December 31, 2012. This study enrolled two arms; ICS users (N = 85, mean age = 66.7 ± 8.9 years) and non-ICS users (N = 893, mean age = 63.7 ± 9.7 years). Results: Compared to the non-ICS users, the ICS users had a higher rate of pneumonia, tuberculosis, and acute exacerbations (P<0.05). Hospitalization due to respiratory causes was also higher among ICS users (P<0.05). Multivariate analysis showed that acute exacerbation was independently associated with the development of pneumonia (P<0.05), whereas ICS therapy had a tendency to be associated with pneumonia. Another multivariate analysis demonstrated that old age, FEV1, ICS therapy, and pneumonia were independently associated with the occurrence of acute exacerbation (P<0.05). The concomitant pneumonia (HR = 3.353, P = 0.004) was independently associated with higher mortality (P<0.05). Conclusion: Our data demonstrated that the ICS users had a higher rate of pneumonia and tuberculosis and the concomitant pneumonia was independently associated with higher mortality, highlighting the importance of cautious and targeted administration of ICS in COPD.

COVID-19 Vaccine-Associated Pneumonitis in the Republic of Korea: A Nationwide Multicenter Survey.

BACKGROUND: Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. METHODS: In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. RESULTS: From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. CONCLUSION: These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

New prognostic scoring system for mortality in idiopathic pulmonary fibrosis by modifying the gender, age, and physiology model with desaturation during the six-minute walk test.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry. Materials and methods: This is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model. Results: Among 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38-3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60-4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p < 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality. Conclusion: The GAP6 model adding nadir SpO2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system.

Pneumocystis Pneumonia in a Non-Immunocompromised Lung Cancer Patient after Surgery: A Case Report.

We present the Pneumocystis pneumonia case of a 64-year-old man with no remarkable history except for hypertension, who had not undergone any treatment other than surgery. On postoperative day 7, high-resolution computed tomography findings revealed multifocal ground-glass opacifications with interlobular septal thickening in both lungs; therefore, atypical pneumonia was suspected. Polymerase chain reaction (PCR) test performed after bronchoalveolar lavage was positive for Pneumocystis jirovecii (P. jirovecii). Based on the PCR results, a final diagnosis of Pneumocystis pneumonia (PCP) was made. After treatment, he improved and was discharged. This is a unique case of PCP diagnosis in a non-immunocompromised patient, with no remarkable history except for hypertension, who had not undergone any treatment other than surgery for cancer. Thus, it is necessary to consider additional risk factors for PCP and timing of preventive treatment.

Broken Needle Embedded in the Body during Vascular Puncture.

The use of needles is essential in most medical procedures and surgery; however, needle breakage is not known to happen very frequently. Even if it does, it is most likely to occur during dental procedures, sutures, aspiration, biopsy, anesthesia, and drug abuse. To our knowledge, this is the first report about needle detachment from the syringe during a vascular puncture for blood collection. In this case, an 87-year-old obese woman with generalized edema had repeated vascular punctures to the femoral artery for arterial blood gas analysis (ABGA). After blood collection at this instance, when the syringe was pulled out, the needle was detached from it. Radiography revealed that the broken needle was lodged in the groin. A surgical incision with the fluoroscopic radiography located the embedded needle in the soft tissue and allowed the retrieval of its fragments from the groin soft tissue. Obesity and repeated punctures may increase the risk of needle breakage and prior inspection of needles for such procedures may be necessary.

Pulmonary cryptococcosis after recovery from COVID-19 in an immunocompetent patient: A rare case report.

RATIONALE: Cryptococcus neoformans (C neoformans) infection typically occurs in immunocompromised patients infected with human immunodeficiency virus (HIV), or those taking immunosuppressive drugs, corticosteroids, or chemotherapy. Recently, there have been an increasing number of reports of cryptococcosis as opportunistic infections in COVID-19 patients, all of which have been related to immunocompromising conditions, underlying medical diseases, immune suppression drugs, or corticosteroids. Here, we report the first case of pulmonary cryptococcosis in an immunocompetent patient with a history of COVID-19 who had no history of underlying diseases or immune modulation drugs. PATIENT CONCERNS: A previously healthy 46-year-old man presented with tiny lung nodules. He had quit smoking 6 years prior. He had no significant medical history except for COVID-19 3 months prior, and had not received corticosteroids or cytokine blockers when he had COVID-19. He had been coughing since he recovered from COVID-19. DIAGNOSIS: Bronchoalveolar lavage cultures showed the growth of C neoformans. A CT-guided percutaneous needle biopsy of the lung lesion was performed. Histopathology of the biopsy specimen showed granulomas with encapsulated yeast. There was no growth of C neoformans in the CSF or blood. He was diagnosed with pulmonary cryptococcosis. INTERVENTION: Antifungal drug (fluconazole) was administered for 6 months in the outside clinic. OUTCOMES: The lung lesions disappeared after 6 months medication. LESSONS: This case may illustrate the risk of pulmonary cryptococcosis after SARS-CoV-2 infection in an immunocompetent patient. Opportunistic infections can occur even after recovery from COVID-19 for several reasons. First, SARS-CoV-2 infection causes immune dysregulation including lymphocytopenia. Second, T lymphocytes play a principal role against Cryptococcus. Third, these changes in the immune system due to COVID-19 may last for several weeks. Thus, we suggest careful consideration of lung lesions in patients with a history of COVID-19.

Triple primary lung cancer: a case report.

BACKGROUND: The risk of developing lung cancer is increased in smokers, patients with chronic obstructive pulmonary disease, individuals exposed to environmental carcinogens, and those with a history of lung cancer. Automobile exhaust fumes containing carcinogens are a risk factor for lung cancer. However, we go through life unaware of the fact that automobile exhaust is the cause of cancer. Especially, in lung cancer patient, it is important to search out pre-existing risk factors and advice to avoid them, and monitor carefully for recurrence after treatment. CASE PRESENTATION: This is the first report of a case with triple lung cancers with different histologic types at different sites, observed in a 76-year-old parking attendant. The first adenocarcinoma and the second squamous cell carcinoma were treated with stereotactic radiosurgery because the patient did not want to undergo surgery. Although the patient stopped intermittent smoking after the diagnosis, he continued working as a parking attendant in the parking lot. After 29 months from the first treatment, the patient developed a third new small cell lung cancer; he was being treated with chemoradiation. CONCLUSIONS: New mass after treatment of lung cancer might be a multiple primary lung cancer rather than metastasis. Thus, precision evaluation is important. This paper highlights the risk factors for lung cancer that are easily overlooked but should not be dismissed, and the necessity of discussion with patients for the surveillance after lung cancer treatment. We should look over carefully the environmental carcinogens already exposed, and counsel to avoid pre-existing lung cancer risk factors at work or residence in patients with lung cancer.

Radiation-induced pseudomembranous tracheobronchitis: A report of two cases.

Radiation therapy can cause radiation pneumonitis, organizing pneumonia, and lung fibrosis. Radiation-induced pseudomembranous bronchitis is a rare condition. Here, we describe a rare case each of pseudomembranous tracheobronchitis and pseudomembrane with total bronchial obstruction which developed after thoracic radiotherapy. A 50-year-old man presented paroxysmal severe cough 1 month after concurrent chemoradiotherapy for small-cell lung cancer. Bronchoscopy revealed a whitish membrane in the trachea and bronchus, which were the fields of radiation. Another 60-year-old man complained of dyspnea 7 months after radiation therapy for metastatic lymph node adenocarcinoma. Bronchoscopy demonstrated a membrane with total obstruction of right lower lobar bronchus, which was the area of radiation. The pathological findings of histological examination in both cases demonstrated radiation-induced pseudomembranous tracheobronchitis. Patients in both cases responded well to steroids and the pseudomembrane disappeared. If patients who have received thoracic radiation therapy complain of persistent cough, bronchoscopy may be helpful.

The role of nafamostat mesilate as a regional anticoagulant during extracorporeal membrane oxygenation.

BACKGROUND: Anticoagulation during extracorporeal membrane oxygenation (ECMO) usually is required to prevent thrombosis. The aim of this study was to investigate the usefulness of nafamostat mesilate (NM) as a regional anticoagulant during veno-arterial ECMO (VA-ECMO) treatment. METHODS: We retrospectively reviewed the medical records of 16 patients receiving VA-ECMO and NM from January 2017 to June 2020 at Haeundae Paik Hospital. We compared clinical and laboratory data, including activated partial thromboplastin time (aPTT), which was measured simultaneously in patients and the ECMO site, to estimate the efficacy of regional anticoagulation. RESULTS: The median patient age was 68.5 years, and 56.3% of patients were men. Cardiovascular disease was the most common primary disease (75.0%) requiring ECMO treatment, followed by respiratory disease (12.5%). The median duration of ECMO treatment was 7.5 days. Among 16 patients, seven were switched to NM after first using heparin as an anticoagulation agent, and nine received only NM. When comparing aPTT values in the NM group between patients and the ECMO site, that in patients was significantly lower than that at the ECMO site (73.57 vs. 79.25 seconds; P=0.010); in contrast, no difference was observed in the heparin group. CONCLUSIONS: NM showed efficacy as a regional anticoagulation method by sustaining a lower aPTT value compared to that measured at the ECMO site. NM should be considered as a safer regional anticoagulation method in VA-ECMO for patients at high risk of bleeding.

Polyhexamethylene guanidine phosphate-induced necrosis may be linked to pulmonary fibrosis.

Following the humidifier disinfectant incident in Korea, polyhexamethylene guanidine phosphate (PHMG-P) has been used to establish lung fibrosis model animals. Herein, we investigated time-dependent changes after a single PHMG-P instillation (22 µg/lung) to identify the underlying pathogenesis and immune response involved in PHMG-P-induced lung fibrosis. Compared to control mice, body weight loss and blood biochemical and hematological changes were more remarkable in PHMG-P-instilled mice, an increase of total cell counts, infiltration of macrophages and neutrophils and necrotic cell death were also more notable in the lungs of PHMG-P-instilled mice. Pathological lesions were detected from Day 1 after exposure, deteriorating with time. In addition, secretion of anti-inflammatory mediators was rapidly inhibited from 6 h after exposure, and level of IL-24, a tissue repair-related cytokine, was up-regulated in the lungs of PHMG-P-instilled mice until Day 21 post-exposure. In vitro tests using BEAS-2B cells showed that PHMG-P disturbed structural and functional homeostasis of organelles and that intracellular ROS increase was considered as an important cause of PHMG-P-induced cell death. Additionally, co-culture with DNA, a polyanionic compound, clearly inhibited PHMG-P-induced necrosis, and increased IL-1ß and TNF-α level and decreased IL-6 and IL-8 levels were observed following exposure to PHMG-P. Meanwhile, IL-8 secretion increased in cells exposed to PHMG-P-induced cell debris. Therefore, we suggest that necrotic cell debris may importantly contribute to the PHMG-P-induced inflammatory response and pathogenesis. In addition, PHMG-P-induced necrosis may be initiated by high affinity between PHMG-P and cell membrane.

Association Between Vitamin D Level and Respiratory Symptoms in Patients with Stable Chronic Obstructive Pulmonary Disease.

Purpose: Vitamin D insufficiency or deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD). However, the association between vitamin D levels and respiratory symptoms in patients with stable COPD has not been fully investigated. This study evaluated the association between vitamin D levels and respiratory symptoms in patients with stable COPD. Patients and Methods: Patients with COPD who had their serum 25-hydroxyvitamin D (25-OH vitamin D) level measured within 6 months of spirometry between January 2016 and April 2020 were retrospectively included. Respiratory symptoms were assessed using the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT) score. Results: Of the 329 included patients, 193, 88, and 48 were categorized as having vitamin D deficiency (<20 ng/mL), insufficiency (20-29 ng/mL), and sufficiency (≥30 ng/mL), respectively. The mean serum 25-OH vitamin D level of each group was 13.45 ng/mL, 24.61 ng/mL, and 38.90 ng/mL, respectively. Patients with vitamin D insufficiency/deficiency showed higher CAT scores than those with vitamin D sufficiency (p = 0.004). In multivariable adjusted models, vitamin D insufficiency/deficiency was significantly associated with a CAT score of 10 or more (adjusted odds ratio [aOR] = 2.41, 95% confidence interval [CI] = 1.20-4.82, p = 0.013) and mMRC ≥ 2 (aOR = 2.39, 95% CI = 1.08-5.32, p = 0.032). Among CAT items, the amount of phlegm (p = 0.008), chest tightness (p = 0.030), breathlessness walking upstairs (p < 0.001), home activity limitations (p = 0.002), and lack of energy (p = 0.003) were significantly associated with vitamin D insufficiency/deficiency after adjustment for age, sex, body mass index, smoking history, Charlson comorbidity index, post-bronchodilator forced expiratory volume in 1 second, and season of blood draw. Conclusion: Vitamin D insufficiency/deficiency were associated with worse respiratory symptoms in patients with stable COPD.

Comparison of clinical characteristics between chronic bronchitis and non-chronic bronchitis in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB versus severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores. METHODS: This study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥ 3; severe CB was defined as CAT1 and CAT2 scores ≥ 4, while mild CB was defined as either a CAT1 or a CAT2 score < 4. Baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline were compared in non-CB versus CB patients and in patients with mild CB versus severe CB. RESULTS: Among the 2162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV1, FEV1/FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p < 0.01). More severe exacerbation was also present in patients with severe CB than in patients with mild CB (OR = 2.52, p = 0.01). The difference in annual FEV1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB. CONCLUSIONS: CB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB.

A pilot investigation of e-cigarette use and smoking behaviour among patients with chronic airway disease or respiratory symptoms.

BACKGROUND: This pilot study aimed to investigate the current status of e-cigarettes (ECs) use patterns among patients with chronic airway disease or chronic respiratory symptoms and the effects of ECs use on respiratory and mental health. METHODS: A cross-sectional survey was conducted at the outpatient clinic of eight teaching hospitals in South Korea between November 2019 and December 2019. All adult ECs users (19 years and above) who visited the outpatient clinic as a patient with chronic airway disease or chronic respiratory symptoms were eligible to participate in this study. RESULTS: A total of 51 subjects responded to the survey. Most of the participants were male (92.2%) and the mean age was 41.8 years. Dominant airway diseases were asthma and chronic obstructive pulmonary disease. Most of the subjects had a history of cigarette smoking, and 19 subjects were dual users of current cigarettes and ECs. Most of the subjects started ECs use due to health-related reasons. When comparing exclusive ECs users and dual users, St. George's respiratory questionnaire (SGRQ) scores, the proportion of cases with moderate to severe depressive symptoms, and average Fagerstrom test for nicotine dependence scores for ECs were higher in dual users than exclusive ECs users (mean 4.64 vs. 2.38, p = 0.006), respectively. CONCLUSION: Most of the subjects started ECs use due to health concerns, but dual users have more respiratory symptoms and higher nicotine dependence in this pilot study. One hypothesis that comes from these results is that greater nicotine dependence may influence behaviours, habits, and views about ECs. These preliminary observations need confirmation in a large cohort.

Clinical Features, Diagnosis, Management, and Outcomes of Idiopathic Pulmonary Fibrosis in Korea: Analysis of the Korea IPF Cohort (KICO) Registry.

BACKGROUND: The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients. METHODS: Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015. RESULTS: A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-agephysiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality. CONCLUSION: In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.

E-cigarette-associated Severe Pneumonia in Korea Using Data Linkage between the Korea National Health and Nutrition Examination Survey (KNHANES, 2013-2019) and the National Health Insurance Service (NHIS) Claims Database.

BACKGROUND: This study aimed to investigate the association between e-cigarette (EC) use and development of acute severe pneumonia in the Korean population using a national database. METHODS: We conducted a retrospective analysis using linkage of data between the Korean National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service (NHIS) administrative claims database. The primary endpoint of this study was development of severe pneumonia requiring hospital admission according to EC use during the study period. The secondary endpoints were in-hospital mortality, intensive care unit (ICU) admission, ventilator care, and days of hospital stay. RESULTS: The final analysis included 28,950 individuals, of which 578 (2.0%) were EC users. EC users were younger and more often male than non-EC users. The EC users showed higher level of education and household income and had fewer comorbidities. Severe pneumonia was noted in 37 of 28,372 non-EC users (0.13%), but there were no occurrences of severe pneumonia in EC users. The incidence of pneumonia occurrence was not different between the two groups (P = 1.000). CONCLUSIONS: Since e-cigarette or vaping use-associated lung injury (EVALI) is most likely included in acute severe pneumonia occurring within 3 months of EC use, it is considered that there might be no EVALI patients in Korea during the investigation period. A large-scale, prospective study is necessary to evaluate the association between EC use and acute lung injury.

Pharmacokinetics and Monte Carlo Simulation of Meropenem in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation.

Objectives: There have been few clinical studies of ECMO-related alterations of the PK of meropenem and conflicting results were reported. This study investigated the pharmacokinetics (PK) of meropenem in critically ill adult patients receiving extracorporeal membrane oxygenation (ECMO) and used Monte Carlo simulations to determine appropriate dosage regimens. Methods: After a single 0.5 or 1 g dose of meropenem, 7 blood samples were drawn. A population PK model was developed using nonlinear mixed-effects modeling. The probability of target attainment was evaluated using Monte Carlo simulation. The following treatment targets were evaluated: the cumulative percentage of time during which the free drug concentration exceeds the minimum inhibitory concentration of at least 40% (40% fT>MIC), 100% fT>MIC, and 100% fT>4xMIC. Results: Meropenem PK were adequately described by a two-compartment model, in which creatinine clearance and ECMO flow rate were significant covariates of total clearance and central volume of distribution, respectively. The Monte Carlo simulation predicted appropriate meropenem dosage regimens. For a patient with a creatinine clearance of 50-130 ml/min, standard regimen of 1 g q8h by i. v. infusion over 0.5 h was optimal when a MIC was 4 mg/L and a target was 40% fT>MIC. However, the standard regimen did not attain more aggressive target of 100% fT>MIC or 100% fT>4xMIC. Conclusion: The population PK model of meropenem for patients on ECMO was successfully developed with a two-compartment model. ECMO patients exhibit similar PK with patients without ECMO. If more aggressive targets than 40% fT>MIC are adopted, dose increase may be needed.

Favorable Response to Long-Term Azithromycin Therapy in Bronchiectasis Patients with Chronic Airflow Obstruction Compared to Chronic Obstructive Pulmonary Disease Patients without Bronchiectasis.

PURPOSE: Long-term macrolide treatment is recommended for patients with chronic obstructive pulmonary disease (COPD) with frequent exacerbations. Bronchiectasis is a common comorbid condition in patients with COPD, for which long-term azithromycin is effective in preventing exacerbation. This study aimed to compare the effect of long-term azithromycin between bronchiectasis patients with chronic airflow obstruction (CAO) and COPD patients without bronchiectasis. PATIENTS AND METHODS: Patients with CAO who received azithromycin for more than 12 weeks were retrospectively identified at a single referral hospital. CAO was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7, and bronchiectasis was determined using computed tomography. The development of exacerbation and symptom improvement were compared between bronchiectasis patients with CAO and COPD patients without bronchiectasis. RESULTS: A total of 59 patients (43 in bronchiectasis with CAO group vs 16 in COPD without bronchiectasis group) were included in this study. Compared to COPD patients without bronchiectasis, those in bronchiectasis with CAO group were younger, more likely to be female, and never smokers. There was no difference in the previous exacerbation history or FEV1 between the two groups. The median duration of azithromycin treatment was 15 months (interquartile range, 8-25 months). At the 12-month follow-up, the development of ≥2 moderate or ≥1 severe exacerbations was significantly lower in bronchiectasis with CAO group than in COPD without bronchiectasis group (46.5% vs 87.5%, P = 0.005). The proportion of patients with symptom improvement determined by the COPD assessment test score was also significantly higher in bronchiectasis with CAO group than COPD without bronchiectasis group at the 12-month follow-up (68.2% vs 16.7%, P = 0.004). CONCLUSION: Bronchiectasis patients with CAO could benefit more from long-term azithromycin treatment than COPD patients without bronchiectasis.

Understanding racial differences of COPD patients with an ecological model: two large cohort studies in the US and Korea.

BACKGROUND: There are limited data about the racial difference in the characteristics of chronic obstructive pulmonary disease (COPD) patients who are treated at clinics. We aimed to compare sociodemographic and clinical characteristics between US and Korean COPD patients using large-scale nationwide COPD cohorts. METHODS: We used the baseline demographic and clinical data of COPD patients aged 45 years or older with at least a 10 pack-per year smoking history from the Korean COPD Subtype Study (KOCOSS, n = 1686) cohort (2012-2018) and phase I (2008-2011) of the US Genetic Epidemiology of COPD (COPDGene) study (n = 4477, 3461 were non-Hispanic whites [NHW], and 1016 were African Americans [AA]). RESULTS: Compared to NHW, AA had a significantly lower adjusted prevalence ratio (aPR) of cough >3 months (aPR: 0.67; 95% CI [confidence interval]: 0.60-0.75) and phlegm >3 months (aPR: 0.78, 95% CI: 0.70-0.86), but higher aPR of dyspnea (modified Medical Round Council scale ⩾2) (aPR: 1.22; 95% CI: 1.15-1.29), short six-minute walk distance (<350 m) (aPR: 1.98; 95% CI: 1.81-2.14), and poor quality of life (aPR: 1.10; 95% CI: 1.05-1.15). Compared to NHW, Koreans had a significantly lower aPR of cough >3 months (aPR: 0.53; 95% CI: 0.47-0.59), phlegm >3 months (aPR: 0.75; 95% CI: 0.67-0.82), dyspnea (aPR: 0.72; 95% CI: 0.66-0.79), and moderate-to-severe acute exacerbation in the previous year (aPR: 0.73; 95% CI: 0.65-0.82). NHW had the highest burden related to chronic bronchitis symptoms and cardiovascular diseases related to comorbidities. CONCLUSION: There are substantial differences in sociodemographic characteristics, clinical presentation, and comorbidities between COPD patients from the KOCOSS and COPDGene, which might be caused by interactions between various intrapersonal, interpersonal, and environmental factors of the ecological model. Thus, a broader and more comprehensive approach would be necessary to understand the racial differences of COPD patients.