Intrapulmonary and Systemic Pharmacokinetics of Colistin Following Nebulization of Low-Dose Colistimethate Sodium in Patients with Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii.

Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration-time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP.

Blood Concentrations of Lead, Cadmium, and Mercury Are Associated With Alcohol-Related Liver Disease.

BACKGROUND: An association between environmental pollutants and alcohol-related liver disease (ALD) has not been determined until now. The objectives of this study were to examine the association of the pollutants with ALD, and whether the pollutants together increased the risk of ALD. METHODS: Data were extracted from the Korea National Health and Nutrition Examination Survey (2010-2013 and 2016-2017; n = 11,993). Blood levels of lead, cadmium, and mercury were measured. ALD was defined by a combination of excessive alcohol consumption and ALD/non-alcoholic fatty liver disease index > 0. The aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 score were used to evaluate ALD FIB. RESULTS: The odds ratios (ORs) of ALD for the highest versus the lowest quartiles of exposure were for lead, 7.39 (95% confidence interval [CI], 5.51-9.91); cadmium, 1.68 (95% CI, 1.32-2.14); and mercury, 5.03 (95% CI, 3.88-6.53). Adjusting for age, gender, smoking, occupation, education, and personal income attenuated the associations but indicated significant positive trends (all Ptrend < 0.001). A positive additive interaction between cadmium and lead was observed. The relative excess OR due to the interaction was 0.96 (95% CI, 0.41-1.51); synergy index = 2.92 (95% CI, 0.97-8.80). Among 951 subjects with ALD, advanced FIB was associated with lead and cadmium (OR, 3.46, 95% CI, 1.84-6.53; OR, 8.50, 95% CI, 2.54-28.42, respectively), but not with mercury. The effect estimates for lead and cadmium remained significant even after adjustment for daily alcohol intake. CONCLUSION: Blood levels of lead, cadmium, and mercury were significantly associated not only with the risk of ALD but also with ALD FIB. Cadmium and lead have synergistic effects that increase the risk of ALD.

Prevalence and clinical impacts of obstructive sleep apnea in patients with idiopathic pulmonary fibrosis: A single-center, retrospective study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with chronic, progressive lung fibrosis with a poor prognosis. Recent studies have reported a high prevalence of obstructive sleep apnea (OSA) in IPF patients and an association with poor prognosis. This study aimed to evaluate the prevalence, risk factors, and clinical effects on mortality of OSA in patients with IPF. METHODS: Clinical data were retrospectively analyzed in 167 patients with IPF at Haeundae-Paik Hospital, Republic of Korea. A type 4 portable device was used to monitor OSA, and an apnea-hypopnea index of 5 events per sleep hour and above was diagnosed as OSA. RESULTS: The mean follow-up period and age were 26.9 months and 71.4 years, respectively, with male predominance. OSA was confirmed in 108 patients (64.7%). Mild OSA was the most common (62.1%). Independent risk factors for OSA in the multivariate logistic regression analysis were age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.13, p = 0.007), body weight (OR 1.05, 95% CI 1.02-1.09, p = 0.002), and risk based on the Berlin questionnaire (OR 2.76, 95% CI 1.12-6.80, p = 0.028). Shorter six-minute walk distance (6MWD) (hazard ratio [HR] 1.00, 95% CI: 1.00-1.00, p < 0.001), acute exacerbation (AE) (HR 13.83, 95% CI: 5.71-33.47, p < 0.001), and higher percentage of cumulative time with oxygen saturation below 90% in total sleep time (HR 1.08, 95% CI: 1.02-1.14, p = 0.007) were risk factors for mortality in IPF patients in the Cox regression analysis. CONCLUSION: Approximately two-thirds of the IPF patients had OSA. Older age, higher body weight, and high risk based on the Berlin questionnaire were independent risk factors for OSA in IPF patients. Shorter 6MWD, experience of AE, and night hypoxemia during sleep were associated with a higher risk of mortality in patients with IPF.

The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea.

BACKGROUND: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. METHODS: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation-Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. RESULTS: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death (P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.55-0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% CI, 0.56-0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79-1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65-2.17; P = 0.582). CONCLUSION: In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

The Efficacy of Pulmonary Rehabilitation in Patients with Idiopathic Pulmonary Fibrosis.

Background: This study evaluated the efficacy and safety of pulmonary rehabilitation (PR) on functional performance, exercise-related oxygen saturation, and health-related quality of life among patients with idiopathic pulmonary fibrosis (IPF). Methods: A total of 25 patients with IPF (13 in the PR group and 12 in the non-PR group) were enrolled between August 2019 and October 2021 at Haeundae-Paik Hospital in the Republic of Korea. A cardiopulmonary exercise test (CPET), six-minute walk test (6MWT), pulmonary function test (PFT), Saint George's Respiratory Questionnaire (SGRQ), muscle strength test, and bioelectrical impedance analysis were performed in each group at baseline and after eight weeks of PR. Results: The mean age was 68 years of age and most subjects were male. Baseline characteristics were similar between the two groups. The distance during 6MWT after PR was significantly improved in the PR group (inter-group p-value = 0.002). VO2max and VE/VCO2 slopes showed a significant difference after eight weeks only in the PR group, but the rate of change did not differ significantly from the non-PR group. Total skeletal muscle mass, PFT variables, and SGRQ scores did not differ significantly between the groups. Conclusions: PR improved exercise capacity, as measured using CPET and 6 MWT. Further studies in larger samples are needed to evaluate the long-term efficacy of PR in IPF patients.

The clinical efficacy of a mixture of ivy leaf extract and coptidis rhizome in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis and cough is the one of most common and major symptoms in IPF. The aim of this study was to evaluate the clinical efficacy of a Mixture of Ivy Leaf Extract and Coptidis rhizome (Synatura®) in patients with IPF. This was a prospective, open-label, single-center, and single-arm study in Korea from October 2019 to September 2020. IPF patients with chronic bronchitis were enrolled. Between baseline and eight weeks after use of Synatura®, clinical measures regarding cough and health-related quality of life, and the systemic inflammatory markers was prospectively collected. Thirty patients were enrolled. Median age was 73 years and 86.7% were men. The median gender-age-pulmonary function stage of IPF was 3. Baseline total score of Leicester cough questionnaire (LCQ) and St. George respiratory questionnaire (SGRQ) were 104.5 and 30.59 respectively. After eight weeks, there was no significant improvement in LCQ (16.8 [15.6-19.1] vs 17.5 [15.2-18.9], P = .772) and SGRQ (30.6 [19.4-37.8] vs 29.9 [19.6-41.8], P = .194) scores. Also, there was no significant difference of systemic inflammatory markers. In analysis of minimal clinically important differences (MCID), one third (33.3%) patients fulfilled the criteria of MCID (1.3) in LCQ scores and median differences was 14 (range: 10-18). In terms of SGRQ, 6 patients (20%) reached MCID (4.0) without significant predictive factors. In our study, use of Synatura® during 8 weeks improved cough-specific life quality in one third patients with IPF. Large-scale, randomized, double-blind, and placebo-controlled clinical trials are needed.

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.

Clinical usefulness of biomarkers for diagnosis and prediction of prognosis in sepsis and septic shock.

Sepsis is a life-threatening condition and remains a major cause of mortality. The aim of this study was to evaluate the role of biomarkers in the diagnosis of sepsis and septic shock in patients admitted to the emergency department (ED). Medical records of patients who underwent measurement of serum biomarkers including lactic acid, C-reactive protein, procalcitonin (PCT), and presepsin in the ED between May 2019 and May 2020 were retrospectively reviewed. Patients were subdivided into 3 groups; non-sepsis, sepsis, and septic shock according to the new definition using the sequential organ failure assessment score. The mean age was 69.3 years, and 55.8% of the study population was female. Of 249 subjects, 98 patients confined to sepsis group, and 35.7% of them were septic shock. In the multivariable analysis, a high level of PCT was an independent predictor of sepsis (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.006-1.051; P = .011) along with a simplified acute physiology score III (SAPS III) (OR, 1.082; 95% CI, 1.062-1.103, P < .001). PCT was also an independent risk factor for septic shock (OR, 1.043; 95% CI, 1.016-1.071, P = .02). In the receiver operating characteristic curve analysis, the area under the curve of PCT to predict sepsis and septic shock were 0.691 (P < .001) and 0.734 (P < .001), respectively. The overall 30-days mortality rate was 8.8%, and the mortality rate was significantly higher in the sepsis group (sepsis vs non-sepsis, 15.3% vs 4.6%; P = .004). In the multivariate Cox analysis, a higher level of lactic acid (hazard ratio [HR], 1.328; 95% CI, 1.061-1.663, P = .013), predisposing chronic pulmonary diseases (HR, 7.035; 95% CI, 1.687-29.341, P = .007), and a high SAPSIII value (HR, 1.046; 95% CI, 1.015-1.078, P = .003) were independent risk factors for mortality in sepsis patients. PCT was a useful biomarker for predicting sepsis and septic shock in the ED. A higher level of lactic acid, predisposing chronic pulmonary diseases, and a high SAPS III score were associated with a greater mortality risk in patients with sepsis.

Current status and trends of pulmonary rehabilitation in South Korea: National level data analysis using Health Insurance Review and Assessment Service (HIRA) database from 2016 to 2018.

In South Korea, there are few studies to understand the current status of pulmonary rehabilitation in clinical practice and develop it. This study aimed to assess the current status and annual changes in the number and pattern of prescriptions for pulmonary rehabilitation before and after its insurance coverage. The trends of pulmonary rehabilitation before and after its insurance coverage commencement were evaluated using the data of 24,380 patients during the 3-year period from 2016 to 2018 that were archived by the National Health Information Database of the Health Insurance Review and Assessment Service in South Korea. The annual total number of patients who received pulmonary rehabilitation was stratified by the type of prescription, sex, age, type of insurance, medical institution, and region. In addition, the frequencies of pulmonary rehabilitation for various diagnoses were investigated using the major codes of the Korean Standard Classification of Disease. The patients who received pulmonary rehabilitation increased by approximately 2 times from 5936 in 2016 (before insurance coverage) to 10,474 in 2019. Before 2017, most patients underwent simple pulmonary rehabilitation coded as MM290. However, since the insurance coverage of rehabilitation exercise for pulmonary disease (MM440), the proportions of patients receiving them increased. Men underwent pulmonary rehabilitation more often than women, and >70% of the patients were aged >60 years. Most patients received pulmonary rehabilitation at tertiary hospitals in Seoul. In 2016, pulmonary rehabilitation was prescribed more frequently for cerebral infarction; after 2017, it was prescribed more frequently for lung cancer. This study summarized the current status and trends of pulmonary rehabilitation in South Korea before and after National Health Insurance Service coverage, which commenced on January 1, 2017. A significant increase in the number of pulmonary rehabilitations was confirmed after the insurance coverage.

Peak oxygen uptake and respiratory muscle performance in patients with chronic obstructive pulmonary disease: Clinical findings and implications.

The maximal oxygen uptake (VO2max) is the gold standard measure of aerobic exercise capacity and is an important outcome measure in patients with chronic obstructive pulmonary disease (COPD). And respiratory muscle performance is also an important functional parameter for COPD patients. In addition to the traditional respiratory muscle strength test, the Test of Incremental Respiratory Endurance has recently been introduced and validated in patients with COPD. However, the relationship between VO2 and respiratory muscle performance in COPD is not well understood. Therefore, this study investigated the correlations among VO2 and respiratory muscle performance and other functional markers in COPD. A total of 32 patients with COPD were enrolled. All study participants underwent the following assessments: cardiopulmonary exercise test, pulmonary function test, respiratory muscle strength test, peripheral muscle strength test, and bioelectrical impedance analysis. When comparing VO2peak and respiratory muscle parameters, the sustained maximal inspiratory pressure (SMIP) was the only factor with a significant relationship with VO2peak. Among other functional parameters, the forced expiratory volume in one second (FEV1) showed the strongest correlation with VO2peak. It was followed by phase angle values of lower limbs, leg extension peak torque, age, and total skeletal muscle mass. When comparing respiratory muscle performance with other functional parameters, the SMIP showed the strongest correlation with hand grip strength, followed by peak cough flow, forced vital capacity, maximal inspiratory pressure, and FEV1. The results showed that the SMIP was more significantly correlated with VO2peak than the static measurement of respiratory muscle strength. This suggests that TIRE may be a useful assessment tool for patients with COPD. Additionally, FEV1 and other functional markers were significantly correlated with VO2peak, suggesting that various parameters may be used to evaluate aerobic power indirectly.

Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Disease: A Retrospective Single-Center Experience.

BACKGROUND: An accurate diagnosis in patients with interstitial lung diseases (ILDs) by multidisciplinary discussion (MDD) based on histopathologic information is essential for optimal treatment. Transbronchial lung cryobiopsy (TBLC) has increasingly been used as a diagnostic alternative to surgical lung biopsy. This study aimed to evaluate the appropriate methods of TBLC in patients with ILD in Korea. METHODS: A total of 27 patients who underwent TBLC were included. TBLC procedure details and clinical MDD diagnosis using TBLC histopathologic information were retrospectively analyzed. RESULTS: All procedures were performed under general anesthesia with the fluoroscopic guidance in the operation room using flexible bronchoscopy and endobronchial balloon blocker. The median procedure duration was less than 30 minutes, and the median number of biopsies per participant was 2. Most of the bleeding after TBLC was not severe, and the rate of pneumothorax was 25.9%. The most common histopathologic pattern was alternative (48.2%), followed by indeterminate (33.3%) and usual interstitial pneumonia (UIP)/probable UIP (18.5%). In the MDD after TBLC, the most common diagnosis was idiopathic pulmonary fibrosis (33.3%), followed by smoking-related ILD (25.9%), nonspecific interstitial pneumonia (18.6%), unclassifiable-ILD (14.8%), and others (7.4%). CONCLUSION: This first single-center experience showed that TBLC using a flexible bronchoscopy and endobronchial balloon blocker with the fluoroscopic guidance under general anesthesia may be a safe and adequate diagnostic method for ILD patients in Korea. The diagnostic yield of MDD was 85.2%. Further studies are needed to evaluate the diagnostic yield and confidence of TBLC.

Predicting Antibiotic Effect of Vancomycin Using Pharmacokinetic/Pharmacodynamic Modeling and Simulation: Dense Sampling versus Sparse Sampling.

This study aimed to investigate the effect of a structural pharmacokinetic (PK) model with fewer compartments developed following sparse sampling on the PK parameter estimation and the probability of target attainment (PTA) prediction of vancomycin. Two- and three-compartment PK models of vancomycin were used for the virtual concentration-time profile simulation. Datasets with reduced blood sampling times were generated to support a model with a lesser number of compartments. Monte Carlo simulation was conducted to evaluate the PTA. For the two-compartment PK profile, the total clearance (CL) of the reduced one-compartment model showed a relative bias (RBias) and relative root mean square error (RRMSE) over 90%. For the three-compartment PK profile, the CL of the reduced one-compartment model represented the largest RBias and RRMSE, while the steady-state volume of distribution of the reduced two-compartment model represented the largest absolute RBias and RRMSE. A lesser number of compartments corresponded to a lower predicted area under the concentration-time curve of vancomycin. The estimated PK parameters and predicted PK/PD index from models built with sparse sampling designs that cannot support the PK profile can be significantly inaccurate and unprecise. This might lead to the misprediction of the PTA and selection of improper dosage regimens when clinicians prescribe antibiotics.

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.

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.

Acute respiratory distress syndrome caused by carbon monoxide poisoning and inhalation injury recovered after extracorporeal membrane oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column: a case report.

BACKGROUND: Inhalation injury from smoke or chemical products and carbon monoxide poisoning are major causes of death in burn patients from fire accidents. Respiratory tract injuries from inhalation injury and carbon monoxide poisoning can lead to acute respiratory distress syndrome and cytokine storm syndrome. In the case of acute respiratory failure needing mechanical ventilation accompanied by cytokine storm, mortality is high and immediate adequate treatment at the emergency department is very important. CASE PRESENTATION: This report describes a case of acute respiratory distress syndrome and cytokine storm followed by carbon monoxide poisoning in a 34-year-old Korean male patient who was in a house fire, and was successfully treated by extracorporeal membrane oxygenation and direct hemoperfusion with polymyxin B-immobilized fiber column at emergency department. CONCLUSIONS: To prevent mortality in acute respiratory distress syndrome with cytokine storm from inhalation injury and to promote a better prognosis, we suggest that early implication of extracorporeal membranous oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column even at the emergency department should be considered.

The role of interleukin-6 as a prognostic biomarker for predicting acute exacerbation in interstitial lung diseases.

BACKGROUND: Interstitial lung diseases (ILDs) are chronic, parenchymal lung diseases with a variable clinical course and a poor prognosis. Within various clinical courses, acute exacerbation (AE) is a devastating condition with significant morbidity and high mortality. The aim of this study was to investigate the role of interleukin-6 (IL-6) to predict AE and prognosis in patients with ILD. METHODS: Eighty-three patients who were diagnosed with ILD from 2016 to 2019 at the Haeundae Paik Hospital, Busan, South Korea, were included and their clinical data were retrospectively analyzed. RESULTS: The median follow-up period was 20 months. The mean age was 68.1 years and 65.1% of the patients were men with 60.2% of patients being ever-smokers. Among ILDs, idiopathic pulmonary fibrosis was the most common disease (68.7%), followed by connective tissue disease-associated ILD (14.5%), cryptogenic organizing pneumonia (9.6%), and nonspecific interstitial pneumonia (6.0%). The serum levels of IL-6 were measured at diagnosis with ILD and sequentially at follow-up visits. During the follow-ups, 15 (18.1%) patients experienced an acute exacerbation (AE) of ILD and among them, four (26.7%) patients died. In the multivariable analysis, high levels of IL-6 (OR 1.014, 95% CI: 1.001-1.027, p = 0.036) along with lower baseline saturations of peripheral oxygen (SpO2) were independent risk factors for AE. In the receiver operating characteristic curve analysis, the area under the curve was 0.815 (p < 0.001) and the optimal cut-off value of serum IL-6 to predict AE was 25.20 pg/mL with a sensitivity of 66.7% and specificity of 80.6%. In the multivariable Cox analysis, a high level of serum IL-6 (HR 1.007, 95% CI: 1.001-1.014, p = 0.018) was only an independent risk factor for mortality in ILD patients. CONCLUSIONS: In our study, a high level of serum IL-6 is a useful biomarker to predict AE and poor prognosis in patients with ILD.

The effects of direct hemoperfusion with polymyxin B-immobilized fiber in patients with acute exacerbation of interstitial lung disease.

BACKGROUND: Acute exacerbation of interstitial lung disease (AE-ILD) causes clinically significant deterioration and has an extremely poor prognosis with high mortality. Recently, several studies reported the effectiveness of direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) in patients with AE-ILD as a potential therapy. This study describes the clinical effectiveness and safety of PMX-DHP in patients with AE-ILD. METHODS: We retrospectively reviewed the medical records of 10 patients (11 episodes) with AE-ILD treated with PMX-DHP from January 2018 to June 2019. We compared laboratory and physiologic data of the ratio of partial pressure arterial oxygen to fraction of inspired oxygen (P/F ratio) and level of inflammatory markers before and after implementation of PMX-DHP. RESULTS: Ten patients were included according to the 2016 revised definition of acute exacerbation of idiopathic pulmonary fibrosis (IPF). Nine patients had IPF and one patient had fibrotic nonspecific interstitial pneumonia. Most patients (90.9%) were treated with a steroid pulse, and four patients (36.4%) were treated with an immunosuppressant. The median number of PMX-DHP cycles was 2, and the median duration of each cycle was 6 hours. After PMX-DHP, the mean P/F ratio improved (86 [range, 63-106] vs. 145 [86-260], P=0.030) and interleukin-6 and c-reactive protein decreased (79 [35-640] vs. 10 [5-25], P=0.018 and 14 [4-21] vs. 5 [2-6], P=0.019, respectively). The 30-day mortality rate was 27.3% and the 90-day mortality rate was 72.7%. CONCLUSIONS: PMX-DHP treatment improved P/F ratio and reduced inflammatory markers in AE-ILD patients.

Unilateral pleuroparenchymal fibroelastosis as a rare form of idiopathic interstitial pneumonia: A case report.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by predominantly upper lobe involvement with pleural fibrosis and subjacent parenchymal fibrosis. Recently, there have been increasing reports of PPFE, and PPFE might coexist with other interstitial lung diseases in the lower lobe and upper lobe. However, cases of unilateral PPFE are scarce. CASE SUMMARY: A 75-year-old Korean male presented to our hospital with chronic dry cough and exertional dyspnea. The patient's symptoms started 6 mo previously and had been gradually worsening. At the time of presentation, he felt dyspnea when walking at his own pace. Radiologic findings suggested PPFE, but the lesion was localized in the upper lobe of the right lung. After multidisciplinary discussion, a transbronchial lung biopsy in the right upper lobe revealed collapsed alveoli with parenchymal fibroelastosis, and elastic van Gieson staining demonstrated septal elastosis with intra-alveolar collagenosis, which met the histopathologic criteria of definite PPFE. After multidisciplinary discussion in an experienced interstitial lung disease center, we confirmed the diagnosis of unilateral PPFE. Furthermore, we confirmed the progression of PPFE on radiologic findings during the follow-up period. CONCLUSION: Clinicians should consider PPFE, even in cases with unilateral, predominantly upper lung involvement in interstitial lung disease patients through multidisciplinary discussion.

The change in prevalence of suspected non-alcoholic fatty liver disease in Korean adolescents from 2001 to 2017.

AIM: Data on trends in the prevalence of suspected non-alcoholic fatty liver disease (NAFLD) in adolescents are scarce, especially in the Asia-Pacific region. The purpose of this study was to determine whether the prevalence of suspected NAFLD changed between 2001-2005 and 2015-2017. METHODS: Data were extracted from the Korea National Health and Nutrition Examination Survey (2001-2005 to 2015-2017, n = 4448). Suspected NAFLD was defined by an elevated alanine aminotransferase (ALT) level of >26 IU/L in boys and >22 IU/L in girls. In addition, the analysis was repeated using the Korean cut-off levels for ALT of 33 IU/L for boys and 25 IU/L for girls. RESULTS: The prevalence of suspected NAFLD increased, with a relative increase of 44% from 7.8% (95% CI 6.6-9.2%) in 2001-2005 to 11.2% (95% CI 9.7-12.9%) in 2015-2017 (p = 0.001). This increase was evident in both boys (10.6 vs 14.7%, p = 0.01) and girls (4.6 vs 7.4%, p = 0.02). Increases were also observed in obesity (7.3 vs 10.6%), central obesity (10.0 vs 12.8%) and ALT level (14.9 vs 16.7 IU/L). The prevalence of suspected NAFLD was approximately 40-45% in obese/central obese adolescents in 2015-2017. Using the Korean cut-off levels, the prevalence of suspected NAFLD has increased, with a relative increase of 55%, from 4.6% (95% CI 3.7-5.7%) in 2001-2005 to 7.2% (95% CI 6.1-8.5%) in 2015-2017 (p = 0.01). CONCLUSIONS: The prevalence of suspected NAFLD continues to increase in Korean adolescents. ABBREVIATIONS: ALT, alanine aminotransferase; BMI, body mass index; KNHANES, Korea National Health and Nutrition Examination Survey; NAFLD, non-alcoholic fatty liver disease.

Direct hemoperfusion with polymyxin B-immobilized fiber column in a patient with acute exacerbation of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterized by dyspnea and a worsening of the lung function. Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are defined by a clinically significant respiratory deterioration, that typically develops in less than 1 month, accompanied by new radiologic abnormalities on high-resolution computed tomography, including diffused and bilateral ground-glass opacification, along with an absence of other obvious clinical etiologies. Recently, AE-IPF has gained significant importance as a major cause of mortality and morbidity. However, despite the extremely poor prognosis of the condition, no well-validated therapeutic interventions are currently available. Therefore, novel treatment modalities are being investigated and applied in addition to conventional treatments. Among them, several studies have reported that a direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP), developed for endotoxin removal in septic shock, has an effect on AE-IPF. We describe two cases of PMX-DHP treatment with conflicting results. One patient successfully recovered via a PMX-DHP in severe AE-IPF that required extracorporeal membrane oxygenation (ECMO). PMX-DHP subsequently improved oxygenation (PaO2/FiO2 ratio) and decreased the levels of inflammatory markers (interleukin-6, C-reactive protein, and white blood cells). The patient dramatically recovered without the need for ECMO. PMX-DHP may be considered an alternative therapy in AE-IPF patients requiring mechanical ventilation or ECMO.