Efficacy of lower dose pirfenidone for idiopathic pulmonary fibrosis in real practice: a retrospective cohort study

Background/Aims@#Pirfenidone slows the progression of idiopathic pulmonary fibrosis (IPF). We investigated its efficacy and safety in terms of dose and disease severity in real-world patients with IPF. @*Methods@#This multicenter retrospective cohort study investigated 338 patients treated with pirfenidone between July 2012 and March 2018. Demographics, pulmonary function, mortality, and pirfenidone-related adverse events were also investigated. Efficacy was analyzed according to pirfenidone dose and disease severity using linear mixed-effects models to assess the annual decline rate of forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). @*Results@#The mean %FVCpredicted and %DLCOpredicted values were 72.6% ± 13.1% and 61.4% ± 17.9%, respectively. The mean duration of pirfenidone treatment was 16.1 ± 9.0 months. In the standard dose (1,800 mg/day) group, the mean %FVCpredicted was −6.56% (95% confidence interval [CI], −9.26 to −3.87) per year before, but −4.43% (95% CI, −5.87 to −3.00) per year after treatment with pirfenidone. In the non-standard lower dose group, the mean %FVCpredicted was −4.96% (95% CI, −6.82 to −3.09) per year before, but −1.79% (95% CI, −2.75 to −0.83) per year after treatment with pirfenidone. The FVC decline rate was significantly reduced, regardless of the Gender-Age-Physiology (GAP) stage. Adverse events and mortality were similar across dose groups; however, they were more frequent in GAP stages II–III than in the stage I group. @*Conclusions@#The effect of pirfenidone on reducing disease progression of IPF persisted even with a consistently lower dose of pirfenidone.

Prevalence and Risk Factors of Occupational Skin Disease in Korean Workers from the 2014 Korean Working Conditions Survey

Clinical Significance of Pleural Attachment and Indentation of Subsolid Nodule Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Lung cancers presenting as subsolid nodule commonly have peripheral location, making the cancer-pleura relationship noteworthy. We aimed to evaluate the effect of pleural attachment and/or indentation on visceral pleural invasion (VPI) and recurrence-free survival. MATERIALS AND METHODS: Patients who underwent curative resection of lung cancer as subsolid nodules from April 2007 to January 2016 were retrospectively evaluated. They were divided into four groups according to their relationship with the pleura. Clinical, radiographical, and pathological findings were analyzed. RESULTS: Among 404 patients with malignant subsolid nodule, 120 (29.7%) had neither pleural attachment nor indentation, 26 (6.4%) had attachment only, 117 (29.0%) had indentation only, and 141 (34.9%) had both. VPI was observed in nodules of 36 patients (8.9%), but absent in nonsolid nodules and in those without pleural attachment and/or indentation. Compared to subsolid nodules with concurrent pleural attachment and indentation, those with attachment only (odds ratio, 0.12; 95% confidence interval [CI], 0.02 to 0.98) and indentation only (odds ratio, 0.10; 95% CI, 0.03 to 0.31) revealed lower odds of VPI. On subgroup analysis, the size of the solid portion was associated with VPI among those with pleural attachment and indentation (p=0.021). Such high-risk features for VPI were associated with earlier lung cancer recurrence (adjusted hazard ratio, 3.31; 95% CI, 1.58 to 6.91). CONCLUSION: Concurrent pleural attachment and indentation are risk factors for VPI, and the odds increase with larger solid portion in subsolid nodules. Considering the risk of recurrence, early surgical resection could be encouraged in these patients.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 2. Idiopathic Pulmonary Fibrosis / 결핵

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 2. Idiopathic Pulmonary Fibrosis / 결핵및호흡기질환

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

Effects of Bisoprolol Are Comparable with Carvedilol in Secondary Prevention of Acute Myocardial Infarction in Patients Undergoing Percutaneous Coronary Intervention / 전남의대학술지

Although the benefits of carvedilol have been demonstrated in the era of percutaneous coronary intervention (PCI), very few studies have evaluated the efficacy of bisoprolol in the secondary prevention of acute myocardial infarction (MI) in patients treated with PCI. We hypothesized that the effect of bisoprolol would not be different from carvedilol in post-MI patients. A total of 13,813 patients who underwent PCI were treated either with carvedilol or bisoprolol at the time of discharge. They were enrolled from the Korean Acute MI Registry (KAMIR). After 1:2 propensity score matching, 1,806 patients were enrolled in the bisoprolol group and 3,612 patients in the carvedilol group. The primary end point was the composite of major adverse cardiac events (MACEs), which was defined as cardiac death, nonfatal MI, target vessel revascularization, and coronary artery bypass surgery. The secondary end point was defined as all-cause mortality, cardiac death, nonfatal MI, any revascularization, or target vessel revascularization. After adjustment for differences in baseline characteristics by propensity score matching, the MACE-free survival rate was not different between the groups (HR=0.815, 95% CI:0.614–1.081, p=0.156). In the subgroup analysis, the cumulative incidence of MACEs was lower in the bisoprolol group in patients having a Killip class of III or IV than in the carvedilol group (HR=0.512, 95% CI: 0.263–0.998, p=0.049). The incidence of secondary end points was similar between the two beta-blocker groups. In conclusion, the benefits of bisoprolol were comparable with those of carvedilol in the secondary prevention of acute MI.

Transcultural Adaptation and Validation of the Family Satisfaction in the Intensive Care Unit Questionnaire in a Korean Sample / 대한중환자의학회지

BACKGROUND: A number of questionnaires designed for analyzing family members' inconvenience and demands in intensive care unit (ICU) care have been developed and validated in North America. The family satisfaction in the intensive care Unit-24 (FS-ICU-24) questionnaire is one of the most widely used of these instruments. This study aimed to translate the FS-ICU-24 questionnaire into Korean and validate the Korean version of the questionnaire. METHODS: The study was conducted in the medical, surgical, and emergency ICUs at three tertiary hospitals. Relatives of all patients hospitalized for at least 48 hours were enrolled for this study participants. The validation process included the measurement of construct validity, internal consistency, and interrater reliability. The questionnaire consists of 24 items divided between two subscales: satisfaction with care (14 items) and satisfaction with decision making (10 items). RESULTS: In total, 200 family members of 176 patients from three hospitals completed the FS-ICU-24 questionnaire. Construct validity for the questionnaire was superior to that observed for a visual analog scale (Spearman's r = 0.84, p < 0.001). Cronbach's αs were 0.83 and 0.80 for the satisfaction with care and satisfaction with decision making subscales, respectively. The mean (± standard deviation) total FS-ICU-24 score was 75.44 ± 17.70, and participants were most satisfied with consideration of their needs (82.13 ± 21.03) and least satisfied with the atmosphere in the ICU waiting room (35.38 ± 34.84). CONCLUSIONS: The Korean version of the FS-ICU-24 questionnaire demonstrated good validity and could be a useful instrument with which to measure family members' satisfaction about ICU care.

Differences in the Clinical Characteristics of Rapid Response System Activation in Patients Admitted to Medical or Surgical Services

Variability in rapid response system (RRS) characteristics based on the admitted wards is unknown. We aimed to compare differences in the clinical characteristics of RRS activation between patients admitted to medical versus surgical services. We reviewed patients admitted to the hospital who were detected by the RRS from October 2012 to February 2014 at a tertiary care academic hospital. We compared the triggers for RRS activation, interventions performed, and outcomes of the 2 patient groups. The RRS was activated for 460 patients, and the activation rate was almost 2.3 times higher for surgical services than that for medical services (70% vs. 30%). The triggers for RRS activation significantly differed between patient groups (P = 0.001). They included abnormal values for the respiratory rate (23.2%) and blood gas analysis (20.3%), and low blood pressure (18.8%) in the medical group; and low blood pressure (32.0%), low oxygen saturation (20.8%), and an abnormal heart rate (17.7%) in the surgical group. Patients were more likely classified as do not resuscitate or required intensive care unit admission in the medical group compared to those in the surgical group (65.3% vs. 54.7%, P = 0.045). In multivariate analysis, whether the patient belongs to medical services was found to be an independent predictor of mortality after adjusting for the modified early warning score, Charlson comorbidity index, and intervention performed by the RRS team. Our data suggest that RRS triggers, interventions, and outcomes greatly differ between patient groups. Further research is needed to evaluate the efficacy of an RRS approach tailored to specific patient groups.

Who Dies after ICU Discharge? Retrospective Analysis of Prognostic Factors for In-Hospital Mortality of ICU Survivors

We investigated the causes of inpatient death after intensive care unit (ICU) discharge and determined predictors of in-hospital mortality in Korea. Using medical ICU registry data of Seoul National University Hospital, we performed a retrospective cohort study involving patients who were discharged alive from their first ICU admission with at least 24 hours of ICU length of stay (LOS). From January 2011 to August 2013, 723 patients were admitted to ICU and 383 patients were included. The estimated in-hospital mortality rate was 11.7% (45/383). The most common cause of death was respiratory failure (n = 25, 56%) followed by sepsis and cancer progression; the causes of hospital death and ICU admission were the same in 64% of all deaths; sudden unexpected deaths comprised about one-fifth of all deaths. In order to predict in-hospital mortality among ICU survivors, multivariate analysis identified presence of solid tumor (odds ratio [OR], 4.06; 95% confidence interval [CI], 2.01–8.2; P < 0.001), hematologic disease (OR, 4.75; 95% CI, 1.51–14.96; P = 0.013), Sequential Organ Failure Assessment (SOFA) score upon ICU admission (OR, 1.08; 95% CI, 0.99–1.17; P = 0.075), and hemoglobin (Hb) level (OR, 0.67; 95% CI, 0.52–0.86; P = 0.001) and platelet count (Plt) (OR, 0.99; 95% CI, 0.99–1.00; P = 0.033) upon ICU discharge as significant factors. In conclusion, a significant proportion of in-hospital mortality is predictable and those who die in hospital after ICU discharge tend to be severely-ill, with comorbidities of hematologic disease and solid tumor, and anemic and thrombocytopenic upon ICU discharge.

Comparing tuberculin skin test and interferon γ release assay (T-SPOT.TB) to diagnose latent tuberculosis infection in household contacts

BACKGROUND/AIMS: The tuberculin skin test (TST) and interferon γ release assay are currently used as diagnostic tools to detect latent tuberculosis (TB) infection; however, there are inconsistencies about the degree of agreement between the tests. We aimed to evaluate the concordance rate between the two tests in household contacts of a country with intermediate TB burden, where most people were vaccinated. METHODS: We recruited household contacts who spent > 8 hours daily with patients with microbiologically confirmed active pulmonary TB, and received both TST and T-SPOT.TB (Oxford Immunotec) simultaneously. The degree of agreement was analysed according to TST cutoff and Bacille Calmette-Guerin (BCG) vaccination status. Relevant factors were analysed to establish the association with TST or T-SPOT.TB. RESULTS: Among 298 household contacts, 122 (40.9%) were spouses, and 250 (83.9%) had received BCG vaccination. In the contact sources, 117 (39.3%) showed a positive result for acid-fast bacillus (AFB) sputum smear and 109 (36.6%) had cavities. The highest agreement rate of 69.5% and κ value of 0.378 were found with a 10 mm cutoff. Spouse, time interval from TB diagnosis to test, and AFB sputum smear positivity were significantly associated with a positive result for T-SPOT.TB. Sex, BCG vaccination, and cavity on chest computed tomography were related to TST positivity. CONCLUSIONS: The present study suggested it was not possible for TST and T-SPOT.TB to replace each other because of considerable discrepancy between the two tests in household contacts in a country with intermediate TB prevalence.

Comparing tuberculin skin test and interferon γ release assay (T-SPOT.TB) to diagnose latent tuberculosis infection in household contacts

BACKGROUND/AIMS: The tuberculin skin test (TST) and interferon γ release assay are currently used as diagnostic tools to detect latent tuberculosis (TB) infection; however, there are inconsistencies about the degree of agreement between the tests. We aimed to evaluate the concordance rate between the two tests in household contacts of a country with intermediate TB burden, where most people were vaccinated. METHODS: We recruited household contacts who spent > 8 hours daily with patients with microbiologically confirmed active pulmonary TB, and received both TST and T-SPOT.TB (Oxford Immunotec) simultaneously. The degree of agreement was analysed according to TST cutoff and Bacille Calmette-Guerin (BCG) vaccination status. Relevant factors were analysed to establish the association with TST or T-SPOT.TB. RESULTS: Among 298 household contacts, 122 (40.9%) were spouses, and 250 (83.9%) had received BCG vaccination. In the contact sources, 117 (39.3%) showed a positive result for acid-fast bacillus (AFB) sputum smear and 109 (36.6%) had cavities. The highest agreement rate of 69.5% and κ value of 0.378 were found with a 10 mm cutoff. Spouse, time interval from TB diagnosis to test, and AFB sputum smear positivity were significantly associated with a positive result for T-SPOT.TB. Sex, BCG vaccination, and cavity on chest computed tomography were related to TST positivity. CONCLUSIONS: The present study suggested it was not possible for TST and T-SPOT.TB to replace each other because of considerable discrepancy between the two tests in household contacts in a country with intermediate TB prevalence.

Transcultural Adaptation and Validation of the Family Satisfaction in the Intensive Care Unit Questionnaire in a Korean Sample / 대한구급학회지

BACKGROUND: A number of questionnaires designed for analyzing family members' inconvenience and demands in intensive care unit (ICU) care have been developed and validated in North America. The family satisfaction in the intensive care Unit-24 (FS-ICU-24) questionnaire is one of the most widely used of these instruments. This study aimed to translate the FS-ICU-24 questionnaire into Korean and validate the Korean version of the questionnaire. METHODS: The study was conducted in the medical, surgical, and emergency ICUs at three tertiary hospitals. Relatives of all patients hospitalized for at least 48 hours were enrolled for this study participants. The validation process included the measurement of construct validity, internal consistency, and interrater reliability. The questionnaire consists of 24 items divided between two subscales: satisfaction with care (14 items) and satisfaction with decision making (10 items). RESULTS: In total, 200 family members of 176 patients from three hospitals completed the FS-ICU-24 questionnaire. Construct validity for the questionnaire was superior to that observed for a visual analog scale (Spearman's r = 0.84, p < 0.001). Cronbach's αs were 0.83 and 0.80 for the satisfaction with care and satisfaction with decision making subscales, respectively. The mean (± standard deviation) total FS-ICU-24 score was 75.44 ± 17.70, and participants were most satisfied with consideration of their needs (82.13 ± 21.03) and least satisfied with the atmosphere in the ICU waiting room (35.38 ± 34.84). CONCLUSIONS: The Korean version of the FS-ICU-24 questionnaire demonstrated good validity and could be a useful instrument with which to measure family members' satisfaction about ICU care.

Multiplex Assay of Second-Line Anti-Tuberculosis Drugs in Dried Blood Spots Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

As dried blood spots (DBSs) have various advantages over conventional venous blood sampling, some assays for detection of one or two anti-tuberculosis (TB) drugs in DBSs have been developed. However, there are no assays currently available for the simultaneous measurement of three or more anti-TB drugs in DBSs. In this study, we developed and evaluated a multiplex method for detecting nine anti-TB drugs including streptomycin, kanamycin, clarithromycin, cycloserine, moxifloxacin, levofloxacin, para-aminosalicylic acid, prothionamide, and linezolid in DBSs by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Seventy-nine patient samples of DBS were analyzed on the UPLC-MS/MS system. All drug concentrations were determined within 4 min, and assay performance was evaluated. All drugs were clearly separated without ion suppression. Within-run and between-run precisions were 1.7-13.0% and 5.7-17.0%, respectively, at concentrations representing low and high levels for the nine drugs. Lower limits of detection and quantification were 0.06-0.6 and 0.5-5.0 µg/mL, respectively. Linearity was acceptable at five level concentrations for each drug. Correlations between drug concentrations in plasma and DBSs by using Passing-Bablock regression and Pearson's rho (ρ, 0.798-0.989) were acceptable. In conclusion, we developed a multiplex assay to measure nine second-line anti-TB drugs in DBSs successfully. This assay provided convenient and rapid drug quantification and could have applications in drug monitoring during treatment.

Intermediate risk of multidrug-resistant organisms in patients who admitted intensive care unit with healthcare-associated pneumonia

BACKGROUND/AIMS: Healthcare-associated pneumonia (HCAP) was proposed asa new pneumonia category in 2005, and treatment recommendations includebroad-spectrum antibiotics directed at multidrug-resistant (MDR) pathogens.However, this concept continues to be controversial, and microbiological data arelacking for HCAP patients in the intensive care unit (ICU). This study was conductedto determine the rate and type of antibiotic-resistant organisms and theclinical outcomes in patients with HCAP in the ICU, compared to patients withcommunity-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). METHODS: We conducted a retrospective cohort analysis of patients with pneumonia(n = 195) who admitted to medical ICU in tertiary teaching hospital fromMarch 2011 to February 2013. Clinical characteristics, microbiological distributions,treatment outcomes, and prognosis of HCAP (n = 74) were compared tothose of CAP (n = 75) and HAP (n = 46). RESULTS: MDR pathogens were significantly higher in HCAP patients (39.1%) thanin CAP (13.5%) and lower than in HAP (79.3%, p < 0.001). The initial use of inappropriateantibiotic treatment occurred more frequently in the HCAP (32.6%) andHAP (51.7%) groups than in the CAP group (11.8%, p = 0.006). There were no differencesin clinical outcomes. The significant prognostic factors were pneumoniaseverity and treatment response. CONCLUSIONS: MDR pathogens were isolated in HCAP patients requiring ICU admissionat intermediate rates between those of CAP and HAP.

The Anti-Inflammatory Effect of Arginine-Vasopressin on Lipopolysaccharide-Induced IkappaBalpha/Nuclear Factor-kappaB Cascade / 대한중환자의학회지

BACKGROUND: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IkappaBalpha)/nuclear factor-kappa B (NF-kappaB) pathway in RAW 264.7 cells. METHODS: Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IkappaBalpha and nuclear translocation of NF-kappaB p65 were measured by Western blotting, and IkappaB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IkappaBalpha/NF-kappaB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. RESULTS: The increase of IL-6 and TNF-alpha in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IkappaBalpha degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-kappaB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IkappaBalpha degradation and NF-kappaB transcription by AVP was abolished by tolvaptan treatment. CONCLUSIONS: Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IkappaBalpha/NF-kappaB cascade in mouse macrophages via V2 receptors.

Readmission to Medical Intensive Care Units: Risk Factors and Prediction

PURPOSE: The objectives of this study were to find factors related to medical intensive care unit (ICU) readmission and to develop a prediction index for determining patients who are likely to be readmitted to medical ICUs. MATERIALS AND METHODS: We performed a retrospective cohort study of 343 consecutive patients who were admitted to the medical ICU of a single medical center from January 1, 2008 to December 31, 2012. We analyzed a broad range of patients' characteristics on the day of admission, extubation, and discharge from the ICU. RESULTS: Of the 343 patients discharged from the ICU alive, 33 (9.6%) were readmitted to the ICU unexpectedly. Using logistic regression analysis, the verified factors associated with increased risk of ICU readmission were male sex [odds ratio (OR) 3.17, 95% confidence interval (CI) 1.29-8.48], history of diabetes mellitus (OR 3.03, 95% CI 1.29-7.09), application of continuous renal replacement therapy during ICU stay (OR 2.78, 95% CI 0.85-9.09), white blood cell count on the day of extubation (OR 1.13, 95% CI 1.07-1.21), and heart rate just before ICU discharge (OR 1.03, 95% CI 1.01-1.06). We established a prediction index for ICU readmission using the five verified risk factors (area under the curve, 0.76, 95% CI 0.66-0.86). CONCLUSION: By using specific risk factors associated with increased readmission to the ICU, a numerical index could be established as an estimation tool to predict the risk of ICU readmission.

Successful High Flow Nasal Oxygen Therapy for Excessive Dynamic Airway Collapse: A Case Report / 결핵및호흡기질환

Excessive dynamic airway collapse (EDAC) is a disease entity of excessive reduction of the central airway diameter during exhalation, without cartilage collapse. An 80-year-old female presented with generalized edema and dyspnea at our hospital. The patient was in a state of acute decompensated heart failure due to pneumonia with respiratory failure. We accordingly managed the patient with renal replacement therapy, mechanical ventilation and antibiotics. Bronchoscopy confirmed the diagnosis of EDAC. We scheduled extubation after the improvement of pneumonia and heart condition. However, extubation failure occurred due to hypercapnic respiratory failure with poor expectoration. Her EDAC was improved in response to high flow nasal oxygen therapy (HFNOT). Subsequently, the patient was stabilized and transferred to the general ward. HFNOT, which generates physiologic positive end expiratory pressure (PEEP) effects, could be an alternative and effective management of EDAC. Further research and clinical trials are needed to demonstrate the therapeutic effect of HFNOT on EDAC.

Drug-induced Hepatotoxicity of Anti-tuberculosis Drugs and Their Serum Levels

The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.

Drug-induced Hepatotoxicity of Anti-tuberculosis Drugs and Their Serum Levels

The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.

The Anti-Inflammatory Effect of Arginine-Vasopressin on Lipopolysaccharide-Induced IkappaBalpha/Nuclear Factor-kappaB Cascade / 대한구급학회지

BACKGROUND: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IkappaBalpha)/nuclear factor-kappa B (NF-kappaB) pathway in RAW 264.7 cells. METHODS: Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IkappaBalpha and nuclear translocation of NF-kappaB p65 were measured by Western blotting, and IkappaB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IkappaBalpha/NF-kappaB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. RESULTS: The increase of IL-6 and TNF-alpha in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IkappaBalpha degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-kappaB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IkappaBalpha degradation and NF-kappaB transcription by AVP was abolished by tolvaptan treatment. CONCLUSIONS: Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IkappaBalpha/NF-kappaB cascade in mouse macrophages via V2 receptors.