Effects of comorbid chronic kidney disease on mortality in idiopathic pulmonary fibrosis patients and influence of pirfenidone.

Chronic kidney disease (CKD) is a comorbidity in idiopathic pulmonary fibrosis (IPF), and managing IPF with CKD is challenging due to limited options for antifibrotic therapy. The aim of this study was to examine the prevalence of CKD and prescription status of pirfenidone in IPF patients and to analyze its impact on mortality. Data from the Korean National Health Insurance Service (NHIS) database between October 2015 and September 2021 were used. IPF and CKD were defined based on both International Classification of Diseases 10th Revision (ICD-10) codes and Rare Intractable Disease (RID) codes. The risk of mortality was assessed based on accompanying CKD with or without antifibrotic therapy. Among 5038 patients with IPF, 8.4% had comorbid CKD and 83.3% with CKD did not receive renal replacement therapy (RRT). Patients with IPF and CKD were older, predominantly male, and had more frequent comorbidities such as cardiovascular disease and diabetes mellitus than subjects without CKD. Pirfenidone was prescribed to 105 (24.6%) of 426 CKD patients, and 89.5% of them did not receive RRT. Pirfenidone was also prescribed to 775 (16.8%) of 4612 IPF patients without CKD. Significant difference was not found in all-cause mortality between the IPF patients with or without CKD regardless of pirfenidone treatment. The use of antifibrotics in IPF patients with CKD is limited due to CKD severity; however, evidence is lacking. Mortality did not increase with accompanying CKD regardless of antifibrotic use. Further research on IPF and CKD is needed.

Clinical Characteristics and Medical Utilization of Smokers with Preserved Ratio Impaired Spirometry.

Purpose: To investigate the clinical characteristics and medical utilization of smokers with preserved ratio impaired spirometry (PRISm). Patients and Methods: We used data from the Korean National Health and Nutrition Examination Survey between 2007 and 2012, linked to the Health Insurance Review and Assessment Service. Clinical characteristics and medical utilization, including inpatient admission, emergency department visit, prescribed medication, and medical cost, were retrospectively compared among three groups: normal spirometry, PRISm, and chronic obstructive pulmonary disease (COPD). Results: A total of 7115 smokers were included (4743 normal spirometry, 689 PRISm, and 1683 COPD subjects). The mean age was the highest in the COPD group, followed by the PRISm and normal groups, and the proportion of women was the highest in the PRISm group. The tobacco exposure, socioeconomic status (SES), and schooling level of the PRISm group were at levels between those of the normal and COPD groups. However, the PRISm group had the highest proportion of current smokers, highest body mass index (BMI), and lowest mean FEV1 and FVC % predicted. During the study period, the medical utilization of 92 smokers (13.4%) in the PRISm group and 436 smokers (25.9%) in the COPD group was related to respiratory diseases. Emergency department visit or hospitalization and overall medical cost of the PRISm group were comparable to those of the COPD group, except for outpatient clinic visit. Old age, women, low BMI, low SES, low schooling level, high amount of tobacco exposure, wheezing, and decreased FEV1 and FVC % predicted were factors associated with medical utilization in PRISm. Conclusion: Medical utilization was comparable between the PRISm and COPD groups. Smokers with PRISm who were older, women, or heavy smokers with low BMI, low SES and schooling level, wheezing, or low FEV1 and FVC might need close observation and early treatment.

Eupatilin Alleviates Hyperlipidemia in Mice by Inhibiting HMG-CoA Reductase.

Artemisia princeps (family Asteraceae) is a natural product broadly used as an antioxidative, hepatoprotective, antibacterial, and anti-inflammatory agent in East Asia. In the present study, eupatilin, the main constituent of Artemisia princeps, was investigated as an antihyperlipidemic agent. Eupatilin inhibited 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HCR), an enzyme that is a therapeutic target for hyperlipidemia, in an ex vivo assay using rat liver. In addition, oral administration of eupatilin significantly lowered the serum levels of total cholesterol (TC) and triglycerides (TG) in corn oil-induced and Triton WR-1339-induced hyperlipidemic mice. These results suggest that eupatilin can alleviate hyperlipidemia by inhibiting HCR.

Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice.

Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

Prevalence, characteristics, and risk of exacerbation in young patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Early identification of chronic obstructive pulmonary disease (COPD) in young individuals could be beneficial to attempt preventive interventions. The objective of this study was to investigate clinical features and outcomes of young individuals with COPD from the general population cohort. METHODS: We included individuals from the Korean National Health and Nutrition Examination Survey (KNHANES) with spirometry and identifiable smoking status. Young subjects with COPD were defined as aged between 40 and 50 years and had baseline forced expiratory volume in 1 s [FEV1]/forced vital capacity [FVC] ratio less than 0.7. Outcomes include the risk of exacerbation and medical expenses during 3 years of follow-up. RESULTS: Among 2236 individuals aged between 40 and 50 years, 95 (4.2%) had COPD, including 36 who were never-smokers and 59 who were ever-smokers. Approximately 98% of COPD subjects had mild to moderate airflow limitation. Inhaler treatment was given to only 6.3% patients in the COPD group. The risk of exacerbation for a 3-year period was analyzed using the never-smoker, non-COPD group as a comparator. Hazards ratio for exacerbation was 1.60 (95% confidence interval [CI] 0.18-14.20) in the never-smoker COPD group and 1.94 (95% CI 0.31-12.07) in the ever-smoker COPD group of young subjects. COPD related medical costs were not significantly different between non-COPD and COPD groups of young individuals. CONCLUSIONS: The risk of exacerbation showed an increasing trend in COPD patients regardless of smoking status compared to non-COPD. More attention to early identification and provision of preventive measures are needed to reduce disease progression and improve outcome.

Risk factors for early readmission after acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND AND AIMS: Patients discharged after treatment for acute exacerbation of chronic obstructive pulmonary disease (COPD) are at high risk for readmission. We aimed to identify the prevalence and risk factors for readmission. METHODS: We included 16,105 patients who had claimed their medical expenses from 1 May 2014 to 1 May 2016 after discharge from any medical facility in Korea, following treatment for acute exacerbation of COPD. We analysed the potential risk factors for readmission within 30 days of discharge. RESULTS: Readmission rate was 26.4% (3989 patients among 15,101 patients) and over 50% of readmissions occurred within 10 days of discharge. Approximately 57% of readmissions occurred due to respiratory causes. Major causes of readmission were COPD (27%), pneumonia (14.2%), and lung cancer (7.1%), in that order. Patients who were readmitted were male, had more comorbidities and were less frequently admitted to tertiary hospitals than those who were not readmitted. Risk factors for readmission within 30 days of discharge were male sex, medical aid coverage, longer hospital stay, longer duration of systemic steroid use during hospital stay, high comorbid condition index, and discharge to skilled nursing facility. CONCLUSION: Readmission occurred in approximately one-quarter of patients, and was associated with patient-related and clinical factors. Using these results, we can identify high-risk patients for readmission and precautions are needed to be taken before deciding on a discharge plan. Further research is needed to develop accurate tools for predicting the risk of readmission before discharge, and development and evaluation of an effective care programme for COPD patients are necessary.The reviews of this paper are available via the supplemental material section.

Clinical characteristics and economic burden of tuberculous-destroyed lung in Korea: a National Health Insurance Service-National Sample Cohort-based study.

BACKGROUND: Tuberculous destroyed lung (TDL) contributes to patient mortality via acute exacerbation and combined medical comorbidities. This study characterized the clinical characteristics and economic burden of patients with TDL using large scale database, Health Insurance Review and Assessment Service (HIRA) data. METHODS: We searched the HIRA national database to identify patients diagnosed with TDL from January 01, 2011 to December 31, 2015. The clinical characteristics of the patients were collected and the 5-year claims data were analyzed. RESULTS: In total, 645,031 patients (55% male, mean age, 59.6 years) were enrolled over the 5 years. During the study period, 98.5% of the patients visited a primary care clinic and 71.1% and 93.2% visited secondary and tertiary hospitals, respectively. Patients spent a median of 5 days for inpatient services, and were admitted to the hospital a median of 0.62±1.2 times per person annually. Annual total cost per person was $1,838 and half of the total cost was expended for inpatient services. About 68.9% of the patients were prescribed respiratory medications, and $12 million was paid. Oral bronchodilators (46.5%) and methylxanthine (35.2%) were used more frequently than inhaled corticosteroids (ICSs)/long-acting ß2 agonist (LABA) combination agents (11.6%) or inhaled long-acting muscarinic antagonists (LAMAs) (7.5%). CONCLUSIONS: TDL imposes a high medical economic burden in Korea. The estimated economic costs were mainly made up of inpatient services and outpatient medication prescriptions. Interventions to prevent acute disease exacerbations and progression of comorbid conditions should be accompanied to alleviate the clinical and economic burden of TDL.

Effects of PRELI in Oxidative-Stressed HepG2 Cells.

Protein of relevant evolutionary and lymphoid interest (PRELI) is known for preventing apoptosis by mediating intramitochondrial transport of phosphatidic acid. However, the role of PRELI remains unclear. This study has demonstrated functions of PRELI through PRELI-knockdown in hepatocellular carcinoma (HepG2) cells exposed to oxidative stress by hydrogen peroxide. Results show that PRELI has three functions in HepG2 cells with regard to oxidative stress. First, PRELI affects expressional regulation of SOD-1 and caspase-3 genes in HepG2 cells. PRELI knockdown HepG2 cells have shown up-regulation of caspase-3 and down-regulation of SOD-1. Second, PRELI suppresses mitochondrial apoptosis in HepG2 cells. Fluorescence intensity related to mitochondrial apoptosis in PRELI-knockdown HepG2 cells increased more than two-fold compared to normal HepG2 cells. Third, PRELI suppresses senescence of HepG2 cells with oxidative stress. PRELI knockdown HepG2 cells showed higher levels of senescence than normal HepG2 cells. These results suggest that PRELI is a crucial protein in the suppression of apoptosis in HepG2 cells in response to oxidative stress.

DISTINCTIVE LOCALIZATION OF GROUP 3 LATE EMBRYOGENESIS ABUNDANT SYNTHESIZING CELLS DURING BRINE SHRIMP DEVELOPMENT.

Despite numerous studies on late embryogenesis abundant (LEA) proteins, their functions, roles, and localizations during developmental stages in arthropods remain unknown. LEA proteins protect crucial proteins against osmotic stress during the development and growth of various organisms. Thus, in this study, fluorescence in situ hybridization was used to determine the crucial regions protected against osmotic stress as well as the distinctive localization of group 3 (G3) LEA(+) cells during brine shrimp development. Several cell types were found to synthesize G3 LEA RNA, including neurons, muscular cells, APH-1(+) cells, and renal cells. The G3 LEA(+) neuronal cell bodies outside of the mushroom body projected their axonal bundles to the central body, but those inside the mushroom body projected their axonal bundles toward the deutocerebrum without innervating the central body. The cell bodies inside the mushroom body received axons of the G3 LEA(+) sensory cells at the medial ventral cup of the nauplius eye. Several glands were found to synthesize G3 LEA RNA during the nauplius stages of brine shrimp, including the sinus, antennal I and II, salt, and three ectodermal glands. This study provides the first demonstration of the formation of G3 LEA(+) sinus glands at the emergence stages of brine shrimp. These results suggest that G3 LEA protein is synthesized in several cell types. In particular, specific glands play crucial roles during the emergence and nauplius stages of brine shrimp.

An exclusively dopamine secreting paraganglioma in the retroperitoneum: a first clinical case in Korea.

Exclusively dopamine producing retroperitoneal paragangliomas are extremely rare. We have experienced the first Korean case managed successfully based on the proper evaluation. A 26-year-old female patient came to our attention after the accidental detection of an adrenal mass. She had no symptoms and denied any family history. Laboratory evaluations were normal but serum dopamine (425 ng/L) and 24-hour urine dopamine levels (1,565.3 µg/day) were elevated. She underwent laparoscopic right adrenalectomy. Histopathological diagnosis was a paraganglioma. After operation, dopamine levels in serum and 24-hour urine dropped to 0.09 ng/L and 388.4 µg/day. Dopamine producing paraganglioma elicit no clinical symptoms. Only the dopamine level is elevated in serum and 24-hour urine samples. Surgical resection without using preoperative alpha blockage is the treatment of choice. The prognosis for patients with this tumor tends to be poor because the diagnosis is usually delayed due to lack of symptoms.

Hypocholesterolemic effect of sonication-killed Bifidobacterium longum isolated from healthy adult Koreans in high cholesterol fed rats.

We have previously reported that live Bifidobacterium longum SPM1207, a strain isolated from healthy adult Koreans, significantly reduced serum cholesterol in broth and rat. We here examined the effect of oral administration of sonication-killed B. longum SPM1207 on serum cholesterol in rats in order to investigate whether this killed strain could be utilized as a potent probiotics for human and animals. Dietary treatments consisted of 3 treatment groups of 24 rats each randomly assigned to either normal diet, high cholesterol diet and saline (HCS), or high cholesterol diet and sonication-killed B. longum SPM1207 (HCKB) for 3 weeks. Although HDL-cholesterol levels in the serum were not significantly (p > 0.05) different between HCKB rats and HCS rats, total and LDL-cholesterol levels in the serum were significantly (p < 0.05) less increased in HCKB (total: 177.71 mg/dL, LDL-: 60.50 mg/dL) rats when compared to HCS (total: 237.17 mg/dL, LDL-: 71.50 mg/dL) rats. AI was significantly (p < 0.05) lower in HCKB (4.95 mg/dL) rats when compared to HCS (9.22 mg/dL) rats. Body weight increase and relative liver weight were significantly (p < 0.05) lower in HCKB rats when compared to HCS rats. Over the time, high cholesterol diet caused dry feces accompanied by decreased fecal water content (66.00 to 61.94%) but sonication-killed B. longum SPM1207 administration increased fecal water content (71.58 to 74.25%). The results in the current study provide evidence that the sonication-killed cells of B. logum SPM1207 isolated from healthy adult Koreans have a greater potential to be used as a cholesterol-lowering agent. Furthermore, the current study suggest that this killed specific strain may play role in part in blocking the body weight increase and relieving or eliminating constipation.