Background: Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea. Methods: We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients’ electronic medical records were reviewed to identify clinical characteristics. Results: During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m 2 .Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754–18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439–35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321–37.357), and combined blood stream infection (OR, 7.092;95% CI, 1.061–18.181) were identified as independent predictors of mortality in total patients.Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group.The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m 2 ), and the one remaining patient died from a secondary infection. Conclusion About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m2 ) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.

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.

Background/Aims: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a key role in Th2-mediated inflammation, both directly by promoting the proliferation of naïve CD4 Th2 cells, and indirectly by activating dendritic cells (DCs). TSLP-activated DCs induce the expansion of chemoattractant receptor homologous molecule expressed on Th2 (CRTH2)+ CD4+ Th2 memory cells, which undergo a Th2 response and express prostaglandin D2 (PGD2) synthase. CRTH2, a PGD2 receptor, is a selective Th2-cell surface marker. We investigated the effects of an anti-TSLP antibody (Ab) and a CRTH2 antagonist, as well as their mechanisms of action, in a mouse model of acute asthma. Methods: BALB/c mice were sensitized and challenged with ovalbumin. We then evaluated the effects of the administration of an anti-TSLP Ab either alone or together with a CRTH2 antagonist on cell counts, Th2 cytokine levels in bronchoalveolar fluid, and the levels of epithelium-derived cytokines such as TSLP, interleukin (IL) 33, and IL-25 in lung homogenates, as well as airway hyper-responsiveness (AHR). Results: Anti-TSLP Ab and the CRTH2 antagonist significantly attenuated eosinophilic airway inflammation, AHR, and the expression of Th2 cytokines. The expression of GATA-3 and the levels of IL-33 and IL-25 in lung tissues were affected by the combined anti-TSLP and CRTH2 antagonist treatment. Conclusions These results suggest that the dual blockade of TSLP and CRTH2 may serve as an effective treatment target for eosinophilic asthma.

Background/Aims: Many chronic obstructive pulmonary disease (COPD) patientshave physical limitations. We investigated EuroQol five-dimensions five-level (EQ-5D-5L) of COPD patients to assess quality of life, and assessed indirect burden including time expenditure to visit doctor, home care rate, and caregiver related burden. Methods: We recruited 355 COPD patients according to severity of airflow limitationthat severity was set at 10% mild, 40% moderate, 30% severe, and 20% very severe in two primary and 11 secondary/tertiary hospitals. Eligible patients were aged ≥ 40 years, who have been diagnosed with COPD for more than 1 year. Patients were recruited between June 2015 and October 2016. Results: The quality of life tended to decline with age, from mild to very severe impairment, as revealed by the EQ-5D-5L scores and the EQ visual analog scale.Family caregivers accompanied 22.6% of patients who visited outpatient clinics,and 25% of stage IV COPD patients. During emergency visits and hospitalization,this figure increased to > 60%. The home care rates were 28.5% for stage I patients, and 34.4, 31.8, and 52% for stage II to IV patients, respectively. The percentage of caregivers who stopped working was 13.6%. The EQ-5D index was strongly associated with the dyspnea scale (r = –0.64, p < 0.001). The average required time to see a doctor and visit the pharmacy was 154 minutes. Conclusions In patients with COPD, the EQ-5D index decreased and disease-relatedhome caregiving increased with airflow limitation. We considered the caregiver-related burden when making a strategy for COPD managemen

BACKGROUND/AIMS: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. METHODS: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. RESULTS: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. CONCLUSIONS: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.
Adult ; Dyspnea ; Hematologic Neoplasms ; Humans ; Immunocompromised Host* ; Logistic Models ; Organ Transplantation ; Pneumocystis jirovecii* ; Pneumocystis* ; Pneumonia ; Pneumonia, Pneumocystis ; Polymerase Chain Reaction* ; Prevalence ; Retrospective Studies ; Risk Factors ; Transplants

BACKGROUND/AIMS: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. METHODS: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. RESULTS: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. CONCLUSIONS: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.
Adult ; Dyspnea ; Hematologic Neoplasms ; Humans ; Immunocompromised Host* ; Logistic Models ; Organ Transplantation ; Pneumocystis jirovecii* ; Pneumocystis* ; Pneumonia ; Pneumonia, Pneumocystis ; Polymerase Chain Reaction* ; Prevalence ; Retrospective Studies ; Risk Factors ; Transplants

BACKGROUND: Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion. METHODS: PC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions. RESULTS: Compared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells. CONCLUSION: Repeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.
Apoptosis ; Blotting, Western ; Brain ; Caspase 3 ; Cell Death* ; Cell Survival ; Cognition Disorders ; Eagles ; Glucose* ; Hypoglycemia ; Neurons ; Phosphatidylinositol 3-Kinase ; Reperfusion ; Reperfusion Injury ; Transcription Factors*

BACKGROUND/AIMS: Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated with fluticasone and/or nilotinib intranasally during the OVA challenge. RESULTS: Mice chronically exposed to OVA developed eosinophilic airway inflammation and showed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Both fluticasone and nilotinib attenuated airway smooth muscle thickening. However, only nilotinib suppressed fibrotic changes, demonstrating inhibition of collagen deposition. Fluticasone reduced pro-inflammatory cells, such as eosinophils, and several cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, induced by repeated OVA challenges. On the other hand, nilotinib reduced transforming growth factor β1 levels in bronchoalveolar lavage fluid and inhibited fibroblast proliferation significantly. CONCLUSIONS: These results suggest that fluticasone and nilotinib suppressed airway remodeling in this chronic asthma model through anti-inflammatory and anti-fibrotic pathways, respectively.
Adrenal Cortex Hormones ; Airway Remodeling ; Animals ; Asthma* ; Bronchoalveolar Lavage Fluid ; Collagen ; Cytokines ; Eosinophils ; Female ; Fibroblasts ; Fluticasone* ; Hand ; Humans ; Inflammation ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Mice ; Muscle, Smooth ; Ovalbumin ; Ovum ; Protein-Tyrosine Kinases ; Receptors, Platelet-Derived Growth Factor ; Transforming Growth Factors

BACKGROUND: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. MATERIALS AND METHODS: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. RESULTS: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.
Antiviral Agents ; Aspartate Aminotransferases ; Coronavirus Infections* ; Disease Outbreaks ; Dyspnea ; Extracorporeal Membrane Oxygenation ; Fever ; Humans ; Hypotension ; Leukocytosis ; Leukopenia ; Lung Diseases ; Middle East Respiratory Syndrome Coronavirus ; Middle East* ; Mortality ; Pneumonia ; Polymerase Chain Reaction ; Republic of Korea* ; Respiration, Artificial ; Thrombocytopenia

BACKGROUND: In vitro experiments using only beta-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially alpha- and beta-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with alpha- and beta-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets. METHODS: alpha TC-6 cells and beta TC-1 cells were maintained in Dulbecco's Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5x10(5)) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS). RESULTS: alpha TC-6 and beta TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. beta TC-1 cells showed both beta-beta and beta-alpha cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than beta TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for beta-cells alone (P=0.04). Compared to islets, the alpha-/beta-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09). CONCLUSION: alpha TC-6 and beta TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.
Cell Culture Techniques ; Coculture Techniques* ; Endocrine Cells ; Glucagon ; Glucose ; Immunoassay ; Insulin ; Islets of Langerhans