Associations among sleep-disordered breathing, sleep quality, and lung cancer in Korean patients.

PURPOSE: Intermittent hypoxia and sleep fragmentation, two main features of sleep-disordered breathing (SDB), have been shown to increase the aggressiveness of lung cancer, mainly in animal and in vitro studies. However, the association between SDB and lung cancer has not been well described in human studies. In this study, we investigated the associations among SDB, sleep quality, and lung cancer in Korean patients. METHODS: Patients with histologically diagnosed lung cancer performed a home sleep apnea test. Sleep questionnaires including the Epworth Sleepiness Scale (ESS), Insomnia Severity Index, and Pittsburgh Sleep Quality Index were also administered. Clinical information related to lung cancer was collected during the study. RESULTS: Sixty-nine patients were enrolled, 31 of whom were poor sleepers. The overall prevalence of SDB was 57% and that of moderate to severe SDB was 27%. Underlying chronic obstructive pulmonary disease (COPD) and smoking history were significantly more frequent in patients with moderate to severe SDB compared to patients without or with mild SDB. No significant differences were observed in the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), or time with oxygen saturation < 90% (T90) according to cancer cell types, mutations, stages, and survival. However, small-cell lung cancer patients showed a trend toward higher AHI, ODI, and T90 values. CONCLUSION: The prevalence of SDB and proportion of poor sleepers were high in Korean patients with lung cancer. Paying more attention to sleep status may be helpful for patients with COPD, a smoking history, and small-cell lung cancer.

Association of Underlying Comorbidities and Sites of tuberculosis: an analysis using surveillance data.

BACKGROUND: Tuberculosis (TB) is a highly heterogeneous disease that can affect any organ. Extrapulmonary TB (EPTB) is more difficult to diagnose due to various clinical presentations. Depending on the characteristics of the patient, the involved site of TB may vary. However, data on clinical characteristics of EPTB are inconsistent and insufficient. This study aimed to identify the characteristics of patients with pulmonary TB (PTB) and EPTB and describe characteristic differences for each involved site. METHODS: We systemically collected data of TB patients included in the national surveillance system in South Korea from July 2018 to June 2019 and compared the characteristics of patients with EPTB with that of PTB. RESULTS: A total of 7674 patients with a mean age of 60.9 years were included. Among them, 6038 (78.7%) patients were diagnosed with PTB and 1636 (21.3%) with EPTB. In PTB group, the mean age (61.7 ± 18.7 vs. 57.8 ± 19.9) and proportion of male sex (63.3% vs. 50.1%) were higher, but the body mass index was lower (21.2 ± 3.4 vs. 22.7 ± 3.5) than that of the EPTB group. Prevalence of diabetes (20.5% vs. 16.9%) and chronic lung disease (5.1% vs. 2.9%) were higher in PTB group, meanwhile, those of chronic kidney disease (CKD) (2.7% vs. 5.4%) and long-term steroid use (0.4% vs. 1.0%) were higher in EPTB group. Abdominal TB was more prevalent in patients with chronic liver disease (odds ratio [OR]: 2.69, 95% CI: 1.52-4.74), and urogenital TB was more prevalent in patients with CKD (OR: 2.75, 95% CI: 1.08-6.99). CONCLUSIONS: We found that underlying comorbidities were closely associated with the location of TB development, and therefore, the possibility of EPTB should be carefully evaluated while monitoring for underlying disease in TB-endemic areas.

Increased Healthcare Delays in Tuberculosis Patients During the First Wave of COVID-19 Pandemic in Korea: A Nationwide Cross-Sectional Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems, consequently endangering tuberculosis (TB) control. We investigated delays in TB treatment among notified patients during the first wave of the COVID-19 pandemic in Korea. METHODS: We systemically collected and analyzed data from the Korea TB cohort database from January to May 2020. Groups were categorized as 'before-pandemic' and 'during-pandemic' based on TB notification period. Presentation delay was defined as the period between initial onset of symptoms and the first hospital visit, and healthcare delay as the period between the first hospital visit and anti-TB treatment initiation. A multivariate logistic regression analysis was performed to evaluate factors associated with delays in TB treatment. RESULTS: Proportion of presentation delay > 14 days was not significantly different between two groups (48.3% vs. 43.7%, P = 0.067); however, proportion of healthcare delay > 5 days was significantly higher in the during-pandemic group (48.6% vs. 42.3%, P = 0.012). In multivariate analysis, the during-pandemic group was significantly associated with healthcare delay > 5 days (adjusted odds ratio = 0.884, 95% confidence interval = 0.715-1.094). CONCLUSION: The COVID-19 pandemic was associated with healthcare delay of > 5 days in Korea. Public health interventions are necessary to minimize the pandemic's impact on the national TB control project.

Association of serum hemoglobin level with the risk of carotid plaque beyond metabolic abnormalities among asymptomatic adults without major adverse clinical events: a cross-sectional cohort study.

BACKGROUND: The serum hemoglobin (Hb) level is closely related to adverse clinical outcomes. However, data on the association of Hb levels with subclinical atherosclerosis beyond metabolic abnormalities are limited. METHODS: This study evaluated the association among serum Hb level, metabolic syndrome (MetS), and the risk of carotid plaque formation in asymptomatic adults without a history of major adverse clinical events. RESULTS: A total of 2560 participants (mean age: 60 ± 8 years, 32.9% men) were stratified into four groups based on Hb quartiles, as follows: ≤ 12.8 g/dL (group I), 12.9-13.6 g/dL (group II), 13.7-14.5 g/dL (group III), and ≥ 14.6 g/dL (group IV). The overall prevalence of MetS and carotid plaque was 37.2% and 33.4%, respectively. The prevalence of MetS increased with increasing Hb level (group I: 27.4% vs. group II: 35.9% vs. group III: 42.6% vs. group IV: 44.1%, p < 0.001). The prevalence of carotid plaque was 34.3%, 28.1%, 32.8%, and 39.5% in groups I, II, III, and IV, respectively. Univariate logistic regression analysis showed that MetS was associated with an increased risk of carotid plaque (odds ratio [OR] 1.568, 95% confidence interval [CI] 1.326-1.856, p < 0.001). Only group II showed a lower risk of carotid plaque than group I (OR 0.750, 95% CI 0.596-0.943, p = 0.014). Multiple logistic regression models showed consistent results after adjusting for clinical factors, including MetS and its individual components. CONCLUSION: Serum Hb level is associated with the risk of carotid plaque beyond MetS and its components in a relatively healthy adult population.

Independent association of serum uric acid levels with arterial stiffness in the absence of established cardiovascular disorders.

BACKGROUND: The impact of serum uric acid (SUA) on atherosclerosis has been suspected to be epiphenomenal owing to its close relationship with metabolic abnormalities. The aim of the present study was to evaluate the association between SUA levels and arterial stiffness in the absence of established cardiovascular (CV) disorders. METHODS: The relationship between SUA levels and brachial-ankle pulse wave velocity (baPWV) was examined in 353 asymptomatic adults (57 ± 8 years, 11.9% men) without established CV disorders defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥ 90 mmHg; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol <40 mg/dL; fasting glucose ≥126 mg/dL; body mass index ≥25.0 kg/m2 ; current smoking; and history of medication for hypertension, diabetes, and dyslipidemia. Subjects were stratified into four groups based on the quartiles of their SUA levels. RESULTS: Mean baPWV was significantly different in all groups: group I, 1320 ± 195 cm/s; group II, 1336 ± 195 cm/s; group III, 1404 ± 199 cm/s; and group IV, 1483 ± 248 cm/s (P < .001). SUA levels were significantly correlated with baPWV (r = .364) (P < .001). Multivariate linear regression analysis showed that SUA (ß: 32.93; 95% confidence interval [CI]: 18.99-54.87), together with age (ß: 11.44; 95% CI: 9.36-13.53) and systolic BP (ß: 8.98; 95% CI: 6.80-11.16), was significantly associated with baPWV (P < .001). CONCLUSIONS: High SUA levels have an independent association with increased arterial stiffness even in subjects without established CV disorders.

Histiocytic pleural effusion: the strong clue to malignancy.

BACKGROUND: There have been many studies on the clinical characteristics of neutrophilic, lymphocytic, and/or eosinophilic pleural effusion. While caring for patients with pleural effusion, we found that histiocytic pleural effusion (HisPE) was not uncommon. However, few studies have explored HisPE. The purpose of the present study was to determine the clinical characteristics and etiologies of HisPE. METHODS: In this retrospective study, HisPE was defined as pleural fluid white blood cells comprised of ≥ 50% histiocytes. Using a clinical data warehouse, patients with HisPE among all patients aged >18 years who underwent thoracentesis and pleural fluid analysis between January 2010 and December 2019 at Ulsan University Hospital were enrolled. A total of 295 (9.0%) of 3279 patients who underwent thoracentesis were identified as HisPE patients. Among them, 201 with exudative HisPE were included. Clinical characteristics and etiologies were extracted from medical records and analyzed. RESULTS: Among the 201 patients with exudative HisPE, the major causes were malignant pleural effusion (n = 102 [50.7%]), parapneumonic effusion (n = 9 [4.5%]), and tuberculous pleurisy (n = 9 [4.5%]). In the 102 patients with malignant pleural effusion, the main types of cancer were lung (n = 42 [41.2%]), breast (n = 16 [15.7%]), and stomach cancer (n = 11 [10.8%]). Among lung cancers, adenocarcinoma (n = 34 [81.0%]) was the most common histology. CONCLUSIONS: The leading cause of exudative HisPE was malignancy, particularly lung cancer. Physicians should consider the possibility of malignant disease if histiocytes are predominantly present in pleural effusion.

Effects of chronic intermittent hypoxia caused by obstructive sleep apnea on lipopolysaccharide-induced acute lung injury.

AIM OF THE STUDY: Obstructive sleep apnea (OSA) is a common disease associated with significant morbidity and mortality. Sleep quality is an important issue; some patients with acute lung injury (ALI) have underlying OSA. However, the potential influences of OSA on ALI have not been reported until now. In this study, we evaluated the impact of preceding intermittent hypoxia (IH), a typical characteristic of OSA, on lipopolysaccharide (LPS)-induced ALI in a mouse model. METHODS: C57BL/6J mice were randomly divided into four groups: room air-control (RA-CTL), intermittent hypoxia-control (IH-CTL), room air-lipopolysaccharide (RA-LPS), and intermittent hypoxia-lipopolysaccharide (IH-LPS) groups. The mice were exposed to RA or IH (20 cycles/h, FiO2 nadir 7 ± 0.5%, 8 h/day) for 30 days. The LPS groups received intratracheal LPS on day 28. RESULTS: The IH-LPS group tended to exhibit more severe inflammation, fibrosis, and oxidative stress compared to the other groups, including the RA-LPS group. Total cell, neutrophil, and eosinophil counts in bronchoalveolar lavage fluid increased significantly in the IH-LPS group compared to the RA-LPS group. Compared to the RA-LPS group, the hydroxyproline level increased significantly in the IH-LPS group. In addition, the IH-LPS group exhibited significantly more terminal deoxynucleotidyl transferase dUTP nick end labeled-positive cells compared to the RA-LPS group. CONCLUSIONS: We found that prior IH may negatively impact LPS-induced ALI in a mouse model. This result suggests that ALI in patients with OSA may be more of a concern. Further research into the mechanisms underlying the effects of IH on ALI is needed.

Effects of long term normobaric hyperoxia exposure on lipopolysaccharide-induced lung injury.

Purpose/Aim of the study: Prolonged exposure to hyperoxia can cause injury to normal lung tissue. However, patients with acute hypoxic respiratory failure are frequently exposed to very high oxygen levels. This study investigated the effects of long term normobaric hyperoxia exposure in a mouse model of acute severe lung injury (SLI).Meterials and Methods: C57BL/6J mice were injected intratracheally with lipopolysaccharide (LPS, 4 mg/kg) to induce acute lung injury. After 2 h, mice were divided into two groups, and then exposed to room air or hyperoxic conditions for 48 h. Animals in the hyperoxia group were placed within their cages in a Plexiglass chamber with an atmosphere of 95% O2 maintained constant using an oxygen analyzer. After exposure to normoxia (N) or hyperoxia (H) for 48 h, the left lungs were collected for tissue paraffin block or oxidative stress assay. One lobe of the right lung was collected for lung/body weight ratio. The lung injury score and the mean linear intercept were evaluated in hematoxylin and eosin -stained lungs. The biochemical tests were performed by using ELISA assay.Results: Lung injury scoring, lung/body weight, and mean linear intercept were not significantly different between the N + LPS (NLPS) and H + LPS (HLPS) groups. Similar trends were observed in hydroxyproline and transforming growth factor-ß (TGF-ß) levels. Total cell and neutrophil counts in bronchoalveolar lavage fluid showed no significant differences between NLPS and HLPS groups. Histological analyses demonstrated more severe lung injury and fibrosis in the NLPS group than in the HLPS group. In addition, interleukin (IL)-1ß was significantly decreased in the HLPS group compared to the NLPS group. Other inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and IL-6, showed similar trends. The malondialdehyde (MDA) level was significantly lower in the HLPS group than in the NLPS group.Conclusions: Exposure to hyperoxia did not augment lung injury in the LPS-induced lung injury model, and some indicators even showed better outcomes. These results suggest that long-term high-oxygen therapy in patients with SLI has low risk of lung injury.

Association between triglyceride glucose index and obstructive sleep apnea risk in Korean adults: a cross-sectional cohort study.

BACKGROUND: Triglyceride glucose (TyG) index is a reliable marker of insulin resistance, which is linked to obstructive sleep apnea (OSA). However, the relationship between TyG index and OSA has not been adequately assessed. This study aimed to evaluate the association between TyG index and OSA. METHODS: TyG index was assessed in 180 (mean age: 48.6 ± 13.8 years; 73.9% male) consecutive Korean adults with suspected OSA admitted to the sleep clinic at St. Paul's Hospital between 2010 and 2012. The occurrence of more than 5 apnea-hypopnea index (AHI) events/h was used to define OSA. TyG index was calculated using the following equation: In [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. All participants were grouped according to TyG index tertiles. Multivariate logistic regression analysis was used to determine factors associated with increased OSA risk. RESULTS: The overall prevalence of OSA in study participants was determined to be 83.9%. The prevalence of OSA increased (I [lowest]: 71.6%; II: 88.7%; III [highest]: 91.4%), and lowest peripheral oxygen saturation (SpO2) levels decreased (I: 83.3 ± 8.5%; II: 79.9 ± 8.7%; III: 79.0 ± 8.3%), as TyG index tertile increased (P < 0.05). TyG index was correlated with AHI (r = 0.179) and lowest SpO2 (r = - 0.188) (P < 0.05, respectively). Univariate linear regression analysis revealed an association between TyG and AHI (ß = 10.084; P = 0.016). Multivariate logistic regression analysis showed that TyG index (odds ratio [OR]: 3.348; 95% confidence interval [CI]: 1.081-10.372), age ≥ 55 years (OR: 5.426; 95% CI: 1.642-17.935), and obesity (OR: 3.801; 95% CI: 1.468-9.842) were associated with increased OSA risk (all P < 0.05). The optimal TyG index cut-off value for predicting OSA was 8.83 (sensitivity: 61.6%; specificity: 69.0%; area under the curve: 0.688; P = 0.001). The predictive value of the OSA cut-off value improved when age ≥ 55 years and obesity were considered. CONCLUSION: Increased TyG index was independently associated with increased OSA risk.

Chronic intermittent hypoxia induces liver fibrosis in mice with diet-induced obesity via TLR4/MyD88/MAPK/NF-kB signaling pathways.

Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model. Inflammatory and oxidative stress markers, TLR4, MyD88, Toll/interleukin-1-receptor-domain-containing adaptor-inducing interferon-ß (TRIF), I-κB, NF-κB, p38 MAPK, c-JNK, and ERK activation, were measured in the serum and liver. As a result, α1(I)-collagen mRNA was significantly higher in DIO mice exposed to CIH than in the control groups. CIH mice exhibited liver fibrosis and significantly higher protein expression of TLR4, MyD88, phosphorylated (phospho-) I-κB, and phospho-ERK1/2 activation in the liver, and higher expression of NF-κB than that in the controls. TRIF, p38 MAPK, and JNK activation did not differ significantly between groups. We conclude that CIH in DIO mice leads to liver fibrosis via TLR4/MyD88/MAPK/NF-kB signaling pathways.

Long-term azithromycin ameliorates not only airway inflammation but also remodeling in a murine model of chronic asthma.

OBJECTIVES: We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling. METHODS: Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated. RESULTS: Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group. CONCLUSIONS: This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.

The apoptotic effect of simvastatin via the upregulation of BIM in nonsmall cell lung cancer cells.

PURPOSE: Statins are known to have pleiotropic effects that induce cell death in certain cancer cells. BIM is a member of the bcl-2 gene family, which promotes apoptotic cell death. This study investigated the hypothesis that simvastatin has pro-apoptotic effects in epidermal growth factor receptor (EGFR)-mutated lung cancer cell lines via the upregulation of the expression of the BIM protein. MATERIALS AND METHODS: The cytotoxic effects of simvastatin on gefitinib-sensitive (HCC827, E716-A750del) and -resistant (H1975, T790M + L858R) nonsmall cell lung cancer (NSCLC) cells were compared. Cell proliferation and expression of apoptosis-related and EGFR downstream signaling proteins were evaluated. Expression of BIM was compared in H1975 cells after treatment with simvastatin or gefitinib. SiRNA-mediated BIM depletion was performed to confirm whether the cytotoxicity of simvastatin was mediated by the expression of BIM. RESULTS: H1975 cells showed significantly reduced viability compared with HCC827 cells after treatment with simvastatin (2 µM) for 48 hours. In simvastatin-treated H1975 cells, expression of pro-apoptotic proteins was increased and the phosphorylation of ERK 1/2 (p-ERK 1/2) was reduced. Expression of BIM was suppressed by gefitinib (1 µM) treatment in H1975 cells, but it was significantly increased by treatment with simvastatin. BIM depletion by siRNA transfection enhanced the viability of H1975 cells that received simvastatin treatment and increased their expression of anti-apoptotic proteins. CONCLUSIONS: Simvastatin restored the expression of BIM to induce apoptotic cell death in NSCLC cells harboring an EGFR-resistant mutation. Our study suggests the potential utility of simvastatin as a BIM-targeted treatment for NSCLC.

Knowledge and Attitudes Toward Obstructive Sleep Apnea Among Korean Pulmonologists: A Nationwide Survey.

BACKGROUND: Obstructive sleep apnea (OSA) significantly impacts cardiovascular, metabolic, and respiratory health. In Korea, OSA patients are treated by specialists in internal medicine, otolaryngology, neurology, and psychiatry, but the participation rate of pulmonologists in OSA management is relatively low compared to other specialties. This study investigated the knowledge and attitudes about OSA among Korean pulmonologists. MATERIALS AND METHODS: An online survey was conducted, targeting respiratory specialists listed in the Korean Academy of Tuberculosis and Respiratory Diseases directory. The survey used the validated "Obstructive Sleep Apnea Knowledge and Attitudes" (OSAKA) questionnaire, which consists of questions about knowledge and attitudes on OSA. To maximize participation, email invitations were sent three times to the target audience. RESULTS: Out of 634 queried pulmonologists, 127 (20%) responded to the survey. The mean age of respondents was 45.4 ± 8.6 years. The respondents' years of specialty acquisition ranged from the 1980s to the 2010s. Additionally, 74 (58.3%) held a doctor's degree, and 96 (75.6%) worked in hospitals with a sleep center. Furthermore, 71 (55.9%) of the pulmonologists reported having experience with OSA patients. Pulmonologists with experience managing OSA patients had significantly higher knowledge and attitude scores compared to those without such experience. Interestingly, older respondents and those who completed their pulmonology training earlier had higher attitude scores. In addition, the knowledge score significantly correlated with responses to the five items of the attitude questionnaire. CONCLUSION: This study provides valuable insights into the knowledge and attitudes of Korean pulmonologists regarding OSA. The findings indicate that their knowledge levels are comparable to or better than those in previous studies. These results underscore the need for targeted educational programs and practical training, especially for younger pulmonologists, to enhance their proficiency in managing OSA and to encourage a more active role in its treatment.

Protective effect of pravastatin on lipopolysaccharide-induced acute lung injury during neutropenia recovery in mice.

Although neutropenia recovery is associated with deterioration of preexisting acute lung injury (ALI), there are few reports of the preventive strategies. Statins have been found to attenuate inflammatory responses in murine models of lipopolysaccharide (LPS)-induced ALI. The aim of this study was to determine whether pravastatin could attenuate ALI during neutropenia recovery in mice. Cyclophosphamide was administered to mice to induce neutropenia. Mice were given intratracheal LPS 7 days after cyclophosphamide administration, after which pravastatin was administered by intraperitoneal injection. In order to study the effects of pravastatin, mice were killed on day 5. Pravastatin attenuated the pulmonary edema and histopathological changes of LPS-induced lung injury. The accumulation of neutrophils and the concentrations of TNF-α, IL-1ß, IL-6, and MPO in BAL fluids were also effectively inhibited by pravastatin. The expression levels of Toll-like receptor 4, nuclear factor kappa B, tumor growth factor-ß and matrix metalloproteinase-9 were significantly reduced by pravastatin. Taken together, pravastatin significantly attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the potential of pravastatin in the treatment of ALI during neutropenia recovery.

Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery.

INTRODUCTION: Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of preexisting acute lung injury (ALI). The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in mice. METHODS: Mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry weight ratio and protein levels in the BAL fluid or lung tissue were determined. RESULTS: Treatment with imatinib or nilotinib significantly attenuated the LPS-induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and myeloperoxidase in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet-derived growth factor receptor-ß and c-KIT in imatinib or nilotinib group were significantly lower than LPS group. CONCLUSIONS: Our data indicated that imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery.

Cluster analysis categorizes five phenotypes of pulmonary tuberculosis.

Tuberculosis (TB) has a heterogeneous phenotype, which makes it challenging to diagnose. Our study aimed to identify TB phenotypes through cluster analysis and compare their initial symptomatic, microbiological and radiographic characteristics. We systemically collected data of notified TB patients notified in Korea and constructed a prospective, observational cohort database. Cluster analysis was performed using K-means clustering, and the variables to be included were determined by correlation network. A total of 4,370 subjects with pulmonary TB were enrolled in the study. Based on the correlation network, age and body mass index (BMI) were selected for the cluster analysis. Five clusters were identified and characterised as follows: (1) middle-aged overweight male dominance, (2) young-aged relatively female dominance without comorbidities, (3) middle-aged underweight male dominance, (4) overweight elderly with comorbidities and (5) underweight elderly with comorbidities. All clusters had distinct demographic and symptomatic characteristics. Initial microbiologic burdens and radiographic features also varied, including the presence of cavities and bilateral infiltration, which reflect TB-related severity. Cluster analysis of age and BMI identified five phenotypes of pulmonary TB with significant differences at initial clinical presentations. Further studies are necessary to validate our results and to assess their clinical implications.

Time delays and risk factors in the management of patients with active pulmonary tuberculosis: nationwide cohort study.

Estimating the time delay and identifying associated factors is essential for effective tuberculosis control. We systemically analysed data obtained from the Korea Tuberculosis Cohort in 2019 by classifying delays as presentation and healthcare delays of pulmonary tuberculosis (PTB). Of 6593 patients with active PTB, presentation and healthcare delays were recorded in 4151 and 5571 patients, respectively. The median presentation delay was 16.0 (5.0-40.0) days. Multivariable logistic regression analysis showed that longer presentation delays were associated with neuropsychiatric disease [adjusted odds ratio (OR) 2.098; 95% confidence interval (CI) 1.639-2.687; p < 0.001] and heavy alcohol intake (adjusted OR 1.505; 95% CI 1.187-1.907; p < 0.001). The median healthcare delay was 5.0 (1.0-14.0) days. A longer healthcare delay was associated with malignancy (adjusted OR 1.351; 95% CI 1.069-1.709; p = 0.012), autoimmune disease (adjusted OR 2.445; 95% CI 1.295-4.617; p = 0.006), and low bacterial burden manifested as an acid-fast bacillus smear-negative and tuberculosis polymerase chain reaction-negative status (adjusted OR 1.316; 95% CI 1.104-1.569; p = 0.002). Active case-finding programmes need to focus on patients with heavy alcoholism or neuropsychiatric diseases. To ensure early PTB detection, healthcare providers must carefully monitor patients with malignancy, autoimmune disease, or a high index of suspicion for PTB.

Additional Usefulness of Bronchoscopy in Patients with Initial Microbiologically Negative Pulmonary Tuberculosis: A Retrospective Analysis of a Korean Nationwide Prospective Cohort Study.

Purpose: Bronchoscopy is widely used for microbiological diagnosis of patients with minimal sputum production. However, the usefulness of bronchoscopy in patient groups who benefit from subsequent microbiological confirmation has not been established. Patients and Methods: We retrospectively analyzed Korean tuberculosis (TB) cohort data from September 2018 to October 2019 to evaluate the usefulness of bronchoscopy in patients with microbiologically negative pulmonary TB (based on initial sputum polymerase chain reaction and culture results). The primary outcome was the proportion of microbiological diagnoses made after bronchoscopy. Secondary outcomes were the predictors of microbiological confirmation and the percentage of additional resistance detection after bronchoscopy. Results: A total of 5194 patients were diagnosed with pulmonary TB, 937 of whom were microbiologically negative for pulmonary TB based on the initial sputum findings. Of these, 319 patients underwent bronchoscopy, and further microbiological confirmation was achieved in 157 (49.1%) patients. The predictors of microbiological confirmation after bronchoscopy were age >65 years, female sex, and low body mass index (BMI). The rate of additional resistance detection was 10.5% (multidrug resistant/rifampin-resistant 3.8%; isoniazid-resistant 5.7%). Conclusion: Bronchoscopy can be used for the detection of resistant pathogens. Bronchoscopy should be considered for microbiologically negative pulmonary TB in women aged >65 years and with low BMI for subsequent microbiological confirmation.

Validity and reliability of the Korean version of the Wisconsin Smoking Withdrawal Scale.

BACKGROUND/AIMS: This study evaluated the validity and reliability of the Korean version of the Wisconsin Smoking Withdrawal Scale (WSWS-K) for use in clinical practice and research on Korean smokers. METHODS: The Wisconsin Smoking Withdrawal Scale was translated into Korean and then back-translated into English. The authors reviewed the translation and back-translation and approved the final questionnaire draft. The validity and reliability of the WSWS-K were evaluated based on data collected from 300 participants. Construct validity was evaluated with a confirmatory factor analysis. Criterion-related validity was assessed by examining the relationships between the subscales of the WSWS-K and the matched items of the Korean version of the Minnesota Nicotine Withdrawal Scale (MNWS-K). RESULTS: The participants were predominantly male (93.6%) and the mean age was 59.23 ± 15.19 years. The confirmatory factor analysis revealed that fit indices (namely, the goodness-of-fit index, adjusted goodness-of-fit index, comparative fit index, and the normed fit index) exceeded or approached 0.9. Cronbach's alpha for the entire scale was 0.87. The total score of the WSWS-K had a statistically significant positive correlation with that of the MNWS-K (Pearson's correlation coefficient, 0.768; p < 0.01). Additionally, we performed linear regression between the WSWS-K and MNWS-K scores after adjusting for age, gender, comorbidity, and smoking history. After this adjustment, the p value of the WSWS- K was < 0.001. CONCLUSION: The WSWS-K had satisfactory validity and reliability. The WSWS- K can be used with acceptable validity and reliability in research and clinical evaluation of Korean smokers.

The Influence of Gastroesophageal Reflux Disease on Daytime Sleepiness and Depressive Symptom in Patients With Obstructive Sleep Apnea.

BACKGROUND/AIMS: As there is insufficient evidence for a relationship between gastroesophageal reflux disease (GERD) and obstructive sleep apnea (OSA), we investigated whether OSA diagnosed by polysomnography (PSG) is related to GERD. METHODS: A total of 402 subjects was evaluated. Overnight PSG was performed and a few questionnaires on GERD, anxiety, depression, and daytime sleepiness were administered. An apnea-hypopnea index < 5 was the classification criterion for subjects without OSA. Subjects with heartburn or acid regurgitation at least once a week were classified as having GERD. RESULTS: Among the 402 subjects, 318 had OSA and 84 did not. The prevalence of GERD was 12.9% among patients with OSA and 10.7% among those without (P = 0.590). The prevalence of GERD did not correlate with OSA severity (P = 0.474). Patients with OSA with GERD had higher Stanford Sleepiness Scale (P = 0.004), Epworth Sleepiness Scale (P = 0.001), and depression (P < 0.001) scores than patients with OSA without GERD. Subjects with nocturnal gastroesophageal reflux symptoms had a higher body mass index, waist-to-height ratio, and waist circumference-to-height index than those without symptoms. Multiple logistic regression showed that higher Epworth Sleepiness Scale and depression scores were independent factors associated with GERD in patients with OSA. CONCLUSIONS: The prevalence of GERD in patients with OSA was 12.9%. The prevalence of GERD did not correlate with OSA severity. Daytime sleepiness and depression seem to be associated with GERD in patients with OSA, while nocturnal reflux symptoms seem to be related to obesity in OSA.