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ObjectiveAcute respiratory distress syndrome (ARDS) presents a global health challenge, characterized by significant morbidity and mortality. However, the role of natural killer T (NKT) cells in human ARDS remains poorly understood. Therefore, this study explored the numerical and functional status of NKT cells in patients with ARDS, examining their clinical relevance and interactions with macrophages and fibroblasts during various stages of the syndrome.MethodsPeripheral blood from 40 ARDS patients and 30 healthy controls was analyzed, with paired samples of peripheral blood and bronchoalveolar lavage fluid (BALF) from seven ARDS patients. We measured levels of NKT cells, cytokines, CD69, programmed death-1 (PD-1), and annexin-V using flow cytometry, and extracellular matrix (ECM) protein expression using real-time PCR.ResultsARDS patients exhibited decreased circulating NKT cells with elevated CD69 expression and enhanced IL-17 production. The reduction in NKT cells correlated with PaO2/FiO2 ratio, albumin, and C-reactive protein levels. Proliferative responses to α-galactosylceramide (α-GalCer) were impaired, and co-culturing NKT cells with monocytes or T cells from ARDS patients resulted in a reduced α-GalCer response. Increased and activated NKT cells in BALF induced proinflammatory cytokine release by macrophages and ECM protein expression in fibroblasts.ConclusionARDS is associated with a numerical deficiency but functional activation of circulating NKT cells, showing impaired responses to α-GalCer and altered interactions with immune cells. The increase in NKT cells within BALF suggests their role in inducing inflammation and remodeling/fibrosis, highlighting the potential of targeting NKT cells as a therapeutic approach for ARDS.

Abstract In this study, we aimed to investigate the feasibility of serum Krebs von den Lungen-6 (KL-6) as a potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited patients with lung cancer in whom KL-6 was measured to differentiate between pneumonia and ILD (category 1), diagnose and assess the severity of suspicious ILD (category 2), or evaluate baseline levels before cancer treatment (category 3). Among 1,297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 195 patients. In categories 1–2, median KL-6 level was higher in drug-induced ILD or acute exacerbation of underlying ILD than in no ILD or radiation-induced pneumonitis, and it was correlated with the severity of TR-ILD. High KL-6 level (cut-off: > 436U/mL) was an independent risk factor for severe TR-ILD, and low KL-6 level with high procalcitonin level (> 0.5 ng/mL) could exclude severe TR-ILD. Patients with severe TR-ILD had worse overall survival than those without, whereas high baseline KL-6 level was associated with worse survival, especially in patients without severe TR-ILD. Therefore, serum KL-6 may be a surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspected ILD and before lung cancer treatment.

BackgroundHyperuricemia is common during tuberculosis (TB) treatment, especially in association with pyrazinamide (PZA). This study investigated the relationship between major adverse cardiovascular events (MACEs) and hyperuricemia during TB treatment.MethodsWe conducted a single-center retrospective cohort study. From January 2010 through June 2017, we assessed all consecutive TB patients at Chonnam National University Hospital in South Korea. Hyperuricemia was defined as serum uric acid levels exceeding 7.0 mg/dL (men) and 6.0 mg/dL (women).ResultsOf the 1,143 patients included, PZA was administered to 1,081 (94.6%), and hyperuricemia was detected in 941 (82.3%). Eight patients experienced MACEs. Multivariate analysis using logistic regression indicated that prior ischemic heart disease was associated with MACE development (OR,14.087; 95% CI,3.304-60.061; P < 0.000), while hyperuricemia was not (OR, 1.505; 95% CI, 0.184-12.299; P = 0.703). For patients without drug-resistant TB, the absence of hyperuricemia was associated with higher mortality (OR, 2.609; 95% CI, 1.066-6.389; P = 0.036), whereas hyperuricemia was associated with less worse outcomes (OR,0.316; 95% CI,0.173-0.576; P < 0.000).ConclusionsAlthough most patients treated with PZA developed hyperuricemia, it was not associated with MACE development. Hyperuricemia during TB treatment was associated with better outcomes, possibly due to consistent adherence to TB treatment.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms, but can cause a chronic pulmonary infection in some patients. Therefore, there could be host factors susceptible to this disease. A structural lung disease including damages of lungs caused by previous respiratory infection has been suggested as a host factor. Here we presented a case of NTM pulmonary disease which developed in a structural lung disease caused by a rare congenital lung disease. A 46-year-old male, was transferred to our hospital with an unexpandable lung after a closed thoracostomy due to spontaneous pneumothorax. His chest computed tomography showed an absence of left pulmonary artery at the time of admission. Mycobacterial culture in sputum, bronchial washing fluid, and pleural fluid showed the growth of NTM. Mycobacterium intracellulare was isolated from all positive cultures in the specimens. Combinations of drugs for M. intracellulare pulmonary disease including azithromycin, rifampin, and ethambutol were administered for 16 months. Amikacin intra venous treatment used for 6 months after treatment initiation. Culture conversion was achieved at 4 months of treatment. There was no evidence of recurrence of NTM pulmonary disease for 6 months after treatment. In conclusion, patients who have structural lung disease need to be careful monitoring about development of NTM pulmonary disease.

COVID-19 can lead to pulmonary complications, including organizing pneumonia. Steroids are essential in treating post-COVID-19 organizing pneumonia. However, research on the clinical benefits of initiating steroid treatment early for this condition is limited. To investigate the steroid initiation time in its association with treatment duration and corticosteroid dose for treating post-COVID-19 organizing pneumonia, we analyzed the data of 91 patients with post-COVID-19 organizing pneumonia at Chonnam National University Hospital between October 2020 and December 2022. Patients were categorized into early and late groups based on time from COVID-19 diagnosis to steroid initiation time for organizing pneumonia. The mean time interval between COVID-19 infection and steroid initiation time for treating organizing pneumonia, was 18.4±8.6 days. Within the early treatment group (treatment initiated <18.4 days after COVID-19), which included 55 patients, the mean duration of steroid treatment was 43.1±18.3days. In contrast, the late treatment group (initiated ≥18.4 days after COVID-19), which consisted of 36 patients, had a longer mean duration of steroid treatment 59.1±22.6 days) (p<0.01). Regarding corticosteroid dosing, the early treatment group had an average dosage of 0.5±0.3 mg/kg/day, in contrast to the late group, which averaged 0.8±0.3 mg/kg/day (p<0.01). Regression analysis showed steroid initiation time significantly influenced treatment duration (β=0.80, p<0.01) and dosage (β=0.03, p<0.01). The clinical benefits of early steroid treatment for post-COVID-19 organizing pneumonia may lie in its association with reduced steroid treatment duration and dosage. [ABSTRACT FROM AUTHOR]

Air embolism is a rare, fatal complication of computed tomography (CT)‐guided transthoracic needle biopsy (TTNB) of the lung. Here, we report a patient who developed an air embolism after CT‐guided TTNB, which led to ST‐elevation myocardial infarction and acute cerebral ischemia. The patient recovered completely without critical sequelae and was diagnosed with adenocarcinoma harboring activating epidermal growth factor receptor (EGFR) mutation. The patient responded to subsequent treatment with gefitinib. Key points Signficant findings of the study Air embolism is a rare, fatal complication of CT‐guided transthoracic lung biopsy. Only a few cases have been previously reported where myocardial and cerebral infarction occurred after TTNB, demonstrated not only on CT scan, but also electrocardiogram and electroencephalogram. What this study adds Detection of driver gene mutation is crucial for planning lung cancer treatment. Despite the need for tissue biopsy, air embolism propagation to vital organs could result in severe end‐organ damage and multidisciplinary approaches are needed to improve initial outcomes.

Background The fractional exhaled nitric oxide (FENO) test is useful in asthma patients. However, a few studies on its usefulness in chronic obstructive pulmonary disease (COPD) patients have been reported. We analyzed the FENO level distribution and clinical characteristics according to the FENO level in COPD patients. Methods From December 2014 to June 2019, COPD patients who underwent pulmonary function and FENO tests at Chonnam National University Hospital were retrospectively evaluated for FENO, comorbidities, asthma history, blood eosinophil, and pulmonary function test. The high FENO group was defined as those with FENO level>25 parts per billion (ppb). Results A total of 849 COPD patients (mean age, 70.3±9.4 years) were included. The mean forced expiratory volume at 1 second was 66.5±21.7% and the mean FENO level was 24.3±20.5 ppb. Patients with FENO ≤25 ppb were 572 (67.4%) and those with FENO >25 ppb were 277 (32.6%). Blood eosinophil percentage was significantly higher (4.2±4.8 vs. 2.7±2.5, p3% (46.9% vs. 34.8%, p=0.001) and asthma history (25.6% vs. 8.6%, p3%, and positive bronchodilator response (BDR) were independent risk factors for the high FENO level (adjusted odds ratio [aOR], 3.85; p

Abstract Background The concurrence of sarcoidosis and primary lung cancer is very rare. We report a very rare case with a delayed diagnosis of primary lung cancer due to its misdiagnosis as worsening of pulmonary sarcoidosis. Case presentation A 68-year-old man presented to the outpatient department for evaluation of a mass in the right hilar area with lymphadenopathies in subcarinal and both interlobar areas on chest computed tomography (CT). Sufficient core samples were obtained from subcarinal and bilateral interlobar lymph nodes using endobronchial ultrasonography (EBUS) guided transbronchial needle aspiration (TBNA). EBUS could not reach the right hilar lymph node due to its high angle. The pathologic findings were consistent with sarcoidosis. After 5 months, chest CT revealed aggravation of the right upper paratracheal lymphadenopathy. Assuming worsening of sarcoidosis, he was prescribed an oral corticosteroid for 5 months. However, follow-up chest CT showed a newly developed right lower paratracheal lymphadenopathy and worsening right hilar lymphadenopathy. Bronchoscopy and EBUS were performed once again. Transbronchial lung biopsy from the right upper lobe and EBUS-TBNA from the right lower paratracheal lymph node revealed adenocarcinoma from the lung. Conclusions Although coexistence of sarcoidosis and lung cancer is very rare, the clinician should consider the possibility of accompanying lung cancer in sarcoidosis patients who are not responding to initial corticosteroid therapy.

ObjectiveIn-hospital tuberculosis (TB) transmission remains a concern. Airborne infection isolation (AII) can be discontinued in hospitalized patients with suspected active pulmonary TB when the results of three consecutive sputum acid-fast bacilli (AFB) smears are negative. However, fiberoptic bronchoscopy can be performed in patients who may have difficulty in producing sputum samples. This study aimed to investigate the usefulness of Mycobacterium tuberculosis-polymerase chain reaction (MTB-PCR) with bronchial washing specimens in predicting AII discontinuation in hospitalized patients with suspected active pulmonary TB.MethodsWe reviewed the medical charts of patients admitted to a tertiary hospital who were isolated and underwent fiberoptic bronchoscopy for suspicious pulmonary TB from January 2016 to December 2019. Patients with positive MTB-PCR results in the initial sputum examination were excluded. Criteria for discontinuing AII were defined as negative results for three consecutive AFB smears from respiratory specimens, or cases diagnosed other than TB. The study patients were divided into two groups: TB group and non-TB group.ResultsIn total, 166 patients were enrolled in the study. Of them, 35 patients were diagnosed with TB. There was no significant difference between the number of males in the TB (81; 61.8%) and non-TB (21; 60.0%) group. Though 139 patients had negative results on MTB-PCR using washing specimens, eight showed positive AFB culture. Of the 139 patients with negative MTB-PCR results, 138 had negative results for three consecutive AFB smears or were established to not have pulmonary TB. Therefore, the predictive accuracy of MTB-PCR with bronchial washing samples for discontinuing AII was 99.2%.ConclusionAlthough a negative result from MTB-PCR with bronchial washing samples cannot exclude pulmonary TB, it can predict AII discontinuation in hospitalized patients with suspected active pulmonary TB.

ObjectivePulmonary arteriovenous malformation (PAVM) is a rare pulmonary disease. Although most patients with PAVMs are asymptomatic, cerebral complications associated with PAVMs are often fatal. This study aimed to evaluate the risk factors for cerebral complications in patients with PAVMs.MethodsWe retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital.ResultsFifty-five patients diagnosed with PAVMs were enrolled in this study. Most patients were female (89.1%), and the median age was 53 years. Thirty patients (54.5%) had incidentally detected PAVMs without symptoms. Twenty-four patients (43.7%) with PAVMs were treated with embolotherapy or surgery. Thirteen patients (23.6%) had cerebral complications. There was no significant difference in the development of cerebral complications according to treatment; however, older age (≥ 65 years) was associated with the development of new cerebral complications in untreated patients with PAVMs (odds ratio, 17.09; 95% confidence interval, 1.16-250.31; P = 0.038).ConclusionOlder age (≥ 65 years) was a risk factor for the development of cerebral complications in patients with PAVMs; therefore, treatment should be considered in older patients with PAVMs.

Tracheal tumors are rare diseases. They can cause narrowing of a central airway, a severe respiratory distress, and death. The objective of this case series is to highlight the role of rigid bronchoscopy in diagnosing and treating carina masses which are difficult to remove surgically. Tumor excision was performed by the rigid bronchoscopic intervention. Additional treatment was administered according to the diagnosis of each individual patient. After the procedure, patients’ symptoms were improved and stenotic central airways were reopened. Rigid bronchoscopy can be a good therapeutic option to reestablish airway patency and a bridge treatment for further definitive treatment.

BackgroundDendritic cells (DCs) are specialized antigen-presenting cells known to bridge innate and adaptive immune reactions. However, the relationship between circulating DCs and Orientia tsutsugamushi infection is unclear. Therefore, this study aimed to examine the level and function of plasmacytoid DCs (pDCs) and conventional DCs (cDCs), two subsets of circulating DCs, in scrub typhus patients.MethodsThe study included 35 scrub typhus patients and 35 healthy controls (HCs). pDC and cDC levels, CD86 and CD274 expression, and cytokine levels were measured using flow cytometry.ResultsCirculating pDC and cDC levels were found to be significantly reduced in scrub typhus patients, which were correlated with disease severity. The patients displayed increased percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs in the peripheral blood. The alterations in the levels and surface phenotypes of pDCs and cDCs were recovered in the remission state. In addition, the production of interferon (IFN)-α and tumor necrosis factor (TNF)-α by circulating pDCs, and interleukin (IL)-12 and TNF-α by circulating cDCs was reduced in scrub typhus patients. Interestingly, our in vitro experiments showed that the percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs were increased in cultures treated with cytokines including IFN-γ, IL-12, and TNF-α.ConclusionsThis study demonstrates that circulating pDCs and cDCs are numerically deficient and functionally impaired in scrub typhus patients. In addition, alterations in the expression levels of surface phenotypes of pDCs and cDCs could be affected by pro-inflammatory cytokines.

Background/Aims Peripheral eosinophilia during tuberculosis (TB) treatment is common, but has not been fully evaluated. The aim of this study was to determine the prevalence and clinical significance of peripheral blood eosinophilia in patients undergoing anti-TB treatment. Methods We retrospectively reviewed the clinical and laboratory data of patients who received anti-TB treatment and had peripheral blood eosinophilia (> 5% of the total white blood cell count) at the Chonnam National University Hospital between January 2010 and December 2014. Results Of all 2,234 patients with TB who received anti-TB treatment, 397 (17.8%) had peripheral blood eosinophilia. Of the 397 with eosinophilia, we reviewed the data of 262 (66%), and cutaneous adverse drug reactions (CADRs) were observed in 161 (61.5%). Of the 161 with CADRs, itching (47.2%) and skin rash (47.8%) were common. Older age, abnormal liver function, and higher peak blood eosinophil percentage were associated with CADRs in multivariate analysis. There was a significant relationship between increased peak eosinophil counts and the degree of severity of CADRs. Conclusions Peripheral blood eosinophilia is a relatively common occurrence during anti-TB treatment. Peripheral blood eosinophil counts were higher according to the degree of severity of CADRs.

Background Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. Methods We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. Results From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS

ObjectivePneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP.MethodsWe retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC).ResultsThe IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016).ConclusionsPatients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.

ObjectiveThis study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs.MethodsWe retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs).ResultsTwenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2-73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0-3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543).ConclusionsMultiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.

The sensitivity of interferon-gamma release assays (IGRAs) in the detection of Mycobacterium tuberculosis infection could be affected by conditions of immune dysregulation. For this reason, diabetes mellitus (DM) may increase the frequency of indeterminate results of IGRAs. However, there have been inconsistent reports of role of DM on indeterminate IGRA results.We retrospectively reviewed all patients who underwent QuantiFERON-TB Gold In-Tube testing (QFT-GIT) at Chonnam National University Hospital. We collected the clinical and laboratory data of these patients.Of all 3,391 subjects, 1,265 (37.3%) had a positive QFT-GIT result, 266 (7.8%) had an indeterminate result, and 1,860 (54.9%) had a negative result. The mean age was 54.8 ± 18.1 years and 55.0% of the patients were male. There were 512 (15.1%) patients with DM. Multivariable analysis revealed that systemic corticosteroid use, tuberculosis, lymphocytopenia, low serum albumin, and high serum C-reactive protein (CRP) levels were significantly associated with indeterminate QFT-GIT results. However, DM was not associated with indeterminate QFT-GIT results (adjusted odds ratio, 0.98; 95% confidence interval, 0.69-1.41; P = 0.939). After propensity score matching, DM was not associated with indeterminate results of QFT-GIT.In this large cohort study, DM does not affect the incidence of indeterminate results of QFT-GIT.

The presence of human norovirus in the aquatic environment can cause outbreaks related to recreational activities and the consumption of norovirus-contaminated clams. In this study, we investigated the prevalence of norovirus genogroups I (GI) and II (GII) in the coastal aquatic environment in South Korea (March 2014 to February 2015). A total of 504 water samples were collected periodically from four coastal areas (total sites = 63), of which 44 sites were in estuaries (clam fisheries) and 19 were in inflow streams. RT-PCR analysis targeting ORF2 region C revealed that 20.6% of the water samples were contaminated by GI (13.3%) or GII (16.6%). The prevalence of human norovirus was higher in winter/spring than in summer/fall, and higher in inflow streams (50.0%) than in estuaries (7.9%). A total of 229 human norovirus sequences were identified from the water samples, and phylogenetic analysis showed that the sequences clustered into eight GI genotypes (GI.1, 2, 3, 4, 5, 6, 7, and 9) and nine GII genotypes (GII.2, 3, 4, 5, 6, 11, 13, 17, and 21). This study highlighted three issues: 1) a strong correlation between norovirus contamination via inflow streams and coastal areas used in clam fisheries; 2) increased prevalence of certain non-GII.4 genotypes, exceeding that of the GII.4 pandemic variants; 3) seasonal shifts in the dominant genotypes of both GI and GII.