Jae Chol Choi

The Effect of Previous Tuberculin Skin Test on the Follow-up Examination of Whole-Blood Interferon-γ Assay in the Screening for Latent Tuberculosis Infection

BACKGROUND A two-step procedure using a tuberculin skin test (TST) followed by an interferon (IFN)-gamma assay in cases in which the TST result is positive has been advocated to screen for latent tuberculosis infection. However, TST could also boost the in vitro immune response. In this study, we evaluated the effect of TST on the results of the IFN-gamma assay. METHODS Our study included 84 health-care workers who had been working in the department of pulmonary medicine for > 1 year. First, a whole-blood IFN-gamma assay was performed, and then the TST was applied. Two to 4 weeks later, a follow-up IFN-gamma assay was performed. A commercially available IFN-gamma assay (QuantiFERON-TB GOLD; Cellestis Ltd; Carnegie, VIC, Australia) was used. RESULTS Valid TST results were available in 82 individuals because 2 participants refused to undergo the TST after the IFN-gamma assay. The TST result was positive in 36 of 82 participants (42.7%), and the IFN-gamma assay was positive in 16 of 82 participants (19.5%). The overall agreement between the two tests was 67.5% (kappa = 0.31; 95% confidence interval, 0.22 to 0.40). The IFN-gamma levels increased significantly from 0.05 to 0.19 (p = 0.011), and 3 of 18 participants (16.7%) had conversion of their IFN-gamma assay results in the TST-positive group. However, in the TST-negative group, the IFN-gamma levels did not change after the TST. CONCLUSION The agreement between the results of the TST and the IFN-gamma assay was low, and IFN-gamma level could be influenced by the TST, in the TST-positive population, when a follow-up IFN-gamma assay is performed 2 to 4 weeks later.

Familial Occurrence of Pulmonary Embolism after Intravenous, Adipose Tissue-Derived Stem Cell Therapy

The therapeutic potential of human multipotent mesenchymal stromal cells, especially human adipose tissue-derived stem cells (hASC), is promising. However, there are concerns about the safety of infusion of hASC in human. Recently, we have experienced pulmonary embolism and infarct among family members who have taken multiple infusions of intravenous autologous hASC therapy. A 41-year-old man presented with chest pain for one month. Chest CT showed multiple pulmonary artery embolism and infarct at right lung. Serum D-dimer was 0.8 µg/mL (normal; 0-0.5 µg/mL). He had received intravenous autologous adipose tissue-derived stem cell therapy for cervical herniated intervertebral disc three times (one, two, and three months prior to the visit). His parents also received the same therapy five times and their chest CT also showed multiple pulmonary embolism. These cases represent artificial pulmonary embolisms and infarct after IV injection of hASC. Follow-up chest CT showed spontaneous resolution of lesions in all three patients.

HRCT and Whole-Blood Interferon-γ Assay for the Rapid Diagnosis of Smear-Negative Pulmonary Tuberculosis

Background: Early diagnosis of active pulmonary tuberculosis (PTB) is critical for TB control, and difficult in patients with smear-negative sputum. Objective: We wanted to evaluate the usefulness of clinical findings, high-resolution computed tomography (HRCT), interferon-γ-releasing assay (IGRA) and polymerase chain reaction (PCR) of sputum in the diagnosis of smear-negative PTB. Methods: From June 2006 to September 2008, 178 patients with suspected PTB on the basis of clinical and radiological findings visited our institute. After excluding smear-positive cases (n = 77) and cases with an inconclusive diagnosis (n = 17), we studied 84 patients. Their clinical records, HRCT, sputum TB-PCR assay and IGRA results were retrospectively evaluated. A QuantiFeron-TB Gold (QFT-G; Cellestis Ltd., Carnegie, Vic., Australia) assay was used for the IGRA. Results: Active PTB was diagnosed in 40 (48%) of 84 patients; lack of sputum and young age were significantly associated with an increased risk of PTB. The sensitivities of sputum PCR assay, IGRA, and HRCT were 43.2, 84.4 and 80.0%, respectively, and the specificities were 97.7, 82.9 and 70.5%, respectively. Among the 38 patients suspected of having PTB based on HRCT, 24 patients showed positive results on the IGRA, and 23 of these were diagnosed with active PTB. Among the 35 patients suggested not to have TB based on HRCT, 25 showed negative results on the IGRA, and 23 (92%) of these were diagnosed as not to have TB. Conclusion: The combined results of HRCT and the IGRA could help decision-making for early initiation of treatment in smear-negative patients.

A fatal case of intravascular coagulation after bee sting acupuncture.

Bee stings can cause severe adverse reactions, leading to anaphylaxis, cardiovascular collapse, and death. In some cases, bee venom also induces disseminated intravascular coagulation (DIC). However, to our knowledge, there has been no fatal case of intravascular coagulation accompanied by anaphylaxis caused by bee sting acupuncture. Here, we report a fatal case of a 65-year-old woman with DIC, following anaphylactic shock after bee sting acupuncture. This case emphasizes that practitioners should consider anaphylaxis followed by coagulation abnormalities when a patients vital signs are unstable after bee sting acupuncture.

The difference in clinical presentations between healthcare-associated and community-acquired pneumonia in university-affiliated hospital in Korea.

Purpose Healthcare-associated pneumonia (HCAP) has been proposed as a new category of pneumonia. However, epidemiological studies for HCAP in South Korea are limited. This study aimed to reveal the differences between HCAP and community-acquired pneumonia (CAP), especially in elderly patients, in university-affiliated hospital in South Korea. Materials and Methods We conducted a retrospective observational study of patients with HCAP and CAP (older than 60 years old) who were hospitalized between January 2007 and December 2008. We compared the baseline characteristics, comorbidities, severity, pathogen distribution, antibiotics, and clinical outcomes. Results A total of 210 patients were evaluated, including 35 patients with HCAP (17%) and 175 with CAP (83%). The most common causative organism was Streptococcus pneumoniae in CAP (33.3%), whereas, Staphylococcus aureus was most common pathogen in HCAP (40.0%). Initial inappropriate antibiotics (6.3% vs. 22.9%; p < 0.005) and initial treatment failure (15.4% vs. 31.4%; p = 0.018) were more frequent in HCAP than CAP. However, mortality (11.4% vs. 5.7%; p = 0.369) was not different between the two groups. Conclusion The present study provides additional evidence that HCAP should be distinguished from CAP, even in elderly patients, in South Korea. Physicians should consider S. aureus and MDR pathogens in selecting initial empirical antibiotics of HCAP in South Korea.

Copy number variation of CCL3L1 influences asthma risk by modulating IL-10 expression.

BACKGROUND Copy number of Chemokine ligand 3-like 1 (CCL3L1) is associated with various immune disorders. This study was conducted to assess the role of CCL3L1 in asthma by both association analyses of human subjects and in vitro functional analyses. METHODS We analyzed the copy number of the CCL3L1 gene in 533 Korean subjects (372 controls and 161 asthma patients) by real-time PCR, and investigated the effect of recombinant CCL3L1 protein on THP-1 human monocytic cells that were stimulated with house dust mite extract. RESULTS The mean copy number of CCL3L1 in asthma subjects was significantly lower than that of control subjects (3.18 vs. 3.75, p=0.001). A low copy number of ≤1 was significantly associated with increased asthma risk with an odds ratio of 2.47, and a high copy number of ≥5 was associated with decreased asthma risk with an odds ratio of 0.40. Subjects with ≤1 copy of CCL3L1 had significantly lower mRNA levels of CCL3L1 in peripheral blood cells, and significantly higher serum IgE levels (p<0.05). In the house dust mite extract-simulated THP-1 monocytic cells, CCL3L1 protein dose-dependently up-regulated the expression of IL-10, an anti-inflammatory cytokine. CONCLUSION Copy number of CCL3L1 may influence asthma risk by modulating IL-10 expression.

The Role of Keratinocyte-derived Chemokine in Hemorrhage-induced Acute Lung Injury in Mice

Dominant inflammatory cytokines might be different depending on the underlying causes of acute lung injury (ALI). The role of kertinocyte-derived chemokine (KC), a potent chemoattractant for neutrophils, has not been clearly established in hemorrhage-induced ALI. In this study, lung injury and cytokine expressison were evaluated in LPS- or hemorrhage-induced ALI models of BALB/c mice. The myeloperoxidase activities at 4 hr after hemorrhage and LPS-injection were 47.4±13.0 and 56.5±16.4 U/g, respectively. NF-κB activity peaked at 4 hr after hemorrhage, which was suppressed to the control level by anti-high mobility group B1 (HMGB1) antibody. Lung expressions of TNF-α, MIP-2, and IL-1β were increased by LPS injection. However, there was only a minimal increase in IL-1β and no expressions of TNF-α or MIP-2 in hemorrhage-induced ALI. In contrast, lung KC increased significantly at 4 hr after hemorrhage compared to control levels (83.1±12.3 vs. 14.2±1.6 pg/mL/mg by ELISA) (P<0.05). By immunohistochemical staining, lung neutrophils stained positive for KC. Increased KC was also observed in bronchoalveolar lavage fluid and plasma. KC plays an important role in hemorrhage-induced ALI.

Clinical Characteristics According to Sensitized Allergens in Adult Korean Patients With Bronchial Asthma

Purpose Allergic sensitization is a risk factor for the development of bronchial asthma. This study was conducted to investigate clinical manifestations according to sensitized allergens in adult Korean patients with bronchial asthma. Methods In total, 523 adult patients who were diagnosed with bronchial asthma between March 2002 and March 2008 were included in the study. All patients underwent skin prick tests for approximately 45 allergens or a specific IgE test. Sensitized allergens were grouped into the following categories: house dust mites, fungus, pollen, and animal dander. Atopy was defined as a positive skin prick test response or the presence of a specific IgE to one or more allergens. Results Of the 523 patients, 295 (56%) were sensitized to one or more allergens. A younger median age, greater proportion of males, higher eosinophil counts, and higher total IgE levels were observed in the atopic asthma group compared to the non-atopic asthma group. The PC20 value was negatively correlated with eosinophil counts and total IgE in the atopic asthma group. In the subgroup analysis, patients sensitized to Cladosporium showed poorer pulmonary function and a higher response to bronchodilators. In addition, patients sensitized to Alternaria showed severer bronchial hyperresponsiveness than non-atopic patients with asthma. Finally, a gradual increase in the number of sensitized allergens was noted with increasing age, eosinophil counts, and total IgE levels. Conclusions We suggest the need for identifying the existence of atopy and exact offending allergens at the time of asthma diagnosis, since significant differences in sex, age, blood test results, and lung function were observed according to atopy and sensitized allergens.

The effect of diabetes control status on treatment response in pulmonary tuberculosis: a prospective study

Background Uncontrolled diabetes, unlike controlled diabetes, is associated with an impaired immune response. However, little is known about the impact of the status of diabetes control on clinical features and treatment outcomes in patients with pulmonary TB (PTB). We conducted this study to evaluate whether the status of diabetes control influences clinical manifestations and treatment responses in PTB. Methods A multicentre prospective study was performed between September 2012 and September 2014. The patients were categorised into three groups according to the glycated haemoglobin (HbA1C) level: PTB without diabetes mellitus (non-DM), PTB with controlled diabetes (controlled-DM) and PTB with uncontrolled diabetes (uncontrolled-DM). The primary outcome was the sputum culture conversion rate after 2 months of intensive treatment. Results Among 661 patients with PTB, 157 (23.8%) had diabetes and 108 (68.8%) had uncontrolled diabetes (HbA1C≥7.0%). The uncontrolled-DM group exhibited more symptoms, positive sputum smears (p<0.001) and presence of cavities (p<0.001) than the non-DM group. Regarding treatment responses, patients with uncontrolled-DM were more likely to have a positive culture after 2 months (p=0.009) and either treatment failure (p=0.015) or death (p=0.027) compared with the non-DM group. In contrast, those with controlled-DM showed similar treatment responses to the non-DM group. In multivariable analysis, uncontrolled diabetes was an independent risk factor for a positive sputum culture after 2 months of treatment (adjusted OR, 2.11; p=0.042) and either treatment failure or death (adjusted OR, 4.11; p=0.022). Conclusions Uncontrolled diabetes is an independent risk factor for poor treatment response in PTB.

Four Year Trend of Carbapenem-Resistance in Newly Opened ICUs of a University-Affiliated Hospital of South Korea.

Background Carbapenem-resistance is rapidly evolving among the pathogenic microbes in intensive care units (ICUs). This study aimed to determine annual trend of carbapenem-resistance in the ICU for 4 years, since the opening of a university-affiliated hospital in South Korea. Methods From 2005 to 2008, microbial samples from consecutive 6,772 patients were screened in the ICU. Three hundred and ninety-seven patients (5.9%) and their first isolates of carbapenem-resistant pathogens were analyzed. Results The percentage of patients infected with carbapenem-resistant organisms increased constantly during the initial three years (2.3% in 2005, 6.2% in 2006, 7.8% in 2007), then it declined to 6.5% in 2008. Acute Physiology and Chronic Health Evaluation (APACHE) III score at admission was 58.0±23.5, the median length of the ICU stay was 37 days, and the mortality rate was 37.5%. The sampling sites were endotracheal suction (67%), catheterized urine (17%), wound (6%) and others (10%). Bacteria with carbapenem-resistance were Pseudomonas aeruginosa (247 isolates, 62%), Acinetobacter baumannii (117 isolates, 30%), Enterobacteriaceae (12 isolates, 3%), and others (21, 5%). Of note, peak isolation of carbapenem-resistant microorganisms in medical ICU was followed by the same epidemic at surgical ICU. Conclusion Taken together, carbapenem-resistant pathogens are of growing concern in the ICU.