Soon Kew Park

Adipose-Derived Stromal Cells Inhibit Allergic Airway Inflammation in Mice

Allergic asthma is an inflammatory airway disease caused by T helper type 2 (Th2)-driven immune responses. Recent studies have demonstrated that adipose-derived stromal cells (ASC) have an immunosuppressive effect on T-cell activity. This study was performed to investigate whether ASC can inhibit Th2-dependent allergic airway inflammation in mice. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection. To investigate the effect of ASC on the development of asthma phenotypes, 2 × 10⁶ ASC were injected intravenously before OVA challenge. We evaluated the airway hyperresponsiveness (AHR), the proportion of eosinophils and cytokine production in bronchoalveolar lavage fluid (BALF), airway inflammation, and the intracellular cytokine staining of T cells in the BALF and spleen. Airway hyperresponsiveness, airway eosinophilia, and mucus production were markedly reduced after ASC administration before OVA challenge. The increased interleukin (IL)-4, IL-5, and transforming growth factor (TGF)-β1 levels in the BALF after OVA challenge were significantly reduced by the administration of ASC. This inhibition was accompanied by decreased IL-4(+) CD4(+) T cells and increased interferon (IFN)-γ(+) CD4(+) T cells in the BALF and spleen. The results of this study suggest that ASC administration before an allergen challenge inhibits AHR, lung inflammation, and Th2 cytokine production induced by an allergen challenge through inhibition of Th2 cell activity.

pncA mutations in clinical Mycobacterium tuberculosis isolates from Korea

BackgroundPyrazinamide (PZA) is among the first-line drugs for the treatment of tuberculosis. In vitro, it kills semidormant mycobacteria only at low pH. The purpose of this study was to compare PZA resistance with pyrazinamidase (PZase) activity and the genotype to better understand the molecular basis of PZA resistance and to expand the profile of pncA mutations worldwide.ResultsOf the 28 tested strains of Mycobacterium tuberculosis, 6 were susceptible to PZA and positive for PZase activity and had no pncA mutations. Twenty-one strains were resistant to PZA and negative for PZase activity and had mutations in the pncA gene, including 15 point mutations, 5 insertions, and 2 deletions. One strain had no mutation in the pncA gene, even though it was resistant to PZA and negative for PZase activity. Three isolates had adenine to guanine point mutations in the -11 upstream region, making this the most common type of pncA mutations in this study, with at least two different RFLP patterns.ConclusionThese data help in the understanding of the molecular basis of PZA resistance. An adenine to guanine point mutation in the -11 upstream region was the most common type of pncA mutation in our isolates. The results of pncA mutation analyses should be carefully interpreted for epidemiologic purposes.

Patterns of pncA mutations in drug-resistant Mycobacterium tuberculosis isolated from patients in South Korea.

BACKGROUND Pyrazinamide (PZA), one of the most effective anti-tuberculosis drugs, becomes toxic to Mycobacterium tuberculosis when converted to pyrazinoic acid by pyrazinamidase (PZase). PZA resistance is caused mainly by the loss of enzyme activity by mutation. OBJECTIVE To investigate the patterns of pncA mutations in PZA-resistant mycobacteria isolated from South Korean patients. METHODS Mycobacterial isolates with clinically proven drug resistance were cultured to determine susceptibility to anti-tuberculosis agents. pncA mutations were recognised by sequencing and compared with the relevant wild-type DNA sequence. RESULTS Among 108 isolates, 102 were successfully cultured and underwent drug susceptibility testing; all were multidrug-resistant (MDR). pncA mutations were found in 86 cultured isolates (85.1%): 55 (84.6%) in MDR and 31 (86.1%) in extensively drug-resistant isolates. Substitution of a single nucleotide was most common. The most frequent mutations were a deletion that caused a frameshift at nucleotide (nt) 71, a substitution at nt 403 and a substitution at nt 11. Combined, these accounted for ≈ 40% of all mutations. However, 15 samples (14.9%) with defective PZase activity showed no mutation. CONCLUSION pncA mutation in M. tuberculosis is a major mechanism of PZA resistance in MDR isolates from patients in South Korea. The patterns of mutation might be more scattered and diverse. DNA-based diagnosis of PZA resistance has potential for the rapid detection of drug resistance.

Outcome of pandemic H1N1 pneumonia: clinical and radiological findings for severity assessment.

Background/Aims Pandemic influenza A (H1N1) virus infection presents with variable severity. However, little is known about clinical predictors of disease severity. We studied the clinical predictors of severe pandemic H1N1 pneumonia and their correlation with radiological findings. Methods We reviewed medical and radiological records of adults with pandemic H1N1 pneumonia. After classification of patients into severe and non-severe groups, the following data were evaluated: demographic data, pneumonia severity index (PSI), CURB65, risk factors, time to first dose of antiviral medication, routine laboratory data, clinical outcome, and radiological characteristics. Results Of 37 patients with pandemic H1N1 pneumonia, 12 and 25 were assigned to the severe and non-severe groups, respectively. PSI score, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dyhydrogenase (LDH) levels were higher in the severe group than in the non-severe group (p = 0.035, 0.0003, 0.0023, and 0.0002, respectively). AST, ALT, and LDH levels were positively correlated with the radiological findings (p < 0.0001, 0.0003, and < 0.0001, respectively) and with the number of involved lobes (p = 0.663, 0.0134, and 0.0019, respectively). The most common finding on high resolution computed tomography (HRCT) scans was ground-glass attenuation with consolidation (n = 22, 60%), which had a predominantly patchy distribution (n = 31). Conclusions We demonstrated a positive correlation between clinical findings, such as serum AST, ALT, and LDH levels, and radiological findings. A combination of clinical and HRCT indicators would be useful in predicting the clinical outcome of pandemic H1N1 pneumonia.

Macrophage Migration Inhibitory Factor Isolated from a Parasite Inhibited Th2 Cytokine Production in PBMCs of Atopic Asthma Patients

Background. In a previous study, we demonstrated that the human macrophage migration inhibitory factor (MIF)-like protein (As-MIF) isolated from helminths could inhibit allergic airway inflammation via the recruitment of CD4+CD25+Foxp3+ T cells. Objective. To evaluate the clinical importance of As-MIF as an antiasthma drug, we evaluated immune responses after recombinant As-MIF (rAs-MIF) treatment in peripheral blood mononuclear cell (PBMC) cultures. Methods. PBMC was isolated from 10 patients with atopic asthma, 8 patients with nonatopic asthma, and 12 nonatopic healthy subjects, and various concentrations of rAs-MIF were transferred into the PBMC culture medium. After 3 days, we measured the levels of T helper 2 and T helper 1 cytokines via ELISA. Results. In atopic asthma, IL-4 and IL-5 production was significantly reduced in the PBMC cultures after rAs-MIF treatment. These inhibitory effects were not observed in the nonatopic asthma group. By way of contrast, IL-10 production in the PMBC cultures was significantly increased after rAs-MIF treatment in all experimental groups. Conclusion. The results of this study are similar to those previously reported in a mouse study, suggesting that As-MIF might be a candidate for the specific treatment of asthma.

Group 5 drugs for multidrug-resistant tuberculosis: individual patient data meta-analysis

The role of so-called “group 5” second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB. Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death. Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1–6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study. The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority. A meta-analysis of patient data found that group 5 drugs have limited benefit in treating patients with MDR-TB http://ow.ly/TIrH304QBci

Association between the interleukin-18 promoter polymorphism and pulmonary tuberculosis in a Korean population.

OBJECTIVE To examine the role of the -667G/T, -618A/C and -148G/C single nucleotide polymorphisms in the promoter region of the human interleukin (IL) 18 gene in the development of pulmonary tuberculosis (PTB), and its radiographic characteristics and severity. DESIGN Differences in the allele and genotype distributions of the -667G/T, -618A/C, and -148G/C polymorphisms between 251 patients with PTB and 225 healthy controls, between patients with single- and multilobe involvement, and between patients with and without cavities were explored. Serum IL-18 levels were measured using an enzyme-linked immunosorbent assay. RESULTS The -148G/G genotype was more common in patients with cavities than in those without (82.8% vs. 70.9%, P = 0.04), but an analogous trend was not observed for the -667G/T and -618A/C genotypes. However, there were no significant differences in allele and genotype distributions between patients with PTB and healthy controls, or between patients with single- and multilobe involvement (P > 0.05). Serum IL-18 levels were higher in patients with cavities (P = 0.01) and in patients with the -148G/G genotype (P = 0.02). CONCLUSION Considering serum IL-18 levels, the -148G/G genotype is associated with a cavitary formation of PTB rather than its development.

Carbamate poisoning: high resolution CT and pathologic findings.

Carbamate insecticides are commonly used agricultural insecticides. The major cause of morbidity and mortality in acute carbamate poisoning is respiratory failure associated with pulmonary edema. Although carbamate poisoning is well recognized in the clinical literature, the findings of high resolution CT (HRCT) with carbamate have not been reported. We report the radiographic and HRCT findings of a patient with acute carbamate poisoning who had pathologically proven interstitial pneumonitis after resolution of initial pulmonary edema.

Prognostic factors of patients requiring prolonged mechanical ventilation in a medical intensive care unit of Korea.

Background We evaluated the clinical outcomes and prognostic factors of patients requiring prolonged mechanical ventilation (PMV), defined as ventilator care for ≥21 days, who were admitted to the medical intensive care unit (ICU) of a university hospital in Korea. Methods During the study period, a total of 2,644 patients were admitted to the medical ICU, and 136 patients (5.1%) were enrolled between 2005 and 2010. Results The mean age of the patients was 61.3±14.5 years, and 94 (69.1%) were male. The ICU and six-month cumulative mortality rates were 45.6 and 58.8%, respectively. There were 96 patients with tracheostomy placement after admission and their mean period from admission to the day of tracheostomy was 21.3±8.4 days. Sixty-three patients (46.3%) were successfully weaned from ventilator care. Of the ICU survivors (n=74), 34 patients (45.9%) were transferred to other hospitals (not university hospitals). Two variables (thrombocytopenia [hazard ratio (HR), 1.964; 95% confidence interval (CI), 1.225~3.148; p=0.005] and the requirement for vasopressors [HR, 1.822; 95% CI, 1.111~2.986; p=0.017] on day 21) were found to be independent factors of survival on based on the Cox proportional hazard model. Conclusion We found that patients requiring PMV had high six-month cumulative mortality rates, and that two clinical variables (measured on day 21), thrombocytopenia and requirement for vasopressors, may be associated with prognostic indicators.

Comparison of the clinical efficacy and safety of salmeterol/fluticasone propionate versus current care in the management of persistent asthma in Korea

ABSTRACT Objectives: In the Asia-Pacific region there is a general preference for prescribing oral over inhaled medications for the treatment of asthma. This study compared inhaled salmeterol/fluticasone propionate therapy (SFC) with physician-determined current care (CC) in the management of persistent asthma in Korea. Methods: Adult patients with a documented history of reversibility in FEV1 (≥ 12%) or PEF (≥ 15%), were randomised in a 2:1 ratio to unblinded treatment with SFC (50/250 μg bd or 50/500 μg bd) via Diskus (N = 284) or CC (N = 140) for 52 weeks. Morning peak expiratory flow (PEF) (primary endpoint), exacerbations, asthma symptoms and patient-reported outcome measures were recorded. Trial registration: GSK study number:100614. Results: At baseline, mean morning PEF in the SFC and CC group was 374 and 401 L/min respectively. The adjusted mean morning PEF at 52 weeks was 423 ± 3 and 396 ± 4 L/min for SFC and CC respectively (treatment difference of 27 ± 5 in favour of SFC; 95% CI 17, 37; p < 0.0001). The mean rate of exacerbations over 52 weeks was significantly lower in the SFC group (SFC/CC odds ratio 0.57; 95% CI 0.44, 0.74; p < 0.0001). Treatment with SFC also resulted in a significantly greater improvement in asthma symptoms, in the number of patients assessed to have well controlled asthma (Asthma Control Test score ≥ 20), and in a clinically significant improvement in overall Quality of Life. The incidence of adverse events was low and similar between the two groups and events were of the type expected in this population. Conclusions: The results of this open-label, randomised study showed that SFC provided greater asthma control than CC in the management of persistent asthma.