Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic asthma in the elderly.

BACKGROUND: Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma. OBJECTIVE: We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study. METHODS: A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period. RESULTS: At baseline, serum SE-IgE concentrations were significantly higher in patients with asthma than in controls [median 0.16 (interquartile range 0.04-0.53) vs. 0.10 (0.01-0.19), P < 0.001]. Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of covariables [SE-IgE-high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86-30.03, P = 0.005]. Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly.

Development of a genetic marker set to diagnose aspirin-exacerbated respiratory disease in a genome-wide association study.

We developed a genetic marker set of single nucleotide polymorphisms (SNPs) by summing risk scores of 14 SNPs showing a significant association with aspirin-exacerbated respiratory disease (AERD) from our previous 660 W genome-wide association data. The summed scores were higher in the AERD than in the aspirin-tolerant asthma (ATA) group (P=8.58 × 10(-37)), and were correlated with the percent decrease in forced expiratory volume in 1 s after aspirin challenge (r(2)=0.150, P=5.84 × 10(-30)). The area under the curve of the scores for AERD in the receiver operating characteristic curve was 0.821. The best cutoff value of the summed risk scores was 1.01328 (P=1.38 × 10(-32)). The sensitivity and specificity of the best scores were 64.7% and 85.0%, respectively, with 42.1% positive and 93.4% negative predictive values. The summed risk score may be used as a genetic marker with good discriminative power for distinguishing AERD from ATA.

The effect of diabetic control status on the clinical features of pulmonary tuberculosis.

The aim of this study was to determine whether control status of diabetes mellitus influences clinical and radiographic manifestations and treatment responses in patients with tuberculosis (TB). The medical records of 492 patients who started anti-TB medication between January 2005 and December 2009 were retrospectively reviewed. Diabetes was diagnosed in 124 patients (25.2%). Of these, 74 (59.7%) were uncontrolled (HbA1C≥7.0), 25 (20.2%) were controlled (HbA1C<7.0), and HbA1C levels were not assessed in the remaining 25 (20.2%). There were no differences in clinical symptoms between diabetics and non-diabetics, regardless of diabetes control status. There were also no differences in radiographic findings or AFB results between controlled diabetics and non-diabetics. However, uncontrolled diabetics had more cavitary lesions (p=0.008) and higher positive smear rates (p<0.001) compared with non-diabetics. After adjustment for age, cavities and positive smears before initiation of treatment, uncontrolled diabetes was a significant risk factor for a positive sputum culture at 2 months (odds ratio, 4.316; 95% CI, 1.306-14.267; p=0.017). Uncontrolled diabetics seem to have more cavities, higher positive smear rates and lack of culture conversion after two months of therapy. Therefore, TB patients with uncontrolled diabetes should be carefully managed and treated.

Variations in the STK10 gene and possible associations with aspirin-intolerant asthma in a Korean population.

BACKGROUND AND OBJECTIVE: Lymphocyte-oriented kinase deficiency encoded by the serine/threonine kinase 10 (STK10) gene correlates with the intracellular adhesion molecule 1 (ICAM-1)/lymphocyte function associated antigen 1 (LFA-1) complex in aspirin hypersensitivity. This study investigated the association between single nucleotide polymorphisms (SNPs) of STK10 and aspirin-intolerant asthma (AIA). METHODS: A total of 54 SNPs were genotyped in 163 AIA patients and 429 aspirin-tolerant asthma (ATA) controls. RESULTS: Logistic regression revealed that a synonymous variant (rs2306961G>A) had the most significant association with AIA (P = .008 under the codominant model; P = .004 under the dominant model), suggesting that tissue-specific codon usage between Lys_TTT and Lys_CTT could play a role in regulating expression of STK10 in airway epithelium. Haplotype analysis revealed that 4 haplotypes, including STK10_BL4-ht1, which is unique to rs2306961G>A, were significantly associated with aspirin hypersensitivity in asthmatics (P < .05). CONCLUSIONS: Although replications in independent cohorts and further functional evaluations are needed, our preliminary findings suggest that STK10 polymorphisms might be susceptible genetic markers of AIA and that gene expression could be mediated by tissue-specific codon usage.

Poor nutritional intake is a dominant factor for weight loss in chronic obstructive pulmonary disease.

Increase in energy expenditure and/or decrease in nutritional intake leads to low body mass index (BMI). The balance between energy expenditure and nutritional intake has rarely been evaluated in a large population of patients with chronic obstructive pulmonary disease (COPD). To evaluate BMI, nutritional intake and physical activity and the association of these factors with the severity of airflow obstruction in COPD patients. We analysed the Korean National Health and Nutrition Examination Survey (KNHANES) data set from 2012 to 2015. Among the 9682 individuals (1601 with COPD and 8081 without COPD) recruited, BMI was lower in COPD patients than in non-COPD participants (males, 23.86 ± 2.76 vs. 24.28 ± 2.80, P < 0.001; females, 23.63 ± 2.94 vs. 23.98 ± 3.10, P < 0.05). As the stage of COPD advanced, BMI, intake of nutrients (food, water and carbohydrates) and total energy levels declined in COPD patients. Total time spent walking in the preceding week decreased with advancing COPD stage in male patients with COPD. COPD severity was an important risk factor for the limitation of physical activity due to respiratory problems (OR 3.92, 95%CI 2.77∼5.34, P < 0.001). Patients with COPD had a low nutritional intake with little physical activity, which worsened with advancing COPD stage. In late-stage COPD, impaired nutritional intake outweighed the decrease in physical activity, resulting in weight loss. .

Clinical significance of multidetector coronary computed tomography angiography to evaluate the prevalence and severity of coronary artery disease in asymptomatic kidney transplantation recipients.

BACKGROUND: Coronary artery disease (CAD) is one of the leading causes of mortality in kidney transplantation (KT) recipients. Noninvasive coronary angiography with the use of multidetector computerized tomography (MDCT) is feasible with high sensitivity and negative predictive value to evaluate CAD. However, few studies have been conducted to elucidate the applicability of MDCT in KT. This study was designed to evaluate the prevalence and severity of CAD with the use of MDCT angiography in asymptomatic KT recipients. METHODS: From September 2011 to November 2013, MDCT angiography was performed on 90 renal transplant recipients who had no pre-transplantation CAD history and stabilized post-transplantation renal function for 6-18 months. According to the MDCT results, we divided our study population into 2 groups: The no-CAD group (n = 36; 40.0%) and the CAD group (n = 54; 60.0%). Severity of CAD was categorized as follows: mild CAD, 1 vessel obstructive, 2 vessels obstructive (or in the proximal left anterior descending), and 3 vessels obstructive (or left main). RESULTS: Among the risk factors, pre-transplantation diabetes mellitus and lower levels of high-density lipoprotein, higher parathyroid hormone levels, higher coronary artery calcification scores, and rejection episodes were independent factors for CAD. Thirty-two (59.3%) of the CAD group had mild obstructive lesions and 22 (40.7%) had obstructive lesions in >1 vessel according to MDCT angiography. CONCLUSIONS: MDCT angiography is a useful and noninvasive method for detecting CAD even in asymptomatic KT recipients.

Unusually stable helical kink in the antimicrobial peptide--a derivative of gaegurin.

The structure of an active analog of the antibacterial peptide gaegurin was investigated by CD and NMR spectroscopy. The NOE connectivities showed that 21 out of 24 residues formed an a-helix despite the presence of a central proline. CD and NMR analysis indicates that the helix is in fast equilibrium with random coil. From chemical shift analysis of the amide protons, the distances of hydrogen bonding in the helix were calculated, and manifested obvious periodicity which implied a kink in the middle of the helix. 1D amide proton exchange experiments provided further evidence of an exceptionally stable kink. It is inferred that this kink is important not only to the function of the peptide but also to the early stage of the folding as a nucleation site.

Clinical and hemodynamic significance of left ventricular diastolic volume changes by exercise radionuclide ventriculography in coronary artery disease.

Recent studies have suggested that left ventricular (LV) dilatation during exercise radionuclide ventriculography may identify coronary artery disease (CAD). Coronary anatomy and LV end-diastolic pressure at catheterization were compared with results of supine exercise radionuclide ventriculography in 66 patients evaluated for chest pain. Forty-six patients had significant CAD (greater than 75% diameter stenosis) and 20 patients were normal. Radionuclide ventriculography was performed within 18 hours of catheterization, at rest and at peak exercise. Relative LV end-diastolic volumes were extrapolated from end-diastolic counts. LV end-diastolic counts increased during exercise in 19 of 20 normal subjects. In patients with CAD, LV end-diastolic counts increased in 35 (group A) and decreased in 11 (group B). The percent change in LV end-diastolic counts from rest to exercise, rest ejection fraction, exercise ejection fraction and rest LV end-diastolic pressure for each group were 20 +/- 23%, 60 +/- 13%, 67 +/- 13% and 8 +/- 3 mm Hg in normal subjects; 20 +/- 20%, 50 +/- 12%, 47 +/- 13% and 12 +/- 4 mm Hg in group A; and -9 +/- 8%, 54 +/- 21%, 49 +/- 18% and 21 +/- 7 mm Hg in group B (mean +/- standard deviation). An increase in LV end-diastolic counts was unrelated to ejection fraction response or presence of underlying CAD but only correlated to rest LV end-diastolic pressure (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Miliary tuberculosis and acute respiratory distress syndrome.

OBJECTIVE: Miliary tuberculosis is a life-threatening disease caused by the haematogenous spread of Mycobacterium tuberculosis. We evaluated the clinical manifestations of 34 patients with miliary tuberculosis. DESIGN: A retrospective case review. RESULTS: The diagnosis of miliary tuberculosis was based on the identification of miliary nodules on chest radiography and one of the three following criteria: 1) acid-fast bacilli smear and/or culture positive in clinical specimens (22/34), 2) histopathological identification of TB granuloma (6/34), and 3) radiological and clinical improvement after anti-tuberculosis treatment (6/34). The median age (+/-SD) of the patients was 42.7 +/- 21.6 years, with two peaks, in the age group 20-30 and in those over 60. There were 16 underlying diseases in 14 patients, of which liver cirrhosis was the most common. The drug sensitivity pattern was available for 17 isolates of M. tuberculosis: 14 were sensitive, while the other three were resistant to at least one anti-tuberculosis drug. Eight patients developed acute respiratory distress syndrome (ARDS), five of whom died during intensive care. Platelet count, serum albumin and liver enzyme level at the time of admission were significant factors both for ARDS development and for survival. CONCLUSION: ARDS caused by miliary TB is associated with a high fatality rate; scope remains for improvement in its management.

Distribution of tritiated dihydromicrocystin in swine.

The distribution of tritiated dihydromicrocystin [3H]2H-MCLR was studied in anesthetized specific-pathogen-free pigs. Two doses were administered i.m. and one dose was given via an isolated ileal loop. At 4 hr after i.v. administration of the toxin at 25 micrograms/kg, 64.6% of the total dose (%TD) was located in the liver, with smaller amounts distributed to the kidneys (1.2% TD), lungs (1.75% TD), heart (0.22% TD), ileum (0.13% TD) and spleen (0.04% TD). A similar distribution was found at 4 hr postdosing in pigs given 75 micrograms/kg, although the liver contained a lower fraction of the total dose, at 46.99% TD, and the kidneys had somewhat more, at 2.19% TD, than the low dose. At the high dose, the fractions of the amount given accounted for by the lungs (0.55% TD), heart (0.23% TD), ileum (0.20% TD) and spleen (0.07% TD) were similar to those at the low dose. The livers of the pigs given 75 micrograms/kg via the ileal loop, at 5 hr postdosing, contained 49.5% TD and the ileum had 33.94% TD. Smaller amounts were distributed to kidneys (1.04% TD), lungs (0.65% TD), heart (0.81% TD) and spleen (0.16% TD). The livers of both groups dosed at 75 micrograms/kg contained higher concentrations of toxin, but lower percentages of the total dose, than the livers of pigs dosed at 25 micrograms/kg. Larger increases in serum arginase in the two 75 micrograms/kg groups were associated with histological evidence of more severe liver damage than at the 25 micrograms/kg dose. Analysis of radiolabeled compounds from hepatic tissue using fast atom bombardment mass spectrometry determined that the primary constituent was [3H]2H-MCLR, but two minor radioactive components were also isolated. These findings indicate that [3H]2H-MCLR is rapidly concentrated in the liver of swine, whether given i.v. or via an isolated ileal loop, that at extremely toxic doses uptake is slowed, and that it is as toxicologically active as the parent compound.

CT and MR findings of primary cardiac lymphoma: report upon 2 cases and review.

Although primary cardiac lymphoma was a near fatal disease in the past, recent advances in imaging diagnosis and chemotherapy have dramatically improved survival. We describe the CT and MR findings of primary cardiac lymphoma in two immunocompetent subjects who recovered after chemotherapy. The primary cardiac lymphomas manifested as a poorly enhancing mass on CT, relatively hyperintense on a T2-weighted image and a heterogeneously enhanced mass on contrast-enhanced MR. The tumor also showed a predilection for right heart chambers and contiguous infiltration along adjacent structures.

Radiologic findings of Mirizzi syndrome with emphasis on MRI.

We have reported a case of Mirizzi syndrome preoperatively diagnosed using MR cholangiopancreatography. MRCP and T2-weighted image using a single-shot fast spin-echo sequence accurately depicted all components of Mirizzi syndrome, including impacted stone in the neck of the gallbladder compressing the common hepatic duct and wall-thickening of the gallbladder without any evidence of malignancy. The combination of MRCP and T2-weighted image can be counted on to replace conventional modalities of diagnosing Mirizzi syndrome without any loss of diagnostic accuracy.

Prevalence of antibodies to PPD and lipoarabinomannan of Mycobacterium tuberculosis among patients with an indication of fine needle aspiration biopsy.

Recent increase in the incidence of lung cancer often makes it difficult to differentiate between lung cancer and tuberculosis (TB), due to their radiologic similarities. Fine needle aspiration biopsy (FNAB) has been widely employed for the diagnosis of lung cancer and TB, but the diagnostic accuracy of TB is not high enough. As a rapid screening test for tuberculosis, we evaluated serological tests using Mycobacterium tuberculosis PPD and lipoarabinomannan (LAM) antigens. A total of 95 patients with indication of FNAB cytology from initial CT findings were enrolled. 25 patients had TB, 76 thoracic malignancy, and six (7.9%) of the lung cancer patients also had TB, indicating much higher prevalence of TB in thoracic tumor patients. Antibodies to PPD were elevated in 18 (72.0%) of 25 TB patients and in 22 (31.4%) of 70 patients with thoracic malignancy. In contrast, only 3 (4.7%) of 64 healthy controls aged 40 or above were seropositive to PPD antigen. The prevalence of anti-PPD antibodies in thoracic tumor patients was therefore significantly greater than that amongst the healthy controls (p<0.001, chi-square test). However, no significant difference in the prevalence of anti-LAM antibodies was found between study subjects and controls. This study demonstrates that thoracic tumor patients have significantly elevated antibodies to PPD; therefore, high anti-PPD seroreactivity in thoracic tumor patients should be cautiously interpreted. A longitudinal investigation on seropositive thoracic tumor patients is required to determine the role of the serological test for TB in lung cancer patients.

A new antioxidant monoterpene glycoside, alpha-benzoyloxypaeoniflorin from Paeonia suffruticosa.

Alpha-benzoyloxypaeoniflorin (1), a new antioxidant monoterpene alpha-glycoside anomer was isolated from Paeonia suffruticosa along with known compounds, beta-benzoyloxypaeoniflorin (2), paeonolide, paeoniflorin and mudanpioside H. The structure of 1 has been determined by comparing spectral data with those of beta-benzoyloxypaeoniflorin (2). Compound 1 exhibited moderately potent radical scavenging activity on DPPH radical.

Factors related to the development of myelopathy in patients with cervical ossification of the posterior longitudinal ligament.

This study evaluates factors related to myelopathic symptoms in patients with ossification of the posterior longitudinal ligament (OPLL). A total of 87 patients with OPLL were included. Of these, 53 (Group I) had no symptoms or presented with neck pain and radiculopathy and 34 (Group II) had myelopathic symptoms. Gender, age, and history of trauma were evaluated in the two groups. The range of movement of the cervical spine was measured using plain radiographs. The number of involved segments, type of OPLL, and maximal compression ratio were analysed using CT and signal change in the spinal cord was evaluated using MRI. The patients' age was found to be significant (p = 0.001). No difference was found between gender and the range of movement in the two groups. The maximum compression of the spinal canal showed a difference (p = 0.03). The signal change of the spinal cord was different between the two groups. In patients with OPLL of the cervical spine, myelopathic symptoms are not related to the range of movement or the number of involved segments.

The impact of total antioxidant capacity on pulmonary function in asthma patients.

BACKGROUND: Oxidative stress, mediated by an imbalance between oxidants and antioxidants, contributes significantly to the pathogenesis of asthma. OBJECTIVE: To evaluate the impact of serum total antioxidant capacity (TAC) on the pulmonary function of Korean asthma patients. METHOD: A total of 104 adult asthma patients enrolled from the COREA (Cohort for Reality and Evolution of Adult Asthma in Korea) programme participated in the study. Baseline clinical parameters at enrolment, and the results of pulmonary function tests at baseline and 1 and 2 years after enrolment were collected. TAC at baseline was measured using a Trolox-equivalent antioxidant capacity assay. Patients were divided into two groups based on TAC levels, and various clinical parameters were compared. RESULT: Serum TAC levels correlated with forced expiratory volume in 1 second (FEV(1)) at baseline (r = 0.22, P = 0.03). The group with higher baseline TAC levels maintained greater mean FEV(1) both 1 and 2 years after enrolment, even after adjusting for sex, age, height, weight, body mass index and smoking status. CONCLUSION: These results suggest an important link between serum TAC levels and pulmonary function, indicating that higher TAC levels may be a biomarker for favourable prognosis in asthma patients.

Reliability and validity of the St George's Respiratory Questionnaire for asthma.

BACKGROUND: The St George's Respiratory Questionnaire (SGRQ) is a self-administered questionnaire that has been used to evaluate the health-related quality of life of patients with chronic respiratory diseases. OBJECTIVE: To assess the validity and reliability of the SGRQ for a large population with asthma. DESIGN: We used the previously developed Korean version of the SGRQ (SGRQ-K) to assess 676 asthma patients enrolled from the Cohort for Reality and Evolution of Adult Asthma in Korea study. Cronbach's α was used to assess test reliability and Pearson's correlation coefficient was used to assess the correlation between SGRQ scores and various clinical factors. RESULTS: The total SGRQ-K score had acceptable reliability (Cronbach's α = 0.92). The total SGRQ-K score was significantly correlated with symptom duration (r = 0.157, P < 0.001), pulmonary function (% FEV(1) of predicted r = -0.314, P < 0.001; % FVC of predicted r = -0.224, P < 0.001; FEV(1)/FVC r = -0.224, P < 0.001), asthma severity (r = 0.278, P < 0.001) and history of asthma exacerbation. CONCLUSION: With the exception of the SGRQ-K symptoms, SGRQ-K is a reliable and valid test for evaluation of the quality of life of patients with asthma. Scores were well correlated with duration of symptoms, lung function and previous history of asthma exacerbation.