Irisin promotes odontogenic differentiation and angiogenic potential in human dental pulp cells.

AIM: To determine whether irisin, a newly discovered myokine that links exercise-induced and metabolic homeostasis, is able to promote odontogenic differentiation and angiogenesis in human dental pulp cells (HDPCs). METHODOLOGY: Cell viability in the presence of irisin was measured. Real-time PCR and Western blot analysis were performed to evaluate the expression levels of irisin, odontogenic and angiogenic markers. The involvement of mitogen-activated protein kinase (MAPK) and the protein kinase B (Akt) signalling pathway was evaluated by Western blot. To evaluate mineralization nodule formation, alkaline phosphatase (ALP) staining and alizarin red S staining were performed. Scratch wound assays were performed to evaluate the effects of irisin on cell migration. The data were analysed using one-way analysis of variance (anova) followed by Tukey post hoc test and Student's t-test. Statistical significance was considered at P < 0.05. RESULTS: Irisin significantly promoted odontogenic differentiation as evidenced by formation of mineralized nodules, induction of ALP activity and upregulation of odontogenic and angiogenic markers (P < 0.05). Scratch wound assays revealed that irisin significantly increased migration of HDPCs (P < 0.05). Phosphorylation of both MAPK and Akt was increased by irisin. MAPK and Akt inhibitors inhibited mineralization, cell migration and the increased expression of odontogenic and angiogenic markers. CONCLUSIONS: Irisin promoted odontogenic differentiation and mineralization and has the potential for angiogenesis through activation of the MAPK and Akt signalling pathways in HDPCs.

A genetic variation in microRNA target site of KRT81 gene is associated with survival in early-stage non-small-cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA-mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (n = 479). Renilla luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs. RESULTS: Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, KRT81 rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50-0.85; P = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of KRT81 in tumor tissues. CONCLUSION: The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.

Parental perceived benefits of OROS-methylphenidate treatment for the child with attention-deficit/hyperactivity disorder and for parents themselves.

Given the shortage of studies on parental perceived benefits of OROS-methylphenidate treatment in Asian populations, we assessed parental response to OROS-methylphenidate treatment of Korean children with attention-deficit/hyperactivity disorder (ADHD), in relation to children's academic performance and behavioral symptoms as well as parental rearing stress and depressive symptoms.We enrolled 132 medication-naïve children with ADHD into a multicenter, open-label, 12-week trial of OROS-MPH. The outcome measures were the ADHD rating scale-IV (ADHD-RS), the comprehensive attention test and academic performance rating scale, and the clinical global impression (CGI)-severity/improvement instrument (for the children) and Beck depression inventory and parenting stress index (for their parents).We found parent-perceived improvements in children's ADHD-related behavioral symptoms and academic function and their parents' depressive symptoms and parenting stress. Investigator-rated ADHD symptoms and subjects' neuropsychological function were also improved (p<0.001).Parents of Korean children with ADHD perceive that OROS-methylphenidate treatment improves their children's academic function and behavior as well as their own child-rearing stress and emotional state. These findings must be interpreted with caution, due to a non-comparative open-label trial.

Ethnic and sex differences in the distributions of body mass index and waist circumference among adults: a binationally representative study in South Korea and the United States.

OBJECTIVE: The ethnic and sex differences in the distributions of body mass index (BMI) and waist circumference (WC) among adults are largely unknown. Therefore, we aimed to investigate the percentiles of BMI and WC in groups divided according to age, sex, and ethnicity. PATIENTS AND METHODS: We conducted a population-based binational study of adults aged ≥20 years based on data from two sources: US National Health and Nutrition Examination Survey (2015 to 2020) and Korea National Health and Nutrition Examination Survey (2016 to 2019). RESULTS: Weight, height, and WC were measured in 13,144 American adults and 30,191 Korean adults. Overall, BMI increased at younger ages and decreased at older ages, which indicates a reversed U-shaped relationship, and differed in terms of age, sex, and ethnicity. Women in the other Hispanic, non-Hispanic white, non-Hispanic black, and "other ethnic groups" showed a common BMI peak at ages 50-54 years. The patterns of WC distribution were similar to those of BMI distribution. CONCLUSIONS: In this binational representative study, we found varied distributions of ethnic and sex differences in BMI and WC. Considering the differences in these distributions may help improve individual and personalized treatment strategies.

Expression and regulation of the CC-chemokine ligand 20 during human tuberculosis.

CC-chemokine ligand 20 (CCL20), a unique chemokine ligand of CC-chemokine receptor 6 (CCR6), play roles in various pathologic conditions. However, the characteristic expression profiles of CCL20 during human tuberculosis (TB) have been largely unknown. The present study analyzed the production and regulatory mechanisms of CCL20 in peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM) from active pulmonary TB patients and healthy controls (HC). The 30-kDa antigen (Ag) of Mycobacterium tuberculosis actively induced the production of CCL20 by human PBMC and MDM. A comparative analysis revealed that the expression of CCL20 protein was prominently up-regulated in PBMC, MDM, bronchoalveolar lavage fluids (not in sera) from TB patients compared with the corresponding cells or body fluids from HC. Blockade of either tumour necrosis factor-alpha or interferon-gamma, but not interleukin-10, significantly attenuated the CCL20 production. In addition, recombinant CCL20 induced CCR6 expression by CD45RO+ T lymphocytes in a dose-dependent manner. Furthermore, the expression of CCR6 was significantly increased in CD45RO+ T lymphocytes from TB patients, as compared with those from HC. Pharmacological inhibition studies showed that the 30-kDa Ag-induced CCL20 mRNA expression involves mitogen-activated protein kinases (MAPK; extracellular signal-regulated kinase 1/2 and p38)- and NF-kappaB-dependent signalling. Collectively, the present study demonstrated that TB patients show the up-regulated expression of CCL20, which is modulated by proinflammatory cytokines, and through MAPK/NF-kappaB-mediated transcriptional mechanisms. The findings suggest important implications of potential roles of CCL20-CCR6 in immunopathogenesis of TB.

Impact of abnormal uptakes in bone scan on the prognosis of patients with lung cancer.

The detection of bone metastases is important in the management of patients with lung cancer because bone metastasis has a major impact on the prognosis and choice of treatment modality. Bone scan has been widely used for early detection of bone metastases but its low specificity complicates confirmation of bone scan findings. To evaluate the effects of abnormal bone scan findings on the prognosis of patients with lung cancer, we retrospectively analyzed the effect of abnormal uptakes on the prognosis of patients with primary lung cancer. The overall survival of patients with abnormal bone uptake was not significantly different from those without abnormal uptake. However, the patients with more than two abnormal bone uptakes had significantly shorter survival than those with no abnormal uptake (P<0.05). To confirm the effect of abnormal bone uptakes on survival, we compared the survival curves of three patient groups without knowledge of bone scan findings: group A, stage I-IIIB with more than two abnormal bone uptakes (potential stage IV); group B, stage IIIB with no abnormal bone uptake (true stage IIIB); and group C, stage IV with no abnormal bone uptake. Group A revealed shorter survival than group B (P<0.05). But, there was no significant difference in survival times between group A and group C. In the Cox regression analysis, the presence of more than two abnormal bone uptakes was a significant prognostic factor (P=0.0277), together with performance status, stage, and albumin. These results suggest that one or two abnormal bone uptake at diagnosis did not affect overall survival of the patients, and that the patients with more than two abnormal bone uptakes are considered as clinical stage IV because of high probability of bone metastases.

Microsatellite alteration in histologically normal lung tissue of patients with non-small cell lung cancer.

Microsatellite alteration (MSA) has been observed in a fraction of non-small cell lung cancer (NSCLC). Most prior studies regarding MSA in lung cancer have usually used adjacent non-malignant lung tissues as a source of constitutional DNA. However, these normal tissues might have genetic alterations because the entire field of bronchial tree is exposed to the same carcinogenic insult. The aim of this study was to search if MSA is present in the histologically normal lung tissue of patients with NSCLC. Tumor and corresponding normal lung tissue specimens were obtained from 20 patients with NSCLC. Normal lung tissue specimens were obtained from either the opposite end of resected surgical samples or as distant from the tumor as possible. They were examined histopathologically and confirmed as normal by H-E stain. Patients' peripheral lymphocytes were used as the source for the normal DNA. Sixteen markers on 3p and 9p (nine and seven markers, respectively) were used. MSA was detected in seven of 20 (35%) histologically normal lung tissue specimens at a frequency similar to that observed in tumor tissue (eight of 20, 40%). Five cases showed MSA in both normal lung tissue and the corresponding tumor. In these five cases, MSA in normal lung tissue was detected at the same microsatellite markers which MSA was detected in the corresponding tumor. The number and size of novel bands in normal lung tissue was identical to that in tumor tissue except in one case. In which case, the same pattern of MSA was found in both normal lung tissue and corresponding tumor tissue at two markers. However, at one marker, while one identical novel band was detected in normal lung tissue and corresponding tumor tissue, another novel band was found only in tumor tissue. In two of 12 patients whose tumor was negative for the presence of MSA, MSA was detected in normal lung tissue. These results indicate that genetic alterations are widely distributed in the lung tissue of patients with lung cancer and provide considerable support for the field cancerization theory. Screening for MSA in resected normal lung tissue might be a new method to identify patients at high risk for developing second primary lung cancers.

STATT: a titrate-to-goal study of simvastatin in Asian patients with coronary heart disease. Simvastatin Treats Asians to Target.

BACKGROUND: Most published studies on the use of lipid-lowering agents to treat hypercholesterolemia have focused on Western populations, with few data on Asian populations. OBJECTIVE: The Simvastatin Treats Asians to Target (STATT) study used a titrate-to-goal protocol to evaluate the efficacy and tolerability of simvastatin 20 to 80 mg/d in the treatment of Asian patients with coronary heart disease. METHODS: This was a multicenter, open-label, uncontrolled, 14-week study in patients with coronary heart disease and serum low-density lipoprotein cholesterol (LDL-C) levels of 115-180 mg/dL and triglyceride levels of < or = 400 mg/dL. The dose of simvastatin was titrated from 20 to 80 mg/d to achieve the National Cholesterol Education Program (NCEP) LDL-C target of < or = 100 mg/dL. The primary efficacy measure was the percentage of patients achieving the NCEP target. Among secondary measures were the percentage of patients achieving European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension target LDL-C levels of < or = 115 mg/dL and the percentage change from baseline in lipid parameters. Tolerability was assessed in terms of the overall incidence of adverse experiences and the incidences of the most commonly reported adverse experiences. RESULTS: The intent-to-treat analysis included 133 Asian patients (93 men, 40 women; mean age, 59.5 years), of whom 125 completed 14 weeks of therapy. Their mean blood pressure was 130.2/79.4 mm Hg. Overall, 104 (78.2%) patients treated with simvastatin achieved LDL-C levels < or = 100 mg/dL at week 14, and 125 (94.0%) achieved this target at some point during the study. Similarly, 122 (91.7%) patients achieved an LDL-C level < or = 115 mg/dL at week 14, and 130 (97.7%) achieved this target at some point during the study. Treatment with simvastatin had favorable effects on the lipid profile, producing significant percentage changes from baseline in all parameters (P < 0.001). Simvastatin was well tolerated across the dose range. Overall, 40 patients (30.1%) had > or = 1 clinical adverse experience. Only 14 (10.5%) had adverse experiences that were possibly, probably, or definitely related to study drug; none of these experiences were considered serious. The most common adverse experiences (> or = 3% incidence) were abdominal pain (6%); chest pain (5%); dizziness (4%); and asthenia/fatigue, fibromyalgia, headache, insomnia, and upper respiratory tract infection (3% each). No new or unexpected adverse experiences were seen at the higher doses. CONCLUSIONS: Simvastatin was effective and well tolerated at doses of 20, 40, and 80 mg/d in Asian patients with coronary heart disease. Titration enabled the majority to achieve target LDL-C levels of < or = 100 mg/dL.

Non-lipid effects of statin on hypercholesterolemic patients established to have coronary artery disease who remained hypercholesterolemic while eating a step-II diet.

BACKGROUND: Results of clinical trials of statin therapy demonstrate that an improvement in incidence of cardiovascular end points and coronary stenosis can be achieved. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that affect endothelial function, such as inflammatory responses, formation of thrombi, and stabilization of plaque. OBJECTIVE: To investigate levels of serologic markers, which may be useful surrogates for activity of vascular disease after administration of statin. METHODS: We administered 20-40 mg simvastatin daily for 14 weeks to 13 patients established to have coronary artery disease who remained hypercholesterolemic during step-II diet therapy. RESULTS: Administration of simvastatin significantly lowered lipoprotein levels and the low: high-density lipoprotein cholesterol level ratio and apolipoprotein B:A-I level ratio compared with pretreatment values (P < 0.01). Administration of simvastatin significantly lowered plasma levels of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-I [33+/-46 and 13+/-19%, respectively (P = 0.027 and 0.020, respectively)]. Furthermore, administration of simvastatin tended to lower plasma levels of plasminogen activator inhibitor type-1 and tumor necrosis factor-alpha [by 20+/-44 and 13+/-29%, respectively (P= 0.066 and 0.110, respectively)]. There were significant inverse correlations between pretreatment levels of MMP-9 and the degree of change in those levels after administration of simvastatin (r = -0.714, P= 0.005). However, there was no significant correlation between levels of lipoprotein and levels of MMP-9, monocyte chemoattractant protein-I, and plasminogen activator inhibitor type-1 during administration of simvastatin. CONCLUSIONS: Our current data support the hypothesis that nonlipid mechanisms elicited by administration of simvastatin contribute to the decrease in incidence of cardiovascular events and explain the early clinical benefit observed in clinical trials, independent of changes in levels of lipoprotein.

Variant angina with a strong spasmodic trait.

A 55-year-old man came to the hospital because of chest pain, mostly occurring in the early morning at rest. He had to get isosorbide dinitrate intravenously with continuous infusion. Following ergonovine provocation test, total occlusion of mid-left anterior descending artery was identified with marked elevation of ST segment as exercise test showed despite isosorbide dinitrate.

Recurrent restenosis following stent and rotational atherectomy of coronary artery stenosis in Takayasu's arteritis.

We report a patient with Takayasu's arteritis who had recurrent restenosis following intracoronary bifurcation stenting of proximal left anterior descending and first diagonal arteries, and rotational atherectomy for in-stent restenosis. After all, the patient underwent coronary artery bypass grafts (CABG) and has remained asymptomatic during 3 months without damaging myocardium. We suggest that endoluminal stenting or rotational atherectomy may be an alternative treatment for the patients with coronary artery stenosis due to active Takayasu's arteritis as a therapy to postpone CABG.

Effect of hormone replacement therapy on nitric oxide bioactivity and monocyte chemoattractant protein-1 levels.

BACKGROUND: Vascular inflammation plays an important role in the pathogenesis of atherosclerosis. We investigated the effect of hormone replacement therapy (HRT) on vasomotor function and monocyte chemoattractant protein (MCP)-1 levels, an important serological marker of inflammation. METHODS: We administered micronized progesterone (MP) 200 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and remaining 5 days off cyclically during 2 months to 20 healthy postmenopausal women (PMW). We measured NO bioactivity and plasma levels of MCP-1 before and after HRT in 20 PMW. And we measured plasma levels of MCP-1 in each 20 subjects of premenopausal women, men <50, and men >50 years, respectively. RESULTS: MP combined with CEE significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P<0.001). PMW receiving HRT had lower levels of MCP-1 than those not receiving HRT (121+/-38 versus 146+/-44 pg/ml, P<0.001). In all comparisons, subjects with high estrogen status had significantly lower MCP-1 levels than subjects with low estrogen status (P<0.001 by ANOVA). Premenopausal women had lower levels of MCP-1 than men of a similar age (106+/-14 versus 164+/-40 pg/ml, P<0.001). PMW not receiving HRT had similar levels of MCP-1 compared with men of a similar age (146+/-44 versus 143+/-29 pg/ml, P=0.816). Premenopausal women had markedly lower levels of MCP-1 than PMW not receiving HRT (106+/-14 versus 146+/-44 pg/ml, P=0.001). PMW receiving HRT had similar levels of MCP-1 compared with premenopausal women (121+/-38 versus 106+/-14 pg/ml, P=0.323). CONCLUSION: These findings might provide at least a partial explanation for the protection against cardiovascular disease experienced by premenopausal women, and the loss of that protection following menopause.

Primary and elective stenting of unprotected isolated left main coronary ostial stenosis in acute coronary syndrome.

Direct surgical angioplasty or coronary artery bypass graft has been done in patients who have left main coronary ostial stenosis. Recent reports have demonstrated that stenting of unprotected left main coronary artery stenosis has been attempted as an alternative to bypass surgery in selected patients with normal LV function. We report two patients with isolated left main coronary ostial stenosis who are undergoing primary and elective stenting, respectively. Major cardiac events did not occur during a 3-month follow-up. This study suggests that stenting of isolated left main coronary ostial stenosis in acute coronary syndrome is feasible and results in excellent outcomes.

Prevalence, awareness, treatment and control of hypertension in adults with diagnosed diabetes: the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV).

We evaluated the prevalence, awareness, treatment and control of hypertension in Korean adults with diagnosed diabetes using nationally representative data. Among subjects aged ≥30 years who participated in the Fourth Korea National Health and Nutrition Examination Survey in 2007 and 2008, a total of 745 subjects (336 men and 409 women) with a previous diagnosis of diabetes mellitus were analyzed. The prevalence of hypertension in adults with diagnosed diabetes was 55.5%. The rates of awareness, treatment and control were 88.0, 94.2, and 30.8%, respectively. Compared with the general population, the prevalence of hypertension in adults with diagnosed diabetes was higher in all age groups in both genders. Factors independently associated with a high prevalence of hypertension included being male, increasing age, single, <9 years of education, the presence of chronic kidney disease risk, hypercholesterolemia (≥240 mg dl(-1)) and high body mass index (≥25 kg m(-2)). Regular medical screening was positively associated with hypertension control, whereas a high triglyceride level (≥150 mg dl(-1)) was inversely associated. A high prevalence and a low control rate of hypertension in adults with diagnosed diabetes suggest that stringent efforts are needed to control blood pressure in diabetic patients.

Ex vivo responses for interferon-gamma and proinflammatory cytokine secretion to low-molecular-weight antigen MTB12 of Mycobacterium tuberculosis during human tuberculosis.

MTB12 protein, also called CFP-2, is a major and early secreted component of Mycobacterium tuberculosis. However, its role during mycobacterial infection has been poorly characterized. In this study, we purified the native MTB12 protein and investigated the profile of MTB12-induced cytokines [interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6], in early tuberculosis (TB) patients (n = 20) and healthy controls (n = 35). The cytokine profiles were compared with those induced by the 30-kDa antigen (Ag). In healthy controls, MTB12-induced IFN-gamma production was markedly decreased in peripheral blood mononuclear cells compared with 30-kDa Ag-induced IFN-gamma. In TB patients, the mean IFN-gamma level induced by MTB12 was lower than that induced by the 30-kDa Ag, albeit the difference was not significant. After 2 months of anti-TB therapy, both the MTB12- and 30-kDa-induced IFN-gamma levels were significantly increased in TB patients. MTB12-induced TNF-alpha and IL-6 levels were prominently upregulated in monocyte-derived macrophages from TB patients, but they were not significantly different from those induced by the 30-kDa Ag. Further, the activation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase was required for the induction of TNF-alpha and IL-6 by MTB12, as well as by the 30-kDa Ag. Collectively, these data suggest that the MTB12 protein plays an essential role for proinflammatory responses through the MAPK pathway during the early stages of human TB, even though its T-cell immunoreactivity is weaker than that of the 30-kDa Ag.

Oviductural carcinoma in B6C3F1 female mice exosed to 0.5 ppm ozone.

The toxicity and carcinogenecity of ozone was evaluated in B6C3F1 mice exposed to 0.5 ppm ozone via inhalation for 12 w, during which no ozone-related deaths occurred. Decreases in mean body weights of both genders exposed to ozone were sporadically seen, and mean absolute and relative weights of several organs from male and female groups receiving ozone were lower than those of respective air-control groups. No ozone-related increased neoplasm incidences were observed in most organs, including the lung; however, oviductural carcinomas were seen in the ozone-exposed females. Although ozone does not induce lung cancer under our experimental condition, it induces oviductural carcinomas in B6C3F1 mice.

Linkage between bronchial responsiveness to methacholine and gene markers of IL-4 cytokine gene cluster and T-cell receptor alpha/delta gene complex in Korean nuclear families.

BACKGROUND: Several candidate genes have been reported to be linked to intermediate phenotypes of asthma in Caucasian populations. OBJECTIVE: To evaluate linkage between phenotypes of asthma and gene markers of high affinity IgE receptor-beta gene (D11S97), IL-4 cytokine gene cluster (IL-4R1), and T-cell receptor alpha/delta gene complex (D14S50) in Korean nuclear families. METHODS: Nuclear families (127 probands and their 130 siblings) for the linkage analysis were ascertained through asthmatic children. Linkages between total serum IgE response, skin responses to common aeroallergens, and bronchial responsiveness to methacholine were performed using a sib-pair approach. RESULTS: The square difference of the slope of the dose-response curve (DRS) between sib-pairs with two IL-4R1 identical alleles was smaller than with one or with neither IL-4R1 identical allele (P = 0.004). As for D14S50, the differences of DRS between sib-pairs with two identical alleles and with one identical allele were smaller than with neither identical alleles (P = 0.01). As for D11S97, no significant differences were observed among the groups with identical alleles of two, one or zero. With regard to total serum IgE levels, no significant linkage was found between this phenotype and the above three gene markers. As for skin responses to common aeroallergens, significant evidence was obtained to establish a linkage between this phenotype and the marker IL-4R1 (P = 0.01). However, no significant linkage was found between this phenotype and the markers D11S97 and D14S50. CONCLUSION: The expression of bronchial responsiveness to methacholine may be influenced by genetic factors in the IL-4 cytokine gene cluster and/or T-cell receptor alpha/delta gene complex, but the genetic influence of the FcepsilonRI-beta gene may be minimal in the expression of bronchial responsiveness in Korean nuclear families.

Specific IgG, but not specific IgE, antibodies to toluene diisocyanate-human serum albumin conjugate are associated with toluene diisocyanate bronchoprovocation test results.

BACKGROUND: The role of specific IgG to toluene diisocyanate (TDI) in the pathogenesis of TDI-induced asthma still remains unclear. OBJECTIVE: We sought to evaluate the clinical significance of serum-specific IgG to TDI-human serum albumin (HSA) conjugate in subjects with TDI-induced asthma compared with specific IgE antibody. METHODS: One hundred three subjects were enrolled and divided into 4 groups according to specific bronchoprovocation test (BPT) results: 50 subjects with TDI-induced asthma with positive results on TDI BPT were defined as group 1, 13 symptomatic workers exposed to TDI with negative results on TDI BPT were defined as group 2, 20 unexposed patients with allergic asthma were defined as group 3, and 20 unexposed healthy control subjects were defined as group 4. Serum-specific IgG and IgE antibodies to TDI-HSA conjugate were detected by means of ELISA. RESULTS: The prevalence of specific IgG antibody to TDI-HSA conjugate was significantly higher in group 1 than in group 2 (46% vs 7.7%, P =.01) or group 3 (0%, P <.01). No significant difference was noted between group 2 and group 3 (P >. 05). However, the prevalence of specific IgE antibody to TDI-HSA conjugate was not significantly different between group 1 and group 2 (14% vs 7.7%, P >.05) or group 2 and group 3 (7.7% vs 0%, P >.05). There was no significant difference in prevalence of specific IgE or specific IgG according to the type of asthmatic response during the TDI BPT (P >.05). Overall, statistically significant association was noted between the prevalence of specific IgE and IgG antibodies in 103 subjects (P <.05), but no difference was noted within group 1 subjects only (P >.05). CONCLUSION: These findings demonstrate that the presence of serum-specific IgG is closely related to TDI BPT results, and it may contribute to the development of TDI-induced asthma.

Skin reactivity to inhalant allergens, total serum IgE levels, and bronchial responsiveness to methacholine are increased in parents of nonatopic asthmatic children.

BACKGROUND: Family studies suggest that asthma has an increased familial occurrence, but the hypothesis of a genetic predisposition to IgE response and bronchial hyperresponsiveness (BHR) on the expression of nonatopic asthma is controversial. OBJECTIVE: The aim of this study was to evaluate familial predisposition to IgE response and BHR on expression of nonatopic asthma. METHODS: One hundred four parents of nonatopic asthmatic children, 154 parents of atopic asthmatic children, 78 parents of atopic nonasthmatic control children, and 80 parents of nonatopic control children provided questionnaire data and underwent allergy skin prick tests with 10 inhalant allergens and methacholine bronchial provocation tests. Total serum IgE levels were determined in 352 parents (134 with atopic asthmatic children, 87 with nonatopic asthmatic children, 65 with atopic control children, and 66 with nonatopic control children). RESULTS: Prevalence of asthma, based on questionnaire data and on BHR to methacholine, was higher among parents of nonatopic asthmatic children (10.6%) and atopic asthmatic children (9.1%) than among those of nonatopic control children (1.3%). BHR to methacholine was higher among parents of nonatopic asthmatic children (19.2%) and atopic asthmatic children (16.2%) than among those of atopic and nonatopic control children (5.1% and 1.3%, respectively). The percentage of positive skin test responses to 10 inhalant allergens was higher among parents of atopic asthmatic children (43.9%), nonatopic asthmatic children (39.4%), and atopic control children (38.5%) than among those of nonatopic control children (23.7%). Geometric means (IU/mL +/- SEM) of total serum IgE were higher among parents of atopic and nonatopic control children than among those of nonatopic control children (2.11 +/- 0.05 vs 2. 20 +/- 0.06 vs 2.09 +/- 0.07 vs 1.92 +/- 0.06). CONCLUSION: Nonatopic asthma runs in families. The prevalence of positive skin test responses to inhalant allergens, BHR to methacholine, and total serum IgE levels is higher among the parents of nonatopic and atopic asthmatic children than among those of nonatopic control children.