Differences in cytokine levels between the nasal polyps of adolescents with local allergic and adolescents with allergic or nonallergic rhinitis.

BACKGROUND: Local allergic rhinitis (LAR) is rhinitis with a localized nasal allergic response in the absence of systemic allergy. This study aimed to evaluate the pathogenesis specific to LAR compared with allergic rhinitis (AR) and nonallergic rhinitis (NAR) by using cytokines from polypous tissues. METHODS: We recruited 43 patients with AR (n = 15; mean age, 17.4 years), LAR (n = 12; mean age, 15.9 years), and NAR (n = 16; mean age, 15.6 years) who underwent polypectomy. Atopic status was defined as presenting a sufficiently high total immunoglobulin E (IgE) serum concentration and skin-prick test or serum allergen test. Immunoassays were performed by using polyp tissue homogenates to quantify the levels of regulated on activation of normal T cell expressed and secreted (RANTES), tumor necrosis factor (TNF) alpha, interleukin (IL) 5, and sera to assess total IgE and eosinophil cationic protein. RESULTS: RANTES levels were higher in patients with LAR than in patients with AR and NAR. There was a significant correlation in the concentration of RANTES between polyp tissue homogenates and serum (R2 = 0.51, p < 0.05). The levels of IL-5, TNF alpha, and interferon gamma also demonstrated positive correlations between polyp tissue homogenates and serum; however, they were not significantly different. CONCLUSION: Results of our study indicated that RANTES may play an important role and contribute to allergic reaction in LAR, and RANTES may be related to the pathogenesis of LAR.

PLD1 activation mediates Amb a 1-induced Th2-associated cytokine expression via the JNK/ATF-2 pathway in BEAS-2B cells.

The purpose of this study was to identify the role of phospholipase D1 (PLD1) in Amb a 1-induced IL-5 and IL-13 expression. When BEAS-2B cells were stimulated with Amb a 1, PLD activity increased, and knockdown of PLD1 decreased Amb a 1-induced IL-5 and IL-13 expression. Amb a 1 also activated the PLCγ/p70S6K/JNK pathway. Furthermore, Amb a 1-induced PLD activation was also attenuated by PLCγ inhibition, and knockdown of PLD1 decreased Amb a 1-induced activation of P70S6K and JNK. When ATF-2 activity was blocked with ATF-2 siRNA, Amb a 1-induced IL-5 and IL-13 expression was completely abolished, indicating that ATF-2 is a transcriptional factor required for the expression of IL-5 and IL-13 in response to Amb a 1. Taken together, we suggest that PLD1 acts as an important regulator in Amb a 1-induced expression of IL-5 and IL-13 via a PLCγ/p70S6K/JNK/ATF-2 pathway in BEAS-2B cells.

Changes in sensitization rate to weed allergens in children with increased weeds pollen counts in Seoul metropolitan area.

The prevalence of allergic diseases in children has increased for several decades. We evaluated the correlation between pollen count of weeds and their sensitization rate in Seoul, 1997-2009. Airborne particles carrying allergens were collected daily from 3 stations around Seoul. Skin prick tests to pollen were performed on children with allergic diseases. Ragweed pollen gradually increased between 1999 and 2005, decreased after 2005 and plateaued until 2009 (peak counts, 67 in 2003, 145 in 2005 and 83 grains/m(3)/day in 2007). Japanese hop pollen increased between 2002 and 2009 (peak counts, 212 in 2006 and 492 grains/m(3)/day in 2009). Sensitization rates to weed pollen, especially ragweed and Japanese hop in children with allergic diseases, increased annually (ragweed, 2.2% in 2000 and 2.8% in 2002; Japanese hop, 1.4% in 2000 and 1.9% in 2002). The age for sensitization to pollen gradually became younger since 2000 (4 to 6 yr of age, 3.5% in 1997 and 6.2% in 2009; 7 to 9 yr of age, 4.2% in 1997 and 6.4% in 2009). In conclusion, sensitization rates for weed pollens increase in Korean children given increasing pollen counts of ragweed and Japanese hop.

Serum leptin and adiponectin levels correlate with exercise-induced bronchoconstriction in children with asthma.

BACKGROUND: Exercise-induced bronchoconstriction (EIB), a form of bronchial hyperresponsiveness (BHR), is common in children with asthma or obesity. Epidemiological studies have shown that asthma and obesity are increasing in parallel, but obesity- and adipokine-related effects on inflammation and BHR have not yet been demonstrated in the human airway. OBJECTIVE: To address the relationship between leptin and adiponectin and EIB in children with asthma. METHODS: Eighty-five prepubertal children between the ages of 6 and 10 years were included in our study. They comprised obese with asthma (n = 19), normal weight with asthma (n = 23), obese without asthma (n = 23), and healthy (n = 20). We measured serum leptin and adiponectin levels. We also performed pulmonary function tests: baseline, postbronchodilator inhalation, methacholine inhalation, and exercise. The area under the forced expiratory volume in 1 second (FEV(1))-time curve quantified the severity of EIB over a 20-minute period after exercise (AUC(20)). RESULTS: The obese children had significantly elevated levels of leptin and reduced levels of adiponectin. The maximum decreases in %FEV(1) and AUC(20) after exercise were positively correlated with leptin levels and negatively with serum adiponectin levels in children with asthma. The odds for having EIB were incrementally and significantly higher for children with higher levels of serum leptin. CONCLUSIONS: Levels of the adipocyte-derived hormones leptin and adiponectin are significantly correlated with BHR induced by exercise challenge in children with asthma. Further studies are needed to elucidate whether the changes in leptin and adiponectin levels bear a causal relationship to the EIB/BHR.

A new mosaic der(18)t(1;18)(q32.1;q21.3) with developmental delay and facial dysmorphism.

We report the case of a 22-month-old boy with a new mosaic partial unbalanced translocation of 1q and 18q. The patient was referred to our Pediatric Department for developmental delay. He showed mild facial dysmorphism, physical growth retardation, a hearing disability, and had a history of patent ductus arteriosus. White matter abnormality on brain magnetic resonance images was also noted. His initial routine chromosomal analysis revealed a normal 46,XY karyotype. In a microarray-based comparative genomic hybridization (aCGH) analysis, subtle copy number changes in 1q32.1-q44 (copy gain) and 18q21.33-18q23 (copy loss) suggested an unbalanced translocation of t(1;18). Repeated chromosomal analysis revealed a low-level mosaic translocation karyotype of 46,XY,der(18)t(1;18)(q32.1;q21.3)[12]/46,XY[152]. Because his parents had normal karyotypes, his translocation was considered to be de novo. The abnormalities observed in aCGH were confirmed by metaphase fluorescent in situ hybridization. We report this patient as a new karyotype presenting developmental delay, facial dysmorphism, cerebral dysmyelination, and other abnormalities.

Serial Changes in Serum Eosinophil-associated Mediators between Atopic and Non-atopic Children after Mycoplasma pneumoniae pneumonia.

PURPOSE: Mycoplasma pneumoniae pneumonia (MP) is associated with the exacerbation, timing, and onset of asthma. The goal of this study was to elucidate the impact of MP on eosinophil-related hyper-reactive amplification in atopic children. METHODS: We studied 48 patients with MP (26 atopic, 22 non-atopic), between 3 and 12 years of age. Serial changes in blood eosinophil counts, serum interleukin-5 (IL-5), and serum eosinophil cationic protein (ECP) levels were measured in atopic and non-atopic children with MP upon admission, recovery, and at 2 months post-recovery. Serum IL-5 and ECP levels were measured by enzyme-linked immunosorbent assays; eosinophil counts were measured using an autoanalyzer. RESULTS: Serial changes in serum IL-5, ECP, and total eosinophil counts were significantly higher in atopic patients, relative to non-atopic controls (P≤0.001). Serum IL-5 and ECP levels were significantly higher in atopic patients at all three time points tested, while eosinophil counts were higher in the clinical recovery and follow-up phases, but not in the acute phase. Furthermore, among atopic patients, serum ECP levels were significantly higher in the recovery and follow-up phases than in the acute phase. CONCLUSIONS: The present study demonstrated significant differences in eosinophil counts, serum IL-5, and serum ECP levels between atopic and non-atopic children with MP at admission, recovery, and 2 months after clinical recovery. These outcomes are suggestive of eosinophil-related hyperreactivity in atopic children, with this status maintained for at least 2 months after MP.

Ratio of leukotriene e(4) to exhaled nitric oxide and the therapeutic response in children with exercise-induced bronchoconstriction.

PURPOSE: This study assessed the association between the ratio of leukotriene E(4) (LTE(4)) to fractional exhaled nitric oxide (FE(NO)) in the response of children with exercise-induced bronchoconstriction (EIB) enrolled in a therapeutic trial with montelukast or inhaled corticosteroid (fluticasone propionate [FP]). METHODS: Children aged 6 to 18 years with EIB were randomized in a 4-week, placebo-controlled, double-blinded trial with montelukast or FP. Before and after treatment, treadmill exercise challenges were performed. The LTE(4) levels in the induced sputum and urine and the FE(NO) levels were measured in subjects before and 30 minutes after the exercise challenges. The same tests were conducted after treatment. RESULTS: A total of 24 patients completed the study: 12 in the montelukast group and 12 in FP group. Both study groups displayed a similar postexercise maximum decrease in forced expiratory volume in one second (FEV1) before treatment as well as after treatment. However, there were significant differences in the magnitude of change between the two (Δ; -18.38±14.53% vs. -4.67±8.12% for the montelukast and FP groups, respectively; P=0.021). The Δ logarithmic sputum baseline and postexercise LTE(4)/FE(NO) ratio were significantly lower in the montelukast group than in the FP group (baseline; -0.09±0.21 vs. -0.024±0.03, P=0.045; postexercise, -0.61±0.33 vs. -0.11±0.28, P=0.023). CONCLUSIONS: These data indicate that the efficacy of montelukast for preventing a maximum decrease in FEV1 after exercise is significantly higher than that of FP, and the high LTE(4)/FE(NO) ratio is associated with a greater response to montelukast than to FP for EIB therapy. These results suggest that LTE(4) may play an important role in EIB.

Neurological and muscular manifestations associated with influenza B infection in children.

BACKGROUND: Influenza viruses have been associated with various neurological and muscular symptoms. The aim of this study was to evaluate the pediatric neurological and muscular manifestations of influenza B during a 5-month epidemic at a single center. METHODS: We retrospectively reviewed the medical records of 355 pediatric patients with laboratory-confirmed influenza B infection. RESULTS: Neurological and muscular symptoms were exhibited by 28 patients (7.9%). The mean age was 48.7 ± 25.2 months. The mean time between respiratory symptoms and neurological symptoms was 2.2 ± 1.5 days. The most common symptom was seizure (19/28, 67.9%), followed by myositis (5/28, 17.9%), increased intracerebral pressure (1/28, 3.6%), delirium (1/28, 3.6%), and severe headache (1/28, 3.6%). There was one severe case of meningitis with myocarditis (1/28, 3.6%). All seizures were febrile: 15 simple febrile seizures (78.9%), three complex febrile seizures (15.8%), and one febrile status epilepticus (5.3%). The mean age of nine patients with their first seizures was 37.9 ± 22.2 months, which was older than the typical age of onset for febrile seizure. All the patients, except one, were treated with oseltamivir. There were no deaths or chronic debilitating sequelae. CONCLUSIONS: The neurological and muscular complications of influenza B infection in children are relatively mild, and febrile seizure is the most common. However, clinicians should be alert to the possibility of rare severe complications during influenza B outbreaks.

Mycoplasma pneumoniae Infection Affects the Serum Levels of Vascular Endothelial Growth Factor and Interleukin-5 in Atopic Children.

PURPOSE: Previous studies have outlined mechanisms by which Mycoplasma pneumonia (M. pneumonia) infection may promote allergic lung inflammation and airway remodeling, and increasing evidence from human studies suggests that atypical bacterial infections contribute to asthma exacerbation, chronic asthma, and disease severity with changes in cytokine expression. The present study evaluated changes in serum levels of vascular endothelial growth factor (VEGF) and interleukin (IL)-5 in atopic children with Mycoplasma pneumoniae pneumonia. METHODS: We recruited a total of 72 children with pneumonia. The patients were divided into 4 groups: atopic children with M. pneumonia pneumonia (group I, n=24), non-atopic children with M. pneumonia pneumonia (group II, n=23), atopic children with viral pneumonia (group III, n=13), and non-atopic children with viral pneumonia (group IV, n=12). Serum levels of IL-5, IL-13, VEGF, and tumor necrosis factor-α were measured at admission and at recovery using enzyme-linked immunosorbent assays. RESULTS: Serum levels of VEGF and IL-5 were elevated in group I compared with the other groups at both admission phase and clinical recovery phase. In group I, serum levels of VEGF and IL-5 were higher at recovery phase than at admission phase (VEGF: 1,102.2±569.4 vs. 874.9±589.9 pg/mL, respectively; IL-5: 150.5±63.9 vs. 120.2±46.7 pg/mL, respectively). CONCLUSIONS: The serum levels of VEGF and IL-5 were more increased in atopic children with M. pneumonia pneumonia than in the other groups. In this group, the serum levels of VEGF and IL-5 were more increased at recovery phase than at admission phase. The results of this study suggest that increases in VEGF and IL-5 may contribute to the development of hypersensitivity during M. pneumonia infection. These cytokines may act through their respective pro-inflammatory pathways to aggravate the allergic status and induce airway hypersensitivity during M. pneumonia pneumonia in atopic children.

The revised edition of korean calendar for allergenic pollens.

The old calendar of pollens did not reflect current pollen distribution and concentrations that can be influenced by changes of weather and environment of each region in South Korea. A new pollen calendar of allergenic pollens was made based on the data on pollen concentrations obtained in eight regions nationwide between 1997 and 2009. The distribution of pollen was assessed every day at 8 areas (Seoul, Guri, Busan, Daegu, Jeonju, Kwangju, Kangneung, and Jeju) for 12 years between July 1, 1997 and June 30, 2009. Pollens were collected by using Burkard 7-day sampler (Burkard Manufacturing Co Ltd, UK). Pollens which were stained with Calberla's fuchsin staining solution were identified and counted. Pine became the highest pollen in May, and the pollen concentrations of oak and birch also became high. Ragweed appeared in the middle of August and showed the highest pollen concentration in the middles of September. Japanese hop showed a high concentration between the middle of August and the end of September, and mugwort appeared in the middles of August and its concentration increased up until early September. In Kangneung, birch appeared earlier, pine showed a higher pollen concentration than in the other areas. In Daegu, Oriental thuja and alder produced a large concentration of pollens. Pine produced a large concentration of pollens between the middle of April and the end of May. Weeds showed higher concentrations in September and mugwort appeared earlier than ragweed. In Busan the time of flowering is relatively early, and alder and Oriental thuja appeared earliest among all areas. In Kwangju, Oriental thuja and hazelnut appeared in early February. Japanese cedar showed the highest pollen concentration in March in Jeju. In conclusion, update information on pollen calendar in South Korea should be provided for allergic patients through the website to manage and prevent the pollinosis.

Long-term Efficacy of Intravenous Immunoglobulin Therapy for Moderate to Severe Childhood Atopic Dermatitis.

PURPOSE: The present study investigates the long-term effects of intravenous immunoglobulin (IVIg) therapy for the treatment of moderate to severe childhood atopic dermatitis (AD). Previous research indicates that IVIg can treat severe AD; however, the effectiveness of IVIg has not been confirmed in prospective, blinded clinical trials. METHODS: Forty eligible children with moderate to severe AD, as defined by the criteria of Hanifin and Rajka, were enrolled in a randomized, placebo-controlled study. After the completion of an initial screening visit (V0), the patients were randomly allocated into therapy (n=30) and control (n=10) groups (V1). Thirty children were each treated with three injections of 2.0 g/kg IVIg at 1-month intervals over a 12-week period. Ten children were treated with placebo. Assessments were conducted after each injection (V2, V3, and V4) and at 3 (V5) and 6 months (V6) after completed treatment. RESULTS: The disease severity index was significantly decreased at V5 compared with the value at V1 (P<0.05). There were no significant changes in the total IgE level or total eosinophil count in peripheral blood at the last injection (V4) compared with the value at V1. The interleukin (IL)-5/interferon (IFN)-γ ratio was assessed in T-helper 1 (Th1) and Th2 cells. The ratio significantly decreased between V1 and V5, after which it increased, such that the ratio at V6 was not significantly different from that at V1. Compared with the level at V1, the intercellular cell adhesion molecule-1 level at V4 did not differ significantly, but the level at V5 was lower. CONCLUSIONS: This study suggests that IVIg therapy may clinically improve AD in patients after 3 months of therapy, but the improvement may decline by 6 months after therapy.