Montelukast treatment response according to eosinophil-derived neurotoxin level in children with allergic rhinitis.

BACKGROUND: Eosinophil-derived neurotoxin (EDN) is an important biomarker of eosinophilic inflammation. METHODS: This study evaluated Montelukast treatment response according to EDN concentration in children with perennial allergic rhinitis (PAR). Fifty-two children with PAR were recruited and took a combination of Montelukast (5mg) and Levocetirizine (5mg) "Mont/Levo Group" or only Montelukast (5mg) "Mont Group" for 4 weeks. All caregivers were instructed to record rhinitis symptoms for 4 weeks. EDN was measured before and after treatment. RESULTS: Daytime nasal symptom scores (DNSS) significantly decreased in both the Mont/Levo (p = 0.0001; n = 20) and Mont Group (p < 0.0001; n = 20), but there were no significant differences between the two groups. EDN concentration also significantly decreased after treatment in both groups (p < 0.0001 and p < 0.001, respectively). For secondary analysis, children with a high initial EDN concentration (EDN ≥ 53 ng/mL) were placed in the "High EDN Group", while those with a lower initial EDN concentration (EDN < 53 ng/mL) were put in the "Low EDN Group". Both groups experienced significant reductions in DNSS after either treatment regimen (p < 0.0001 and p = 0.0027, respectively) but the High EDN Group had greater reductions. EDN concentrations in the High EDN Group decreased significantly from either treatment (p < 0.0001). CONCLUSION: We found that children with AR and a high serum EDN concentration may respond well to Montelukast treatment. A therapeutic strategy using EDN concentrations in patients with AR to evaluate therapeutic response may help improve quality of care.

Comparison of serum eosinophil-derived neurotoxin levels between wheezing and non-wheezing groups in children with respiratory tract infection.

Objective: Eosinophil-derived neurotoxin (EDN) is associated with recurrent wheezing episodes after bronchiolitis, childhood asthma, and allergic rhinitis. We investigated if there is a measurable difference between serum EDN levels in children with wheezing and non-wheezing respiratory infections.Methods: 171 children who visited a university hospital with respiratory infections were enrolled in the study. Subjects were divided into two groups: wheezing (n = 46) and non-wheezing (n = 125). Serum EDN levels were compared.Results: Serum EDN levels in the wheezing group were significantly higher than in the non-wheezing group (P < 0.001). The non-wheezing group was divided into three sub-groups: pneumonia, common cold, and tonsillitis. Serum EDN levels in the wheezing group were significantly higher than in the pneumonia, common cold, or tonsillitis subgroups (P < 0.001). There was no significant difference in serum EDN levels among the pneumonia, common cold, and tonsillitis subgroups.Conclusions: These findings suggest that elevated serum EDN levels could be a distinctive feature of respiratory infections with wheezing. EDN's utility as a biomarker for wheezing-associated disease should be explored through further study.

Utility of serum eosinophil-derived neurotoxin (EDN) measurement by ELISA in young children with asthma.

BACKGROUND: This study was done to compare the efficacy of a recently developed eosinophil-derived neurotoxin (EDN) ELISA kit ("BioTracer™ K® EDN ELISA Kit") to a commercially available EDN ELISA kit ("MBL EDN ELISA Kit") and demonstrate the usefulness of serum EDN measurement in young asthmatic children. METHODS: Forty-eight children with physician-diagnosed asthma (Asthma group) and 31 age-matched normal controls (Control group) were recruited from the Asthma and Allergy Center at Inje University Sanggye Paik Hospital, Seoul, Korea from January 2010 to September of 2012. EDN levels in each serum specimen were measured 2 times using the: 1) BioTracer™ K® EDN ELISA Kit and 2) MBL EDN ELISA Kit at the Inje University Sanggye Paik Hospital laboratory. EDN level measurements in each serum specimen were compared. RESULTS: EDN measurements from the BioTracer™ K® EDN ELISA Kit correlated well with those from the MBL EDN ELISA Kit: r = 0.9472 at the Inje University Sanggye Paik Hospital laboratory. These r values were considered both clinically relevant (i.e., r > 0.85) and statistically significant (p < 0.0001). EDN measurements from both kits positively correlated with asthma symptom severity (p < 0.0001). No serious adverse events occurred during the study. CONCLUSIONS: The BioTracer™ K® EDN ELISA Kit was accurate and useful in measuring EDN levels in young asthma patient serum. Because of our kit's distinct advantages and utility, we suggest this kit can be used for the timely diagnosis, treatment, and monitoring of asthma in asthma patients of all ages, especially those too young to perform pulmonary function tests.

Biomarkers in allergen immunotherapy: Focus on eosinophilic inflammation.

Asthma and allergic rhinitis (AR) are 2 of the most common chronic inflammatory disorders and they appear to be on the rise. Current pharmacotherapy effectively controls symptoms but does not alter the underlying pathophysiology. Allergen immunotherapy (AIT) is an evidence-based therapy for asthma and AR and has been recognized as the only therapeutic method that actually modifies the allergic disease process. There is a lack of objective markers that accurately and reliably reflect the therapeutic benefits of AIT. A biomarker indicating patients that would benefit most from AIT would be invaluable. Eosinophilic inflammation is a cardinal feature of many allergic diseases. Biomarkers that accurately reflect this inflammation are needed to better diagnose, treat, and monitor patients with allergic disorders. This review examines the current literature regarding AIT's effects on eosinophilic inflammation and biomarkers that may be used to determine the extent of these effects.

Eosinophil-derived neurotoxin levels at 3 months post-respiratory syncytial virus bronchiolitis are a predictive biomarker of recurrent wheezing.

OBJECTIVE: To determine whether eosinophil-derived neurotoxin (EDN) is a predictive marker of recurrent wheezing episodes in post-respiratory syncytial virus (RSV) bronchiolitis. METHODS: EDN levels and recurrent wheezing episodes were serially measured in 200 infants hospitalized with RSV bronchiolitis. RESULTS: Serum EDN levels at 3 months correlated significantly with total wheezing episodes at 12 months in the RSV-PLC (n = 71; r = 0.720, p < 0.0001) and RSV-MONT groups (n = 79; r = 0.531, p < 0.001). Positive predictive value of 3-mo EDN level for total wheezing episodes was 57%; negative predictive value, 76%; sensitivity, 72%; specificity, 62%. CONCLUSION: EDN levels have predictive value for the development of recurrent wheezing post-RSV bronchiolitis.

Dexibuprofen for fever in children with upper respiratory tract infection.

BACKGROUND: The aim of this study was to investigate the safety and efficacy of dexibuprofen compared to ibuprofen. METHODS: This double-blind, double-dummy study enrolled patients from January 2008 to May 2009 presenting at one of five tertiary care centers in Seoul, Korea with febrile illness who were then given one of three active treatments: one dose of dexibuprofen 2.5 or 5 mg/kg (DEX 1); dexibuprofen 3.5 or 7 mg/kg (DEX 2); or ibuprofen 5 or 10 mg/kg (control) syrup. Those with a temperature <38.5°C were given the lower dose. Temperature was measured every hour for 4 h. Primary study outcome was mean change in temperature 4 h after one dose. RESULTS: A total of 264 children (aged 6 months-14 years) with febrile illness due to upper respiratory tract infection were consecutively sampled and screened, with 260 randomized. No patients withdrew due to adverse effects. Mean temperature change after 4 h (mean ± SD: DEX 1, 0.99 ± 0.84°C; DEX 2, 1.12 ± 0.92°C; control, 1.38 ± 0.84°C) differed only between DEX 1 and controls (P = 0.007, 95% confidence interval [CI]: -0.61 to -0.15). When groups were subdivided according to initial temperature, there were no significant differences in mean temperature change after 4 h between DEX 2 subgroups (<38.5°C, 0.88 ± 0.86°C; ≥38.5°C, 1.46 ± 0.90°C) and controls (1.07 ± 0.84°C and 1.72 ± 0.91°C, respectively), but there was a significant difference between DEX 1 (≥38.5°C, 1.25 ± 0.76°C) and controls (P = 0.0222, 95%CI: -0.80 to -0.13). There were no significant differences in adverse events among groups. CONCLUSION: Dexibuprofen (3.5 or 7 mg/kg) is as effective and tolerable as ibuprofen for fever caused by upper respiratory tract infection in children.

Eosinophil granule proteins as a biomarker in managing asthma and allergies.

In the past few decades, biomarkers have been successfully used for the diagnosis, treatment, and monitoring of disease. Taking together clinical, genetic, lifestyle, and information on relevant biomarkers, the therapy of diseases can be personalized to an individual. Several novel biomarkers have been recently reported for allergic diseases. However, to interpret the validity of biomarker data, the validation of their reliability, precision, and reproducibility is imperative. Once validated, they can be used in therapeutic product development and in clinical practice. Eosinophils are multifunctional leukocytes and major effector cells that play a crucial role in the immunological mechanisms of allergic disease. Measuring eosinophils has been the gold standard for treating and monitoring eosinophil-related diseases such as asthma, atopic dermatitis, and allergic rhinitis. However, eosinophil numbers/percentages yield little information about eosinophil activity. Eosinophil activation leads to the extracellular release of 4 granule proteins, with the most promising biomarker of the 4 being eosinophil-derived neurotoxin (EDN). EDN is more easily recovered from measuring instruments and cell surfaces than other eosinophil biomarkers because of its weaker electrical charge. EDN is known to be released from eosinophils at a greater efficiency, adding to its recoverability. It also has antiviral activity in respiratory infections associated with allergic disease development in early life (eg, respiratory syncytial virus and human rhinovirus infections in early childhood). EDN can be measured in several body fluids, including blood, urine, sputum, nasal secretions, and bronchoalveolar lavage. EDN is a stable biomarker utilized to precisely diagnose, treat, and monitor many eosinophil-related allergic diseases. This eosinophil granule protein may prove useful in precision medicine approaches and should always be considered as a useful tool for the clinician to give the best patient care possible.

Natural history of eosinophil­derived neurotoxin levels and the onset of allergic airway disease in preschool children.

'Atopic march' is the progression of allergic conditions through infancy and childhood. The present study investigated the association between blood eosinophil-derived neurotoxin (EDN) levels in preschool children with food allergy (FA) or atopic dermatitis (AD) and the onset of allergic airway disease [bronchial asthma (BA), allergic rhinitis (AR)]. A total of 123 children below the age of 1 year were enrolled in the present study, along with controls (n=37). Blood specimens were taken, serum EDN levels were measured and immunoglobulin E was quantified. Finally, a total of 86 subjects were analyzed. EDN values were measured at 3 time-points: before 1 year of age, before 2 years of age and before 3 years of age. The EDN levels were initially similar between those patients who did and those who did not develop allergic airway disease but then markedly diverged at the 2-year time-point (226.6 vs. 65.0 ng/ml; P<0.01) and remained divergent at the 3-year time-point (173.9 vs. 62.7 ng/ml; P<0.01). EDN levels prior to diagnosis were compared between the two groups and they were much higher in the Onset group (n=10) compared to the Non-onset group (n=67) (171.2±34.28 vs. 81.3±10.02 ng/ml; P=0.003), with 4 cases of BA and 6 cases of AR in the Onset group. After diagnosis, EDN levels were compared twice: i) At 1 and 2 years of age; and ii) 1 and 3 years of age. A significant difference was found only in the comparison at 2 years (P=0.001). In conclusion, young children with elevated EDN levels during the FA/AD disease period were more likely to develop allergic airway disease (BA, AR) in their first three years of life. A factor leading to this progression may be increased eosinophil activity.

Curcumin protects retinal pigment epithelial cells against oxidative stress via induction of heme oxygenase-1 expression and reduction of reactive oxygen.

PURPOSE: To determine whether curcumin induces expression of the defensive enzyme heme oxygenase-1 (HO-1) and protects cells against oxidative stress in cultured human retinal pigment epithelial cells. METHODS: Effective concentrations and toxicities of curcumin were determined after 3 h of curcumin treatment with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Confluent human retinal pigment epithelium cell lines (ARPE-19) were preincubated with curcumin and oxidatively challenged with H(2)O(2). HO-1 expression was determined with western blot analysis. To confirm the protective role of HO-1 in oxidative stress, small interfering RNA (siRNA) against HO-1 or inhibitor of HO-1 was treated with curcumin in retinal pigment epithelium cells. Intracellular levels of reactive oxygen species (ROS) were measured with flow cytometry and confocal microscopy. Apoptosis was evaluated with Annexin V-fluoroscein isothiocyanate staining. RESULTS: Curcumin had little cytotoxicity at concentrations less than 30 µM, and HO-1 expression was the highest at the 15 µM concentration. At this concentration, curcumin also increased the cytoprotective effect against the oxidative stress of H(2)O(2) through the reduction of ROS levels in human retinal pigment epithelial cells. Curcumin's effect on the reduction of ROS was mediated by the increase in HO-1 expression. CONCLUSIONS: Curcumin upregulated the oxidative stress defense enzyme HO-1 and may protect human retinal pigment epithelial cells against oxidative stress by reducing ROS levels.

Airway IFN-γ production during RSV bronchiolitis is associated with eosinophilic inflammation.

STUDY OBJECTIVE: This study was designed to investigate the possible role of IFN-γ in eosinophil degranulation that occurs during respiratory syncytial virus (RSV) bronchiolitis. METHODS: Sixty-seven infants, 2-24 months old and hospitalized with their first episode of acute RSV bronchiolitis, were selected for this study. Eosinophil-active cytokine and chemokine profiles in nasal lavage supernatants taken within the first 48 h of admission were determined by a multiplex bead array system (Luminex). Comparisons were made with control (Control group) subjects (n = 20). RESULTS: Nasal IFN-γ levels were significantly higher (P < 0.0001) in RSV bronchiolitis (median = 4.4 pg/ml) infants compared to controls (0.0 pg/ml). IFN-γ levels correlated significantly with the levels of nasal eotaxin (r = 0.566, P < 0.0001), RANTES (r = 0.627, P < 0.0001), GM-CSF (r = 0.849, P < 0.0001), and EDN (r = 0.693, P < 0.001). Nasal interleukin (IL)-4, IL-5, and IL-13 were below sensitivity levels in most RSV bronchiolitis and control subjects. CONCLUSION: These results suggest that IFN-γ may play an important role in eosinophilic inflammation in RSV bronchiolitis.

Increase in eosinophil-derived neurotoxin level in school children with allergic disease.

Background: Eosinophils are major effector cells of allergic disease and excellent markers of eosinophilic inflammation. Accurate and reliable biomarkers are helpful in the diagnosis, treatment, and control of allergic disease. Objective: This study aimed to investigate an alternate marker of eosinophilic inflammation, eosinophil-derived neurotoxin (EDN), in a number of allergic diseases. Methods: Three hundred ninety-six elementary school-age children with various allergic conditions were recruited for this study. Subgroups included food allergies (FAs), atopic dermatitis (AD), bronchial asthma (BA), and allergic rhinitis (AR). EDN levels in these groups were compared to those in 93 healthy controls (HC). Results: All subjects with allergic disease had elevated levels of serum EDN (median [interquartile range]: FA, 124.2 ng/mL [59.13-160.5 ng/mL]; AD, 110.8 ng/mL [57.52-167.9 ng/mL]; BA, 131.5 ng/mL [60.60-171.0 ng/mL]; AR, 91.32 ng/mL [46.16-145.0 ng/mL]) compared to HC (38.38 ng/mL [32.40-55.62 ng/mL]) (p < 0.0001). These elevated levels were consistent throughout the age range (6-12 years) of the healthy study subjects (p = 0.0679). EDN levels also correlated well with total immunoglobulin E (Rs = 0.5599, p < 0.0001). Looking at all individuals with an allergic disease, the area under the curve was 0.790. Conclusions: Direct measures of eosinophilic inflammation are needed for accurate diagnosis, treatment, and monitoring of allergic diseases. EDN may be a worthy biomarker of eosinophil activity and a useful screening tool for allergic diseases including FA, AD, BA, and AR.

Respiratory viruses, eosinophilia and their roles in childhood asthma.

With the advent of highly sensitive and specific screening of respiratory specimens for viruses, new viruses are discovered, adding to the growing list of those associated with wheezing illness and asthma exacerbations. It is not known whether early childhood infections with these viruses cause asthma, and, if so, what exactly are the pathophysiologic mechanisms behind its development. The current consensus is that respiratory viral infection works together with allergy to produce the immune and physiologic conditions necessary for asthma diasthesis. One link between viruses and asthma may be the eosinophil, a cell that plays a prominent role in asthma and allergy, but can also be found in the body in response to viral infection. In turn, the eosinophil and its associated products may be novel therapeutic targets, or at the very least, used to elucidate the complex pathophysiologic pathways of asthma and other respiratory illnesses. Together or separately, they can be used for diagnosis, treatment and monitoring. Not only symptoms, but also the underlying disease mechanisms must be taken into consideration for the optimal care of a patient.

Eosinophil degranulation is more important than eosinophilia in identifying asthma in chronic cough.

OBJECTIVE: We investigated whether eosinophil degranulation is a distinctive feature of asthma and can distinguish between chronic cough patients with asthma and those without. METHODS: Thirty-seven patients, with a chronic cough for more than 1 month, and nine normal individuals (controls) were enrolled. Subjects were divided into two groups: one group with asthma and positive bronchial hyperresponsiveness (BHR) (Asthma group, n = 18) and the other group without asthma and negative BHR (Non-Asthma group, n = 19). From induced sputum, total cell counts and differentials were determined. Myeloperoxidase levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA), and eosinophil-derived neurotoxin (EDN) and major basic protein (MBP) levels were measured by radioimmunoassay. RESULTS: The percentage of sputum eosinophils was increased in the Asthma (p < .001) and Non-Asthma (p < .05) groups compared with the Control group and when comparing the Asthma and Non-Asthma (p < .001) groups. Sputum EDN and MBP levels were increased in the Asthma group compared with the Non-Asthma (p < .05 and p < .05, respectively) and Control groups (p < .05 and p = .055, respectively). However, EDN and MBP levels were not increased in the Non-Asthma group compared with the Control group. The percentage of sputum eosinophils in the Asthma group correlated positively with sputum EDN (Rs = 0.921, p < .001) and MBP (Rs = 0.882, p < .0001) levels and negatively with maxΔFEV(1) (Rs = -0.501, p < .05) (FEV(1), forced expiratory volume in 1 second). Unexpectedly, the percentage of eosinophils in the Non-Asthma group did not correlate significantly with any of these markers. Increased EDN and MBP levels and significant correlations between the percentage of eosinophils and EDN and MBP were only observed in asthma patients. CONCLUSIONS: These findings suggest that eosinophil degranulation is more important than eosinophilia in identifying asthma.

Efficacy of subcutaneous immunotherapy for patients with asthma and allergic rhinitis in Korea: effect on eosinophilic inflammation.

BACKGROUND: Atopic asthma (AA) and allergic rhinitis (AR) are often seen as comorbidities and specific immunotherapy (SIT) is considered evidence-based treatment for them both. OBJECTIVE: The purpose of this study was to evaluate the efficacy of multiallergen subcutaneous SIT (SCIT) in reducing nasal and sputum eosinophilia, symptom scores, and impaired lung function in Korean pediatric patients with AR and AA. METHODS: Children aged 6-15 years with a documented history of bronchial asthma and seasonal/perennial AR were recruited then randomly selected to 1 of 2 groups: "immunotherapy group" (inhaled corticosteroids [ICS] and short-acting beta2-agonist [SABA] + subcutaneous injection of standardized extracts of up to 4 allergens [n = 53]) or "drug only group" (ICS and SABA only [n = 19]). All data were collected retrospectively. RESULTS: Comparing the 2 treatment groups, the immunotherapy group showed a significantly (p = 0.006) greater reduction in nasal eosinophilia over the 3-year treatment period. Only the immunotherapy group exhibited a significant reduction in sputum eosinophilia over the 3-year treatment period (p = 0.003). Fifty-one point one percent of patients in the immunotherapy group showed significant improvement in the methacholine challenge test negative conversion rate compared to only 17.65% in the drug only group (p = 0.0168). There were significantly greater improvements in symptom scores in the immunotherapy group compared to the drug only group. For all allergens tested, only house dust mite reactivity changed significantly over the treatment period and only in the immunotherapy group (Dermatophagoides pteronyssinus [p < 0.0001] and Dermatophagoides farina [p = 0.035]). CONCLUSION: SCIT was associated with greater improvements in lung function and bronchial hyperresponsiveness and reductions in nasal and sputum eosinophilia and allergen reactivity. Changes in symptom scores were also much greater in patients receiving SCIT when compared to those who did not receive it. Korean children with AA and AR respond well to long-term multiallergen SCIT.

Pretreatment with 6-Gingerol Ameliorates Sepsis-Induced Immune Dysfunction by Regulating the Cytokine Balance and Reducing Lymphocyte Apoptosis.

Sepsis is characterized by an initial net hyperinflammatory response, followed by a period of immunosuppression, termed immunoparalysis. During this immunosuppressive phase, patients may have difficulty eradicating invading pathogens and are susceptible to life-threatening secondary hospital-acquired infections. Due to progress in antimicrobial treatment and supportive care, most patients survive early sepsis. Mortality is more frequently attributed to subsequent secondary nosocomial infections and multiorgan system failure. 6-Gingerol is the major pharmacologically active component of ginger. Although it is known to exhibit a variety of biological activities, including anti-inflammation and antioxidation, the role of 6-gingerol in sepsis-induced immune dysfunction remains elusive. Thus, we investigated whether 6-gingerol improves septic host response to infections during sepsis. 6-Gingerol-treated mice showed significantly lower mortality in polymicrobial sepsis induced by cecal ligation and puncture LPS via enhanced bacterial clearance in the peritoneum, blood, and organs (liver, spleen, and kidney) and inhibited the production of TNF-α and IL-6 in TLR2 and/or TLR4-stimulated macrophages. In addition, we demonstrated that survival improvement of secondary infection following septic insult was associated with an initial response of enhanced neutrophil numbers and function at the infection site, reduced apoptosis of immune cells, and a shift from a T helper cell type 2 (Th2) to a T helper cell type 1 (Th1) cytokine balance in the hypoinflammation phase. Our overall findings suggest that 6-gingerol potentially restores sepsis-induced immune dysfunction by shifting the balance of Th1/Th2 and by regulating apoptosis of immune cells.

A randomized intervention of montelukast for post-bronchiolitis: effect on eosinophil degranulation.

OBJECTIVE: To investigate the effect of montelukast on eosinophil degranulation and recurrent wheezing episodes in post-respiratory syncytial virus (RSV) bronchiolitis. STUDY DESIGN: Two hundred infants (age, 6-24 months) who were hospitalized with their first episode of acute RSV bronchiolitis were randomized in a double-blind, placebo-controlled, parallel comparison of 4-mg montelukast granules (RSV-MONT group) or matching placebo (RSV-PLC group) administered for 3 months. Serum eosinophil-derived neurotoxin (EDN) levels were measured (primary outcome), and recurrent wheezing was documented (secondary outcome) for 12 months. Comparisons were made with control subjects (control group, n = 50). RESULTS: At the end of the 3-month treatment period, the RSV-PLC group (n = 71) exhibited significantly elevated EDN levels (P < .0001), and the RSV-MONT group (n = 79) showed significantly decreased EDN levels (P < .01) when compared with the initial levels. As a result, EDN levels in the 2 RSV groups significantly differed at this point (P < .0001) and remained different for the entire 12-month follow-up period. Cumulative recurrent wheezing episodes at 12 months were significantly lower in the RSV-MONT group (P = .039). CONCLUSION: Montelukast treatment reduces eosinophil degranulation and is associated with a decrease in recurrent wheezing episodes in post-RSV bronchiolitis.

The role of TNF-alpha in eosinophilic inflammation associated with RSV bronchiolitis.

The purpose of our study was to investigate whether tumor necrosis factor (TNF)-alpha correlates with eosinophilic inflammation that occurs during a lower respiratory tract infection with the respiratory syncytial virus (RSV) in children. Sixty children with RSV bronchiolitis (RSV group) and 20 healthy children with no respiratory symptoms (Control group) were enrolled. We measured the nasal lavage fluid (NLF) Th2 cytokine (IL-5), proinflammatory cytokine (TNF-alpha, IL-8), eosinophil-active cytokine [granulocyte-macrophage colony stimulating factor (GM-CSF), IFN-gamma], and eosinophil-active chemokine (eotaxin, regulated on activation normal T cell excreted and secreted) levels for both groups. We also measured serum eosinophil-degranulation product (eosinophil-derived neurotoxin; EDN, eosinophil cationic protein; ECP) levels from RSV group. TNF-alpha, IL-8, GM-CSF, IFN-gamma, and eotaxin levels were significantly higher in the RSV group compared with the Control group. TNF-alpha correlated with GM-CSF (r = 0.87, p < 0.0001), IFN-gamma (r = 0.92, p < 0.0001), eotaxin (r = 0.64, p < 0.0001), and IL-8 (r = 0.84, p < 0.0001). TNF-alpha may have an important role in eosinophilic inflammation of airways in children with RSV bronchiolitis.

The roles of a Th2 cytokine and CC chemokine in children with stable asthma: potential implication in eosinophil degranulation.

Th2 cytokine IL-5 and CC chemokine eotaxin are thought to be key regulators of eosinophils in bronchial asthma. However, their involvement in children with stable asthma (SA) has not been determined. We investigated the roles of IL-5 and eotaxin in eosinophil degranulation in children with SA. Induced sputum was obtained from 30 SA, 21 allergic rhinitis (AR), and 22 non-atopic healthy control (HC) children. We measured sputum levels of IL-5, eotaxin, and eosinophil indices [percentage eosinophils, eosinophil-derived neurotoxin (EDN), and eosinophil-cationic protein (ECP)]. We also examined correlations of IL-5 and eotaxin with eosinophil indices. Sputum percentage eosinophils and EDN and ECP levels were significantly higher in the SA group than in the HC group, while only the sputum EDN and ECP levels were significantly higher in the AR group than in the HC group. Unexpectedly, sputum levels of IL-5 were not significantly different among the three groups; however, the levels of eotaxin were higher in the SA group when compared to the HC group. No significant correlations were found between IL-5 and percentage eosinophils, EDN, or ECP levels; in contrast, eotaxin levels correlated significantly with percentage eosinophils (R(s) = 0.638; p = 0.0001), EDN (R(s) = 0.522; p = 0.003), and ECP levels (R(s) = 0.630 and p = 0.0002). The elevated levels and good correlations of eotaxin with sputum eosinophil indices, and no elevation or correlation of IL-5 with these indices, suggest that CC chemokine eotaxin may play a more important role in eosinophil degranulation in children with SA.

Eosinophil-derived neurotoxin in childhood asthma: correlation with disease severity.

BACKGROUND: Eosinophil numbers and eosinophil cationic protein (ECP) levels have been proposed as markers of disease activity; however, the usefulness of eosinophil-derived neurotoxin (EDN)--another eosinophil granular protein--as a marker in pediatric asthma has not been established. OBJECTIVE: The authors compared the concentrations of blood eosinophil counts (TECs), serum ECP, and serum EDN to asthma symptom severity in young children. METHODS: Forty-three young children with asthma (Asthma group: mean age, 2.9 years; range, 1.4-5.0 years) were evaluated during both the acute and stable phases of disease. Asthma severity was measured using a symptom-scoring technique, and serum eosinophil indices (EDN and ECP levels and TECs) were determined. Nineteen age-matched controls (Control group: mean age, 2.7 years; range, 1.0-5.0 years) were used for comparison. RESULTS: Levels of serum EDN, serum ECP, and TECs were significantly higher in children with acute asthma compared with Controls (p < .0001). However, in stable asthma only EDN and ECP levels differed significantly when compared to Controls (p < .0001 and p < .001, respectively). When comparing acute and stable phases, EDN and TECs differed significantly (p < .0001), whereas ECP did not. Symptom scores correlated significantly with EDN (r = 0.850, p < 0.0001), ECP (r = 0.374, p < 0.01) and TECs (r = 0.457, p < 0.01) in acute asthma patients. When symptom scores were divided into three subgroups based on severity, only EDN levels showed significant differences amongst the three groups. CONCLUSION: These findings suggest that serum EDN is a useful marker for identifying disease activity in children with asthma. EDN levels may better reflect disease severity than ECP levels or total eosinophil counts.

Clinical and epidemiological comparison of human metapneumovirus and respiratory syncytial virus in seoul, Korea, 2003-2008.

Human metapneumovirus (HMPV) shares clinical and epidemiological characteristics with well-known respiratory syncytial virus (RSV). The aim of this study was to investigate the clinical and epidemiological differences between HMPV- and RSV-induced wheezing illnesses. A total of 1,008 nasopharyngeal aspirate specimens was collected from 1,008 pediatric patients hospitalized with acute respiratory tract infection at Inje University Sanggye Paik Hospital from December 2003 to April 2008, and tested for seven common respiratory viruses. Conditions classified as wheezing illness were bronchiolitis, reactive airways disease, and bronchial asthma. HMPV caused a significantly lower proportion of wheezing illness when compared to RSV (48.1% vs. 82.2%, P<0.05). HMPV-induced wheezing illness occurred predominantly in older patients when compared to RSV patients (P<0.001). RSV infections peaked in the fall and winter followed by peaks of HMPV infection in winter and spring. Eosinophil counts were significantly higher (P<0.01) in RSV patients when compared to HMPV patients. These results show that human metapneumovirus patients exhibit several different clinical and epidemiological characteristics, such as higher proportion of wheezing illness, age and seasonal incidence, and eosinophil counts, when compared to RSV patients.