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.

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.

Multicenter Adherence Study of Asthma Medication for Children in Korea.

PURPOSE: Adherence is a major component of successful medical treatment. However, non-adherence remains a barrier to effective delivery of healthcare worldwide. METHODS: Twenty healthcare facilities (secondary or tertiary hospitals) belonging to the Korean Academy of Pediatric Allergy and Respiratory Diseases (KAPARD) participated. Questionnaires were given to patients currently receiving treatment in the form of inhalant useor oral intake or transdermal patch for mild to moderate asthma. RESULTS: A total of 1,838 patients responded to the questionnaire. Mean age was 5.98 ± 3.79 years (range: 0-18 years). With help from their caregivers, the percentage of patients that answered "taking as prescribed" was 38.04% for inhalant users, 50.09% for oral medication users and 67.42% for transdermal users. Transdermal patch users had significantly greater adherence compared to the other 2 groups (P < 0.001). The 34.15% of inhalant users, 70.33% of oral medication users and 93.00% of transdermal patch users felt that their medication delivery system was "Easy" or "Very easy" to use (P < 0.001). "Method of administration" was deemed to be the most difficult part of the treatment regimen to follow, and 76.7% of patients preferred once-daily administration (i.e., "Frequency of administration"). CONCLUSIONS: Asthma medication adherence in young children was found to be better in the transdermal patch group. This may be due to requiring fewer doses and easy to follow instructions. From an adherence point of view, the transdermal patch seems more useful for long-term asthma control in children compared to oral or inhaled medicine.

Increases in airway eosinophilia and a th1 cytokine during the chronic asymptomatic phase of asthma.

BACKGROUND: Studies using allergen challenge models have suggested Th2 cytokines promote airway inflammation in asthma. We assessed mediators of airway inflammation during the chronic asymptomatic phase of asthma. METHODS: Nine non-atopic asthma (NAA) patients, 19 atopic asthma (AA) patients, 20 atopic controls (AC), and 38 normal controls (NC) underwent sputum induction while asymptomatic. Sputum total cell counts and differentials were determined; levels of cytokines IL-4, IL-5, IL-13, GM-CSF, and IFN-gamma, and chemokines eotaxin (CCL11) and RANTES (CCL5) were measured by ELISA; and levels of eosinophil-derived neurotoxin (EDN) were measured by radioimmunoassay. RESULTS: NAA patients showed higher % eosinophils and total eosinophils compared to AA. NAA and AA patients showed higher IFN-gamma and EDN levels compared to AC and NC, with no differences in IL-4, IL-5, or IL-13 levels among the four groups. GM-CSF levels were higher in AA patients compared to AC or NC. In NAA, AA, and AC patients, % eosinophils and EDN levels correlated positively with IFN-gamma, GM-CSF, eotaxin, and RANTES, but not with IL-5 levels. CONCLUSIONS: Baseline airway inflammation of intrinsic and extrinsic asthma is characterized by eosinophilic inflammation and the Th1 cytokine, IFN-gamma. GM-CSF, instead of IL-5, and chemokines may coordinate airway eosinophilia during the chronic asymptomatic phase of asthma.

Acute respiratory distress syndrome by cytomegalovirus infection in an immunocompetent infant.

A 2-month-old female infant was admitted with progressive respiratory distress, fever, and diagnosed with acute respiratory distress syndrome (ARDS). The primary pulmonary pathogen was proven to be cytomegalovirus (CMV) from bronchoalveolar lavage fluid, urine, and blood specimens. Other immunologic findings were normal. CMV-induced ARDS has not been reported previously in immunocompetent infants.

Efficacy of two triple eradication regimens in children with Helicobacter pylori infection.

Triple therapy with bismuth subsalicylate, amoxicillin, metronidazole (BAM) or with omeprazole, amoxicillin, clarithromycin (OAC) has been commonly used for the eradication of Helicobacter pylori infection. We compared the efficacy of these triple therapies in children with H. pylori infection. We retrospectively analyzed results in 233 children with H. pylori infection and treated with OAC (n=141) or BAM (n=92). Overall eradication rates of triple therapy with OAC and BAM were 74% and 85%, respectively, which showed no statistical difference. Our study showed that the triple therapy with BAM was more effective for the first-line eradication of H. pylori infection in Korean children, but has no statistical difference with OAC regimen.